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Sample records for fxr accelerator optimization

  1. FLASH X-RAY (FXR) LINEAR INDUCTION ACCELERATOR (LIA) OPTIMIZATION Upgrade of the OTR Emittance Diagnostic

    SciTech Connect

    Houck, T L; Wargo, P E

    2006-12-01

    Knowing the electron beam parameters at the exit of an accelerator is critical for several reasons. Foremost is to optimize the application of the beam, which is flash radiography in the case of the FXR accelerator. The beam parameters not only determine the theoretical dose, x-ray spectrum, and radiograph resolution (spot size), they are required to calculate the final transport magnetic fields that focus the beam on the bremsstrahlung converter to achieve the theoretical limits. Equally important is the comparison of beam parameters to the design specifications. This comparison indicates the ''health'' of the accelerator, warning the operator when systems are deteriorating or failing. For an accelerator of the size and complexity of FXR, a large suite of diagnostics is normally employed to measure and/or infer beam parameters. These diagnostics are distributed throughout the accelerator and can require a large number of ''shots'' (measurements) to calculate a specific beam parameter. The OTR Emittance Diagnostic, however, has the potential to measure all but one of the beam parameters simultaneous at a specific location. Using measurements from a scan of a few shots, this final parameter can also be determined. Since first deployment, the OTR Emittance Diagnostic has been limited to measuring only one of the seven desired parameters, the beam's divergence. This report describes recent upgrades to the diagnostic that permit full realization of its potential.

  2. FXR LIA Optimization - Time-resolved OTR Emittance Measurement

    SciTech Connect

    Jacob, J; Ong, M; Wargo, P; LeSage, G

    2005-07-21

    The Flash X-Ray Radiography (FXR) facility at Lawrence Livermore National Laboratory utilizes a high current, long pulse linear induction accelerator to produce high doses of x-ray radiation. Accurate characterization of the transverse beam emittance is required in order to facilitate accelerator modeling and tuning efforts and, ultimately, to optimize the final focus spot size, yielding higher resolution radiographs. In addition to conventional magnet scan, pepper-pot, and multiple screen techniques, optical transition radiation (OTR) has been proven as a useful emittance measurement diagnostic and is particularly well suited to the FXR accelerator. We shall discuss the time-resolved emittance characterization of an induction linac electron beam using OTR, and we will present our experimental apparatus and analysis software. We shall also develop the theoretical background of beam emittance and transition radiation.

  3. The LLNL Flash X-Ray Induction Linear Accelerator (FXR)

    SciTech Connect

    Multhauf, L G

    2002-09-19

    The FXR is an induction linear accelerator used for high-speed radiography at the Lawrence Livermore National Laboratory's Experimental Test Site. It was designed specifically for the radiography of very thick explosive objects. Since its completion in 1982, it has been very actively used for a large variety of explosives tests, and has been periodically upgraded to achieve higher performance. Upgrades have addressed machine reliability, radiographic sensitivity and resolution, two-frame imaging by double pulsing improvements that are described in detail in the paper. At the same time, the facility in which it was installed has also been extensively upgraded, first by adding space for optical and interferometric diagnostics, and more recently by adding a containment chamber to prevent the environmental dispersal of hazardous and radioactive materials. The containment addition also further expands space for new non-radiographic diagnostics. The new Contained Firing Facility is still in the process of activation. At the same time, FXR is continuing to undergo modifications aimed primarily at further increasing radiographic resolution and sensitivity, and at improving double-pulsed performance.

  4. Activators of the nuclear hormone receptors PPARalpha and FXR accelerate the development of the fetal epidermal permeability barrier.

    PubMed Central

    Hanley, K; Jiang, Y; Crumrine, D; Bass, N M; Appel, R; Elias, P M; Williams, M L; Feingold, K R

    1997-01-01

    Members of the superfamily of nuclear hormone receptors which are obligate heterodimeric partners of the retinoid X receptor may be important in epidermal development. Here, we examined the effects of activators of the receptors for vitamin D3 and retinoids, and of the peroxisome proliferator activated receptors (PPARs) and the farnesoid X-activated receptor (FXR), on the development of the fetal epidermal barrier in vitro. Skin explants from gestational day 17 rats (term is 22 d) are unstratified and lack a stratum corneum (SC). After incubation in hormone-free media for 3-4 d, a multilayered SC replete with mature lamellar membranes in the interstices and a functionally competent barrier appear. 9-cis or all-trans retinoic acid, 1,25 dihydroxyvitamin D3, or the PPARgamma ligands prostaglandin J2 or troglitazone did not affect the development of barrier function or epidermal morphology. In contrast, activators of the PPARalpha, oleic acid, linoleic acid, and clofibrate, accelerated epidermal development, resulting in mature lamellar membranes, a multilayered SC, and a competent barrier after 2 d of incubation. The FXR activators, all-trans farnesol and juvenile hormone III, also accelerated epidermal barrier development. Activities of beta-glucocerebrosidase and steroid sulfatase, enzymes previously linked to barrier maturation, also increased after treatment with PPARalpha and FXR activators. In contrast, isoprenoids, such as nerolidol, cis-farnesol, or geranylgeraniol, or metabolites in the cholesterol pathway, such as mevalonate, squalene, or 25-hydroxycholesterol, did not alter barrier development. Finally, additive effects were observed in explants incubated with clofibrate and farnesol together in suboptimal concentrations which alone did not affect barrier development. These data indicate a putative physiologic role for PPARalpha and FXR in epidermal barrier development. PMID:9239419

  5. Structural Investigation for Optimization of Anthranilic Acid Derivatives as Partial FXR Agonists by in Silico Approaches

    PubMed Central

    Chen, Meimei; Yang, Xuemei; Lai, Xinmei; Kang, Jie; Gan, Huijuan; Gao, Yuxing

    2016-01-01

    In this paper, a three level in silico approach was applied to investigate some important structural and physicochemical aspects of a series of anthranilic acid derivatives (AAD) newly identified as potent partial farnesoid X receptor (FXR) agonists. Initially, both two and three-dimensional quantitative structure activity relationship (2D- and 3D-QSAR) studies were performed based on such AAD by a stepwise technology combined with multiple linear regression and comparative molecular field analysis. The obtained 2D-QSAR model gave a high predictive ability (R2train = 0.935, R2test = 0.902, Q2LOO = 0.899). It also uncovered that number of rotatable single bonds (b_rotN), relative negative partial charges (RPC−), oprea's lead-like (opr_leadlike), subdivided van der Waal’s surface area (SlogP_VSA2) and accessible surface area (ASA) were important features in defining activity. Additionally, the derived3D-QSAR model presented a higher predictive ability (R2train = 0.944, R2test = 0.892, Q2LOO = 0.802). Meanwhile, the derived contour maps from the 3D-QSAR model revealed the significant structural features (steric and electronic effects) required for improving FXR agonist activity. Finally, nine newly designed AAD with higher predicted EC50 values than the known template compound were docked into the FXR active site. The excellent molecular binding patterns of these molecules also suggested that they can be robust and potent partial FXR agonists in agreement with the QSAR results. Overall, these derived models may help to identify and design novel AAD with better FXR agonist activity. PMID:27070594

  6. Design of a High Field Stress, Velvet Cathode for the Flash X-Ray (FXR) Induction Accelerator

    SciTech Connect

    Houck, T; Brown, C; Fleming, D; Kreitzer, B; Lewis, K; Ong, M; Zentler, J

    2007-06-08

    A new cathode design has been proposed for the Flash X-Ray (FXR) induction linear accelerator with the goal of lowering the beam emittance. The original design uses a conventional Pierce geometry and applies a peak field of 134 kV/cm (no beam) to the velvet emission surface. Voltage/current measurements indicate that the velvet begins emitting near this peak field value and images of the cathode show a very non-uniform distribution of plasma light. The new design has a flat cathode/shroud profile that allows for a peak field stress of 230 kV/cm on the velvet. The emission area is reduced by about a factor of four to generate the same total current due to the greater field stress. The relatively fast acceleration of the beam, approximately 2.5 MeV in 10 cm, reduces space charge forces that tend to hollow the beam for a flat, non-Pierce geometry. The higher field stress achieved with the same rise time is expected to lead to an earlier and more uniform plasma formation over the velvet surface. Simulations and initial testing are presented.

  7. FXR and liver carcinogenesis

    PubMed Central

    Huang, Xiong-fei; Zhao, Wei-yu; Huang, Wen-dong

    2015-01-01

    Farnesoid X receptor (FXR) is a member of the nuclear receptor family and a ligand-modulated transcription factor. In the liver, FXR has been considered a multi-functional cell protector and a tumor suppressor. FXR can suppress liver carcinogenesis via different mechanisms: 1) FXR maintains the normal liver metabolism of bile acids, glucose and lipids; 2) FXR promotes liver regeneration and repair after injury; 3) FXR protects liver cells from death and enhances cell survival; 4) FXR suppresses hepatic inflammation, thereby preventing inflammatory damage; and 5) FXR can directly increase the expression of some tumor-suppressor genes and repress the transcription of several oncogenes. However, inflammation and epigenetic silencing are known to decrease FXR expression during tumorigenesis. The reactivation of FXR function in the liver may be a potential therapeutic approach for patients with liver cancer. PMID:25500874

  8. Accelerating Lead Compound Optimization.

    PubMed

    Poh, Alissa

    2016-04-01

    Chemists at The Scripps Research Institute in La Jolla, CA, and Pfizer's La Jolla Laboratories have devised a new way to rapidly synthesize strained-ring structures, which are increasingly favored to optimize potential drugs. With this method, strain-release amination, Pfizer researchers were able to produce sufficient quantities of a particular structure they needed to evaluate a promising cancer drug candidate.

  9. Accelerating optimization by tracing valley

    NASA Astrophysics Data System (ADS)

    Li, Qing-Xiao; He, Rong-Qiang; Lu, Zhong-Yi

    2016-06-01

    We propose an algorithm to accelerate optimization when an objective function locally resembles a long narrow valley. In such a case, a conventional optimization algorithm usually wanders with too many tiny steps in the valley. The new algorithm approximates the valley bottom locally by a parabola that is obtained by fitting a set of successive points generated recently by a conventional optimization method. Then large steps are taken along the parabola, accompanied by fine adjustment to trace the valley bottom. The effectiveness of the new algorithm has been demonstrated by accelerating the Newton trust-region minimization method and the Levenberg-Marquardt method on the nonlinear fitting problem in exact diagonalization dynamical mean-field theory and on the classic minimization problem of the Rosenbrock's function. Many times speedup has been achieved for both problems, showing the high efficiency of the new algorithm.

  10. Bile acid nuclear receptor FXR and digestive system diseases

    PubMed Central

    Ding, Lili; Yang, Li; Wang, Zhengtao; Huang, Wendong

    2015-01-01

    Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases. PMID:26579439

  11. Bile acid nuclear receptor FXR and digestive system diseases.

    PubMed

    Ding, Lili; Yang, Li; Wang, Zhengtao; Huang, Wendong

    2015-03-01

    Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases. PMID:26579439

  12. Large Scale Shape Optimization for Accelerator Cavities

    SciTech Connect

    Akcelik, Volkan; Lee, Lie-Quan; Li, Zenghai; Ng, Cho; Xiao, Li-Ling; Ko, Kwok; /SLAC

    2011-12-06

    We present a shape optimization method for designing accelerator cavities with large scale computations. The objective is to find the best accelerator cavity shape with the desired spectral response, such as with the specified frequencies of resonant modes, field profiles, and external Q values. The forward problem is the large scale Maxwell equation in the frequency domain. The design parameters are the CAD parameters defining the cavity shape. We develop scalable algorithms with a discrete adjoint approach and use the quasi-Newton method to solve the nonlinear optimization problem. Two realistic accelerator cavity design examples are presented.

  13. Pulsed Inductive Plasma Acceleration: Performance Optimization Criteria

    NASA Technical Reports Server (NTRS)

    Polzin, Kurt A.

    2014-01-01

    Optimization criteria for pulsed inductive plasma acceleration are developed using an acceleration model consisting of a set of coupled circuit equations describing the time-varying current in the thruster and a one-dimensional momentum equation. The model is nondimensionalized, resulting in the identification of several scaling parameters that are varied to optimize the performance of the thruster. The analysis reveals the benefits of underdamped current waveforms and leads to a performance optimization criterion that requires the matching of the natural period of the discharge and the acceleration timescale imposed by the inertia of the working gas. In addition, the performance increases when a greater fraction of the propellant is initially located nearer to the inductive acceleration coil. While the dimensionless model uses a constant temperature formulation in calculating performance, the scaling parameters that yield the optimum performance are shown to be relatively invariant if a self-consistent description of energy in the plasma is instead used.

  14. An Improved SF6 System for the FXR Induction Linac Blumlein Switches

    SciTech Connect

    DeHope, W; Kihara, R; Griffin, K L; Ong, M; Ross, T

    2007-06-16

    The now-mature FXR (Flash X-Ray) radiographic facility at Lawrence Livermore National Laboratory will be briefly described with emphasis on its pulsed power system. The heart of each accelerating cell's pulse forming Blumlein is it's sulfur hexafluoride-based triggered closing switch. FXR's recent upgrade to a recirculating SF{sub 6} gas reclamation system will be described and the resulting accelerator performance and reliability improvements documented. This was accompanied by a detailed switch breakdown study on FXR's Test Stand and the recent analysis of the resulting statistics will be shown.

  15. Reconstruction of FXR Beam Conditions

    SciTech Connect

    Nexen, W E; Scarpetti, R D; Zentler, J

    2001-05-31

    Beam-envelope radius, envelope angle, and beam emittance can be derived from measurements of beam radius for at least three different transport conditions. We have used this technique to reconstruct exit parameters from the FXR injector and accelerator. We use a diamagnetic loop (DML) to measure the magnetic moment of the high current beam. With no assumptions about radial profile, we can derive the beam mean squire radius from the moment under certain easily met conditions. Since it is this parameter which is required for the reconstruction, it is evident that the DML is the ideal diagnostic for this technique. The simplest application of this technique requires at least three shots for a reconstruction but in reality requires averaging over many more shots because of shot to shot variation. Since DML measurements do not interfere with the beam, single shot time resolved measurements of the beam parameters appear feasible if one uses an array of at least three DMLs separated by known transport conditions.

  16. Gradient Optimization for SC CW Accelerators

    SciTech Connect

    Schneider, William; Kneisel, Peter; Rode, Claus

    2003-05-01

    The proposed rare isotope accelerator (RIA) design consists of a normally conducting radio frequency quadruple (RFQ) section, a superconducting (SC) drift tube cavity section, a SC elliptical multi-cell cavity section and two charge strippers with associated charge state selection and beam matching optics. The SC elliptical section uses two or three multi-cell beta cavity types installed into cryomodules to span the energy region of about 84.5 MeV/nucleon up to 400 MeV/nucleon. This paper focuses on the gradient optimization of these SC elliptical cavities that provide a significant portion of the total acceleration to the beam. The choice of gradient coupled with the cavity quality factor has a strong affect on the overall cost of the accelerator. The paper describes the optimization of the capital and operating cost associated with the RIA elliptical cavity cryomodules.

  17. Statins and transcriptional regulation: The FXR connection

    SciTech Connect

    Habeos, Ioannis; Ziros, Panos G.; Psyrogiannis, Agathoklis; Vagenakis, Apostolos G.; Papavassiliou, Athanasios G. . E-mail: papavas@med.upatras.gr

    2005-08-26

    Farnesoid X receptor (FXR) is a nuclear receptor involved in lipoprotein as well as glucose metabolism. Statins are widely used hypolipidemic agents with many pleiotropic actions. It is known that statins affect other nuclear hormone receptors, but no reports are available on the effect of these drugs on FXR. Employing an animal model (Syrian hamsters), we hereby present evidence to demonstrate that Simvastatin, a broadly prescribed statin, decreases the expression of FXR at both the RNA and protein levels and down-regulates its DNA-binding activity. This novel property may have important implications on the mode statins influence on lipoprotein and carbohydrate homeostasis in the organism.

  18. "Real-Life" Pulse Flattening on the LLNL Flash X-ray (FXR) Machine

    SciTech Connect

    DeHope, W J; Jacob, J S; Kihara, R; Ong, M; Zentler, J M

    2007-06-25

    High-resolution radiography using high-current electron accelerators based on the linear induction accelerator principle requires the linac's final spot on the X-ray target to be millimeter-sized. The requisite final focusing solenoid is adjusted for a specific beam energy at its entrance, hence, temporal variation of entrance beam energy results in a less than optimal time-averaged spot size. The FXR (Flash X-Ray) induction linac facility at Lawrence Livermore National Laboratory will be briefly described with an emphasis on its pulsed power system. In principle, the pulsed Blumleins at the heart of the system output a square pulse when discharged at the peak of their charging waveform so that, with correct cell timing synchronization, the effective beam output into the final focusing solenoid should be optimally flat. We have found that real-life consideration of transmission line and pulse power details in both the injector and accelerator sections of the machine results in significant energy variations in the final beam. We have implemented methods of measurement and analysis that permits this situation to be quantified and improved upon. The improvement will be linked to final beam spot size and enhancement in expected radiographic resolution.

  19. Estimating The Reliability of the Lawrence Livermore National Laboratory (LLNL) Flash X-ray (FXR) Machine

    SciTech Connect

    Ong, M M; Kihara, R; Zentler, J M; Kreitzer, B R; DeHope, W J

    2007-06-27

    At Lawrence Livermore National Laboratory (LLNL), our flash X-ray accelerator (FXR) is used on multi-million dollar hydrodynamic experiments. Because of the importance of the radiographs, FXR must be ultra-reliable. Flash linear accelerators that can generate a 3 kA beam at 18 MeV are very complex. They have thousands, if not millions, of critical components that could prevent the machine from performing correctly. For the last five years, we have quantified and are tracking component failures. From this data, we have determined that the reliability of the high-voltage gas-switches that initiate the pulses, which drive the accelerator cells, dominates the statistics. The failure mode is a single-switch pre-fire that reduces the energy of the beam and degrades the X-ray spot-size. The unfortunate result is a lower resolution radiograph. FXR is a production machine that allows only a modest number of pulses for testing. Therefore, reliability switch testing that requires thousands of shots is performed on our test stand. Study of representative switches has produced pre-fire statistical information and probability distribution curves. This information is applied to FXR to develop test procedures and determine individual switch reliability using a minimal number of accelerator pulses.

  20. Torque-based optimal acceleration control for electric vehicle

    NASA Astrophysics Data System (ADS)

    Lu, Dongbin; Ouyang, Minggao

    2014-03-01

    The existing research of the acceleration control mainly focuses on an optimization of the velocity trajectory with respect to a criterion formulation that weights acceleration time and fuel consumption. The minimum-fuel acceleration problem in conventional vehicle has been solved by Pontryagin's maximum principle and dynamic programming algorithm, respectively. The acceleration control with minimum energy consumption for battery electric vehicle(EV) has not been reported. In this paper, the permanent magnet synchronous motor(PMSM) is controlled by the field oriented control(FOC) method and the electric drive system for the EV(including the PMSM, the inverter and the battery) is modeled to favor over a detailed consumption map. The analytical algorithm is proposed to analyze the optimal acceleration control and the optimal torque versus speed curve in the acceleration process is obtained. Considering the acceleration time, a penalty function is introduced to realize a fast vehicle speed tracking. The optimal acceleration control is also addressed with dynamic programming(DP). This method can solve the optimal acceleration problem with precise time constraint, but it consumes a large amount of computation time. The EV used in simulation and experiment is a four-wheel hub motor drive electric vehicle. The simulation and experimental results show that the required battery energy has little difference between the acceleration control solved by analytical algorithm and that solved by DP, and is greatly reduced comparing with the constant pedal opening acceleration. The proposed analytical and DP algorithms can minimize the energy consumption in EV's acceleration process and the analytical algorithm is easy to be implemented in real-time control.

  1. Computational studies and optimization of wakefield accelerators

    SciTech Connect

    Tsung, Frank S.; Bruhwiler, David L.; Cary, John R.; Esarey, Eric H.; Mori, Warren B.; Vay, Jean-Luc; Martins, Samuel F.; Katsouleas, Tom; Cormier-Michel, Estelle; Fawley, William M.; Huang, Chengkun; Wang, Xiadong; Cowan, Ben; Decyk, Victor K.; Fonseca, Ricardo A.; Lu, Wei; Messmer, Peter; Mullowney, Paul; Nakamura, Kei; Paul, Kevin; Plateau, Guillaume R.; Schroeder, Carl B.; Silva, Luis O.; Toth, Csaba; Geddes, C.G.R.; Tzoufras, Michael; Antonsen, Tom; Vieira, Jorge; Leemans, Wim P.

    2008-06-16

    Laser- and particle beam-driven plasma wakefield accelerators produce accelerating fields thousands of times higher than radio-frequency accelerators, offering compactness and ultrafast bunches to extend the frontiers of high energy physics and to enable laboratory-scale radiation sources. Large-scale kinetic simulations provide essential understanding of accelerator physics to advance beam performance and stability and show and predict the physics behind recent demonstration of narrow energy spread bunches. Benchmarking between codes is establishing validity of the models used and, by testing new reduced models, is extending the reach of simulations to cover upcoming meter-scale multi-GeV experiments. This includes new models that exploit Lorentz boosted simulation frames to speed calculations. Simulations of experiments showed that recently demonstrated plasma gradient injection of electrons can be used as an injector to increase beam quality by orders of magnitude. Simulations are now also modeling accelerator stages of tens of GeV, staging of modules, and new positron sources to design next-generation experiments and to use in applications in high energy physics and light sources.

  2. Using Approximations to Accelerate Engineering Design Optimization

    NASA Technical Reports Server (NTRS)

    Torczon, Virginia; Trosset, Michael W.

    1998-01-01

    Optimization problems that arise in engineering design are often characterized by several features that hinder the use of standard nonlinear optimization techniques. Foremost among these features is that the functions used to define the engineering optimization problem often are computationally intensive. Within a standard nonlinear optimization algorithm, the computational expense of evaluating the functions that define the problem would necessarily be incurred for each iteration of the optimization algorithm. Faced with such prohibitive computational costs, an attractive alternative is to make use of surrogates within an optimization context since surrogates can be chosen or constructed so that they are typically much less expensive to compute. For the purposes of this paper, we will focus on the use of algebraic approximations as surrogates for the objective. In this paper we introduce the use of so-called merit functions that explicitly recognize the desirability of improving the current approximation to the objective during the course of the optimization. We define and experiment with the use of merit functions chosen to simultaneously improve both the solution to the optimization problem (the objective) and the quality of the approximation. Our goal is to further improve the effectiveness of our general approach without sacrificing any of its rigor.

  3. Navigation in bile acid chemical space: discovery of novel FXR and GPBAR1 ligands

    PubMed Central

    Finamore, Claudia; Festa, Carmen; Renga, Barbara; Sepe, Valentina; Carino, Adriana; Masullo, Dario; Biagioli, Michele; Marchianò, Silvia; Capolupo, Angela; Monti, Maria Chiara; Fiorucci, Stefano; Zampella, Angela

    2016-01-01

    Bile acids are signaling molecules interacting with nuclear receptors and membrane G-protein-coupled receptors. Among these receptors, the farnesoid X receptor (FXR) and the membrane G-coupled receptor (GPBAR1) have gained increasing consideration as druggable receptors and their exogenous dual regulation represents an attractive strategy in the treatment of enterohepatic and metabolic disorders. However, the therapeutic use of dual modulators could be associated to severe side effects and therefore the discovery of selective GPBAR1 and FXR agonists is an essential step in the medicinal chemistry optimization of bile acid scaffold. In this study, a new series of 6-ethylcholane derivatives modified on the tetracyclic core and on the side chain has been designed and synthesized and their in vitro activities on FXR and GPBAR1 were assayed. This speculation resulted in the identification of compound 7 as a potent and selective GPBAR1 agonist and of several derivatives showing potent dual agonistic activity. PMID:27381677

  4. Electronic accelerator pedal optimal design of intelligent test system

    NASA Astrophysics Data System (ADS)

    Li, Quailing; Lin, Min; Guo, Bin; Luo, Zai

    2010-12-01

    Developed an intelligent test system for the electronic accelerator pedal, and optimized it. The system uses the three-dimensional motion platform driven by servo motor to realize to control the movement of the electronic accelerator pedal automatically and uses the least squares method to optimize the data for the electronic accelerator pedal which is integrated with linear Hall sensors. Carried on the test experiment to the double electric potential signal output electron accelerator pedal and the results show that the system has excellent dynamic and static performance, and the change of motor parameters and load disturbances has strong robustness. Performance indicators have reached the Euro III emission standard configuration of the electronic accelerator pedal and the new technical requirements.

  5. Optimal Staging of Acceleration and Cooling in a Neutrino Factory

    NASA Astrophysics Data System (ADS)

    Johnstone, C.; Berz, M.; Makino, K.

    2005-12-01

    Schemes to produce intense sources of high-energy muons, Neutrino Factories, beta beams, and colliders, require collection, rf capture, and transport of particle beams with unprecedented emittances, both longitudinally and transversely. These large initial emittances must be reduced or cooled both in size and in energy spread before the muons can be efficiently accelerated to multi-GeV energies. The acceleration stage becomes critical in formulating and optimizing muon beams; individual stages are strongly interlinked and not independent as is the case in most conventional acceleration systems. Most importantly, the degree of cooling, or cooling channel, depends on the choice of acceleration. This work discusses two basic, but different approaches to a Neutrino Factory and how the optimal strategy depends on beam parameters and method of acceleration.

  6. Optimization of quasiperiodic structures in a linear resonance ion accelerator

    NASA Astrophysics Data System (ADS)

    Garashchenko, F. G.; Sokolov, L. S.; Tsulaya, A. V.

    1980-06-01

    A method is proposed for optimizing the parameters of a linear ion accelerator with rectangular or trapezoidal shape of the accelerating voltage between the tubes, systematic allowance being made for the quasiperiodicity of their arrangement. Numerical calculations have demonstrated the effectiveness of the method and also the fairly simple structure of its realization. A detailed algorithm is given. An estimate is made of the interval of entrance phases, the maximal value of which exceeds by several percent the limits previously predicted.

  7. Support Vector Machine Based on Adaptive Acceleration Particle Swarm Optimization

    PubMed Central

    Abdulameer, Mohammed Hasan; Othman, Zulaiha Ali

    2014-01-01

    Existing face recognition methods utilize particle swarm optimizer (PSO) and opposition based particle swarm optimizer (OPSO) to optimize the parameters of SVM. However, the utilization of random values in the velocity calculation decreases the performance of these techniques; that is, during the velocity computation, we normally use random values for the acceleration coefficients and this creates randomness in the solution. To address this problem, an adaptive acceleration particle swarm optimization (AAPSO) technique is proposed. To evaluate our proposed method, we employ both face and iris recognition based on AAPSO with SVM (AAPSO-SVM). In the face and iris recognition systems, performance is evaluated using two human face databases, YALE and CASIA, and the UBiris dataset. In this method, we initially perform feature extraction and then recognition on the extracted features. In the recognition process, the extracted features are used for SVM training and testing. During the training and testing, the SVM parameters are optimized with the AAPSO technique, and in AAPSO, the acceleration coefficients are computed using the particle fitness values. The parameters in SVM, which are optimized by AAPSO, perform efficiently for both face and iris recognition. A comparative analysis between our proposed AAPSO-SVM and the PSO-SVM technique is presented. PMID:24790584

  8. Support vector machine based on adaptive acceleration particle swarm optimization.

    PubMed

    Abdulameer, Mohammed Hasan; Sheikh Abdullah, Siti Norul Huda; Othman, Zulaiha Ali

    2014-01-01

    Existing face recognition methods utilize particle swarm optimizer (PSO) and opposition based particle swarm optimizer (OPSO) to optimize the parameters of SVM. However, the utilization of random values in the velocity calculation decreases the performance of these techniques; that is, during the velocity computation, we normally use random values for the acceleration coefficients and this creates randomness in the solution. To address this problem, an adaptive acceleration particle swarm optimization (AAPSO) technique is proposed. To evaluate our proposed method, we employ both face and iris recognition based on AAPSO with SVM (AAPSO-SVM). In the face and iris recognition systems, performance is evaluated using two human face databases, YALE and CASIA, and the UBiris dataset. In this method, we initially perform feature extraction and then recognition on the extracted features. In the recognition process, the extracted features are used for SVM training and testing. During the training and testing, the SVM parameters are optimized with the AAPSO technique, and in AAPSO, the acceleration coefficients are computed using the particle fitness values. The parameters in SVM, which are optimized by AAPSO, perform efficiently for both face and iris recognition. A comparative analysis between our proposed AAPSO-SVM and the PSO-SVM technique is presented. PMID:24790584

  9. Control and optimization of a staged laser-wakefield accelerator

    NASA Astrophysics Data System (ADS)

    Golovin, G.; Banerjee, S.; Chen, S.; Powers, N.; Liu, C.; Yan, W.; Zhang, J.; Zhang, P.; Zhao, B.; Umstadter, D.

    2016-09-01

    We report results of an experimental study of laser-wakefield acceleration of electrons, using a staged device based on a double-jet gas target that enables independent injection and acceleration stages. This novel scheme is shown to produce stable, quasi-monoenergetic, and tunable electron beams. We show that optimal accelerator performance is achieved by systematic variation of five critical parameters. For the injection stage, we show that the amount of trapped charge is controlled by the gas density, composition, and laser power. For the acceleration stage, the gas density and the length of the jet are found to determine the final electron energy. This independent control over both the injection and acceleration processes enabled independent control over the charge and energy of the accelerated electron beam while preserving the quasi-monoenergetic character of the beam. We show that the charge and energy can be varied in the ranges of 2-45 pC, and 50-450 MeV, respectively. This robust and versatile electron accelerator will find application in the generation of high-brightness and controllable x-rays, and as the injector stage for more conventional devices.

  10. Global search acceleration in the nested optimization scheme

    NASA Astrophysics Data System (ADS)

    Grishagin, Vladimir A.; Israfilov, Ruslan A.

    2016-06-01

    Multidimensional unconstrained global optimization problem with objective function under Lipschitz condition is considered. For solving this problem the dimensionality reduction approach on the base of the nested optimization scheme is used. This scheme reduces initial multidimensional problem to a family of one-dimensional subproblems being Lipschitzian as well and thus allows applying univariate methods for the execution of multidimensional optimization. For two well-known one-dimensional methods of Lipschitz optimization the modifications providing the acceleration of the search process in the situation when the objective function is continuously differentiable in a vicinity of the global minimum are considered and compared. Results of computational experiments on conventional test class of multiextremal functions confirm efficiency of the modified methods.

  11. FXR induces SOCS3 and suppresses hepatocellular carcinoma

    PubMed Central

    Zhang, Yan; Jiang, Peng; Huang, Gang; Chen, Shan; Lyu, Xilin; Zheng, Ping; Zhao, Xin; Zeng, Yijun; Wang, Shuguang; He, Fengtian

    2015-01-01

    Suppressor of cytokine signaling 3 (SOCS3) is regarded as a vital repressor in the liver carcinogenesis mainly by inhibiting signal transducer and activator of transcription 3 (STAT3) activity. Farnesoid X Receptor (FXR), highly expressed in liver, has an important role in protecting against hepatocellular carcinoma (HCC). However, it is unclear whether the tumor suppressive activity of FXR involves the regulation of SOCS3. In the present study, we found that activation of FXR by its specific agonist GW4064 in HCC cells inhibited cell growth, induced cell cycle arrest at G1 phase, elevated p21 expression and repressed STAT3 activity. The above anti-tumor effects of FXR were dramatically alleviated by knockdown of SOCS3 with siRNA. Reporter assay revealed that FXR activation enhanced the transcriptional activity of SOCS3 promoter. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay displayed that FXR directly bound to IR9 DNA motif within SOCS3 promoter region. The in vivo study in nude mice showed that treatment with FXR ligand GW4064 could decelerate the growth of HCC xenografts, up-regulate SOCS3 and p21 expression and inhibit STAT3 phosphorylation in the xenografts. These results suggest that induction of SOCS3 may be a novel mechanism by which FXR exerts its anti-HCC effects, and the FXR-SOCS3 signaling may serve as a new potential target for the prevention/treatment of HCC. PMID:26416445

  12. FXR induces SOCS3 and suppresses hepatocellular carcinoma.

    PubMed

    Guo, Fei; Xu, Zhizhen; Zhang, Yan; Jiang, Peng; Huang, Gang; Chen, Shan; Lyu, Xilin; Zheng, Ping; Zhao, Xin; Zeng, Yijun; Wang, Shuguang; He, Fengtian

    2015-10-27

    Suppressor of cytokine signaling 3 (SOCS3) is regarded as a vital repressor in the liver carcinogenesis mainly by inhibiting signal transducer and activator of transcription 3 (STAT3) activity. Farnesoid X Receptor (FXR), highly expressed in liver, has an important role in protecting against hepatocellular carcinoma (HCC). However, it is unclear whether the tumor suppressive activity of FXR involves the regulation of SOCS3. In the present study, we found that activation of FXR by its specific agonist GW4064 in HCC cells inhibited cell growth, induced cell cycle arrest at G1 phase, elevated p21 expression and repressed STAT3 activity. The above anti-tumor effects of FXR were dramatically alleviated by knockdown of SOCS3 with siRNA. Reporter assay revealed that FXR activation enhanced the transcriptional activity of SOCS3 promoter. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay displayed that FXR directly bound to IR9 DNA motif within SOCS3 promoter region. The in vivo study in nude mice showed that treatment with FXR ligand GW4064 could decelerate the growth of HCC xenografts, up-regulate SOCS3 and p21 expression and inhibit STAT3 phosphorylation in the xenografts. These results suggest that induction of SOCS3 may be a novel mechanism by which FXR exerts its anti-HCC effects, and the FXR-SOCS3 signaling may serve as a new potential target for the prevention/treatment of HCC.

  13. Design, Synthesis, and Biological Evaluation of Novel Nonsteroidal Farnesoid X Receptor (FXR) Antagonists: Molecular Basis of FXR Antagonism.

    PubMed

    Huang, Huang; Si, Pei; Wang, Lei; Xu, Yong; Xu, Xin; Zhu, Jin; Jiang, Hualiang; Li, Weihua; Chen, Lili; Li, Jian

    2015-07-01

    Farnesoid X receptor (FXR) plays an important role in the regulation of cholesterol, lipid, and glucose metabolism. Recently, several studies on the molecular basis of FXR antagonism have been reported. However, none of these studies employs an FXR antagonist with nonsteroidal scaffold. On the basis of our previously reported FXR antagonist with a trisubstituted isoxazole scaffold, a novel nonsteroidal FXR ligand was designed and used as a lead for structural modification. In total, 39 new trisubstituted isoxazole derivatives were designed and synthesized, which led to pharmacological profiles ranging from agonist to antagonist toward FXR. Notably, compound 5s (4'-[(3-{[3-(2-chlorophenyl)-5-(2-thienyl)isoxazol-4-yl]methoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid), containing a thienyl-substituted isoxazole ring, displayed the best antagonistic activity against FXR with good cellular potency (IC50 =12.2 ± 0.2 μM). Eventually, this compound was used as a probe in a molecular dynamics simulation assay. Our results allowed us to propose an essential molecular basis for FXR antagonism, which is consistent with a previously reported antagonistic mechanism; furthermore, E467 on H12 was found to be a hot-spot residue and may be important for the future design of nonsteroidal antagonists of FXR.

  14. The bile acid sensor FXR regulates insulin transcription and secretion.

    PubMed

    Renga, Barbara; Mencarelli, Andrea; Vavassori, Piero; Brancaleone, Vincenzo; Fiorucci, Stefano

    2010-03-01

    Farnesoid X Receptor plays an important role in maintaining bile acid, cholesterol homeostasis and glucose metabolism. Here we investigated whether FXR is expressed by pancreatic beta-cells and regulates insulin signaling in pancreatic beta-cell line and human islets. We found that FXR activation induces positive regulatory effects on glucose-induced insulin transcription and secretion by genomic and non-genomic activities. Genomic effects of FXR activation relay on the induction of the glucose regulated transcription factor KLF11. Indeed, results from silencing experiments of KLF11 demonstrate that this transcription factor is essential for FXR activity on glucose-induced insulin gene transcription. In addition FXR regulates insulin secretion by non-genomic effects. Thus, activation of FXR in betaTC6 cells increases Akt phosphorylation and translocation of the glucose transporter GLUT2 at plasma membrane, increasing the glucose uptake by these cells. In vivo experiments on Non Obese Diabetic (NOD) mice demonstrated that FXR activation delays development of signs of diabetes, hyperglycemia and glycosuria, by enhancing insulin secretion and by stimulating glucose uptake by the liver. These data established that an FXR-KLF11 regulated pathway has an essential role in the regulation of insulin transcription and secretion induced by glucose.

  15. Optimization of positrons generation based on laser wakefield electron acceleration

    NASA Astrophysics Data System (ADS)

    Wu, Yuchi; Han, Dan; Zhang, Tiankui; Dong, Kegong; Zhu, Bin; Yan, Yonghong; Gu, Yuqiu

    2016-08-01

    Laser based positron represents a new particle source with short pulse duration and high charge density. Positron production based on laser wakefield electron acceleration (LWFA) has been investigated theoretically in this paper. Analytical expressions for positron spectra and yield have been obtained through a combination of LWFA and cascade shower theories. The maximum positron yield and corresponding converter thickness have been optimized as a function of driven laser power. Under the optimal condition, high energy (>100 MeV ) positron yield up to 5 ×1011 can be produced by high power femtosecond lasers at ELI-NP. The percentage of positrons shows that a quasineutral electron-positron jet can be generated by setting the converter thickness greater than 5 radiation lengths.

  16. Elliptical Cavity Shape Optimization for Acceleration and HOM Damping

    SciTech Connect

    Haipeng Wang; Robert Rimmer; Genfa Wu

    2005-05-01

    We report a survey of center cell shapes developed for Superconducting Radio Frequency (SRF) multi-cell cavities for different projects. Using a set of normalized parameters, we compare the designs for different frequencies and particle velocities for the fundamental mode. Using dispersion curves of High Order Modes (HOM) (frequency verse phase advance) calculated by MAFIA for a single cell, we further optimize the cavity shape to avoid a light cone line crossing at the dangerous resonance frequencies determined by the beam bunch structure and eliminate the trapped (or high R/Q) modes with a low group velocity. We developed this formulation to optimize a 5-cell, 750MHz cavity shape, with good real-estate accelerating gradient and a strong HOM damping waveguide structure for the JLab 1MW ERL-FEL project.

  17. FXR agonist activity of conformationally constrained analogs of GW 4064

    SciTech Connect

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y.; Caldwell, Richard D.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Navas, III, Frank; Parks, Derek J.; Spearing, Paul K.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce

    2010-09-27

    Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  18. FXR agonist activity of conformationally constrained analogs of GW 4064.

    PubMed

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y; Caldwell, Richard D; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Madauss, Kevin P; Marr, Harry B; McFadyen, Robert B; Miller, Aaron B; Navas, Frank; Parks, Derek J; Spearing, Paul K; Todd, Dan; Williams, Shawn P; Bruce Wisely, G

    2009-08-15

    Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  19. Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element

    PubMed Central

    Claudel, Thierry; Sturm, Ekkehard; Duez, Hélène; Torra, Inés Pineda; Sirvent, Audrey; Kosykh, Vladimir; Fruchart, Jean-Charles; Dallongeville, Jean; Hum, Dean W.; Kuipers, Folkert; Staels, Bart

    2002-01-01

    Serum levels of HDL are inversely correlated with the risk of coronary heart disease. The anti-atherogenic effect of HDL is partially mediated by its major protein constituent apoA-I. In this study, we identify bile acids that are activators of the nuclear receptor farnesoid X receptor (FXR) as negative regulators of human apoA-I expression. Intrahepatocellular accumulation of bile acids, as seen in patients with progressive familial intrahepatic cholestasis and biliary atresia, was associated with diminished apoA-I serum levels. In human apoA-I transgenic mice, treatment with the FXR agonist taurocholic acid strongly decreased serum concentrations and liver mRNA levels of human apoA-I, which was associated with reduced serum HDL levels. Incubation of human primary hepatocytes and hepatoblastoma HepG2 cells with bile acids resulted in a dose-dependent downregulation of apoA-I expression. Promoter mutation analysis and gel-shift experiments in HepG2 cells demonstrated that bile acid–activated FXR decreases human apoA-I promoter activity by a negative FXR response element mapped to the C site. FXR bound this site and repressed transcription in a manner independent of retinoid X receptor. The nonsteroidal synthetic FXR agonist GW4064 likewise decreased apoA-I mRNA levels and promoter activity in HepG2 cells. PMID:11927623

  20. An Accelerated Particle Swarm Optimization Algorithm on Parametric Optimization of WEDM of Die-Steel

    NASA Astrophysics Data System (ADS)

    Muthukumar, V.; Suresh Babu, A.; Venkatasamy, R.; Senthil Kumar, N.

    2015-01-01

    This study employed Accelerated Particle Swarm Optimization (APSO) algorithm to optimize the machining parameters that lead to a maximum Material Removal Rate (MRR), minimum surface roughness and minimum kerf width values for Wire Electrical Discharge Machining (WEDM) of AISI D3 die-steel. Four machining parameters that are optimized using APSO algorithm include Pulse on-time, Pulse off-time, Gap voltage, Wire feed. The machining parameters are evaluated by Taguchi's L9 Orthogonal Array (OA). Experiments are conducted on a CNC WEDM and output responses such as material removal rate, surface roughness and kerf width are determined. The empirical relationship between control factors and output responses are established by using linear regression models using Minitab software. Finally, APSO algorithm, a nature inspired metaheuristic technique, is used to optimize the WEDM machining parameters for higher material removal rate and lower kerf width with surface roughness as constraint. The confirmation experiments carried out with the optimum conditions show that the proposed algorithm was found to be potential in finding numerous optimal input machining parameters which can fulfill wide requirements of a process engineer working in WEDM industry.

  1. Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064

    SciTech Connect

    Bass, Jonathan Y.; Caldwell, Richard D.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Parks, Derek J.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce

    2010-09-27

    Starting from the known FXR agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, with the 2,6-dimethyl phenol analog 1t having greater FRET FXR potency than GW 4064 1a.

  2. Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064.

    PubMed

    Bass, Jonathan Y; Caldwell, Richard D; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Madauss, Kevin P; Marr, Harry B; McFadyen, Robert B; Miller, Aaron B; Parks, Derek J; Todd, Dan; Williams, Shawn P; Wisely, G Bruce

    2009-06-01

    Starting from the known FXR agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, with the 2,6-dimethyl phenol analog 1t having greater FRET FXR potency than GW 4064 1a.

  3. DAX1 suppresses FXR transactivity as a novel co-repressor

    SciTech Connect

    Li, Jin; Lu, Yan; Liu, Ruya; Xiong, Xuelian; Zhang, Zhijian; Zhang, Xianfeng; Ning, Guang; Li, Xiaoying

    2011-09-09

    Highlights: {yields} DAX1 is co-localized with FXR and interacts with FXR. {yields} DAX1 acts as a negative regulator of FXR. {yields} Three LXXLL motifs in the N-terminus of DAX1 were required. {yields} DAX1 suppresses FXR transactivation by competing with co-activators. -- Abstract: Bile acid receptor FXR (farnesoid X receptor) is a key regulator of hepatic bile acid, glucose and lipid homeostasis through regulation of numerous genes involved in the process of bile acid, triglyceride and glucose metabolism. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains and acts primarily as a co-repressor of many nuclear receptors. Here, we demonstrated that DAX1 is co-localized with FXR in the nucleus and acted as a negative regulator of FXR through a physical interaction with FXR. Our study showed that over-expression of DAX1 down-regulated the expression of FXR target genes, whereas knockdown of DAX1 led to their up-regulation. Furthermore, three LXXLL motifs in the N-terminus of DAX1 were required for the full repression of FXR transactivation. In addition, our study characterized that DAX1 suppresses FXR transactivation via competing with co-activators such as SRC-1 and PGC-1{alpha}. In conclusion, DAX1 acts as a co-repressor to negatively modulate FXR transactivity.

  4. Optimizing laser-driven proton acceleration from overdense targets.

    PubMed

    Stockem Novo, A; Kaluza, M C; Fonseca, R A; Silva, L O

    2016-07-20

    We demonstrate how to tune the main ion acceleration mechanism in laser-plasma interactions to collisionless shock acceleration, thus achieving control over the final ion beam properties (e. g. maximum energy, divergence, number of accelerated ions). We investigate this technique with three-dimensional particle-in-cell simulations and illustrate a possible experimental realisation. The setup consists of an isolated solid density target, which is preheated by a first laser pulse to initiate target expansion, and a second one to trigger acceleration. The timing between the two laser pulses allows to access all ion acceleration regimes, ranging from target normal sheath acceleration, to hole boring and collisionless shock acceleration. We further demonstrate that the most energetic ions are produced by collisionless shock acceleration, if the target density is near-critical, ne ≈ 0.5 ncr. A scaling of the laser power shows that 100 MeV protons may be achieved in the PW range.

  5. Optimizing laser-driven proton acceleration from overdense targets

    PubMed Central

    Stockem Novo, A.; Kaluza, M. C.; Fonseca, R. A.; Silva, L. O.

    2016-01-01

    We demonstrate how to tune the main ion acceleration mechanism in laser-plasma interactions to collisionless shock acceleration, thus achieving control over the final ion beam properties (e. g. maximum energy, divergence, number of accelerated ions). We investigate this technique with three-dimensional particle-in-cell simulations and illustrate a possible experimental realisation. The setup consists of an isolated solid density target, which is preheated by a first laser pulse to initiate target expansion, and a second one to trigger acceleration. The timing between the two laser pulses allows to access all ion acceleration regimes, ranging from target normal sheath acceleration, to hole boring and collisionless shock acceleration. We further demonstrate that the most energetic ions are produced by collisionless shock acceleration, if the target density is near-critical, ne ≈ 0.5 ncr. A scaling of the laser power shows that 100 MeV protons may be achieved in the PW range. PMID:27435449

  6. Optimizing laser-driven proton acceleration from overdense targets

    NASA Astrophysics Data System (ADS)

    Stockem Novo, A.; Kaluza, M. C.; Fonseca, R. A.; Silva, L. O.

    2016-07-01

    We demonstrate how to tune the main ion acceleration mechanism in laser-plasma interactions to collisionless shock acceleration, thus achieving control over the final ion beam properties (e. g. maximum energy, divergence, number of accelerated ions). We investigate this technique with three-dimensional particle-in-cell simulations and illustrate a possible experimental realisation. The setup consists of an isolated solid density target, which is preheated by a first laser pulse to initiate target expansion, and a second one to trigger acceleration. The timing between the two laser pulses allows to access all ion acceleration regimes, ranging from target normal sheath acceleration, to hole boring and collisionless shock acceleration. We further demonstrate that the most energetic ions are produced by collisionless shock acceleration, if the target density is near-critical, ne ≈ 0.5 ncr. A scaling of the laser power shows that 100 MeV protons may be achieved in the PW range.

  7. LLNL flash x-ray radiography machine (FXR) double-pulse upgrade diagnostics

    SciTech Connect

    Ong, M.; Avalee, C.; Richardson, R.; Zentler, J.

    1997-06-26

    When the FXR machine was first tuned on the 1980`s, a minimal amount of diagnostics was available and consisted mostly of power monitors. During the recent accelerator upgrade, additional beam diagnostics were added. The sensor upgrades included beam bugs (resistive wall beam motion sensors) and high-frequency B-dot. Even with this suite of measurement tools, tuning was difficult. For the current Double- Pulse Upgrade, beam transport is a more complex problem--the beam characteristics must be measured better. Streak and framing cameras, which measure beam size and motions, are being added. Characterization of the beam along the entire accelerator is expected and other techniques will be evaluated also. Each sensor has limitations and only provides a piece of the puzzle. Besides providing more beam data, the set of diagnostics used should be broad enough so results can be cross validated. Results will also be compared to theoretical calculations and computer models, and successes and difficulties will be reported.

  8. Farnesoid X receptor (FXR) gene deficiency impairs urine concentration in mice

    PubMed Central

    Zhang, Xiaoyan; Huang, Shizheng; Gao, Min; Liu, Jia; Jia, Xiao; Han, Qifei; Zheng, Senfeng; Miao, Yifei; Li, Shuo; Weng, Haoyu; Xia, Xuan; Du, Shengnan; Wu, Wanfu; Gustafsson, Jan-Åke; Guan, Youfei

    2014-01-01

    The farnesoid X receptor (FXR) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. FXR is mainly expressed in liver and small intestine, where it plays an important role in bile acid, lipid, and glucose metabolism. The kidney also has a high FXR expression level, with its physiological function unknown. Here we demonstrate that FXR is ubiquitously distributed in renal tubules. FXR agonist treatment significantly lowered urine volume and increased urine osmolality, whereas FXR knockout mice exhibited an impaired urine concentrating ability, which led to a polyuria phenotype. We further found that treatment of C57BL/6 mice with chenodeoxycholic acid, an FXR endogenous ligand, significantly up-regulated renal aquaporin 2 (AQP2) expression, whereas FXR gene deficiency markedly reduced AQP2 expression levels in the kidney. In vitro studies showed that the AQP2 gene promoter contained a putative FXR response element site, which can be bound and activated by FXR, resulting in a significant increase of AQP2 transcription in cultured primary inner medullary collecting duct cells. In conclusion, the present study demonstrates that FXR plays a critical role in the regulation of urine volume, and its activation increases urinary concentrating capacity mainly via up-regulating its target gene AQP2 expression in the collecting ducts. PMID:24464484

  9. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice.

    PubMed

    Zhang, Yanqiao; Lee, Florence Ying; Barrera, Gabriel; Lee, Hans; Vales, Charisse; Gonzalez, Frank J; Willson, Timothy M; Edwards, Peter A

    2006-01-24

    Farnesoid X receptor (FXR) plays an important role in maintaining bile acid and cholesterol homeostasis. Here we demonstrate that FXR also regulates glucose metabolism. Activation of FXR by the synthetic agonist GW4064 or hepatic overexpression of constitutively active FXR by adenovirus-mediated gene transfer significantly lowered blood glucose levels in both diabetic db/db and wild-type mice. Consistent with these data, FXR null mice exhibited glucose intolerance and insulin insensitivity. We further demonstrate that activation of FXR in db/db mice repressed hepatic gluconeogenic genes and increased hepatic glycogen synthesis and glycogen content by a mechanism that involves enhanced insulin sensitivity. In view of its central roles in coordinating regulation of both glucose and lipid metabolism, we propose that FXR agonists are promising therapeutic agents for treatment of diabetes mellitus.

  10. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice

    NASA Astrophysics Data System (ADS)

    Zhang, Yanqiao; Lee, Florence Ying; Barrera, Gabriel; Lee, Hans; Vales, Charisse; Gonzalez, Frank J.; Willson, Timothy M.; Edwards, Peter A.

    2006-01-01

    Farnesoid X receptor (FXR) plays an important role in maintaining bile acid and cholesterol homeostasis. Here we demonstrate that FXR also regulates glucose metabolism. Activation of FXR by the synthetic agonist GW4064 or hepatic overexpression of constitutively active FXR by adenovirus-mediated gene transfer significantly lowered blood glucose levels in both diabetic db/db and wild-type mice. Consistent with these data, FXR null mice exhibited glucose intolerance and insulin insensitivity. We further demonstrate that activation of FXR in db/db mice repressed hepatic gluconeogenic genes and increased hepatic glycogen synthesis and glycogen content by a mechanism that involves enhanced insulin sensitivity. In view of its central roles in coordinating regulation of both glucose and lipid metabolism, we propose that FXR agonists are promising therapeutic agents for treatment of diabetes mellitus. glucose | GW4064 | farnesoid X receptor-VP16 | triglyceride | cholesterol

  11. Optimization of THz Radiation Generation from a Laser Wakefield Accelerator

    SciTech Connect

    Plateau, G. R.; Matlis, N. H.; Toth, C.; Geddes, C. G. R.; Schroeder, C. B.; Tilborg, J. van; Albert, O.; Esarey, E.; Leemans, W. P.

    2009-01-22

    Ultrashort terahertz pulses with energies in the {mu}J range can be generated with laser wakefield accelerators (LWFA), which are novel, compact accelerators that produce ultrashort electron bunches with energies up to 1 GeV and energy spreads of a few-percent. Laser pulses interacting with a plasma create accelerated electrons which upon exiting the plasma emit terahertz pulses via transition radiation. Because these electron bunches are ultrashort (<50 fs), they can radiate coherently (coherent transition radiation--CTR) in a wide bandwidth ({approx}1-10 THz) yielding high intensity terahertz pulses. In addition to providing a non-invasive bunch-length diagnostic and thus feedback for the LWFA, these high peak power THz pulses are suitable for high field (MV/cm) pump-probe experiments. Here we present energy-based measurements using a Golay cell and an electro-optic technique which were used to characterize these THz pulses.

  12. Upregulation of decorin by FXR in vascular smooth muscle cells

    SciTech Connect

    He Fengtian; Zhang Qiuhong; Kuruba, Ramalinga; Gao Xiang; Li Jiang; Li Yong; Gong Wei; Jiang, Yu; Xie Wen; Li Song

    2008-08-08

    Decorin is a member of the family of small leucine-rich proteoglycans that are present in blood vessels and synthesized by vascular smooth muscle cells (VSMCs). Decorin plays complex roles in both normal vascular physiology and the pathogenesis of various types of vascular disorders. However, the mechanisms of regulation of decorin expression in vasculature are not clearly understood. Particularly little information is available about a role of nuclear receptors in the regulation of decorin expression. In the present study, we report that activation of vascular FXR by a specific ligand resulted in upregulation of decorin at the levels of both mRNA and protein. FXR appears to induce decorin expression at a transcriptional level because (1) upregulation of decorin mRNA expression was abolished by the treatment of a transcription inhibitor, actinomycin D; and (2) decorin promoter activity was significantly increased by activation of FXR. Functional analysis of human decorin promoter identified an imperfect inverted repeat DNA motif, IR8 (-2313TGGTCAtagtgtcaTGACCT-2294), as a likely FXR-responsive element that is involved in decorin regulation.

  13. Origami Optimization: Role of Symmetry in Accelerating Design

    NASA Astrophysics Data System (ADS)

    Buskohl, Philip; Fuchi, Kazuko; Bazzan, Giorgio; Durstock, Michael; Reich, Gregory; Joo, James; Vaia, Richard

    Origami structures morph between 2D and 3D conformations along predetermined fold lines that efficiently program the form, function and mobility of the structure. Design optimization tools have recently been developed to predict optimal fold patterns with mechanics-based metrics, such as the maximal energy storage, auxetic response and actuation. Origami actuator design problems possess inherent symmetries associated with the grid, mechanical boundary conditions and the objective function, which are often exploited to reduce the design space and computational cost of optimization. However, enforcing symmetry eliminates the prediction of potentially better performing asymmetric designs, which are more likely to exist given the discrete nature of fold line optimization. To better understand this effect, actuator design problems with different combinations of rotation and reflection symmetries were optimized while varying the number of folds allowed in the final design. In each case, the optimal origami patterns transitioned between symmetric and asymmetric solutions depended on the number of folds available for the design, with fewer symmetries present with more fold lines allowed. This study investigates the interplay of symmetry and discrete vs continuous optimization in origami actuators and provides insight into how the symmetries of the reference grid regulate the performance landscape. This work was supported by the Air Force Office of Scientific Research.

  14. FXR regulates organic solute transporters alpha and beta in the adrenal gland, kidney, and intestine.

    PubMed

    Lee, Hans; Zhang, Yanqiao; Lee, Florence Y; Nelson, Stanley F; Gonzalez, Frank J; Edwards, Peter A

    2006-01-01

    Expression of the farnesoid X receptor (FXR; NR1H4) is limited to the liver, intestine, kidney, and adrenal gland. However, the role of FXR in the latter two organs is unknown. In the current study, we performed microarray analysis using RNA from H295R cells infected with constitutively active FXR. Several putative FXR target genes were identified, including the organic solute transporters alpha and beta (OSTalpha and OSTbeta). Electromobility shift assays and promoter-reporter studies identified functional farnesoid X receptor response elements (FXREs) in the promoters of both human genes. These FXREs are conserved in both mouse genes. Treatment of wild-type mice with 3-(2,6-dichlorophenyl)-4-(3'-carboxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazole (GW4064), a synthetic FXR agonist, induced OSTalpha and OSTbeta mRNAs in the intestine and kidney. Both mRNAs were also induced when wild-type, but not FXR-deficient (FXR-/-), adrenals were cultured in the presence of GW4064. OSTalpha and OSTbeta mRNA levels were also induced in the adrenals and kidneys of wild-type, but not FXR-/-, mice after the increase of plasma bile acids in response to the hepatotoxin alpha-naphthylisothiocyanate. Finally, overexpression of human OSTalpha and OSTbeta facilitated the uptake of conjugated chenodeoxycholate and the activation of FXR target genes. These results demonstrate that OSTalpha and OSTbeta are novel FXR target genes that are expressed in the adrenal gland, kidney, and intestine.

  15. Bioenergetic cues shift FXR splicing towards FXRα2 to modulate hepatic lipolysis and fatty acid metabolism

    PubMed Central

    Correia, Jorge C.; Massart, Julie; de Boer, Jan Freark; Porsmyr-Palmertz, Margareta; Martínez-Redondo, Vicente; Agudelo, Leandro Z.; Sinha, Indranil; Meierhofer, David; Ribeiro, Vera; Björnholm, Marie; Sauer, Sascha; Dahlman-Wright, Karin; Zierath, Juleen R.; Groen, Albert K.; Ruas, Jorge L.

    2015-01-01

    Objective Farnesoid X receptor (FXR) plays a prominent role in hepatic lipid metabolism. The FXR gene encodes four proteins with structural differences suggestive of discrete biological functions about which little is known. Methods We expressed each FXR variant in primary hepatocytes and evaluated global gene expression, lipid profile, and metabolic fluxes. Gene delivery of FXR variants to Fxr−/− mouse liver was performed to evaluate their role in vivo. The effects of fasting and physical exercise on hepatic Fxr splicing were determined. Results We show that FXR splice isoforms regulate largely different gene sets and have specific effects on hepatic metabolism. FXRα2 (but not α1) activates a broad transcriptional program in hepatocytes conducive to lipolysis, fatty acid oxidation, and ketogenesis. Consequently, FXRα2 decreases cellular lipid accumulation and improves cellular insulin signaling to AKT. FXRα2 expression in Fxr−/− mouse liver activates a similar gene program and robustly decreases hepatic triglyceride levels. On the other hand, FXRα1 reduces hepatic triglyceride content to a lesser extent and does so through regulation of lipogenic gene expression. Bioenergetic cues, such as fasting and exercise, dynamically regulate Fxr splicing in mouse liver to increase Fxrα2 expression. Conclusions Our results show that the main FXR variants in human liver (α1 and α2) reduce hepatic lipid accumulation through distinct mechanisms and to different degrees. Taking this novel mechanism into account could greatly improve the pharmacological targeting and therapeutic efficacy of FXR agonists. PMID:26909306

  16. Activation of the nuclear receptor FXR enhances hepatocyte chemoprotection and liver tumor chemoresistance against genotoxic compounds.

    PubMed

    Vaquero, Javier; Briz, Oscar; Herraez, Elisa; Muntané, Jordi; Marin, Jose J G

    2013-10-01

    The success of pharmacological treatments in primary liver cancers is limited by the marked efficacy of mechanisms of chemoresistance already present in hepatocytes. The role of the nuclear receptor FXR is unclear. Although, in non-treated liver tumors, its expression is reduced, the refractoriness to anticancer drugs is high. Moreover, the treatment with cisplatin up-regulates FXR. The aim of this study was to investigate whether FXR is involved in stimulating chemoprotection/chemoresistance in healthy and tumor liver cells. In human hepatocytes, the activation of FXR with the agonist GW4064 resulted in a significant protection against cisplatin-induced toxicity. In human hepatoma Alexander cells, with negligible endogenous expression of FXR, GW4064 also protected against cisplatin-induced toxicity, but only if they were previously transfected with FXR/RXR. Investigation of 109 genes potentially involved in chemoresistance revealed that only ABCB4, TCEA2, CCL14, CCL15 and KRT13 were up-regulated by FXR activation both in human hepatocytes and FXR/RXR-expressing hepatoma cells. In both models, cisplatin, even in the absence of FXR agonists, such as bile acids and GW4064, was able to up-regulate FXR targets genes, which was due to FXR-mediated trans-activation of response elements in the promoter region. FXR-dependent chemoprotection was also efficient against other DNA-damaging compounds, such as doxorubicin, mitomycin C and potassium dichromate, but not against non-genotoxic drugs, such as colchicine, paclitaxel, acetaminophen, artesunate and sorafenib. In conclusion, ligand-dependent and independent activation of FXR stimulates mechanisms able to enhance the chemoprotection of hepatocytes against genotoxic compounds and to reduce the response of liver tumor cells to certain pharmacological treatments.

  17. FERMI&Elettra Accelerator Technical Optimization Final Report

    SciTech Connect

    Cornacchia, M.; Craievich, P.; Di Mitri, S.; Pogorelov, I.; Qiang, J.; Venturini, M.; Zholents, A.; Wang, D.; Warnock, R.; /SLAC

    2007-04-30

    This chapter describes the accelerator physics aspects, the engineering considerations and the choice of parameters that led to the accelerator design of the FERMI Free-Electron-Laser. The accelerator (also called the ''electron beam delivery system'') covers the region from the exit of the injector to the entrance of the first FEL undulator. The considerations that led to the proposed configuration were made on the basis of a study that explored various options and performance limits. This work follows previous studies of x-ray FEL facilities (SLAC LCLS [1], DESY XFEL [2], PAL XFEL [3], MIT [4], BESSY FEL [5], LBNL LUX [6], Daresbury 4GLS [7]) and integrates many of the ideas that were developed there. Several issues specific to harmonic cascade FELs, and that had not yet been comprehensively studied, were also encountered and tackled. A particularly difficult issue was the need to meet the requirement for high peak current and small slice energy spread, as the specification for the ratio of these two parameters (that defines the peak brightness of the electron beam) is almost a factor of two higher than that of the LCLS's SASE FEL. Another challenging aspect was the demand to produce an electron beam with as uniform as possible peak current and energy distributions along the bunch, a condition that was met by introducing novel beam dynamics techniques. Part of the challenge was due to the fact that there were no readily available computational tools to carry out reliable calculations, and these had to be developed. Most of the information reported in this study is available in the form of scientific publications, and is partly reproduced here for the convenience of the reader.

  18. Optimization of accelerator system performance at the NSLS

    SciTech Connect

    Krinsky, S.

    1994-10-01

    There is an active program of accelerator development at the NSLS aimed at improving reliability, stability and brightness. Work is primarily focused on providing improved performance for the NSLS user community, however, important elements of our work have a generic character and should be of value to other synchrotron radiation facilities. In particular, we have successfully operated a small gap undulator with a full vertical beam aperture of only 3.8 mm, with no degradation of beam lifetime. This provides strong support for the belief that small gap, short period devices will play an important role in the future.

  19. Optimizing a mobile robot control system using GPU acceleration

    NASA Astrophysics Data System (ADS)

    Tuck, Nat; McGuinness, Michael; Martin, Fred

    2012-01-01

    This paper describes our attempt to optimize a robot control program for the Intelligent Ground Vehicle Competition (IGVC) by running computationally intensive portions of the system on a commodity graphics processing unit (GPU). The IGVC Autonomous Challenge requires a control program that performs a number of different computationally intensive tasks ranging from computer vision to path planning. For the 2011 competition our Robot Operating System (ROS) based control system would not run comfortably on the multicore CPU on our custom robot platform. The process of profiling the ROS control program and selecting appropriate modules for porting to run on a GPU is described. A GPU-targeting compiler, Bacon, is used to speed up development and help optimize the ported modules. The impact of the ported modules on overall performance is discussed. We conclude that GPU optimization can free a significant amount of CPU resources with minimal effort for expensive user-written code, but that replacing heavily-optimized library functions is more difficult, and a much less efficient use of time.

  20. Optimizing chirped laser pulse parameters for electron acceleration in vacuum

    SciTech Connect

    Akhyani, Mina; Jahangiri, Fazel; Niknam, Ali Reza; Massudi, Reza

    2015-11-14

    Electron dynamics in the field of a chirped linearly polarized laser pulse is investigated. Variations of electron energy gain versus chirp parameter, time duration, and initial phase of laser pulse are studied. Based on maximizing laser pulse asymmetry, a numerical optimization procedure is presented, which leads to the elimination of rapid fluctuations of gain versus the chirp parameter. Instead, a smooth variation is observed that considerably reduces the accuracy required for experimentally adjusting the chirp parameter.

  1. FERMI&Elettra Accelerator Technical Optimization FinalReport

    SciTech Connect

    Cornacchia, M.; Craievich, P.; Di Mitri, S.; Pogorelov, I.; Qiang, J.; Venturini, M.; Zholents, A.; Wang, D.; Warnock, R.

    2006-07-01

    This report describes the accelerator physics aspects, theengineering considerations and the choice of parameters that led to theaccelerator design of the FERMI Free-Electron-Laser. The accelerator(also called the "electron beam delivery system") covers the region fromthe exit of the injector to the entrance of the first FEL undulator. Theconsiderations that led to the proposed configuration were made on thebasis of a study that explored various options and performance limits.This work follows previous studies of x-ray FEL facilities (SLAC LCLS[1], DESY XFEL [2], PAL XFEL [3], MIT [4], BESSY FEL[5], LBNL LUX [6],Daresbury 4GLS [7]) and integrates many of the ideas that were developedthere. Several issues specific to harmonic cascade FELs, and that had notyet been comprehensively studied, were also encountered and tackled. Aparticularly difficult issue was the need to meet the requirement forhigh peak current and small slice energy spread, as the specification forthe ratio of these two parameters (that defines the peak brightness ofthe electron beam) is almost a factor of two higher than that of theLCLS's SASE FEL. Another challenging aspect was the demand to produce anelectron beam with as uniform as possible peak current and energydistributions along the bunch, a condition that was met by introducingnovel beam dynamics techniques. Part of the challenge was due to the factthat there were no readily available computational tools to carry outreliable calculations, and these had to be developed. Most of theinformation reported in this study is available in the form of scientificpublications, and is partly reproduced here for the convenience of thereader.

  2. A Parallel Particle Swarm Optimization Algorithm Accelerated by Asynchronous Evaluations

    NASA Technical Reports Server (NTRS)

    Venter, Gerhard; Sobieszczanski-Sobieski, Jaroslaw

    2005-01-01

    A parallel Particle Swarm Optimization (PSO) algorithm is presented. Particle swarm optimization is a fairly recent addition to the family of non-gradient based, probabilistic search algorithms that is based on a simplified social model and is closely tied to swarming theory. Although PSO algorithms present several attractive properties to the designer, they are plagued by high computational cost as measured by elapsed time. One approach to reduce the elapsed time is to make use of coarse-grained parallelization to evaluate the design points. Previous parallel PSO algorithms were mostly implemented in a synchronous manner, where all design points within a design iteration are evaluated before the next iteration is started. This approach leads to poor parallel speedup in cases where a heterogeneous parallel environment is used and/or where the analysis time depends on the design point being analyzed. This paper introduces an asynchronous parallel PSO algorithm that greatly improves the parallel e ciency. The asynchronous algorithm is benchmarked on a cluster assembled of Apple Macintosh G5 desktop computers, using the multi-disciplinary optimization of a typical transport aircraft wing as an example.

  3. FXR silencing in human colon cancer by DNA methylation and KRAS signaling.

    PubMed

    Bailey, Ann M; Zhan, Le; Maru, Dipen; Shureiqi, Imad; Pickering, Curtis R; Kiriakova, Galina; Izzo, Julie; He, Nan; Wei, Caimiao; Baladandayuthapani, Veerabhadran; Liang, Han; Kopetz, Scott; Powis, Garth; Guo, Grace L

    2014-01-01

    Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue (n = 238), polyps (n = 32), and adenocarcinomas, staged I-IV (n = 43, 39, 68, and 9), of the colon; RT-quantitative PCR, reverse-phase protein array, and Western blot analysis in 15 colon cancer cell lines; NR1H4 promoter methylation and mRNA expression in colon cancer samples from The Cancer Genome Atlas; DNA methyltransferase inhibition; methyl-DNA immunoprecipitation (MeDIP); bisulfite sequencing; and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) knockdown assessment to investigate FXR regulation in colon cancer development. Immunohistochemistry and quantitative RT-PCR revealed that expression and function of FXR was reduced in precancerous lesions and silenced in a majority of stage I-IV tumors. FXR expression negatively correlated with phosphatidylinositol-4, 5-bisphosphate 3 kinase signaling and the epithelial-to-mesenchymal transition. The NR1H4 promoter is methylated in ~12% colon cancer The Cancer Genome Atlas samples, and methylation patterns segregate with tumor subtypes. Inhibition of DNA methylation and KRAS silencing both increased FXR expression. FXR expression is decreased early in human colon cancer progression, and both DNA methylation and KRAS signaling may be contributing factors to FXR silencing. FXR potentially suppresses epithelial-to-mesenchymal transition and other oncogenic signaling cascades, and restoration of FXR activity, by blocking silencing mechanisms or increasing residual FXR activity, represents promising therapeutic options for the treatment of colon cancer.

  4. Preferential enhancement of laser-driven carbon ion acceleration from optimized nanostructured surfaces

    PubMed Central

    Dalui, Malay; Wang, W.-M.; Trivikram, T. Madhu; Sarkar, Subhrangshu; Tata, Sheroy; Jha, J.; Ayyub, P.; Sheng, Z. M.; Krishnamurthy, M.

    2015-01-01

    High-intensity ultrashort laser pulses focused on metal targets readily generate hot dense plasmas which accelerate ions efficiently and can pave way to compact table-top accelerators. Laser-driven ion acceleration studies predominantly focus on protons, which experience the maximum acceleration owing to their highest charge-to-mass ratio. The possibility of tailoring such schemes for the preferential acceleration of a particular ion species is very much desired but has hardly been explored. Here, we present an experimental demonstration of how the nanostructuring of a copper target can be optimized for enhanced carbon ion acceleration over protons or Cu-ions. Specifically, a thin (≈0.25 μm) layer of 25–30 nm diameter Cu nanoparticles, sputter-deposited on a polished Cu-substrate, enhances the carbon ion energy by about 10-fold at a laser intensity of 1.2×1018  W/cm2. However, particles smaller than 20 nm have an adverse effect on the ion acceleration. Particle-in-cell simulations provide definite pointers regarding the size of nanoparticles necessary for maximizing the ion acceleration. The inherent contrast of the laser pulse is found to play an important role in the species selective ion acceleration. PMID:26153048

  5. Preferential enhancement of laser-driven carbon ion acceleration from optimized nanostructured surfaces.

    PubMed

    Dalui, Malay; Wang, W-M; Trivikram, T Madhu; Sarkar, Subhrangsu; Sarkar, Subhrangshu; Tata, Sheroy; Jha, J; Ayyub, P; Sheng, Z M; Krishnamurthy, M

    2015-01-01

    High-intensity ultrashort laser pulses focused on metal targets readily generate hot dense plasmas which accelerate ions efficiently and can pave way to compact table-top accelerators. Laser-driven ion acceleration studies predominantly focus on protons, which experience the maximum acceleration owing to their highest charge-to-mass ratio. The possibility of tailoring such schemes for the preferential acceleration of a particular ion species is very much desired but has hardly been explored. Here, we present an experimental demonstration of how the nanostructuring of a copper target can be optimized for enhanced carbon ion acceleration over protons or Cu-ions. Specifically, a thin (≈ 0.25 μm) layer of 25-30 nm diameter Cu nanoparticles, sputter-deposited on a polished Cu-substrate, enhances the carbon ion energy by about 10-fold at a laser intensity of 1.2 × 10(18)  W/cm(2). However, particles smaller than 20 nm have an adverse effect on the ion acceleration. Particle-in-cell simulations provide definite pointers regarding the size of nanoparticles necessary for maximizing the ion acceleration. The inherent contrast of the laser pulse is found to play an important role in the species selective ion acceleration. PMID:26153048

  6. Optimization of Drive-Bunch Current Profile for Enhanced Transformer Ratio in Beam-Driven Acceleration Techniques

    SciTech Connect

    Lemery, F.; Mihalcea, D.; Prokop, C.R.; Piot, P.; /Northern Illinois U. /Fermilab

    2012-07-08

    In recent years, wakefield acceleration has gained attention due to its high acceleration gradients and cost effectiveness. In beam-driven wakefield acceleration, a critical parameter to optimize is the transformer ratio. It has been shown that current shaping of electron beams allows for enhanced (> 2) transformer ratios. In this paper we present the optimization of the pulse shape of the drive bunch for dielectric-wakefield acceleration.

  7. FXR1, an autosomal homolog of the fragile X mental retardation gene.

    PubMed Central

    Siomi, M C; Siomi, H; Sauer, W H; Srinivasan, S; Nussbaum, R L; Dreyfuss, G

    1995-01-01

    Fragile X mental retardation syndrome, the most common cause of hereditary mental retardation, is directly associated with the FMR1 gene at Xq27.3. FMR1 encodes an RNA binding protein and the syndrome results from lack of expression of FMR1 or expression of a mutant protein that is impaired in RNA binding. We found a novel gene, FXR1, that is highly homologous to FMR1 and located on chromosome 12 at 12q13. FXR1 encodes a protein which, like FMR1, contains two KH domains and is highly conserved in vertebrates. The 3' untranslated regions (3'UTRs) of the human and Xenopus laevis FXR1 mRNAs are strikingly conserved (approximately 90% identity), suggesting conservation of an important function. The KH domains of FXR1 and FMR1 are almost identical, and the two proteins have similar RNA binding properties in vitro. However, FXR1 and FMR1 have very different carboxy-termini. FXR1 and FMR1 are expressed in many tissues, and both proteins, which are cytoplasmic, can be expressed in the same cells. Interestingly, cells from a fragile X patient that do not have any detectable FMR1 express normal levels of FXR1. These findings demonstrate that FMR1 and FXR1 are members of a gene family and suggest a biological role for FXR1 that is related to that of FMR1. Images PMID:7781595

  8. Deletion of mouse FXR gene disturbs multiple neurotransmitter systems and alters neurobehavior

    PubMed Central

    Huang, Fei; Wang, Tingting; Lan, Yunyi; Yang, Li; Pan, Weihong; Zhu, Yonghui; Lv, Boyang; Wei, Yuting; Shi, Hailian; Wu, Hui; Zhang, Beibei; Wang, Jie; Duan, Xiaofeng; Hu, Zhibi; Wu, Xiaojun

    2015-01-01

    Farnesoid X receptor (FXR) is a nuclear hormone receptor involved in bile acid synthesis and homeostasis. Dysfunction of FXR is involved in cholestasis and atherosclerosis. FXR is prevalent in liver, gallbladder, and intestine, but it is not yet clear whether it modulates neurobehavior. In the current study, we tested the hypothesis that mouse FXR deficiency affects a specific subset of neurotransmitters and results in an unique behavioral phenotype. The FXR knockout mice showed less depressive-like and anxiety-related behavior, but increased motor activity. They had impaired memory and reduced motor coordination. There were changes of glutamatergic, GABAergic, serotoninergic, and norepinephrinergic neurotransmission in either hippocampus or cerebellum. FXR deletion decreased the amount of the GABA synthesis enzyme GAD65 in hippocampus but increased GABA transporter GAT1 in cerebral cortex. FXR deletion increased serum concentrations of many bile acids, including taurodehydrocholic acid, taurocholic acid, deoxycholic acid (DCA), glycocholic acid (GCA), tauro-α-muricholic acid, tauro-ω-muricholic acid, and hyodeoxycholic acid (HDCA). There were also changes in brain concentrations of taurocholic acid, taurodehydrocholic acid, tauro-ω-muricholic acid, tauro-β-muricholic acid, deoxycholic acid, and lithocholic acid (LCA). Taken together, the results from studies with FXR knockout mice suggest that FXR contributes to the homeostasis of multiple neurotransmitter systems in different brain regions and modulates neurobehavior. The effect appears to be at least partially mediated by bile acids that are known to cross the blood-brain barrier (BBB) inducing potential neurotoxicity. PMID:25870546

  9. Optimal design of multiple stress constant accelerated life test plan on non-rectangle test region

    NASA Astrophysics Data System (ADS)

    Chen, Wenhua; Gao, Liang; Liu, Juan; Qian, Ping; Pan, Jun

    2012-11-01

    For optimal design of constant stress accelerated life test(CSALT) with two-stress, if the stresses could not reach the highest levels simultaneously, the test region becomes non-rectangular. For optimal CSALT design on non-rectangle test region, the present method is only focused on non-rectangle test region with simple boundary, and the optimization algorithm is based on experience which can not ensure to obtain the optimal plan. In this paper, considering the linear-extreme value model and the optimization goal to minimize the variance of lifetime estimate under normal stress, the optimal design method of two-stress type-I censored CSALT plan on general non-rectangular test region is proposed. First, two properties of optimal test plans are proved and the relationship of all the optimal test plans is determined analytically. Then, on the basis of the two properties, the optimal problem is simplified and the optimal design method of two-stress CSALT plan on general non-rectangular test region is proposed. Finally, a numerical example is used to illustrate the feasibility and effectiveness of the method. The result shows that the proposed method could obtain the optimal test plan on non-rectangular test regions with arbitrary boundaries. This research provides the theory and method for two-stress optimal CSALT planning on non-rectangular test regions.

  10. Optimization of Aero Engine Acceleration Control in Combat State Based on Genetic Algorithms

    NASA Astrophysics Data System (ADS)

    Li, Jie; Fan, Ding; Sreeram, Victor

    2012-03-01

    In order to drastically exploit the potential of the aero engine and improve acceleration performance in the combat state, an on-line optimized controller based on genetic algorithms is designed for an aero engine. For testing the validity of the presented control method, detailed joint simulation tests of the designed controller and the aero engine model are performed in the whole flight envelope. Simulation test results show that the presented control algorithm has characteristics of rapid convergence speed, high efficiency and can fully exploit the acceleration performance potential of the aero engine. Compared with the former controller, the designed on-line optimized controller (DOOC) can improve the security of the acceleration process and greatly enhance the aero engine thrust in the whole range of the flight envelope, the thrust increases an average of 8.1% in the randomly selected working states. The plane which adopts DOOC can acquire better fighting advantage in the combat state.

  11. Microbunching Instability Effect Studies and Laser Heater Optimization for the SPARX FEL Accelerator

    SciTech Connect

    Vaccarezza, C.; Chiadroni, E.; Ferrario, M.; Giannessi, L.; Quattromini, M.; Ronsivalle, C.; Venturini, C.; Migliorati, M.; Dattoli, G.

    2010-05-23

    The effects of microbunching instability for the SPARX accelerator have been analyzed by means of numerical simulations. The laser heater counteracting action has been addressed in order to optimize the parameters of the compression system, either hybrid RF plus magnetic chicane or only magnetic, and possibly enhance the FEL performance.

  12. The Nuclear Receptor FXR Uncouples the Actions of miR-33 from SREBP-2

    PubMed Central

    Tarling, Elizabeth J.; Ahn, Hannah; de Aguiar Vallim, Thomas Q.

    2015-01-01

    Objective To determined whether activation of FXR alters cellular and plasma cholesterol homeostasis as a result of regulation of Srebp-2 and miR-33. Approach and Results ChIP-seq data identified an FXR-response element within intron 10 of the Srebp-2 gene. Consistent with this observation, treatment of mice with FXR-specific agonists (GSK2324 or GW4064) rapidly increased hepatic levels of Srebp-2 mRNA, pSREBP-2 protein, and miR-33. Further, miR-33 targets, that include ABCA1, NSF and CPT1, were all reduced in GSK2324-treated mice. In contrast, neither nSREBP-2 protein, nor SREBP-2 target genes were induced following FXR activation. The inability to process pSREBP-2 to nSREBP-2 is likely a consequence of induction of INSIG-2a by FXR agonists. Finally, we show that FXR-dependent induction of both Srebp-2 and miR-33 is ablated in Scap−/− mice that lack nSREBP-2. Conclusions We demonstrate that activation of FXR uncouples the expression of nSREBP-2 and miR-33, and the regulation of their respective target genes. Further, we conclude that the FXR agonist-dependent increase in miR-33 requires transcription of the Srebp-2 gene. PMID:25593129

  13. A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity

    PubMed Central

    Kim, Dong-Hyun; Xiao, Zhen; Kwon, Sanghoon; Sun, Xiaoxiao; Ryerson, Daniel; Tkac, David; Ma, Ping; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Zhou, Edward; Xu, H Eric; Palvimo, Jorma J; Chen, Lin-Feng; Kemper, Byron; Kemper, Jongsook Kim

    2015-01-01

    Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and acetylation-defective K217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, macrophage infiltration, and liver cytokine and triglyceride levels, impaired insulin signaling, and increased glucose intolerance. Mechanistically, acetylation of FXR blocked its interaction with the SUMO ligase PIASy and inhibited SUMO2 modification at K277, resulting in activation of inflammatory genes. SUMOylation of agonist-activated FXR increased its interaction with NF-κB but blocked that with RXRα, so that SUMO2-modified FXR was selectively recruited to and trans-repressed inflammatory genes without affecting FXR/RXRα target genes. A dysregulated acetyl/SUMO switch of FXR in obesity may serve as a general mechanism for diminished anti-inflammatory response of other transcriptional regulators and provide potential therapeutic and diagnostic targets for obesity-related metabolic disorders. PMID:25425577

  14. Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064.

    PubMed

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y; Caldwell, Richard D; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Jones, Stacey A; Kaldor, Istvan; Liu, Yaping; Madauss, Kevin P; Marr, Harry B; McFadyen, Robert B; Miller, Aaron B; Iii, Frank Navas; Parks, Derek J; Spearing, Paul K; Todd, Dan; Williams, Shawn P; Wisely, G Bruce

    2008-08-01

    Starting from the known FXR agonist GW 4064 1a, a series of stilbene replacements were prepared. The 6-substituted 1-naphthoic acid 1b was an equipotent FXR agonist with improved developability parameters relative to 1a. Analog 1b also reduced the severity of cholestasis in the ANIT acute cholestatic rat model.

  15. Non-linear stochastic optimal control of acceleration parametrically excited systems

    NASA Astrophysics Data System (ADS)

    Wang, Yong; Jin, Xiaoling; Huang, Zhilong

    2016-02-01

    Acceleration parametrical excitations have not been taken into account due to the lack of physical significance in macroscopic structures. The explosive development of microtechnology and nanotechnology, however, motivates the investigation of the acceleration parametrically excited systems. The adsorption and desorption effects dramatically change the mass of nano-sized structures, which significantly reduces the precision of nanoscale sensors or can be reasonably utilised to detect molecular mass. This manuscript proposes a non-linear stochastic optimal control strategy for stochastic systems with acceleration parametric excitation based on stochastic averaging of energy envelope and stochastic dynamic programming principle. System acceleration is approximately expressed as a function of system displacement in a short time range under the conditions of light damping and weak excitations, and the acceleration parametrically excited system is shown to be equivalent to a constructed system with an additional displacement parametric excitation term. Then, the controlled system is converted into a partially averaged Itô equation with respect to the total system energy through stochastic averaging of energy envelope, and the optimal control strategy for the averaged system is derived from solving the associated dynamic programming equation. Numerical results for a controlled Duffing oscillator indicate the efficacy of the proposed control strategy.

  16. Recent advances in non-steroidal FXR antagonists development for therapeutic applications.

    PubMed

    Huang, Huang; Xu, Yong; Zhu, Jin; Li, Jian

    2014-01-01

    Farnesoid X receptor (FXR, NR1H4), a nuclear receptor (NR) highly expressed in the liver, intestine, kidney, adrenal glands and other cholesterol-rich tissues, functions as the master regulator for bile acid homeostasis. FXR, which regulates the expression of genes encoding proteins involved in cholesterol homeostasis, plays an essential role in regulating cholesterol, lipid, and glucose metabolism. Recently, some FXR agonists are reported to have low selectivity on NRs, which forces the researchers to move their eyes onto the development of FXR antagonists with high selectivity. The development of non-steroidal FXR antagonists with different scaffolds including AGN34, tuberatolides, atractylenolides, andrographolides, GW4064 derivatives and 1,3,4-trisubstitutedpyrazolones, provides us a prospect for the therapy of in ammation, metabolic syndrome, diabetes, cholesterol gallstones, and cancer. PMID:25388534

  17. Development of time resolved fluorescence resonance energy transfer-based assay for FXR antagonist discovery.

    PubMed

    Yu, Donna D; Lin, Wenwei; Chen, Taosheng; Forman, Barry M

    2013-07-15

    FXR (farnesoid X receptor, NRIH4), a nuclear receptor, plays a major role in the control of cholesterol metabolism. FXR ligands have been investigated in preclinical studies for targeted therapy against metabolic diseases, but have shown limitations. Therefore, there is a need for new agonist or antagonist ligands of FXR, both for potential clinical applications, as well as to further elucidate its biological functions. Here we describe the use of the X-ray crystal structure of FXR complexed with the potent small molecule agonist GW4064 to design and synthesize a novel fluorescent, high-affinity probe (DY246) for time resolved fluorescence resonance energy transfer (TR-FRET) assays. We then used the TR-FRET assay for high throughput screening of a library of over 5000 bioactive compounds. From this library, we identified 13 compounds that act as putative FXR transcriptional antagonists.

  18. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance

    PubMed Central

    Fang, Sungsoon; Suh, Jae Myoung; Reilly, Shannon M; Yu, Elizabeth; Osborn, Olivia; Lackey, Denise; Yoshihara, Eiji; Perino, Alessia; Jacinto, Sandra; Lukasheva, Yelizaveta; Atkins, Annette R; Khvat, Alexander; Schnabl, Bernd; Yu, Ruth T; Brenner, David A; Coulter, Sally; Liddle, Christopher; Schoonjans, Kristina; Olefsky, Jerrold M; Saltiel, Alan R; Downes, Michael; Evans, Ronald M

    2015-01-01

    The systemic expression of the bile acid (BA) sensor farnesoid X receptor (FXR) has led to promising new therapies targeting cholesterol metabolism, triglyceride production, hepatic steatosis and biliary cholestasis. In contrast to systemic therapy, bile acid release during a meal selectively activates intestinal FXR. By mimicking this tissue-selective effect, the gut-restricted FXR agonist fexaramine (Fex) robustly induces enteric fibroblast growth factor 15 (FGF15), leading to alterations in BA composition, but does so without activating FXR target genes in the liver. However, unlike systemic agonism, we find that Fex reduces diet-induced weight gain, body-wide inflammation and hepatic glucose production, while enhancing thermogenesis and browning of white adipose tissue (WAT). These pronounced metabolic improvements suggest tissue-restricted FXR activation as a new approach in the treatment of obesity and metabolic syndrome. PMID:25559344

  19. Role of FXR in β-cells of lean and obese mice.

    PubMed

    Schittenhelm, Björn; Wagner, Rebecca; Kähny, Verena; Peter, Andreas; Krippeit-Drews, Peter; Düfer, Martina; Drews, Gisela

    2015-04-01

    We have recently shown that the bile acid (BA) taurochenodeoxycholate (TCDC) acutely stimulates insulin secretion via activation of the farnesoid X receptor (FXR). Aims of the current investigation were to discriminate between nongenomic (≤1 h) and genomic effects (24-48 h) of BAs on β-cells and to evaluate whether FXR can modulate the adverse effects of a high-fat diet (HFD). TCDC (500 nM) as well as glycine-conjugated and unconjugated CDC (chenodeoxycholate) increased insulin secretion in acute incubations but did not evoke additional effects after 1-2 days of preincubation. The BAs did not stimulate β-cells of FXR-knockout (KO) mice and activation of the G protein-coupled BA receptor TGR5 was ineffective, suggesting that FXR is the sole BA receptor in β-cells activated by TCDC and its analogues. As opposed to lean mice, obese FXR-KO mice did not show HFD-induced glucose intolerance and increased fasting glucose. The beneficial impact of FXR-KO on glucose metabolism cannot be explained by an adaptive compensation of insulin secretion or β-cell mass. Interestingly, in contrast to its effect on islets from lean mice, the FXR agonist GW4064 was ineffective in stimulating insulin secretion of islets from wild type mice fed a HFD or isolated islets kept in a glucolipotoxic medium. Additional feeding of CDC restored the effect of GW4064. CDC prevented HFD-induced impairment of glucose tolerance and in vitro effects of glucolipotoxicity. The data show that the FXR is the most important BA receptor in β-cells and that FXR signaling in β-cells is impaired by overnutrition, which alters activatability of the FXR.

  20. FXR Primes the Liver for Intestinal FGF15 Signaling by Transient Induction of β-Klotho.

    PubMed

    Fu, Ting; Kim, Young-Chae; Byun, Sangwon; Kim, Dong-Hyun; Seok, Sunmi; Suino-Powell, Kelly; Xu, H Eric; Kemper, Byron; Kemper, Jongsook Kim

    2016-01-01

    The bile acid (BA)-sensing nuclear receptor, farnesoid X receptor (FXR), regulates postprandial metabolic responses, including inhibition of BA synthesis, by inducing the intestinal hormone, fibroblast growth factor (FGF)15 (FGF19 in human). In this study, we tested a novel hypothesis that FXR not only induces intestinal FGF15 but also primes the liver for effectively responding to the signal by transcriptional induction of the obligate coreceptor for FGF15, β-Klotho (βKL). Activation of FXR by a synthetic agonist, GW4064, in mice increased occupancy of FXR and its DNA-binding partner, retinoid X receptor-α, at FGF15-signaling component genes, particularly βKL, and induced expression of these genes. Interestingly, mRNA levels of Fgfr4, the FGF15 receptor, were not increased by GW4064, but protein levels increased as a result of βKL-dependent increased protein stability. Both FGF receptor 4 and βKL protein levels were substantially decreased in FXR-knockout (KO) mice, and FGF19 signaling, monitored by phosphorylated ERK, was blunted in FXR-KO mice, FXR-KO mouse hepatocytes, and FXR-down-regulated human hepatocytes. Overexpression of βKL in FXR-lacking hepatocytes partially restored FGF19 signaling and inhibition by FGF19 of Cyp7a1, which encodes the rate-limiting BA biosynthetic enzyme. In mice, transient inductions of intestinal Fgf15 and hepatic βKL were temporally correlated after GW4064 treatment, and pretreatment of hepatocytes with GW4064 before FGF19 treatment enhanced FGF19 signaling, which was abolished by transcriptional inhibition or βKL down-regulation. This study identifies FXR as a gut-liver metabolic coordinator for FGF15/19 action that orchestrates transient induction of hepatic βKL and intestinal Fgf15/19 in a temporally correlated manner.

  1. Multilevel Optimization Framework for Hierarchical Stiffened Shells Accelerated by Adaptive Equivalent Strategy

    NASA Astrophysics Data System (ADS)

    Wang, Bo; Tian, Kuo; Zhao, Haixin; Hao, Peng; Zhu, Tianyu; Zhang, Ke; Ma, Yunlong

    2016-09-01

    In order to improve the post-buckling optimization efficiency of hierarchical stiffened shells, a multilevel optimization framework accelerated by adaptive equivalent strategy is presented in this paper. Firstly, the Numerical-based Smeared Stiffener Method (NSSM) for hierarchical stiffened shells is derived by means of the numerical implementation of asymptotic homogenization (NIAH) method. Based on the NSSM, a reasonable adaptive equivalent strategy for hierarchical stiffened shells is developed from the concept of hierarchy reduction. Its core idea is to self-adaptively decide which hierarchy of the structure should be equivalent according to the critical buckling mode rapidly predicted by NSSM. Compared with the detailed model, the high prediction accuracy and efficiency of the proposed model is highlighted. On the basis of this adaptive equivalent model, a multilevel optimization framework is then established by decomposing the complex entire optimization process into major-stiffener-level and minor-stiffener-level sub-optimizations, during which Fixed Point Iteration (FPI) is employed to accelerate convergence. Finally, the illustrative examples of the multilevel framework is carried out to demonstrate its efficiency and effectiveness to search for the global optimum result by contrast with the single-level optimization method. Remarkably, the high efficiency and flexibility of the adaptive equivalent strategy is indicated by compared with the single equivalent strategy.

  2. The glucocorticoid mometasone furoate is a novel FXR ligand that decreases inflammatory but not metabolic gene expression

    PubMed Central

    Bijsmans, Ingrid T. G. W.; Guercini, Chiara; Ramos Pittol, José M.; Omta, Wienand; Milona, Alexandra; Lelieveld, Daphne; Egan, David A.; Pellicciari, Roberto; Gioiello, Antimo; van Mil, Saskia W. C.

    2015-01-01

    The Farnesoid X receptor (FXR) regulates bile salt, glucose and cholesterol homeostasis by binding to DNA response elements, thereby activating gene expression (direct transactivation). FXR also inhibits the immune response via tethering to NF-κB (tethering transrepression). FXR activation therefore has therapeutic potential for liver and intestinal inflammatory diseases. We aim to identify and develop gene-selective FXR modulators, which repress inflammation, but do not interfere with its metabolic capacity. In a high-throughput reporter-based screen, mometasone furoate (MF) was identified as a compound that reduced NF-κB reporter activity in an FXR-dependent manner. MF reduced mRNA expression of pro-inflammatory cytokines, and induction of direct FXR target genes in HepG2-GFP-FXR cells and intestinal organoids was minor. Computational studies disclosed three putative binding modes of the compound within the ligand binding domain of the receptor. Interestingly, mutation of W469A residue within the FXR ligand binding domain abrogated the decrease in NF-κB activity. Finally, we show that MF-bound FXR inhibits NF-κB subunit p65 recruitment to the DNA of pro-inflammatory genes CXCL2 and IL8. Although MF is not suitable as selective anti-inflammatory FXR ligand due to nanomolar affinity for the glucocorticoid receptor, we show that separation between metabolic and anti-inflammatory functions of FXR can be achieved. PMID:26369990

  3. Optimization of parameters for the inline-injection system at Brookhaven Accelerator Test Facility

    SciTech Connect

    Parsa, Z.; Ko, S.K.

    1995-10-01

    We present some of our parameter optimization results utilizing code PARMLEA, for the ATF Inline-Injection System. The new solenoid-Gun-Solenoid -- Drift-Linac Scheme would improve the beam quality needed for FEL and other experiments at ATF as compared to the beam quality of the original design injection system. To optimize the gain in the beam quality we have considered various parameters including the accelerating field gradient on the photoathode, the Solenoid field strengths, separation between the gun and entrance to the linac as well as the (type size) initial charge distributions. The effect of the changes in the parameters on the beam emittance is also given.

  4. Optimizing the science of drug development: opportunities for better candidate selection and accelerated evaluation in humans.

    PubMed

    Lesko, L J; Rowland, M; Peck, C C; Blaschke, T F

    2000-08-01

    Two international meetings were convened in 1998 to review the current science of drug development and the potential opportunities to optimize the evaluation of new drugs in humans. This report represents a synopsis of these meetings, and focuses on the current state of knowledge pertaining to drug development, future scientific and technical needs, and the relative merits of various strategies intended to accelerate the clinical development of drugs. PMID:10934664

  5. N-Myristoylation regulates the axonal distribution of the fragile X-related protein FXR2P

    PubMed Central

    Stackpole, Emily E.; Akins, Michael R.; Fallon, Justin R.

    2014-01-01

    Fragile X Syndrome, the leading cause of inherited intellectual disability and autism, is caused by loss of function of Fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein that regulates local protein synthesis in the somatodendritic compartment. However, emerging evidence also indicates important roles for FMRP in axonal and presynaptic function. In particular, FMRP and its homolog FXR2P localize axonally and presynaptically to discrete endogenous structures in the brain termed Fragile X granules (FXGs). FXR2P is a component of all FXGs and is necessary for the axonal and presynaptic localization of FMRP to these structures. We therefore sought to identify and characterize structural features of FXR2P that regulate its axonal localization. Sequence analysis reveals that FXR2P harbors a consensus N-terminal myristoylation sequence (MGXXXS) that is absent in FMRP. Using click chemistry with wild type and an unmyristoylatable G2A mutant we demonstrate that FXR2P is N-myristoylated on glycine 2, establishing it as a lipid-modified RNA binding protein. To investigate the role of FXR2P N-myristoylation in neurons we generated fluorescently tagged wild type and unmyristoylatable FXR2P (WT and G2A, respectively) and expressed them in primary cortical cultures. Both FXR2PWT and FXR2PG2A are expressed at equivalent overall levels and are capable of forming FMRP-containing axonal granules. However, FXR2PWT granules are largely restricted to proximal axonal segments while granules formed with unmyristoylatable FXR2PG2A are localized throughout the axonal arbor, including in growth cones. These studies indicate that N-terminal myristoylation of the RNA binding protein FXR2P regulates its localization within the axonal arbor. Moreover, since FMRP localization within axonal domains requires its association with FXR2P, these findings suggest that FXR2P lipid modification is a control point for the axonal and presynaptic distribution of FMRP. PMID:25109237

  6. Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

    PubMed

    Bjursell, Mikael; Wedin, Marianne; Admyre, Therése; Hermansson, Majlis; Böttcher, Gerhard; Göransson, Melker; Lindén, Daniel; Bamberg, Krister; Oscarsson, Jan; Bohlooly-Y, Mohammad

    2013-01-01

    Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR) is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH) and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

  7. Suppression of interleukin-6-induced C-reactive protein expression by FXR agonists

    SciTech Connect

    Zhang Songwen Liu Qiangyuan; Wang Juan; Harnish, Douglas C.

    2009-02-06

    C-reactive protein (CRP), a human acute-phase protein, is a risk factor for future cardiovascular events and exerts direct pro-inflammatory and pro-atherogenic properties. The farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily, plays an essential role in the regulation of enterohepatic circulation and lipid homeostasis. In this study, we report that two synthetic FXR agonists, WAY-362450 and GW4064, suppressed interleukin-6-induced CRP expression in human Hep3B hepatoma cells. Knockdown of FXR by short interfering RNA attenuated the inhibitory effect of the FXR agonists and also increased the ability of interleukin-6 to induce CRP production. Furthermore, treatment of wild type C57BL/6 mice with the FXR agonist, WAY-362450, attenuated lipopolysaccharide-induced serum amyloid P component and serum amyloid A3 mRNA levels in the liver, whereas no effect was observed in FXR knockout mice. These data provide new evidence for direct anti-inflammatory properties of FXR.

  8. Identification of an N-oxide pyridine GW4064 analog as a potent FXR agonist.

    PubMed

    Feng, Song; Yang, Minmin; Zhang, Zhenshan; Wang, Zhanguo; Hong, Di; Richter, Hans; Benson, Gregory Martin; Bleicher, Konrad; Grether, Uwe; Martin, Rainer E; Plancher, Jean-Marc; Kuhn, Bernd; Rudolph, Markus Georg; Chen, Li

    2009-05-01

    According to the docking studies and the analysis of a co-crystal structure of GW4064 with FXR, a series of 3-aryl heterocyclic isoxazole analogs were designed and synthesized. N-Oxide pyridine analog (7b) was identified as a promising FXR agonist with potent binding affinity and good efficacy, supporting our hypothesis that through an additional hydrogen bond interaction between the pyridine substituent of isoxazole analogs and Tyr373 and Ser336 of FXR, binding affinity and functional activity could be improved.

  9. Knockdown of ATP8B1 expression leads to specific downregulation of the bile acid sensor FXR in HepG2 cells: effect of the FXR agonist GW4064.

    PubMed

    Martínez-Fernández, Pilar; Hierro, Loreto; Jara, Paloma; Alvarez, Luis

    2009-05-01

    Farnesoid X receptor (FXR) is a bile acid-sensing nuclear receptor that controls bile acid homeostasis. It has been suggested that downregulation of FXR contributes to the pathogenesis of an inherited disorder of bile secretion caused by mutations in ATP8B1. We have investigated the relationship between ATP8B1 knockdown and FXR downregulation in the human hepatoblastoma cell line HepG2. Transfection of HepG2 cells with ATP8B1 small interfering RNA (siRNA) duplexes led to a 60% reduction in the endogenous levels of ATP8B1 mRNA and protein and a concomitant decrease in FXR mRNA and protein content, as well as in FXR phosphorylation. This decrease was accompanied by a marked reduction in mRNA levels of a subset of FXR targets, such as bile salt export pump (ABCB11), small heterodimer partner, and uridine 5'-diphosphate-glucuronosyltransferase. ATP8B1 inhibition specifically targeted FXR since mRNA expression of other prominent nuclear receptors, such as pregnane X receptor and constitutive androstane receptor, or liver-enriched transcription factors, such as hepatocyte nuclear factor 1alpha (HNF-1alpha) and HNF-4alpha, was not altered. The expression of other key genes involved in bile acid synthesis, detoxification, and transport also remained unchanged upon ATP8B1 knockdown. Supporting the specificity of the effect, siRNA-mediated silencing of ABCB11, whose defect is associated with another inherited disorder of bile secretion, did not affect FXR expression. Treatment with the synthetic FXR agonist GW4064 was able to partially neutralize ATP8B1 siRNA-mediated FXR downregulation and fully counteract inhibition of FXR target genes. Collectively these findings indicate that ATP8B1 knockdown specifically downregulates FXR, and this action can be circumvented by treatment with FXR agonists.

  10. Three-dimensional magnetic optimization of accelerator magnets using an analytic strip model

    SciTech Connect

    Rochepault, Etienne Aubert, Guy; Vedrine, Pierre

    2014-07-14

    The end design is a critical step in the design of superconducting accelerator magnets. First, the strain energy of the conductors must be minimized, which can be achieved using differential geometry. The end design also requires an optimization of the magnetic field homogeneity. A mechanical and magnetic model for the conductors, using developable strips, is described in this paper. This model can be applied to superconducting Rutherford cables, and it is particularly suitable for High Temperature Superconducting tapes. The great advantage of this approach is analytic simplifications in the field computation, allowing for very fast and accurate computations, which save a considerable computational time during the optimization process. Some 3D designs for dipoles are finally proposed, and it is shown that the harmonic integrals can be easily optimized using this model.

  11. Optimization and beam control in large-emittance accelerators: Neutrino factories;

    SciTech Connect

    Carol Johnstone

    2004-08-23

    Schemes for intense sources of high-energy muons require collection, rf capture, and transport of particle beams with unprecedented emittances, both longitudinally and transversely. These large emittances must be reduced or ''cooled'' both in size and in energy spread before the muons can be efficiently accelerated. Therefore, formation of muon beams sufficiently intense to drive a Neutrino Factory or Muon Collider requires multi-stage preparation. Further, because of the large beam phase space which must be successfully controlled, accelerated, and transported, the major stages that comprise such a facility: proton driver, production, capture, phase rotation, cooling, acceleration, and storage are complex and strongly interlinked. Each of the stages must be consecutively matched and simultaneously optimized with upstream and downstream systems, meeting challenges not only technically in the optics and component design, but also in the modeling of both new and extended components. One design for transverse cooling, for example, employs meter-diameter solenoids to maintain strong focusing--300-500 mr beam divergences--across ultra-large momentum ranges, {ge} {+-}20% {delta}p/p, defying conventional approximations to the dynamics and field representation. To now, the interplay of the different systems and staging strategies has not been formally addressed. This work discusses two basic, but different approaches to a Neutrino Factory and how the staging strategy depends on beam parameters and method of acceleration.

  12. Design and Optimization of Large Accelerator Systems through High-Fidelity Electromagnetic Simulations

    SciTech Connect

    Ng, Cho; Akcelik, Volkan; Candel, Arno; Chen, Sheng; Ge, Lixin; Kabel, Andreas; Lee, Lie-Quan; Li, Zenghai; Prudencio, Ernesto; Schussman, Greg; Uplenchwar1, Ravi; Xiao1, Liling; Ko1, Kwok; Austin, T.; Cary, J.R.; Ovtchinnikov, S.; Smith, D.N.; Werner, G.R.; Bellantoni, L.; /SLAC /TechX Corp. /Fermilab

    2008-08-01

    SciDAC1, with its support for the 'Advanced Computing for 21st Century Accelerator Science and Technology' (AST) project, witnessed dramatic advances in electromagnetic (EM) simulations for the design and optimization of important accelerators across the Office of Science. In SciDAC2, EM simulations continue to play an important role in the 'Community Petascale Project for Accelerator Science and Simulation' (ComPASS), through close collaborations with SciDAC CETs/Institutes in computational science. Existing codes will be improved and new multi-physics tools will be developed to model large accelerator systems with unprecedented realism and high accuracy using computing resources at petascale. These tools aim at targeting the most challenging problems facing the ComPASS project. Supported by advances in computational science research, they have been successfully applied to the International Linear Collider (ILC) and the Large Hadron Collider (LHC) in High Energy Physics (HEP), the JLab 12-GeV Upgrade in Nuclear Physics (NP), as well as the Spallation Neutron Source (SNS) and the Linac Coherent Light Source (LCLS) in Basic Energy Sciences (BES).

  13. Optimal proton acceleration from lateral limited foil sections and different laser pulse durations at relativistic intensity

    SciTech Connect

    Toncian, T.; Swantusch, M.; Toncian, M.; Willi, O.; Andreev, A. A.; Platonov, K. Y.

    2011-04-15

    The proton acceleration from a thin foil irradiated by a laser pulse at relativistic intensities is a process highly dependent on the electron dynamic at the rear side of the foil. By reducing the lateral size of the laser irradiated foil the hot electrons are confined in a small volume leading to an enhancement of both the maximum proton energy and the conversion efficiency in the target normal sheath acceleration regime. In this paper we demonstrate that an optimal lateral size of the target can be found. While a smaller target surface leads to a better hot electron confinement and enhances the Debye sheath accelerating the protons, it also leads to an increase of preplasma formation due to limited laser contrast available experimentally and hence to a decrease of the proton acceleration. The experimentally found optimum is in good agreement with analytic theory and 2D particle in cell simulations. In addition, the maximum proton energy as a function of pulse duration has been investigated. The experimental results fit to an analytical model.

  14. Mice with hepatocyte-specific FXR deficiency are resistant to spontaneous but susceptible to cholic acid-induced hepatocarcinogenesis.

    PubMed

    Kong, Bo; Zhu, Yan; Li, Guodong; Williams, Jessica A; Buckley, Kyle; Tawfik, Ossama; Luyendyk, James P; Guo, Grace L

    2016-03-01

    Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily with its endogenous ligands bile acids. Mice with whole body FXR deficiency develop liver tumors spontaneously, but the underlying mechanism is unclear. Moreover, it is unknown whether FXR deficiency in liver alone serves as a tumor initiator or promoter during liver carcinogenesis. This study aims to evaluate the effects of hepatocyte-specific FXR deficiency (FXR(hep-/-)) in liver tumor formation. The results showed that FXR(hep-/-) mice did not show spontaneous liver tumorigenesis with aging (up to 24 mo of age). Therefore FXR(hep-/-) mice were fed a bile acid (cholic acid)-containing diet alone or along with a liver tumor initiator, diethylnitrosamine (DEN). Thirty weeks later, no tumors were found in wild-type or FXR(hep-/-) mice without any treatment or with DEN only. However, with cholic acid, while only some wild-type mice developed tumors, all FXR(hep-/-) mice presented with severe liver injury and tumors. Interestingly, FXR(hep-/-) mouse livers increased basal expression of tumor suppressor p53 protein, apoptosis, and decreased basal cyclin D1 expression, which may prevent tumor development in FXR(hep-/-) mice. However, cholic acid feeding reversed these effects in FXR(hep-/-) mice, which is associated with an increased cyclin D1 and decreased cell cycle inhibitors. More in-depth analysis indicates that the increased in cell growth might result from disturbance of the MAPK and JAK/Stat3 signaling pathways. In conclusion, this study shows that hepatic FXR deficiency may only serve as a tumor initiator, and increased bile acids is required for tumor formation likely by promoting cell proliferation. PMID:26744468

  15. Data on the optimization of behavioral tasks for senescence-accelerated mouse prone 8 (SAMP8).

    PubMed

    Yanai, Shuichi; Endo, Shogo

    2016-09-01

    This data article contains the supporting information for the research article entitled "Early onset of behavioral alterations in senescence-accelerated mouse prone 8 (SAMP8)" [1]. Senescence-accelerated mouse prone 8 (SAMP8), which originally developed from AKR/J mice, shows learning and memory impairments at the age of 8-12 months. However, little information is still available on phenotypical characteristics of younger SAMP8. To fully understand the phenotype of younger SAMP8, we optimized two behavioral tasks for SAMP8. In the object recognition task, 4-month-old SAMP8 made significantly more contacts with the familiar objects compared to age-matched SAMR1, however, distance traveled for both strains of mice were comparable. In the fear conditioning task, conventionally-used CS-US combination failed to induce robust conditioned fear in both strains of mice. PMID:27331099

  16. FXR1P is a GSK3β substrate regulating mood and emotion processing.

    PubMed

    Del'Guidice, Thomas; Latapy, Camille; Rampino, Antonio; Khlghatyan, Jivan; Lemasson, Morgane; Gelao, Barbara; Quarto, Tiziana; Rizzo, Giuseppe; Barbeau, Annie; Lamarre, Claude; Bertolino, Alessandro; Blasi, Giuseppe; Beaulieu, Jean-Martin

    2015-08-18

    Inhibition of glycogen synthase kinase 3β (GSK3β) is a shared action believed to be involved in the regulation of behavior by psychoactive drugs such as antipsychotics and mood stabilizers. However, little is known about the identity of the substrates through which GSK3β affects behavior. We identified fragile X mental retardation-related protein 1 (FXR1P), a RNA binding protein associated to genetic risk for schizophrenia, as a substrate for GSK3β. Phosphorylation of FXR1P by GSK3β is facilitated by prior phosphorylation by ERK2 and leads to its down-regulation. In contrast, behaviorally effective chronic mood stabilizer treatments in mice inhibit GSK3β and increase FXR1P levels. In line with this, overexpression of FXR1P in the mouse prefrontal cortex also leads to comparable mood-related responses. Furthermore, functional genetic polymorphisms affecting either FXR1P or GSK3β gene expression interact to regulate emotional brain responsiveness and stability in humans. These observations uncovered a GSK3β/FXR1P signaling pathway that contributes to regulating mood and emotion processing. Regulation of FXR1P by GSK3β also provides a mechanistic framework that may explain how inhibition of GSK3β can contribute to the regulation of mood by psychoactive drugs in mental illnesses such as bipolar disorder. Moreover, this pathway could potentially be implicated in other biological functions, such as inflammation and cell proliferation, in which FXR1P and GSK3 are known to play a role. PMID:26240334

  17. VPAC1 expression is regulated by FXR agonists in the human gallbladder epithelium.

    PubMed

    Chignard, Nicolas; Mergey, Martine; Barbu, Véronique; Finzi, Laetitia; Tiret, Emmanuel; Paul, Annick; Housset, Chantal

    2005-09-01

    Vasoactive intestinal peptide receptor-1 (VPAC1) is the high-affinity receptor of vasoactive intestinal peptide (VIP), a major regulator of bile secretion. To better define the level at which VPAC1 stimulates bile secretion, we examined its expression in the different cell types participating in bile formation (i.e., hepatocytes, bile duct, and gallbladder epithelial cells). Because VPAC1 expression was previously shown to be regulated by nuclear receptors, we tested the hypothesis that it may be regulated by the farnesoid X receptor (FXR). Quantitative RT-PCR and immunoblot analyses of cell isolates indicated that VPAC1 is expressed in all three cell types lining the human biliary tree, with predominant expression in the gallbladder. In primary cultures of human gallbladder epithelial cells, VIP induced cAMP production and chloride secretion. Analysis of the VPAC1 gene revealed the presence of potential FXR response element sequences, and both FXR and RXRalpha expressions were detected in gallbladder epithelial cells. In these cells, the FXR pharmacological agonist GW4064 upregulated VPAC1 expression in a dose-dependent manner, and this effect was antagonized by the RXRalpha ligand, 9-cis retinoic acid. Chenodeoxycholate activated endogenous FXR in gallbladder epithelial cells, as ascertained by electromobility shift assay and upregulation of the FXR target gene, small heterodimer partner. Chenodeoxycholate also provoked an increase in VPAC1 mRNA and protein content in these cells. In conclusion, FXR agonists may increase gallbladder fluid secretion through transcriptional activation of VPAC1, which may contribute to the regulation of bile secretion by bile salts and to a protective effect of FXR pharmacological agonists in gallstone disease.

  18. FXR1P is a GSK3β substrate regulating mood and emotion processing

    PubMed Central

    Del’Guidice, Thomas; Latapy, Camille; Rampino, Antonio; Khlghatyan, Jivan; Lemasson, Morgane; Gelao, Barbara; Quarto, Tiziana; Rizzo, Giuseppe; Barbeau, Annie; Lamarre, Claude; Bertolino, Alessandro; Blasi, Giuseppe; Beaulieu, Jean-Martin

    2015-01-01

    Inhibition of glycogen synthase kinase 3β (GSK3β) is a shared action believed to be involved in the regulation of behavior by psychoactive drugs such as antipsychotics and mood stabilizers. However, little is known about the identity of the substrates through which GSK3β affects behavior. We identified fragile X mental retardation-related protein 1 (FXR1P), a RNA binding protein associated to genetic risk for schizophrenia, as a substrate for GSK3β. Phosphorylation of FXR1P by GSK3β is facilitated by prior phosphorylation by ERK2 and leads to its down-regulation. In contrast, behaviorally effective chronic mood stabilizer treatments in mice inhibit GSK3β and increase FXR1P levels. In line with this, overexpression of FXR1P in the mouse prefrontal cortex also leads to comparable mood-related responses. Furthermore, functional genetic polymorphisms affecting either FXR1P or GSK3β gene expression interact to regulate emotional brain responsiveness and stability in humans. These observations uncovered a GSK3β/FXR1P signaling pathway that contributes to regulating mood and emotion processing. Regulation of FXR1P by GSK3β also provides a mechanistic framework that may explain how inhibition of GSK3β can contribute to the regulation of mood by psychoactive drugs in mental illnesses such as bipolar disorder. Moreover, this pathway could potentially be implicated in other biological functions, such as inflammation and cell proliferation, in which FXR1P and GSK3 are known to play a role. PMID:26240334

  19. Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

    PubMed Central

    Noel, Olivier F.; Still, Christopher D.; Argyropoulos, George; Edwards, Michael; Gerhard, Glenn S.

    2016-01-01

    Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D) mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs) as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR) transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes. PMID:27006824

  20. Optimization and control of two-component radially self-accelerating beams

    SciTech Connect

    Vetter, Christian; Eichelkraut, Toni; Ornigotti, Marco; Szameit, Alexander

    2015-11-23

    We report on the properties of radially self-accelerating intensity distributions consisting of two components in the angular frequency domain. We show how this subset of solutions, in literature also known as helicon beams, possesses peculiar characteristics that enable a better control over its properties. In this work, we present a step-by-step optimization procedure to achieve the best possible intensity contrast, a distinct rotation rate and long propagation lengths. All points are discussed on a theoretical basis and are experimentally verified.

  1. Tuning of laser pulse shapes in grating-based compressors for optimal electron acceleration in plasmas

    SciTech Connect

    Toth, Cs.; Faure, J.; van Tilborg, J.; Geddes, C.G.R.; Schroeder, C.B.; Esare y, E.; Leemans, W.P.

    2003-01-22

    The temporal shape (rise time, fall time, skewness) of 50 - 200-fs Ti:sapphire laser pulses has been controlled by appropriate adjustment of a grating-pair compressor. It was found that the skewness of the laser pulse envelope is particularly sensitive to the third-order component of the spectral phase. Introducing such a third-order phase offset by detuning the grating pair relative to the optimum pulse compression settings allowed the generation of skewed pulses. As an example of an application, these skewed pulses were used to optimize a laser-plasma electron accelerator.

  2. Inhibition of endothelin-1-mediated contraction of hepatic stellate cells by FXR ligand.

    PubMed

    Li, Jiang; Kuruba, Ramalinga; Wilson, Annette; Gao, Xiang; Zhang, Yifei; Li, Song

    2010-11-11

    Activation of hepatic stellate cells (HSCs) plays an important role in the development of cirrhosis through the increased production of collagen and the enhanced contractile response to vasoactive mediators such as endothelin-1 (ET-1). The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidneys, adrenals, and intestine. FXR is also expressed in HSCs and activation of FXR in HSCs is associated with significant decreases in collagen production. However, little is known about the roles of FXR in the regulation of contraction of HSCs. We report in this study that treatment of quiescent HSCs with GW4064, a synthetic FXR agonist, significantly inhibited the HSC transdifferentiation, which was associated with an inhibition of the upregulation of ET-1 expression. These GW4064-treated cells also showed reduced contractile response to ET-1 in comparison to HSCs without GW4064 treatment. We have further shown that GW4064 treatment inhibited the ET-1-mediated contraction in fully activated HSCs. To elucidate the potential mechanism we showed that GW4064 inhibited ET-1-mediated activation of Rho/ROCK pathway in activated HSCs. Our studies unveiled a new mechanism that might contribute to the anti-cirrhotic effects of FXR ligands.

  3. Hierarchical incremental path planning and situation-dependent optimized dynamic motion planning considering accelerations.

    PubMed

    Lai, Xue-Cheng; Ge, Shuzhi Sam; Al Mamun, Abdullah

    2007-12-01

    This paper studies a hierarchical approach for incrementally driving a nonholonomic mobile robot to its destination in unknown environments. The A* algorithm is modified to handle a map containing unknown information. Based on it, optimal (discrete) paths are incrementally generated with a periodically updated map. Next, accelerations in varying velocities are taken into account in predicting the robot pose and the robot trajectory resulting from a motion command. Obstacle constraints are transformed to suitable velocity limits so that the robot can move as fast as possible while avoiding collisions when needed. Then, to trace the discrete path, the system searches for a waypoint-directed optimized motion in a reduced 1-D translation or rotation velocity space. Various situations of navigation are dealt with by using different strategies rather than a single objective function. Extensive simulations and experiments verified the efficacy of the proposed approach.

  4. Optimized ion acceleration using high repetition rate, variable thickness liquid crystal targets

    NASA Astrophysics Data System (ADS)

    Poole, Patrick; Willis, Christopher; Cochran, Ginevra; Andereck, C. David; Schumacher, Douglass

    2015-11-01

    Laser-based ion acceleration is a widely studied plasma physics topic for its applications to secondary radiation sources, advanced imaging, and cancer therapy. Recent work has centered on investigating new acceleration mechanisms that promise improved ion energy and spectrum. While the physics of these mechanisms is not yet fully understood, it has been observed to dominate for certain ranges of target thickness, where the optimum thickness depends on laser conditions including energy, pulse width, and contrast. The study of these phenomena is uniquely facilitated by the use of variable-thickness liquid crystal films, first introduced in P. L. Poole et al. PoP21, 063109 (2014). Control of the formation parameters of these freely suspended films such as volume, temperature, and draw speed allows on-demand thickness variability between 10 nanometers and several 10s of microns, fully encompassing the currently studied thickness regimes with a single target material. The low vapor pressure of liquid crystal enables in-situ film formation and unlimited vacuum use of these targets. Details on the selection and optimization of ion acceleration mechanism with target thickness will be presented, including recent experiments on the Scarlet laser facility and others. This work was performed with support from the DARPA PULSE program through a grant from AMRDEC and by the NNSA under contract DE-NA0001976.

  5. Molecule-optimized basis sets and Hamiltonians for accelerated electronic structure calculations of atoms and molecules.

    PubMed

    Gidofalvi, Gergely; Mazziotti, David A

    2014-01-16

    Molecule-optimized basis sets, based on approximate natural orbitals, are developed for accelerating the convergence of quantum calculations with strongly correlated (multireferenced) electrons. We use a low-cost approximate solution of the anti-Hermitian contracted Schrödinger equation (ACSE) for the one- and two-electron reduced density matrices (RDMs) to generate an approximate set of natural orbitals for strongly correlated quantum systems. The natural-orbital basis set is truncated to generate a molecule-optimized basis set whose rank matches that of a standard correlation-consistent basis set optimized for the atoms. We show that basis-set truncation by approximate natural orbitals can be viewed as a one-electron unitary transformation of the Hamiltonian operator and suggest an extension of approximate natural-orbital truncations through two-electron unitary transformations of the Hamiltonian operator, such as those employed in the solution of the ACSE. The molecule-optimized basis set from the ACSE improves the accuracy of the equivalent standard atom-optimized basis set at little additional computational cost. We illustrate the method with the potential energy curves of hydrogen fluoride and diatomic nitrogen. Relative to the hydrogen fluoride potential energy curve from the ACSE in a polarized triple-ζ basis set, the ACSE curve in a molecule-optimized basis set, equivalent in size to a polarized double-ζ basis, has a nonparallelity error of 0.0154 au, which is significantly better than the nonparallelity error of 0.0252 au from the polarized double-ζ basis set.

  6. Selective targeting of nuclear receptor FXR by avermectin analogues with therapeutic effects on nonalcoholic fatty liver disease

    PubMed Central

    Jin, Lihua; Wang, Rui; Zhu, Yanlin; Zheng, Weili; Han, Yaping; Guo, Fusheng; Ye, Frank Bin; Li, Yong

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become a predictive factor of death from many diseases. Farnesoid X receptor (FXR) is an ideal target for NAFLD drug development due to its crucial roles in lipid metabolism. The aim of this work is to examine the molecular mechanisms and functional roles of FXR modulation by avermectin analogues in regulating metabolic syndromes like NAFLD. We found that among avermectin analogues studied, the analogues that can bind and activate FXR are effective in regulating metabolic parameters tested, including reducing hepatic lipid accumulation, lowering serum cholesterol and glucose levels, and improving insulin sensitivity, in a FXR dependent manner. Mechanistically, the avermectin analogues that interact with FXR exhibited features as partial agonists, with distinctive properties in modulating coregulator recruitment. Structural features critical for avermectin analogues to selectively bind to FXR were also revealed. This study indicated that in addition to antiparasitic activity, avermectin analogues are promising drug candidates to treat metabolism syndrome including NAFLD by directly targeting FXR. Additionally, the structural features that discriminate the selective binding of FXR by avermectin analogues may provide a unique safe approach to design drugs targeting FXR signaling. PMID:26620317

  7. SIRT1 controls liver regeneration by regulating BA metabolism through FXR and mTOR signaling

    PubMed Central

    García-Rodríguez, Juan L.; Barbier-Torres, Lucía; Fernández-Álvarez, Sara; Juan, Virginia Gutiérrez-de; Monte, María J.; Halilbasic, Emina; Herranz, Daniel; Álvarez, Luis; Aspichueta, Patricia; Marín, Jose J. G.; Trauner, Michael; Mato, Jose M.; Serrano, Manuel; Beraza, Naiara; Martínez-Chantar, María Luz

    2014-01-01

    Sirtuin1 (SIRT1) regulates central metabolic functions such as lipogenesis, protein synthesis, gluconeogenesis and bile acid (BA) homeostasis through deacetylation. Here, we describe that SIRT1 tightly controls the regenerative response of the liver. We performed partial hepatectomy (PH) to transgenic mice that overexpress SIRT1 (SIRT). SIRT mice showed increased mortality, impaired hepatocyte proliferation, BA accumulation and profuse liver injury after surgery. The damaging phenotype in SIRT mice correlated with impaired FXR activity due to persistent deacetylation and lower protein expression that led to decreased FXR-target gene expression; SHP, BSEP and increased Cyp7A1. Next, we convincingly show that 24-norUrsodeoxycholic acid (NorUDCA) attenuates SIRT protein expression, increases the acetylation of FXR and neighboring histones, restores trimethylation of H3K4 and H3K9 and increases miR34a expression, thus re-establishing BA homeostasis. Consequently, NorUDCA restored liver regeneration in SIRT mice, which showed increased survival and hepatocyte proliferation. Furthermore, a Leucine-enriched diet restored mTOR activation, acetylation of FXR and histones, leading to an overall lower BA production through SHP-inhibition of Cyp7A1 and higher transport (BSEP) and detoxification (Sult2a1) leading to an improved liver regeneration. Finally, we found that human HCC samples have increased presence of SIRT1, which correlated with absence of FXR suggesting its oncogenic potential. Conclusions Overall, we define SIRT1 as a key regulator of the regenerative response in the liver through post-transcriptional modifications that regulate the activity of FXR, histones and mTOR. Moreover, our data suggest that SIRT1 contributes to liver tumorigenesis through dysregulation of BA homeostasis by persistent FXR deacetylation. PMID:24338587

  8. Identification of a potent synthetic FXR agonist with an unexpected mode of binding and activation

    SciTech Connect

    Soisson, Stephen M.; Parthasarathy, Gopalakrishnan; Adams, Alan D.; Sahoo, Soumya; Sitlani, Ayesha; Sparrow, Carl; Cui, Jisong; Becker, Joseph W.

    2008-07-08

    The farnesoid X receptor (FXR), a member of the nuclear hormone receptor family, plays important roles in the regulation of bile acid and cholesterol homeostasis, glucose metabolism, and insulin sensitivity. There is intense interest in understanding the mechanisms of FXR regulation and in developing pharmaceutically suitable synthetic FXR ligands that might be used to treat metabolic syndrome. We report here the identification of a potent FXR agonist (MFA-1) and the elucidation of the structure of this ligand in ternary complex with the human receptor and a coactivator peptide fragment using x-ray crystallography at 1.9-{angstrom} resolution. The steroid ring system of MFA-1 binds with its D ring-facing helix 12 (AF-2) in a manner reminiscent of hormone binding to classical steroid hormone receptors and the reverse of the pose adopted by naturally occurring bile acids when bound to FXR. This binding mode appears to be driven by the presence of a carboxylate on MFA-1 that is situated to make a salt-bridge interaction with an arginine residue in the FXR-binding pocket that is normally used to neutralize bound bile acids. Receptor activation by MFA-1 differs from that by bile acids in that it relies on direct interactions between the ligand and residues in helices 11 and 12 and only indirectly involves a protonated histidine that is part of the activation trigger. The structure of the FXR:MFA-1 complex differs significantly from that of the complex with a structurally distinct agonist, fexaramine, highlighting the inherent plasticity of the receptor.

  9. Analysis of endocardial acceleration during intraoperative optimization of cardiac resynchronization therapy

    PubMed Central

    Hernandez, Alfredo I.; Ziglio, Filippo; Amblard, Amel; Senhadji, Lotfi; Leclercq, Christophe

    2013-01-01

    Cardiac resynchronization therapy (CRT) is the therapy of choice for selected patients suffering from drug-refractory congestive heart failure and presenting an interventricular desynchronization. CRT is delivered by an implantable biventricular pacemaker, which stimulates the right atrium and both ventricles at specific timings. The optimization and personalization of this therapy requires to quantify both the electrical and the mechanical cardiac functions during the intraoperative and postoperative phases. The objective of this paper is to evaluate the feasibility of the calculation of features extracted from endocardial acceleration (EA) signals and the potential utility of these features for the intraoperative optimization of CRT. Endocardial intraoperative data from one patient are analyzed for 33 different pacing configurations, including changes in the atrio-ventricular and inter-ventricular delays and different ventricular stimulation sites. The main EA features are extracted for each pacing configuration and analyzed so as to estimate the intra-configuration and inter-configuration variability. Results show the feasibility of the proposed approach and suggest the potential utility of EA for intraoperative monitoring of the cardiac function and defining optimal, adaptive pacing configurations. PMID:24111356

  10. Analytic characterization of linear accelerator radiosurgery dose distributions for fast optimization.

    PubMed

    Meeks, S L; Bova, F J; Buatti, J M; Friedman, W A; Eyster, B; Kendrick, L A

    1999-11-01

    Linear accelerator (linac) radiosurgery utilizes non-coplanar arc therapy delivered through circular collimators. Generally, spherically symmetric arc sets are used, resulting in nominally spherical dose distributions. Various treatment planning parameters may be manipulated to provide dose conformation to irregular lesions. Iterative manipulation of these variables can be a difficult and time-consuming task, because (a) understanding the effect of these parameters is complicated and (b) three-dimensional (3D) dose calculations are computationally expensive. This manipulation can be simplified, however, because the prescription isodose surface for all single isocentre distributions can be approximated by conic sections. In this study, the effects of treatment planning parameter manipulation on the dimensions of the treatment isodose surface were determined empirically. These dimensions were then fitted to analytic functions, assuming that the dose distributions were characterized as conic sections. These analytic functions allowed real-time approximation of the 3D isodose surface. Iterative plan optimization, either manual or automated, is achieved more efficiently using this real time approximation of the dose matrix. Subsequent to iterative plan optimization, the analytic function is related back to the appropriate plan parameters, and the dose distribution is determined using conventional dosimetry calculations. This provides a pseudo-inverse approach to radiosurgery optimization, based solely on geometric considerations.

  11. Discovery That Theonellasterol a Marine Sponge Sterol Is a Highly Selective FXR Antagonist That Protects against Liver Injury in Cholestasis

    PubMed Central

    Renga, Barbara; Mencarelli, Andrea; D'Amore, Claudio; Cipriani, Sabrina; D'Auria, Maria Valeria; Sepe, Valentina; Chini, Maria Giovanna; Monti, Maria Chiara; Bifulco, Giuseppe; Zampella, Angela; Fiorucci, Stefano

    2012-01-01

    Background The farnesoid-x-receptor (FXR) is a bile acid sensor expressed in the liver and gastrointestinal tract. Despite FXR ligands are under investigation for treatment of cholestasis, a biochemical condition occurring in a number of liver diseases for which available therapies are poorly effective, mice harboring a disrupted FXR are protected against liver injury caused by bile acid overload in rodent models of cholestasis. Theonellasterol is a 4-methylene-24-ethylsteroid isolated from the marine sponge Theonella swinhoei. Here, we have characterized the activity of this theonellasterol on FXR-regulated genes and biological functions. Principal Findings Interrogation of HepG2 cells, a human hepatocyte cell line, by microarray analysis and transactivation assay shows that theonellasterol is a selective FXR antagonist, devoid of any agonistic or antagonistic activity on a number of human nuclear receptors including the vitamin D receptor, PPARs, PXR, LXRs, progesterone, estrogen, glucorticoid and thyroid receptors, among others. Exposure of HepG2 cells to theonellasterol antagonizes the effect of natural and synthetic FXR agonists on FXR-regulated genes, including SHP, OSTα, BSEP and MRP4. A proof-of-concept study carried out to investigate whether FXR antagonism rescues mice from liver injury caused by the ligation of the common bile duct, a model of obstructive cholestasis, demonstrated that theonellasterol attenuates injury caused by bile duct ligation as measured by assessing serum alanine aminostrasferase levels and extent of liver necrosis at histopathology. Analysis of genes involved in bile acid uptake and excretion by hepatocytes revealed that theonellasterol increases the liver expression of MRP4, a basolateral transporter that is negatively regulated by FXR. Administering bile duct ligated mice with an FXR agonist failed to rescue from liver injury and downregulated the expression of MRP4. Conclusions FXR antagonism in vivo results in a positive

  12. Detailed design optimization of the MITICA negative ion accelerator in view of the ITER NBI

    NASA Astrophysics Data System (ADS)

    Agostinetti, P.; Aprile, D.; Antoni, V.; Cavenago, M.; Chitarin, G.; de Esch, H. P. L.; De Lorenzi, A.; Fonnesu, N.; Gambetta, G.; Hemsworth, R. S.; Kashiwagi, M.; Marconato, N.; Marcuzzi, D.; Pilan, N.; Sartori, E.; Serianni, G.; Singh, M.; Sonato, P.; Spada, E.; Toigo, V.; Veltri, P.; Zaccaria, P.

    2016-01-01

    The ITER Neutral Beam Test Facility (PRIMA) is presently under construction at Consorzio RFX (Padova, Italy). PRIMA includes two experimental devices: an ITER-size ion source with low voltage extraction, called SPIDER, and the full prototype of the whole ITER Heating Neutral Beams (HNBs), called MITICA. The purpose of MITICA is to demonstrate that all operational parameters of the ITER HNB accelerator can be experimentally achieved, thus establishing a large step forward in the performances of neutral beam injectors in comparison with the present experimental devices. The design of the MITICA extractor and accelerator grids, here described in detail, was developed using an integrated approach, taking into consideration at the same time all the relevant physics and engineering aspects. Particular care was taken also to support and validate the design on the basis of the expertise and experimental data made available by the collaborating neutral beam laboratories of CEA, IPP, CCFE, NIFS and JAEA. Considering the operational requirements and the other physics constraints of the ITER HNBs, the whole design has been thoroughly optimized and improved. Furthermore, specific innovative concepts have been introduced.

  13. Adaptation and optimization of basic operations for an unstructured mesh CFD algorithm for computation on massively parallel accelerators

    NASA Astrophysics Data System (ADS)

    Bogdanov, P. B.; Gorobets, A. V.; Sukov, S. A.

    2013-08-01

    The design of efficient algorithms for large-scale gas dynamics computations with hybrid (heterogeneous) computing systems whose high performance relies on massively parallel accelerators is addressed. A high-order accurate finite volume algorithm with polynomial reconstruction on unstructured hybrid meshes is used to compute compressible gas flows in domains of complex geometry. The basic operations of the algorithm are implemented in detail for massively parallel accelerators, including AMD and NVIDIA graphics processing units (GPUs). Major optimization approaches and a computation transfer technique are covered. The underlying programming tool is the Open Computing Language (OpenCL) standard, which performs on accelerators of various architectures, both existing and emerging.

  14. FXR agonist GW4064 increases plasma glucocorticoid levels in C57BL/6 mice.

    PubMed

    Hoekstra, Menno; van der Sluis, Ronald J; Li, Zhaosha; Oosterveer, Maaike H; Groen, Albert K; Van Berkel, Theo J C

    2012-10-15

    Since high expression of farnesoid X receptor (FXR) has been detected in glucocorticoid-producing adrenocortical cells, we evaluated the potential role of FXR in adrenal glucocorticoid production. FXR agonist GW4064 increased fasting plasma corticosterone levels (+45%; P<0.01) in C57BL/6 mice, indicative of enhanced adrenal steroidogenesis. GW4064 treatment did not affect plasma ACTH levels, adrenal weight, or adrenal expression of steroidogenic genes. Scavenger receptor BI (SR-BI) mRNA and protein expression, respectively, increased 1.9-fold (P<0.01) and 1.5-fold, which suggests a stimulated lipoprotein-associated cholesterol uptake into the adrenals upon GW4064 treatment. In line with an enhanced flux of cellular cholesterol into the steroidogenic pathway, adrenal unesterified and esterified cholesterol stores were 21-41% decreased (P<0.01) upon GW4064 treatment. In conclusion, we have shown that the FXR agonist GW4064 stimulates plasma corticosterone levels in C57BL/6 mice. Our findings suggest a novel role for FXR in the modulation of adrenal cholesterol metabolism and glucocorticoid synthesis in mice.

  15. Optimization of accelerator parameters using normal form methods on high-order transfer maps

    SciTech Connect

    Snopok, Pavel

    2007-05-01

    Methods of analysis of the dynamics of ensembles of charged particles in collider rings are developed. The following problems are posed and solved using normal form transformations and other methods of perturbative nonlinear dynamics: (1) Optimization of the Tevatron dynamics: (a) Skew quadrupole correction of the dynamics of particles in the Tevatron in the presence of the systematic skew quadrupole errors in dipoles; (b) Calculation of the nonlinear tune shift with amplitude based on the results of measurements and the linear lattice information; (2) Optimization of the Muon Collider storage ring: (a) Computation and optimization of the dynamic aperture of the Muon Collider 50 x 50 GeV storage ring using higher order correctors; (b) 750 x 750 GeV Muon Collider storage ring lattice design matching the Tevatron footprint. The normal form coordinates have a very important advantage over the particle optical coordinates: if the transformation can be carried out successfully (general restrictions for that are not much stronger than the typical restrictions imposed on the behavior of the particles in the accelerator) then the motion in the new coordinates has a very clean representation allowing to extract more information about the dynamics of particles, and they are very convenient for the purposes of visualization. All the problem formulations include the derivation of the objective functions, which are later used in the optimization process using various optimization algorithms. Algorithms used to solve the problems are specific to collider rings, and applicable to similar problems arising on other machines of the same type. The details of the long-term behavior of the systems are studied to ensure the their stability for the desired number of turns. The algorithm of the normal form transformation is of great value for such problems as it gives much extra information about the disturbing factors. In addition to the fact that the dynamics of particles is represented

  16. Accelerated Simplified Swarm Optimization with Exploitation Search Scheme for Data Clustering

    PubMed Central

    Yeh, Wei-Chang; Lai, Chyh-Ming

    2015-01-01

    Data clustering is commonly employed in many disciplines. The aim of clustering is to partition a set of data into clusters, in which objects within the same cluster are similar and dissimilar to other objects that belong to different clusters. Over the past decade, the evolutionary algorithm has been commonly used to solve clustering problems. This study presents a novel algorithm based on simplified swarm optimization, an emerging population-based stochastic optimization approach with the advantages of simplicity, efficiency, and flexibility. This approach combines variable vibrating search (VVS) and rapid centralized strategy (RCS) in dealing with clustering problem. VVS is an exploitation search scheme that can refine the quality of solutions by searching the extreme points nearby the global best position. RCS is developed to accelerate the convergence rate of the algorithm by using the arithmetic average. To empirically evaluate the performance of the proposed algorithm, experiments are examined using 12 benchmark datasets, and corresponding results are compared with recent works. Results of statistical analysis indicate that the proposed algorithm is competitive in terms of the quality of solutions. PMID:26348483

  17. Identification of chemerin as a novel FXR target gene down-regulated in the progression of nonalcoholic steatohepatitis.

    PubMed

    Deng, Yujie; Wang, Hui; Lu, Yan; Liu, Shuang; Zhang, Qiang; Huang, Jian; Zhu, Rongfeng; Yang, Jian; Zhang, Rong; Zhang, Di; Shen, Weili; Ning, Guang; Yang, Ying

    2013-05-01

    Chemerin is an adipokine involved in obesity, inflammation, and innate immune system that is highly expressed in the liver. In the present study, we find that chemerin mRNA expression is decreased in the livers of rodents with nonalcoholic fatty liver disease as well as in HepG2 cells after lipid overloading. Moreover, we report that chemerin expression and secretion are induced in HepG2 cells and primary hepatocytes from wild-type mice, but not farnesoid X receptor (FXR)-/- mice, in response to the synthetic FXR ligand GW4064. Hepatic chemerin expression is decreased in FXR-/- mice but up-regulated by GW4064 administration in wild-type mice. Dual-luciferase reporter assay and chromatin immunoprecipitation analyses further identified a functional FXR response element located in the -258-bp /+121-bp region of the chemerin gene. These data demonstrate that chemerin, a novel target gene of FXR, is related to nonalcoholic steatohepatitis.

  18. Chronic Activation of FXR in Transgenic Mice Caused Perinatal Toxicity and Sensitized Mice to Cholesterol Toxicity

    PubMed Central

    Cheng, Qiuqiong; Inaba, Yuka; Lu, Peipei; Xu, Meishu; He, Jinhan; Zhao, Yueshui; Guo, Grace L.; Kuruba, Ramalinga; de la Vega, Rona; Evans, Rhobert W.; Li, Song

    2015-01-01

    The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage. PMID:25719402

  19. Synthetic FXR agonist GW4064 is a modulator of multiple G protein-coupled receptors.

    PubMed

    Singh, Nidhi; Yadav, Manisha; Singh, Abhishek Kumar; Kumar, Harish; Dwivedi, Shailendra Kumar Dhar; Mishra, Jay Sharan; Gurjar, Anagha; Manhas, Amit; Chandra, Sharat; Yadav, Prem Narayan; Jagavelu, Kumaravelu; Siddiqi, Mohammad Imran; Trivedi, Arun Kumar; Chattopadhyay, Naibedya; Sanyal, Sabyasachi

    2014-05-01

    The synthetic nuclear bile acid receptor (farnesoid X receptor [FXR]) agonist GW4064 is extensively used as a specific pharmacological tool to illustrate FXR functions. We noticed that GW4064 activated empty luciferase reporters in FXR-deficient HEK-293T cells. We postulated that this activity of GW4064 might be routed through as yet unknown cellular targets and undertook an unbiased exploratory approach to identify these targets. Investigations revealed that GW4064 activated cAMP and nuclear factor for activated T-cell response elements (CRE and NFAT-RE, respectively) present on these empty reporters. Whereas GW4064-induced NFAT-RE activation involved rapid intracellular Ca(2+) accumulation and NFAT nuclear translocation, CRE activation involved soluble adenylyl cyclase-dependent cAMP accumulation and Ca(2+)-calcineurin-dependent nuclear translocation of transducers of regulated CRE-binding protein 2. Use of dominant negative heterotrimeric G-protein minigenes revealed that GW4064 caused activation of Gαi/o and Gq/11 G proteins. Sequential pharmacological inhibitor-based screening and radioligand-binding studies revealed that GW4064 interacted with multiple G protein-coupled receptors. Functional studies demonstrated that GW4064 robustly activated H1 and H4 and inhibited H2 histamine receptor signaling events. We also found that MCF-7 breast cancer cells, reported to undergo GW4064-induced apoptosis in an FXR-dependent manner, did not express FXR, and the GW4064-mediated apoptosis, also apparent in HEK-293T cells, could be blocked by selective histamine receptor regulators. Taken together, our results demonstrate identification of histamine receptors as alternate targets for GW4064, which not only necessitates cautious interpretation of the biological functions attributed to FXR using GW4064 as a pharmacological tool but also provides a basis for the rational designing of new pharmacophores for histamine receptor modulation.

  20. Accelerated testing of an optimized closing system for automotive fuel tank

    NASA Astrophysics Data System (ADS)

    Gligor, A.; Ilie, S.; Nicolae, V.; Mitran, G.

    2015-11-01

    Taking into account the legal prescriptions which are in force and the new regulatory requirements that will be mandatory to implement in the near future regarding testing characteristics of automotive fuel tanks, resulted the necessity to develop a new testing methodology which allows to estimate the behaviour of the closing system of automotive fuel tank over a long period of time (10-15 years). Thus, were designed and conducted accelerated tests under extreme assembling and testing conditions (high values for initial tightening torques, extreme values of temperature and pressure). In this paper are presented two of durability tests which were performed on an optimized closing system of fuel tank: (i) the test of exposure to temperature with cyclical variation and (ii) the test of continuous exposure to elevated temperature. In these experimental tests have been used main components of the closing system manufactured of two materials variants, both based on the polyoxymethylene, material that provides higher mechanical stiffness and strength in a wide temperature range, as well as showing increased resistance to the action of chemical agents and fuels. The tested sample included a total of 16 optimized locking systems, 8 of each of 2 versions of material. Over deploying the experiments were determined various parameters such as: the initial tightening torque, the tightening torque at different time points during measurements, the residual tightening torque, defects occurred in the system components (fissures, cracks, ruptures), the sealing conditions of system at the beginning and at the end of test. Based on obtained data were plotted the time evolution diagrams of considered parameter (the residual tightening torque of the system consisting of locking nut and threaded ring), in different temperature conditions, becoming possible to make pertinent assessments on the choice between the two types of materials. By conducting these tests and interpreting the

  1. Advanced Simulation and Optimization Tools for Dynamic Aperture of Non-scaling FFAGs and Accelerators including Modern User Interfaces

    SciTech Connect

    Mills, F.; Makino, Kyoko; Berz, Martin; Johnstone, C.

    2010-09-01

    With the U.S. experimental effort in HEP largely located at laboratories supporting the operations of large, highly specialized accelerators, colliding beam facilities, and detector facilities, the understanding and prediction of high energy particle accelerators becomes critical to the success, overall, of the DOE HEP program. One area in which small businesses can contribute to the ongoing success of the U.S. program in HEP is through innovations in computer techniques and sophistication in the modeling of high-energy accelerators. Accelerator modeling at these facilities is performed by experts with the product generally highly specific and representative only of in-house accelerators or special-interest accelerator problems. Development of new types of accelerators like FFAGs with their wide choices of parameter modifications, complicated fields, and the simultaneous need to efficiently handle very large emittance beams requires the availability of new simulation environments to assure predictability in operation. In this, ease of use and interfaces are critical to realizing a successful model, or optimization of a new design or working parameters of machines. In Phase I, various core modules for the design and analysis of FFAGs were developed and Graphical User Interfaces (GUI) have been investigated instead of the more general yet less easily manageable console-type output COSY provides.

  2. An optimized slab-symmetric dielectric-based laser accelerator structure

    SciTech Connect

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

    1999-10-21

    A slab-symmetric, partially dielectric filled, laser excited structure which maybe used to accelerate charged particles is analyzed theoretically and computationally. The fields associated with the accelerating mode are calculated, as are aspects of the resonant filling and impedance matching of the structure to the exciting laser. It is shown through computer simulation that the accelerating mode in this structure can be excited resonantly and with large quality factor Q. Practical aspects of implementing this structure as an accelerator are discussed.

  3. Comparative study of ion acceleration by linearly polarized laser pulses from optimized targets of solid and near-critical density

    NASA Astrophysics Data System (ADS)

    Bychenkov, V. Yu; Brantov, A. V.; Govras, E. A.

    2016-03-01

    The results of a 3D optimization study of ion acceleration from ultrathin solid density foils (Brantov et al 2015 Phys. Rev. Spec. Top. Accel. Beams 18 021301) are complemented with an improved analytic model of the directed Coulomb explosion. Similarly to optimizing overdense targets, we also optimize low-density targets to obtain maximum ion energy, motivated by progress in producing a new generation of low-density slab targets whose density can be very homogeneous and as low as the relativistic critical density. Using 3D simulations, we show that for the same laser pulse, the ion energy can be significantly increased with low-density targets. A new acceleration mechanism is responsible for such an increase. This mechanism is described qualitatively, and it explains an advantage of low-density targets for high-energy ion production by lasers.

  4. Optimized conditions for the extraction of secondary volatile metabolites in Angelica roots by accelerated solvent extraction.

    PubMed

    Cho, S-K; Abd El-Aty, A M; Choi, J-H; Kim, M R; Shim, J H

    2007-09-01

    Accelerated solvent extraction (ASE) of three common Angelica species found in Asia: Angelica sinensis (Oliv.) Diels from China, Angelica acutiloba (Sieb. et Zucc.) Kitagawa from Japan, and Angelica gigas Nakai from Korea was investigated. Preliminary experiments, including the selection of the solvent, extraction time, pressure, static cycle and time were investigated to optimize experimental parameters. Kováts indices and mass spectra were used to identify the components in the various fractions. These were then confirmed using gas chromatography-mass spectrometry (GC-MS). A total of 18 compounds were identified, with qualitative differences and similarities observed among the cultivars. From the 18 compounds found in the ASE extract of danggui cultivars, the major components were decursin, decursinol angelate (A. gigas); butylidene dihydrophthalide, 4-hydroxy-4-methyl-2-pentanone (A. sinensis); and 9,12-octadecanoic acid in Angelica acutiloba. The optimum ASE operating conditions were n-hexane as extraction solvent, extraction temperature and pressure of 80 degrees C and 1500 atm, respectively, static cycle of 2 min, and static time of 10 min. Under these conditions, the percentages of main analytes were increased.

  5. Acceleration of the Geostatistical Software Library (GSLIB) by code optimization and hybrid parallel programming

    NASA Astrophysics Data System (ADS)

    Peredo, Oscar; Ortiz, Julián M.; Herrero, José R.

    2015-12-01

    The Geostatistical Software Library (GSLIB) has been used in the geostatistical community for more than thirty years. It was designed as a bundle of sequential Fortran codes, and today it is still in use by many practitioners and researchers. Despite its widespread use, few attempts have been reported in order to bring this package to the multi-core era. Using all CPU resources, GSLIB algorithms can handle large datasets and grids, where tasks are compute- and memory-intensive applications. In this work, a methodology is presented to accelerate GSLIB applications using code optimization and hybrid parallel processing, specifically for compute-intensive applications. Minimal code modifications are added decreasing as much as possible the elapsed time of execution of the studied routines. If multi-core processing is available, the user can activate OpenMP directives to speed up the execution using all resources of the CPU. If multi-node processing is available, the execution is enhanced using MPI messages between the compute nodes.Four case studies are presented: experimental variogram calculation, kriging estimation, sequential gaussian and indicator simulation. For each application, three scenarios (small, large and extra large) are tested using a desktop environment with 4 CPU-cores and a multi-node server with 128 CPU-nodes. Elapsed times, speedup and efficiency results are shown.

  6. Energy enhancement of proton acceleration in combinational radiation pressure and bubble by optimizing plasma density

    SciTech Connect

    Bake, Muhammad Ali; Xie Baisong; Shan Zhang; Hong Xueren; Wang Hongyu

    2012-08-15

    The combinational laser radiation pressure and plasma bubble fields to accelerate protons are researched through theoretical analysis and numerical simulations. The dephasing length of the accelerated protons bunch in the front of the bubble and the density gradient effect of background plasma on the accelerating phase are analyzed in detail theoretically. The radiation damping effect on the accelerated protons energy is also considered. And it is demonstrated by two-dimensional particle-in-cell simulations that the protons bunch energy can be increased by using the background plasma with negative density gradient. However, radiation damping makes the maximal energy of the accelerated protons a little reduction.

  7. Bile acid signaling through FXR induces intracellular adhesion molecule-1 expression in mouse liver and human hepatocytes.

    PubMed

    Qin, Pu; Borges-Marcucci, Lisa A; Evans, Mark J; Harnish, Douglas C

    2005-08-01

    Previous studies have demonstrated a dramatic induction of inflammatory gene expression in livers from mice fed a high-fat, high-cholesterol diet containing cholate after 3-5 wk. To determine the contribution of cholate in mediating these inductions, C57BL/6 mice were fed a chow diet supplemented with increasing concentrations of cholic acid (CA) for 5 days. A dose-dependent induction in the hepatic levels of TNF-alpha, VCAM-1, ICAM-1, and SAA-2 mRNA were observed. As positive controls, a dose-dependent repression of cholesterol 7alpha-hydroxylase and a dose-dependent induction of small heterodimer partner (SHP) expression were also observed, suggesting that farnesoid X receptor (FXR) was activated. In addition, ICAM-1 and SHP mRNA levels were also induced in primary human hepatocytes when treated with chenodeoxycholic acid or GW4064, a FXR-selective agonist. The involvement of FXR in CA-induced inflammatory gene expression was further investigated in the human hepatic cell line HepG2. Both ICAM-1 and SHP expression were induced in a dose- and time-dependent manner by treatment with the FXR-selective agonist GW4064. Moreover, the induction of ICAM-1 by GW4064 was inhibited by the FXR antagonist guggulsterone or with transfection of FXR siRNA. Finally, the activity of FXR was mapped to a retinoic acid response element (RARE) site containing an imbedded farnesoid X response element (FXRE) on the human ICAM-1 promoter and FXR and retinoid X receptor were demonstrated to bind to this site. Finally, FXR-mediated activation of ICAM-1 could be further enhanced by TNF-alpha cotreatment in hepatocytes, suggesting a potential cooperation between cytokine and bile acid-signaling pathways during hepatic inflammatory events.

  8. Optimal technique of linear accelerator-based stereotactic radiosurgery for tumors adjacent to brainstem.

    PubMed

    Chang, Chiou-Shiung; Hwang, Jing-Min; Tai, Po-An; Chang, You-Kang; Wang, Yu-Nong; Shih, Rompin; Chuang, Keh-Shih

    2016-01-01

    either DCA or IMRS plans, at 9.2 ± 7% and 8.2 ± 6%, respectively. Owing to the multiple arc or beam planning designs of IMRS and VMAT, both of these techniques required higher MU delivery than DCA, with the averages being twice as high (p < 0.05). If linear accelerator is only 1 modality can to establish for SRS treatment. Based on statistical evidence retrospectively, we recommend VMAT as the optimal technique for delivering treatment to tumors adjacent to brainstem. PMID:27396940

  9. Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling.

    PubMed

    Dossa, Avafia Y; Escobar, Oswaldo; Golden, Jamie; Frey, Mark R; Ford, Henri R; Gayer, Christopher P

    2016-01-15

    Bile acids (BAs) are synthesized in the liver and secreted into the intestine. In the lumen, enteric bacteria metabolize BAs from conjugated, primary forms into more toxic unconjugated, secondary metabolites. Secondary BAs can be injurious to the intestine and may contribute to disease. The epidermal growth factor receptor (EGFR) and the nuclear farnesoid X receptor (FXR) are known to interact with BAs. In this study we examined the effects of BAs on intestinal epithelial cell proliferation and investigated the possible roles for EGFR and FXR in these effects. We report that taurine-conjugated cholic acid (TCA) induced proliferation, while its unconjugated secondary counterpart deoxycholic acid (DCA) inhibited proliferation. TCA stimulated phosphorylation of Src, EGFR, and ERK 1/2. Pharmacological blockade of any of these pathways or genetic ablation of EGFR abrogated TCA-stimulated proliferation. Interestingly, Src or EGFR inhibitors eliminated TCA-induced phosphorylation of both molecules, suggesting that their activation is interdependent. In contrast to TCA, DCA exposure diminished EGFR phosphorylation, and pharmacological or siRNA blockade of FXR abolished DCA-induced inhibition of proliferation. Taken together, these results suggest that TCA induces intestinal cell proliferation via Src, EGFR, and ERK activation. In contrast, DCA inhibits proliferation via an FXR-dependent mechanism that may include downstream inactivation of the EGFR/Src/ERK pathway. Since elevated secondary BA levels are the result of specific bacterial modification, this may provide a mechanism through which an altered microbiota contributes to normal or abnormal intestinal epithelial cell proliferation.

  10. Bile Acids as Hormones: The FXR-FGF15/19 Pathway

    PubMed Central

    Kliewer, Steven A.; Mangelsdorf, David J.

    2015-01-01

    While it has long been recognized that bile acids are essential for solubilizing lipophilic nutrients in the small intestine, the discovery in 1999 that bile acids serve as ligands for the nuclear receptor FXR opened the floodgates in terms of characterizing their actions as selective signaling molecules. Bile acids act on FXR in ileal enterocytes to induce the expression of fibroblast growth factor (FGF) 15/19, an atypical FGF that functions as a hormone. FGF15/19 subsequently acts on a cell surface receptor complex in hepatocytes to repress bile acid synthesis and gluconeogenesis and to stimulate glycogen and protein synthesis. FGF15/19 also stimulates gallbladder filling. Thus, the bile acid-FXR-FGF15/19 signaling pathway regulates diverse aspects of the postprandial enterohepatic response. Pharmacologically, this endocrine pathway provides exciting new opportunities for treating metabolic disease and bile acid-related disorders such as primary biliary cirrhosis and bile acid diarrhea. Both FXR agonists and FGF19 analogs are currently in clinical trials. PMID:26045265

  11. Bile Acids as Hormones: The FXR-FGF15/19 Pathway.

    PubMed

    Kliewer, Steven A; Mangelsdorf, David J

    2015-01-01

    While it has long been recognized that bile acids are essential for solubilizing lipophilic nutrients in the small intestine, the discovery in 1999 that bile acids serve as ligands for the nuclear receptor farnesoid X receptor (FXR) opened the floodgates in terms of characterizing their actions as selective signaling molecules. Bile acids act on FXR in ileal enterocytes to induce the expression of fibroblast growth factor (FGF)15/19, an atypical FGF that functions as a hormone. FGF15/19 subsequently acts on a cell surface receptor complex in hepatocytes to repress bile acid synthesis and gluconeogenesis, and to stimulate glycogen and protein synthesis. FGF15/19 also stimulates gallbladder filling. Thus, the bile acid-FXR-FGF15/19 signaling pathway regulates diverse aspects of the postprandial enterohepatic response. Pharmacologically, this endocrine pathway provides exciting new opportunities for treating metabolic disease and bile acid-related disorders such as primary biliary cirrhosis and bile acid diarrhea. Both FXR agonists and FGF19 analogs are currently in clinical trials. PMID:26045265

  12. Conformationally constrained farnesoid X receptor (FXR) agonists: Heteroaryl replacements of the naphthalene

    SciTech Connect

    Bass, Jonathan Y.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Mills, Wendy Y.; Navas, III, Frank; Parks, Derek J.; Smalley, Jr., Terrence L.; Spearing, Paul K.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce

    2014-08-13

    To improve on the drug properties of GSK8062 1b, a series of heteroaryl bicyclic naphthalene replacements were prepared. The quinoline 1c was an equipotent FXR agonist with improved drug developability parameters relative to 1b. In addition, analog 1c lowered body weight gain and serum glucose in a DIO mouse model of diabetes.

  13. Genome-wide profiling to analyze the effects of FXR activation on mouse renal proximal tubular cells

    PubMed Central

    Gui, Ting; Gai, Zhibo

    2015-01-01

    To assess the effect of farnesoid X receptor (FXR), a bile acid nuclear receptor, on renal proximal tubular cells, primary cultured mouse kidney proximal tubular cells were treated with GW4064 (a FXR agonist) or DMSO (as controls) overnight. Analysis of gene expression in the proximal tubular cells by whole genome microarrays indicated that FXR activation induced genes involved in fatty acid degradation and oxidation reduction. Among them, genes involved in glutathione metabolism were mostly induced. Here we describe in details the contents and quality controls for the gene expression and related results associated with the data uploaded to Gene Expression Omnibus (accession number GSE70296). PMID:26697325

  14. Monte Carlo study of photon beams from medical linear accelerators: Optimization, benchmark and spectra

    NASA Astrophysics Data System (ADS)

    Sheikh-Bagheri, Daryoush

    1999-12-01

    BEAM is a general purpose EGS4 user code for simulating radiotherapy sources (Rogers et al. Med. Phys. 22, 503-524, 1995). The BEAM code is optimized by first minimizing unnecessary electron transport (a factor of 3 improvement in efficiency). The efficiency of the uniform bremsstrahlung splitting (UBS) technique is assessed and found to be 4 times more efficient. The Russian Roulette technique used in conjunction with UBS is substantially modified to make simulations additionally 2 times more efficient. Finally, a novel and robust technique, called selective bremsstrahlung splitting (SBS), is developed and shown to improve the efficiency of photon beam simulations by an additional factor of 3-4, depending on the end- point considered. The optimized BEAM code is benchmarked by comparing calculated and measured ionization distributions in water from the 10 and 20 MV photon beams of the NRCC linac. Unlike previous calculations, the incident e - energy is known independently to 1%, the entire extra-focal radiation is simulated and e- contamination is accounted for. Both beams use clinical jaws, whose dimensions are accurately measured, and which are set for a 10 x 10 cm2 field at 110 cm. At both energies, the calculated and the measured values of ionization on the central-axis in the buildup region agree within 1% of maximum dose. The agreement is well within statistics elsewhere on the central-axis. Ionization profiles match within 1% of maximum dose, except at the geometrical edges of the field, where the disagreement is up to 5% of dose maximum. Causes for this discrepancy are discussed. The benchmarked BEAM code is then used to simulate beams from the major commercial medical linear accelerators. The off-axis factors are matched within statistical uncertainties, for most of the beams at the 1 σ level and for all at the 2 σ level. The calculated and measured depth-dose data agree within 1% (local dose), at about 1% (1 σ level) statistics, at all depths past

  15. Use of marginal distributions constrained optimization (MADCO) for accelerated 2D MRI relaxometry and diffusometry

    NASA Astrophysics Data System (ADS)

    Benjamini, Dan; Basser, Peter J.

    2016-10-01

    Measuring multidimensional (e.g., 2D) relaxation spectra in NMR and MRI clinical applications is a holy grail of the porous media and biomedical MR communities. The main bottleneck is the inversion of Fredholm integrals of the first kind, an ill-conditioned problem requiring large amounts of data to stabilize a solution. We suggest a novel experimental design and processing framework to accelerate and improve the reconstruction of such 2D spectra that uses a priori information from the 1D projections of spectra, or marginal distributions. These 1D marginal distributions provide powerful constraints when 2D spectra are reconstructed, and their estimation requires an order of magnitude less data than a conventional 2D approach. This marginal distributions constrained optimization (MADCO) methodology is demonstrated here with a polyvinylpyrrolidone-water phantom that has 3 distinct peaks in the 2D D-T1 space. The stability, sensitivity to experimental parameters, and accuracy of this new approach are compared with conventional methods by serially subsampling the full data set. While the conventional, unconstrained approach performed poorly, the new method had proven to be highly accurate and robust, only requiring a fraction of the data. Additionally, synthetic T1 -T2 data are presented to explore the effects of noise on the estimations, and the performance of the proposed method with a smooth and realistic 2D spectrum. The proposed framework is quite general and can also be used with a variety of 2D MRI experiments (D-T2,T1 -T2, D -D, etc.), making these potentially feasible for preclinical and even clinical applications for the first time.

  16. Use of marginal distributions constrained optimization (MADCO) for accelerated 2D MRI relaxometry and diffusometry.

    PubMed

    Benjamini, Dan; Basser, Peter J

    2016-10-01

    Measuring multidimensional (e.g., 2D) relaxation spectra in NMR and MRI clinical applications is a holy grail of the porous media and biomedical MR communities. The main bottleneck is the inversion of Fredholm integrals of the first kind, an ill-conditioned problem requiring large amounts of data to stabilize a solution. We suggest a novel experimental design and processing framework to accelerate and improve the reconstruction of such 2D spectra that uses a priori information from the 1D projections of spectra, or marginal distributions. These 1D marginal distributions provide powerful constraints when 2D spectra are reconstructed, and their estimation requires an order of magnitude less data than a conventional 2D approach. This marginal distributions constrained optimization (MADCO) methodology is demonstrated here with a polyvinylpyrrolidone-water phantom that has 3 distinct peaks in the 2D D-T1 space. The stability, sensitivity to experimental parameters, and accuracy of this new approach are compared with conventional methods by serially subsampling the full data set. While the conventional, unconstrained approach performed poorly, the new method had proven to be highly accurate and robust, only requiring a fraction of the data. Additionally, synthetic T1-T2 data are presented to explore the effects of noise on the estimations, and the performance of the proposed method with a smooth and realistic 2D spectrum. The proposed framework is quite general and can also be used with a variety of 2D MRI experiments (D-T2,T1-T2,D-D, etc.), making these potentially feasible for preclinical and even clinical applications for the first time. PMID:27543810

  17. Conformational dynamics of human FXR-LBD ligand interactions studied by hydrogen/deuterium exchange mass spectrometry: insights into the antagonism of the hypolipidemic agent Z-guggulsterone.

    PubMed

    Yang, Liping; Broderick, David; Jiang, Yuan; Hsu, Victor; Maier, Claudia S

    2014-09-01

    Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of transcription factors that plays a key role in the regulation of bile acids, lipid and glucose metabolisms. The regulative function of FXR is governed by conformational changes of the ligand binding domain (LBD) upon ligand binding. Although FXR is a highly researched potential therapeutic target, only a limited number of FXR-agonist complexes have been successfully crystallized and subsequently yielded high resolution structures. There is currently no structural information of any FXR-antagonist complexes publically available. We therefore explored the use of amide hydrogen/deuterium exchange (HDX) coupled with mass spectrometry for characterizing conformational changes in the FXR-LBD upon ligand binding. Ligand-specific deuterium incorporation profiles were obtained for three FXR ligand chemotypes: GW4064, a synthetic non-steroidal high affinity agonist; the bile acid chenodeoxycholic acid (CDCA), the endogenous low affinity agonist of FXR; and Z-guggulsterone (GG), an in vitro antagonist of the steroid chemotype. A comparison of the HDX profiles of their ligand-bound FXR-LBD complexes revealed a unique mode of interaction for GG. The conformational features of the FXR-LBD-antagonist interaction are discussed.

  18. FXR-dependent and -independent interaction of glucocorticoids with the regulatory pathways involved in the control of bile acid handling by the liver.

    PubMed

    Rosales, R; Romero, M R; Vaquero, J; Monte, M J; Requena, P; Martinez-Augustin, O; Sanchez de Medina, F; Marin, J J G

    2013-03-15

    Treatment with glucocorticoids (GCs) may cause adverse effects, including cholestasis. The ability of dexamethasone, prednisolone and budesonide to affect the liver handling of bile acids (BAs) has been investigated. In rats treated with GCs for 4 days, altered serum and bile BA levels, changed conjugation pattern, and delayed and decreased ability to conjugate/secrete exogenously administered deoxycholate, were found using HPLC-MS/MS. RT-QPCR analyses revealed that GC treatment also induced a down-regulation of liver nuclear receptors (Fxr, Gr and Shp), transporters (Ntcp, Mrp4 and Bcrp) and enzymes (Cyp7a1 and Baat), whereas Bsep, Mrp2 and Cyp27a1 were up-regulated. Human HepG2 and Alexander cell lines were used as in vitro models of liver cells with and without constitutive FXR expression, respectively. In HepG2 cells, GCs induced a decreased expression of FXR and SHP, and inhibited the regulatory effect of GW4064 on FXR-target genes. In Alexander cells, only when they were transfected with FXR+RXR, GW4064 caused up-regulation of SHP and OSTβ, and a down-regulation of CYP27A1. GCs had the opposite effect on these genes, both in the absence and in the presence of FXR expression. Co-transfection of Alexander cells with IR-1-Luc and FXR+RXR revealed that GCs did not inhibit but moderately enhanced FXR activity. Moreover, GCs have a synergistic effect on GW4064-induced FXR activation, whereas chenodeoxycholate and GW4064 have an additive effect. In conclusion, GCs are able to directly or indirectly activate FXR but they also antagonize, through FXR-independent mechanisms, the expression of FXR and FXR target genes involved in the hepatic handling of BAs.

  19. Optimization of magnetically accelerated, ultra-high velocity aluminum flyer plates for use in plate impact, shock wave experiments.

    SciTech Connect

    Cochrane, Kyle Robert; Knudson, Marcus D.; Slutz, Stephen A.; Lemke, Raymond William; Davis, J. P.; Harjes, Henry Charles III; Giunta, Anthony Andrew; Bliss, David Emery

    2005-05-01

    The intense magnetic field produced by the 20 MA Z accelerator is used as an impulsive pressure source to accelerate metal flyer plates to high velocity for the purpose of performing plate impact, shock wave experiments. This capability has been significantly enhanced by the recently developed pulse shaping capability of Z, which enables tailoring the rise time to peak current for a specific material and drive pressure to avoid shock formation within the flyer plate during acceleration. Consequently, full advantage can be taken of the available current to achieve the maximum possible magnetic drive pressure. In this way, peak magnetic drive pressures up to 490 GPa have been produced, which shocklessly accelerated 850 {micro}m aluminum (6061-T6) flyer plates to peak velocities of 34 km/s. We discuss magnetohydrodynamic (MHD) simulations that are used to optimize the magnetic pressure for a given flyer load and to determine the shape of the current rise time that precludes shock formation within the flyer during acceleration to peak velocity. In addition, we present results pertaining to plate impact, shock wave experiments in which the aluminum flyer plates were magnetically accelerated across a vacuum gap and impacted z-cut, {alpha}-quartz targets. Accurate measurements of resulting quartz shock velocities are presented and analyzed through high-fidelity MHD simulations enhanced using optimization techniques. Results show that a fraction of the flyer remains at solid density at impact, that the fraction of material at solid density decreases with increasing magnetic pressure, and that the observed abrupt decrease in the quartz shock velocity is well correlated with the melt transition in the aluminum flyer.

  20. Target design optimization for an electron accelerator driven subcritical facility with circular and square beam profiles.

    SciTech Connect

    Gohar, M. Y. A; Sofu, T.; Zhong, Z.; Belch, H.; Naberezhnev, D.; Nuclear Engineering Division

    2008-10-30

    A subcritical facility driven by an electron accelerator is planned at the Kharkov Institute of Physics and Technology (KIPT) in Ukraine for medical isotope production, materials research, training, and education. The conceptual design of the facility is being pursued through collaborations between ANL and KIPT. As part of the design effort, the high-fidelity analyses of various target options are performed with formulations to reflect the realistic configuration and the three dimensional geometry of each design. This report summarizes the results of target design optimization studies for electron beams with two different beam profiles. The target design optimization is performed via the sequential neutronic, thermal-hydraulic, and structural analyses for a comprehensive assessment of each configuration. First, a target CAD model is developed with proper emphasis on manufacturability to provide a basis for separate but consistent models for subsequent neutronic, thermal-hydraulic, and structural analyses. The optimizations are pursued for maximizing the neutron yield, streamlining the flow field to avoid hotspots, and minimizing the thermal stresses to increase the durability. In addition to general geometric modifications, the inlet/outlet channel configurations, target plate partitioning schemes, flow manipulations and rates, electron beam diameter/width options, and cladding material choices are included in the design optimizations. The electron beam interactions with the target assembly and the neutronic response of the subcritical facility are evaluated using the MCNPX code. the results for the electron beam energy deposition, neutron generation, and utilization in the subcritical pile are then used to characterize the axisymmetric heat generation profiles in the target assembly with explicit simulations of the beam tube, the coolant, the clad, and the target materials. Both tungsten and uranium are considered as target materials. Neutron spectra from tungsten

  1. 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.

  2. Beam shaping assembly optimization for (7)Li(p,n)(7)Be accelerator based BNCT.

    PubMed

    Minsky, D M; Kreiner, A J

    2014-06-01

    Within the framework of accelerator-based BNCT, a project to develop a folded Tandem-ElectroStatic-Quadrupole accelerator is under way at the Atomic Energy Commission of Argentina. The proposed accelerator is conceived to deliver a proton beam of 30mA at about 2.5MeV. In this work we explore a Beam Shaping Assembly (BSA) design based on the (7)Li(p,n)(7)Be neutron production reaction to obtain neutron beams to treat deep seated tumors.

  3. Beam shaping assembly optimization for (7)Li(p,n)(7)Be accelerator based BNCT.

    PubMed

    Minsky, D M; Kreiner, A J

    2014-06-01

    Within the framework of accelerator-based BNCT, a project to develop a folded Tandem-ElectroStatic-Quadrupole accelerator is under way at the Atomic Energy Commission of Argentina. The proposed accelerator is conceived to deliver a proton beam of 30mA at about 2.5MeV. In this work we explore a Beam Shaping Assembly (BSA) design based on the (7)Li(p,n)(7)Be neutron production reaction to obtain neutron beams to treat deep seated tumors. PMID:24345525

  4. Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis

    PubMed Central

    Gomez-Ospina, Natalia; Potter, Carol J.; Xiao, Rui; Manickam, Kandamurugu; Kim, Mi-Sun; Kim, Kang Ho; Shneider, Benjamin L.; Picarsic, Jennifer L.; Jacobson, Theodora A.; Zhang, Jing; He, Weimin; Liu, Pengfei; Knisely, A. S.; Finegold, Milton J.; Muzny, Donna M.; Boerwinkle, Eric; Lupski, James R.; Plon, Sharon E.; Gibbs, Richard A.; Eng, Christine M.; Yang, Yaping; Washington, Gabriel C.; Porteus, Matthew H.; Berquist, William E.; Kambham, Neeraja; Singh, Ravinder J.; Xia, Fan; Enns, Gregory M.; Moore, David D.

    2016-01-01

    Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection. PMID:26888176

  5. FXR is a molecular target for the effects of vertical sleeve gastrectomy

    PubMed Central

    Ryan, Karen K.; Tremaroli, Valentina; Clemmensen, Christoffer; Kovatcheva-Datchary, Petia; Myronovych, Andriy; Karns, Rebekah; Wilson-Pérez, Hilary E.; Sandoval, Darleen A.; Kohli, Rohit; Bäckhed, Fredrik; Seeley, Randy J.

    2014-01-01

    SUMMARY Bariatric surgical procedures, such as vertical sleeve gastrectomy (VSG), are currently the most effective therapy for the treatment of obesity, and are associated with substantial improvements in co-morbidities, including type-2 diabetes mellitus. The underlying molecular mechanisms contributing to these benefits remain largely undetermined, despite offering tremendous potential to reveal new targets for therapeutic intervention. The present study demonstrates that the therapeutic value of VSG does not result from mechanical restriction imposed by a smaller stomach. Rather, we report that VSG is associated with increased circulating bile acids, and associated changes to gut microbial communities. Moreover, in the absence of nuclear bile acid receptor FXR, the ability of VSG to reduce body weight and improve glucose tolerance is substantially reduced. These results point to bile acids and FXR signaling as an important molecular underpinning for the beneficial effects of this weight-loss surgery. PMID:24670636

  6. Optimization of Electron Beam Transport for a 3-MeV DC Accelerator

    NASA Astrophysics Data System (ADS)

    Baruah, S.; Bhattacharjee, D.; Tiwari, R.; Sahu, G. K.; Thakur, K. B.; Mittal, K. C.; Gantayet, L. M.

    2012-11-01

    Transport of a low-current-density electron beam is simulated for an electrostatic accelerator system. Representative charged particles are uniformly assigned for emission from a circular indirectly-heated cathode of an axial electron gun. The beam is accelerated stepwise up to energy of 1 MeV electrostatically in a length-span of ~3 m using multiple accelerating electrodes in a column of ten tubes. The simulation is done under relativistic condition and the effect of the magnetic field induced by the cathode-heating filament current is taken into account. The beam diameter is tracked at different axial locations for various settings of the electrode potentials. Attempts have been made to examine and explain data on beam transport efficiency obtained from experimental observations.

  7. Cysteine Sulfinic Acid Decarboxylase Regulation: A Role for FXR and SHP in Murine Hepatic Taurine Metabolism

    PubMed Central

    Kerr, Thomas A.; Matsumoto, Yuri; Matsumoto, Hitoshi; Xie, Yan; Hirschberger, Lawrence L.; Stipanuk, Martha H.; Anakk, Sayeepriyadarshini; Moore, David D.; Watanabe, Mitsuhiro; Kennedy, Susan

    2014-01-01

    Background Bile acid synthesis is regulated by nuclear receptors including farnesoid X receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth factor15/19 (FGF15/19). Because bile acid synthesis involves amino acid conjugation, we hypothesized that hepatic cysteine sulfinic acid decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile acids. Aims To investigate CSAD regulation by bile acids and CSAD regulatory mechanisms. Methods Mice were fed a control diet or a diet supplemented with either 0.5% cholate or 2% cholestyramine. To gain mechanistic insight into CSAD regulation, we utilized GW4064 (FXR agonist), FGF19, or T-0901317 (LXR agonist) and Shp−/− mice. Tissue mRNA expression was determined by qRT-PCR. Amino acids were measured by HPLC. Results Mice supplemented with dietary cholate exhibited reduced hepatic CSAD mRNA expression while those receiving cholestyramine exhibited increased hepatic CSAD mRNA expression. Activation of FXR suppressed CSAD mRNA expression whereas hepatic CSAD mRNA expression was increased in Shp−/− mice. Hepatic hypotaurine concentration (the product of CSAD) was higher in Shp−/− mice with a corresponding increase in serum (but not hepatic) taurine-conjugated bile acids. FGF19 administration suppressed hepatic CYP7A1 mRNA but did not change CSAD mRNA expression. LXR activation induced CYP7A1 mRNA yet failed to induce CSAD mRNA expression. Conclusion CSAD mRNA expression is physiologically regulated by bile acids in a feedback fashion via mechanisms involving SHP and FXR but not FGF15/19 or LXR. These novel findings implicate bile acids as regulators of CSAD mRNA via mechanisms shared in part with CYP7A1. PMID:24033844

  8. A quasi-Newton acceleration for high-dimensional optimization algorithms.

    PubMed

    Zhou, Hua; Alexander, David; Lange, Kenneth

    2011-01-01

    In many statistical problems, maximum likelihood estimation by an EM or MM algorithm suffers from excruciatingly slow convergence. This tendency limits the application of these algorithms to modern high-dimensional problems in data mining, genomics, and imaging. Unfortunately, most existing acceleration techniques are ill-suited to complicated models involving large numbers of parameters. The squared iterative methods (SQUAREM) recently proposed by Varadhan and Roland constitute one notable exception. This paper presents a new quasi-Newton acceleration scheme that requires only modest increments in computation per iteration and overall storage and rivals or surpasses the performance of SQUAREM on several representative test problems.

  9. FXR antagonism of NSAIDs contributes to drug-induced liver injury identified by systems pharmacology approach

    PubMed Central

    Lu, Weiqiang; Cheng, Feixiong; Jiang, Jing; Zhang, Chen; Deng, Xiaokang; Xu, Zhongyu; Zou, Shien; Shen, Xu; Tang, Yun; Huang, Jin

    2015-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are worldwide used drugs for analgesic, antipyretic, and anti-inflammatory therapeutics. However, NSAIDs often cause several serious liver injuries, such as drug-induced liver injury (DILI), and the molecular mechanisms of DILI have not been clearly elucidated. In this study, we developed a systems pharmacology approach to explore the mechanism-of-action of NSAIDs. We found that the Farnesoid X Receptor (FXR) antagonism of NSAIDs is a potential molecular mechanism of DILI through systematic network analysis and in vitro assays. Specially, the quantitative real-time PCR assay reveals that indomethacin and ibuprofen regulate FXR downstream target gene expression in HepG2 cells. Furthermore, the western blot shows that FXR antagonism by indomethacin induces the phosphorylation of STAT3 (signal transducer and activator of transcription 3), promotes the activation of caspase9, and finally causes DILI. In summary, our systems pharmacology approach provided novel insights into molecular mechanisms of DILI for NSAIDs, which may propel the ways toward the design of novel anti-inflammatory pharmacotherapeutics. PMID:25631039

  10. O-GlcNAcylation Links ChREBP and FXR to Glucose-Sensing

    PubMed Central

    Benhamed, Fadila; Filhoulaud, Gaelle; Caron, Sandrine; Lefebvre, Philippe; Staels, Bart; Postic, Catherine

    2015-01-01

    Accumulating evidence suggests that O-GlcNAc transferase, an enzyme responsible for O-GlcNAc post-translational modification acts as a nutrient sensor that links glucose and the hexosamine biosynthetic pathway to the regulation of transcriptional factors involved in energy homeostasis. In liver, glucose signaling is mediated by carbohydrate response element-binding protein (ChREBP), which stimulates glycolytic and lipogenic gene expression through its binding on a specific ChoRE DNA sequence. Modulation of ChREBP by O-GlcNAcylation increases its DNA binding affinity and its activity. ChREBP transcriptional activity also depends on the presence of several other co-factors and transcriptional factors. Among them, the nuclear Farnesoid X Receptor (FXR), a key transcription factor of bile acid metabolism involved in the gut–liver axis homeostasis was recently shown to directly interact with ChREBP, acting as a repressor on the ChoRE of glycolytic genes. Interestingly, similarly to ChREBP, FXR is O-GlcNAcylated in response to glucose. This review discusses the importance of ChREBP and FXR modifications through O-GlcNAcylation in liver and how glucose can modify their mutual affinity and transcriptional activity. PMID:25628602

  11. Optimization of the accelerated curing process of concrete using a fibre Bragg grating-based control system and microwave technology

    NASA Astrophysics Data System (ADS)

    Fabian, Matthias; Jia, Yaodong; Shi, Shi; McCague, Colum; Bai, Yun; Sun, Tong; Grattan, Kenneth T. V.

    2016-05-01

    In this paper, an investigation into the suitability of using fibre Bragg gratings (FBGs) for monitoring the accelerated curing process of concrete in a microwave heating environment is presented. In this approach, the temperature data provided by the FBGs are used to regulate automatically the microwave power so that a pre-defined temperature profile is maintained to optimize the curing process, achieving early strength values comparable to those of conventional heat-curing techniques but with significantly reduced energy consumption. The immunity of the FBGs to interference from the microwave radiation used ensures stable readings in the targeted environment, unlike conventional electronic sensor probes.

  12. Pharmacophore-based discovery of FXR-agonists. Part II: Identification of bioactive triterpenes from Ganoderma lucidum

    PubMed Central

    Grienke, Ulrike; Mihály-Bison, Judit; Schuster, Daniela; Afonyushkin, Taras; Binder, Markus; Guan, Shu-hong; Cheng, Chun-ru; Wolber, Gerhard; Stuppner, Hermann; Guo, De-an; Bochkov, Valery N.; Rollinger, Judith M.

    2011-01-01

    The farnesoid X receptor (FXR) belonging to the metabolic subfamily of nuclear receptors is a ligand-induced transcriptional activator. Its central function is the physiological maintenance of bile acid homeostasis including the regulation of glucose and lipid metabolism. Accessible structural information about its ligand-binding domain renders FXR an attractive target for in silico approaches. Integrated to natural product research these computational tools assist to find novel bioactive compounds showing beneficial effects in prevention and treatment of, for example, the metabolic syndrome, dyslipidemia, atherosclerosis, and type 2 diabetes. Virtual screening experiments of our in-house Chinese Herbal Medicine database with structure-based pharmacophore models, previously generated and validated, revealed mainly lanostane-type triterpenes of the TCM fungus Ganoderma lucidum Karst. as putative FXR ligands. To verify the prediction of the in silico approach, two Ganoderma fruit body extracts and compounds isolated thereof were pharmacologically investigated. Pronounced FXR-inducing effects were observed for the extracts at a concentration of 100 μg/mL. Intriguingly, five lanostanes out of 25 secondary metabolites from G. lucidum, that is, ergosterol peroxide (2), lucidumol A (11), ganoderic acid TR (12), ganodermanontriol (13), and ganoderiol F (14), dose-dependently induced FXR in the low micromolar range in a reporter gene assay. To rationalize the binding interactions, additional pharmacophore profiling and molecular docking studies were performed, which allowed establishing a first structure–activity relationship of the investigated triterpenes. PMID:22014750

  13. RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC.

    PubMed

    Majumder, Mrinmoyee; House, Reniqua; Palanisamy, Nallasivam; Qie, Shuo; Day, Terrence A; Neskey, David; Diehl, J Alan; Palanisamy, Viswanathan

    2016-09-01

    RNA-binding proteins (RBP) regulate numerous aspects of co- and post-transcriptional gene expression in cancer cells. Here, we demonstrate that RBP, fragile X-related protein 1 (FXR1), plays an essential role in cellular senescence by utilizing mRNA turnover pathway. We report that overexpressed FXR1 in head and neck squamous cell carcinoma targets (G-quadruplex (G4) RNA structure within) both mRNA encoding p21 (Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A, Cip1) and the non-coding RNA Telomerase RNA Component (TERC), and regulates their turnover to avoid senescence. Silencing of FXR1 in cancer cells triggers the activation of Cyclin-Dependent Kinase Inhibitors, p53, increases DNA damage, and ultimately, cellular senescence. Overexpressed FXR1 binds and destabilizes p21 mRNA, subsequently reduces p21 protein expression in oral cancer cells. In addition, FXR1 also binds and stabilizes TERC RNA and suppresses the cellular senescence possibly through telomerase activity. Finally, we report that FXR1-regulated senescence is irreversible and FXR1-depleted cells fail to form colonies to re-enter cellular proliferation. Collectively, FXR1 displays a novel mechanism of controlling the expression of p21 through p53-dependent manner to bypass cellular senescence in oral cancer cells. PMID:27606879

  14. Ligand-dependent coactivation of the human bile acid receptor FXR by the peroxisome proliferator-activated receptor gamma coactivator-1alpha.

    PubMed

    Savkur, Rajesh S; Thomas, Jeffrey S; Bramlett, Kelli S; Gao, Yunling; Michael, Laura F; Burris, Thomas P

    2005-01-01

    Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) has been shown to play an important role in energy metabolism by coordinating transcriptional programs involved in mitochondrial biogenesis, adaptive thermogenesis, gluconeogenesis, and fatty acid oxidation. PGC-1alpha also plays a crucial role in cholesterol metabolism by serving as a coactivator of the liver X receptor-alpha and inducing the expression of cholesterol 7-alpha-hydroxylase. Here, we demonstrate that PGC-1alpha also functions as an effective coactivator of farnesoid X receptor (FXR), the bile acid receptor. Transient cotransfection assays demonstrate that PGC-1alpha enhances ligand-mediated FXR transcription when either full-length FXR or Gal4 DNA binding domain-FXR-ligand binding domain chimeras were analyzed. Mammalian two-hybrid analyses, glutathione S-transferase affinity chromatography and biochemical coactivator recruitment assays demonstrate ligand-dependent interaction between the two proteins both in vivo and in vitro. PGC-1alpha-mediated coactivation of FXR was highly ligand-dependent and absolutely required an intact activation function-2 (AF-2) domain of FXR and the LXXLL motif in PGC-1alpha. The integrity of the charge clamp was required, further illustrating the role of the ligand binding domain of FXR in PGC-1alpha recognition. Together, these results indicate that PGC-1alpha functions as a potent coactivator for FXR and further implicates its role in the regulation of genes that are involved in bile acid and lipid metabolism.

  15. RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC

    PubMed Central

    Majumder, Mrinmoyee; House, Reniqua; Palanisamy, Nallasivam; Qie, Shuo; Day, Terrence A.; Neskey, David; Diehl, J. Alan

    2016-01-01

    RNA-binding proteins (RBP) regulate numerous aspects of co- and post-transcriptional gene expression in cancer cells. Here, we demonstrate that RBP, fragile X-related protein 1 (FXR1), plays an essential role in cellular senescence by utilizing mRNA turnover pathway. We report that overexpressed FXR1 in head and neck squamous cell carcinoma targets (G-quadruplex (G4) RNA structure within) both mRNA encoding p21 (Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A, Cip1) and the non-coding RNA Telomerase RNA Component (TERC), and regulates their turnover to avoid senescence. Silencing of FXR1 in cancer cells triggers the activation of Cyclin-Dependent Kinase Inhibitors, p53, increases DNA damage, and ultimately, cellular senescence. Overexpressed FXR1 binds and destabilizes p21 mRNA, subsequently reduces p21 protein expression in oral cancer cells. In addition, FXR1 also binds and stabilizes TERC RNA and suppresses the cellular senescence possibly through telomerase activity. Finally, we report that FXR1-regulated senescence is irreversible and FXR1-depleted cells fail to form colonies to re-enter cellular proliferation. Collectively, FXR1 displays a novel mechanism of controlling the expression of p21 through p53-dependent manner to bypass cellular senescence in oral cancer cells. PMID:27606879

  16. Optimal ion acceleration from ultrathin foils irradiated by a profiled laser pulse of relativistic intensity

    SciTech Connect

    Andreev, A. A.; Steinke, S.; Sokollik, T.; Schnuerer, M.; Nickles, P. V.; Avetsiyan, S. Ter; Platonov, K. Yu.

    2009-01-15

    Recent investigations of relativistic laser plasmas have shown that the energy transfer from the laser field to the kinetic ion energy and therefore the attainable maximum energy of the ions increases when ultrathin targets are irradiated by laser pulse without prepulse. In this paper, the influence of the target thickness and laser pulse contrast on the energy of the accelerated ions has been studied theoretically as well as experimentally. An optimum target was searched if a real laser pulse with a certain prepulse irradiates the target.

  17. Accelerated optimization and automated discovery with covariance matrix adaptation for experimental quantum control

    SciTech Connect

    Roslund, Jonathan; Shir, Ofer M.; Rabitz, Herschel; Baeck, Thomas

    2009-10-15

    Optimization of quantum systems by closed-loop adaptive pulse shaping offers a rich domain for the development and application of specialized evolutionary algorithms. Derandomized evolution strategies (DESs) are presented here as a robust class of optimizers for experimental quantum control. The combination of stochastic and quasi-local search embodied by these algorithms is especially amenable to the inherent topology of quantum control landscapes. Implementation of DES in the laboratory results in efficiency gains of up to {approx}9 times that of the standard genetic algorithm, and thus is a promising tool for optimization of unstable or fragile systems. The statistical learning upon which these algorithms are predicated also provide the means for obtaining a control problem's Hessian matrix with no additional experimental overhead. The forced optimal covariance adaptive learning (FOCAL) method is introduced to enable retrieval of the Hessian matrix, which can reveal information about the landscape's local structure and dynamic mechanism. Exploitation of such algorithms in quantum control experiments should enhance their efficiency and provide additional fundamental insights.

  18. A GPU-accelerated and Monte Carlo-based intensity modulated proton therapy optimization system

    SciTech Connect

    Ma, Jiasen Beltran, Chris; Seum Wan Chan Tseung, Hok; Herman, Michael G.

    2014-12-15

    Purpose: Conventional spot scanning intensity modulated proton therapy (IMPT) treatment planning systems (TPSs) optimize proton spot weights based on analytical dose calculations. These analytical dose calculations have been shown to have severe limitations in heterogeneous materials. Monte Carlo (MC) methods do not have these limitations; however, MC-based systems have been of limited clinical use due to the large number of beam spots in IMPT and the extremely long calculation time of traditional MC techniques. In this work, the authors present a clinically applicable IMPT TPS that utilizes a very fast MC calculation. Methods: An in-house graphics processing unit (GPU)-based MC dose calculation engine was employed to generate the dose influence map for each proton spot. With the MC generated influence map, a modified least-squares optimization method was used to achieve the desired dose volume histograms (DVHs). The intrinsic CT image resolution was adopted for voxelization in simulation and optimization to preserve spatial resolution. The optimizations were computed on a multi-GPU framework to mitigate the memory limitation issues for the large dose influence maps that resulted from maintaining the intrinsic CT resolution. The effects of tail cutoff and starting condition were studied and minimized in this work. Results: For relatively large and complex three-field head and neck cases, i.e., >100 000 spots with a target volume of ∼1000 cm{sup 3} and multiple surrounding critical structures, the optimization together with the initial MC dose influence map calculation was done in a clinically viable time frame (less than 30 min) on a GPU cluster consisting of 24 Nvidia GeForce GTX Titan cards. The in-house MC TPS plans were comparable to a commercial TPS plans based on DVH comparisons. Conclusions: A MC-based treatment planning system was developed. The treatment planning can be performed in a clinically viable time frame on a hardware system costing around 45

  19. Optimizing scan parameters for antibody microarray experiments: accelerating robust systems diagnostics for life sciences.

    PubMed

    Gu, Qiang; Sivanandam, Thamil Mani

    2014-06-01

    Microarray experiments are a centerpiece of postgenomics life sciences and the current efforts to develop systems diagnostics for personalized medicine. The majority of antibody microarray experiments are fluorescence-based, which utilizes a scanner to convert target signals into image files for subsequent quantification. Certain scan parameters such as the laser power and photomultiplier tube gain (PMT) can influence the readout of fluorescent intensities and thus may affect data quantitation. To date, however, there is no consensus of how to determine the optimal settings of microarray scanners. Here we show that different settings of the laser power and PMT not only affect the signal intensities but also the accuracy of antibody microarray experiments. More importantly, we demonstrate an experimental approach using two fluorescent dyes to determine optimal settings of scan parameters for microarray experiments. These measures provide added quality control of microarray experiments, and thus help to improve the accuracy of quantitative outcome in microarray experiments in the above contexts.

  20. Optimal resolution in maximum entropy image reconstruction from projections with multigrid acceleration

    NASA Technical Reports Server (NTRS)

    Limber, Mark A.; Manteuffel, Thomas A.; Mccormick, Stephen F.; Sholl, David S.

    1993-01-01

    We consider the problem of image reconstruction from a finite number of projections over the space L(sup 1)(Omega), where Omega is a compact subset of the set of Real numbers (exp 2). We prove that, given a discretization of the projection space, the function that generates the correct projection data and maximizes the Boltzmann-Shannon entropy is piecewise constant on a certain discretization of Omega, which we call the 'optimal grid'. It is on this grid that one obtains the maximum resolution given the problem setup. The size of this grid grows very quickly as the number of projections and number of cells per projection grow, indicating fast computational methods are essential to make its use feasible. We use a Fenchel duality formulation of the problem to keep the number of variables small while still using the optimal discretization, and propose a multilevel scheme to improve convergence of a simple cyclic maximization scheme applied to the dual problem.

  1. Optimizing Laser-accelerated Ion Beams for a Collimated Neutron Source

    SciTech Connect

    C.L. Ellison and J. Fuchs

    2010-09-23

    High-flux neutrons for imaging and materials analysis applications have typically been provided by accelerator- and reactor-based neutron sources. A novel approach is to use ultraintense (>1018W/cm2) lasers to generate picosecond, collimated neutrons from a dual target configuration. In this article, the production capabilities of present and upcoming laser facilities are estimated while independently maximizing neutron yields and minimizing beam divergence. A Monte-Carlo code calculates angular and energy distributions of neutrons generated by D-D fusion events occurring within a deuterated target for a given incident beam of D+ ions. Tailoring of the incident distribution via laser parameters and microlens focusing modifies the emerging neutrons. Projected neutron yields and distributions are compared to conventional sources, yielding comparable on-target fluxes per discharge, shorter time resolution, larger neutron energies and greater collimation.

  2. μMORE: A microfluidic magnetic oscillation reactor for accelerated parameter optimization in biocatalysis.

    PubMed

    Jussen, Daniel; Soltner, Helmut; Stute, Birgit; Wiechert, Wolfgang; von Lieres, Eric; Pohl, Martina

    2016-08-10

    Enzymatic parameter determination is an essential step in biocatalytic process development. Therefore higher throughput in miniaturized devices is urgently needed. An ideal microfluidic device should combine easy immobilization and retention of a minimal amount of biocatalyst with a well-mixed reaction volume. Together, all criteria are hardly met by current tools. Here we describe a microfluidic reactor (μMORE) which employs magnetic particles for both enzyme immobilization and efficient mixing using two permanent magnets placed in rotating cylinders next to the a glass chip reactor. The chip geometry and agitation speed was optimized by investigation of the mixing and retention characteristics using simulation and dye distribution analysis. Subsequently, the μMORE was successfully applied to determine critical biocatalytic process parameters in a parallelized manner for the carboligation of benzaldehyde and acetaldehyde to (S)-2-hydroxy-1-phenylpropan-1-one with less than 5μg of benzoylformate decarboxylase from Pseudomonas putida immobilized on magnetic beads. Here, one run of the device in six parallelized glass reactors took only 2-3h for an immobilized enzyme with very low activity (∼2U/mg). The optimized parameter set was finally tested in a 10mL enzyme membrane reactor, demonstrating that the μMORE provides a solid data base for biocatalytic process optimization. PMID:27288595

  3. Development and optimization of a beam shaper device for a mobile dedicated IOERT accelerator

    SciTech Connect

    Soriani, Antonella; Iaccarino, Giuseppe; Felici, Giuseppe; Ciccotelli, Alessia; Pinnaro, Paola; Giordano, Carolina; Benassi, Marcello; D'Andrea, Marco; Bellesi, Luca; Strigari, Lidia

    2012-10-15

    Purpose: The aim of this study was to design and build a prototype beam shaper to be used on a dedicated mobile accelerator that protects organs at risk within the radiation field and conforms the beam to the target geometry during intraoperative electron radiotherapy (IOERT). A dosimetric characterization of the beam shaper device was performed based on Monte Carlo (MC) simulations, as well as experimental data, at different energies, field sizes, and source to skin distances. Methods: A mobile light intraoperative accelerator (LIAC{sup Registered-Sign }, Sordina, Italy) was used. The design of the beam shaper prototype was based on MC simulations (BEAMnrc/OMEGA and DOSXYZnrc code) for a selection of materials and thicknesses, as well as for dosimetric characterization. Percentage depth dose (PDD) and profile measurements were performed using a p-type silicon diode and a commercial water phantom, while output factors were measured using a PinPoint ion chamber in a PMMA phantom. Planar doses in planes of interest were carried out using radiochromic films (Gafchromic{sup TM} EBT and EBT2) in PMMA and in a Solid Water{sup Registered-Sign} phantom. Several experimental set-ups were investigated with the beam shaper device fixed on the top of the phantom, varying both the short side of the rectangular field and the air gap between the device and the phantom surface, simulating the clinical situation. The output factors (OFs) were determined using different geometrical set-ups and energies. Results: The beam shaper prototype consists of four blades sliding alongside each other and mounted on a special support at the end of the 10 cm diameter PMMA circular applicator. Each blade is made of an upper layer of 2.6 cm of Teflon{sup Registered-Sign} and a lower layer of 8 mm of stainless steel. All rectangles inscribed in a 5 cm diameter can be achieved in addition to any 'squircle-shaped' field. When one side of the rectangular field is held constant and the second side is

  4. Optimal control with accelerated convergence: Combining the Krotov and quasi-Newton methods

    SciTech Connect

    Eitan, Reuven; Mundt, Michael; Tannor, David J.

    2011-05-15

    One of the most popular methods for solving numerical optimal control problems is the Krotov method, adapted for quantum control by Tannor and coworkers. The Krotov method has the following three appealing properties: (1) monotonic increase of the objective with iteration number, (2) no requirement for a line search, leading to a significant savings over gradient (first-order) methods, and (3) macrosteps at each iteration, resulting in significantly faster growth of the objective at early iterations than in gradient methods where small steps are required. The principal drawback of the Krotov method is slow convergence at later iterations, which is particularly problematic when high fidelity is desired. We show here that, near convergence, the Krotov method degenerates to a first-order gradient method. We then present a variation on the Krotov method that has all the advantages of the original Krotov method but with significantly enhanced convergence (second-order or quasi-Newton) as the optimal solution is approached. We illustrate the method by controlling the three-dimensional dynamics of the valence electron in the Na atom.

  5. Design and high order optimization of the Accelerator Test Facility lattices

    NASA Astrophysics Data System (ADS)

    Marin, E.; Tomás, R.; Bambade, P.; Kubo, K.; Okugi, T.; Tauchi, T.; Terunuma, N.; Urakawa, J.; Seryi, A.; White, G. R.; Woodley, M.

    2014-02-01

    The Accelerator Test Facility 2 (ATF2) aims to test the novel chromaticity correction scheme which is implemented in the final focus systems of future linear colliders such as the International Linear Collider (ILC) and the Compact Linear Collider (CLIC). The ATF2 nominal and ultralow β* lattices are designed to vertically focus the beam at the focal point, or usually referred to as interaction point (IP), down to 37 and 23 nm, respectively. The vertical chromaticities of the nominal and ultralow β* lattices are comparable to those of ILC and CLIC, respectively. When the measured multipole components of the ATF2 magnets are considered in the simulations, the evaluated spot sizes at the IP are well above the design values. In this paper we describe the analysis of the high order aberrations that allows identifying the sources of the observed beam size growth. In order to recover the design spot sizes three solutions are considered, namely final doublet replacement, octupole insertion, and optics modification. Concerning the future linear collider projects, the consequences of magnetic field errors of the focusing quadrupole magnet of the final doublet are also addressed.

  6. A version of the Trasco Intense Proton Source optimized for accelerator driven system purposes

    NASA Astrophysics Data System (ADS)

    Ciavola, G.; Celona, L.; Gammino, S.; Presti, M.; Andò, L.; Passarello, S.; Zhang, XZh.; Consoli, F.; Chines, F.; Percolla, C.; Calzona, V.; Winkler, M.

    2004-05-01

    A full set of measurements of the magnetic field has been carried out to define a different design of the TRASCO Intense Proton Source (TRIPS) magnetic system, based on permanent magnets, in order to increase the reliability of the source. The two coils of the source generate a maximum field of 150 mT and the optimum field was determined around 95 mT. The OPERA-3D package was used to simulate the magnetic field and a new magnetic system was designed as a combination of three rings of NdFeB magnets and soft iron. The high voltage insulation has been completely modified, in order to avoid any electronics at 80 kV voltage. The description of the magnetic measurements and the comparison with the simulations are presented, along with the mechanical design of the new version permanent magnet TRIPS (PM-TRIPS) and the new design of the extraction system. Finally the modification of the low energy beam transfer line (LEBT), which now includes a 30° bending magnet, will be outlined, with special regard to the accelerator availability improvement which can be obtained with the installation of two PM-TRIPS sources or more on the LEBT.

  7. Optimizing transmembrane domain helicity accelerates insulin receptor internalization and lateral mobility.

    PubMed Central

    Goncalves, E; Yamada, K; Thatte, H S; Backer, J M; Golan, D E; Kahn, C R; Shoelson, S E

    1993-01-01

    Transmembrane (TM) domains of integral membrane proteins are generally thought to be helical. However, a Gly-Pro sequence within the TM domain of the insulin receptor is predicted to act as a helix breaker. CD analyses of model TM peptides in a lipid-like environment show that substitution of Gly and Pro by Ala enhances helicity. On this basis, Gly933 and Pro934 within the TM domain of the intact human insulin receptor were mutated to Ala (G-->A, P-->A, GP-->AA) to assess effects of altered helicity on receptor functions. Mutated and wild-type receptors, expressed stably in cultured CHO cells at equivalent levels, were properly assembled, biosynthetically processed, and exhibited similar affinities for insulin. Receptor autophosphorylation and substrate kinase activity in intact cells and soluble receptor preparations were indistinguishable. In contrast, insulin-stimulated receptor internalization was accelerated 2-fold for the GP-->AA mutant, compared to a wild-type control or the G-->A and P-->A mutants. Insulin degradation, which occurs during receptor endocytosis and recycling, was similarly elevated in cells transfected with GP-->AA mutant receptors. Fluorescence photobleaching recovery measurements showed that the lateral mobility of GP-->AA mutant receptors was also increased 2- to 3-fold. These results suggest that lateral mobility directly influences rates of insulin-mediated receptor endocytosis and that rates of endocytosis and lateral mobility are retarded by a kinked TM domain in the wild-type receptor. Invariance of Gly-Pro within insulin receptor TM domain sequences suggests a physiologic advantage for submaximal rates of receptor internalization. Images Fig. 2 Fig. 3 PMID:8390680

  8. Adaptive Particle Swarm Optimizer with Varying Acceleration Coefficients for Finding the Most Stable Conformer of Small Molecules.

    PubMed

    Agrawal, Shikha; Silakari, Sanjay; Agrawal, Jitendra

    2015-11-01

    A novel parameter automation strategy for Particle Swarm Optimization called APSO (Adaptive PSO) is proposed. The algorithm is designed to efficiently control the local search and convergence to the global optimum solution. Parameters c1 controls the impact of the cognitive component on the particle trajectory and c2 controls the impact of the social component. Instead of fixing the value of c1 and c2 , this paper updates the value of these acceleration coefficients by considering time variation of evaluation function along with varying inertia weight factor in PSO. Here the maximum and minimum value of evaluation function is use to gradually decrease and increase the value of c1 and c2 respectively. Molecular energy minimization is one of the most challenging unsolved problems and it can be formulated as a global optimization problem. The aim of the present paper is to investigate the effect of newly developed APSO on the highly complex molecular potential energy function and to check the efficiency of the proposed algorithm to find the global minimum of the function under consideration. The proposed algorithm APSO is therefore applied in two cases: Firstly, for the minimization of a potential energy of small molecules with up to 100 degrees of freedom and finally for finding the global minimum energy conformation of 1,2,3-trichloro-1-flouro-propane molecule based on a realistic potential energy function. The computational results of all the cases show that the proposed method performs significantly better than the other algorithms. PMID:27491033

  9. Adaptive Particle Swarm Optimizer with Varying Acceleration Coefficients for Finding the Most Stable Conformer of Small Molecules.

    PubMed

    Agrawal, Shikha; Silakari, Sanjay; Agrawal, Jitendra

    2015-11-01

    A novel parameter automation strategy for Particle Swarm Optimization called APSO (Adaptive PSO) is proposed. The algorithm is designed to efficiently control the local search and convergence to the global optimum solution. Parameters c1 controls the impact of the cognitive component on the particle trajectory and c2 controls the impact of the social component. Instead of fixing the value of c1 and c2 , this paper updates the value of these acceleration coefficients by considering time variation of evaluation function along with varying inertia weight factor in PSO. Here the maximum and minimum value of evaluation function is use to gradually decrease and increase the value of c1 and c2 respectively. Molecular energy minimization is one of the most challenging unsolved problems and it can be formulated as a global optimization problem. The aim of the present paper is to investigate the effect of newly developed APSO on the highly complex molecular potential energy function and to check the efficiency of the proposed algorithm to find the global minimum of the function under consideration. The proposed algorithm APSO is therefore applied in two cases: Firstly, for the minimization of a potential energy of small molecules with up to 100 degrees of freedom and finally for finding the global minimum energy conformation of 1,2,3-trichloro-1-flouro-propane molecule based on a realistic potential energy function. The computational results of all the cases show that the proposed method performs significantly better than the other algorithms.

  10. FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis

    PubMed Central

    Verbeke, Len; Mannaerts, Inge; Schierwagen, Robert; Govaere, Olivier; Klein, Sabine; Vander Elst, Ingrid; Windmolders, Petra; Farre, Ricard; Wenes, Mathias; Mazzone, Massimiliano; Nevens, Frederik; van Grunsven, Leo A.; Trebicka, Jonel; Laleman, Wim

    2016-01-01

    Hepatic inflammation drives hepatic stellate cells (HSC), resulting in liver fibrosis. The Farnesoid-X receptor (FXR) antagonizes inflammation through NF-κB inhibition. We investigated preventive and therapeutic effects of FXR agonist obeticholic acid (OCA) on hepatic inflammation and fibrosis in toxic cirrhotic rats. Cirrhosis was induced by thioacetamide (TAA) intoxication. OCA was given during or after intoxication with vehicle-treated rats as controls. At sacrifice, fibrosis, hemodynamic and biochemical parameters were assessed. HSC activation, cell turn-over, hepatic NF-κB activation, pro-inflammatory and pro-fibrotic cytokines were determined. The effect of OCA was further evaluated in isolated HSC, Kupffer cells, hepatocytes and liver sinusoidal endothelial cells (LSEC). OCA decreased hepatic inflammation and fibrogenesis during TAA-administration and reversed fibrosis in established cirrhosis. Portal pressure decreased through reduced intrahepatic vascular resistance. This was paralleled by decreased expression of pro-fibrotic cytokines (transforming growth-factor β, connective tissue growth factor, platelet-derived growth factor β-receptor) as well as markers of hepatic cell turn-over, by blunting effects of pro-inflammatory cytokines (e.g. monocyte chemo-attractant protein-1). In vitro, OCA inhibited both LSEC and Kupffer cell activation; while HSC remained unaffected. This related to NF-κB inhibition via up-regulated IκBα. In conclusion, OCA inhibits hepatic inflammation in toxic cirrhotic rats resulting in decreased HSC activation and fibrosis. PMID:27634375

  11. FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis.

    PubMed

    Verbeke, Len; Mannaerts, Inge; Schierwagen, Robert; Govaere, Olivier; Klein, Sabine; Vander Elst, Ingrid; Windmolders, Petra; Farre, Ricard; Wenes, Mathias; Mazzone, Massimiliano; Nevens, Frederik; van Grunsven, Leo A; Trebicka, Jonel; Laleman, Wim

    2016-01-01

    Hepatic inflammation drives hepatic stellate cells (HSC), resulting in liver fibrosis. The Farnesoid-X receptor (FXR) antagonizes inflammation through NF-κB inhibition. We investigated preventive and therapeutic effects of FXR agonist obeticholic acid (OCA) on hepatic inflammation and fibrosis in toxic cirrhotic rats. Cirrhosis was induced by thioacetamide (TAA) intoxication. OCA was given during or after intoxication with vehicle-treated rats as controls. At sacrifice, fibrosis, hemodynamic and biochemical parameters were assessed. HSC activation, cell turn-over, hepatic NF-κB activation, pro-inflammatory and pro-fibrotic cytokines were determined. The effect of OCA was further evaluated in isolated HSC, Kupffer cells, hepatocytes and liver sinusoidal endothelial cells (LSEC). OCA decreased hepatic inflammation and fibrogenesis during TAA-administration and reversed fibrosis in established cirrhosis. Portal pressure decreased through reduced intrahepatic vascular resistance. This was paralleled by decreased expression of pro-fibrotic cytokines (transforming growth-factor β, connective tissue growth factor, platelet-derived growth factor β-receptor) as well as markers of hepatic cell turn-over, by blunting effects of pro-inflammatory cytokines (e.g. monocyte chemo-attractant protein-1). In vitro, OCA inhibited both LSEC and Kupffer cell activation; while HSC remained unaffected. This related to NF-κB inhibition via up-regulated IκBα. In conclusion, OCA inhibits hepatic inflammation in toxic cirrhotic rats resulting in decreased HSC activation and fibrosis. PMID:27634375

  12. Effects of alfalfa saponin extract on mRNA expression of Ldlr, LXRα, and FXR in BRL cells*

    PubMed Central

    Liang, Xin-ping; Zhang, Dong-qiang; Chen, Yan-yan; Guo, Rui; Wang, Jie; Wang, Cheng-zhang; Shi, Ying-hua

    2015-01-01

    We studied the effects of alfalfa saponin extract (ASE) on low density lipoprotein receptor (Ldlr), liver X receptor α (LXRα), and farnesoid X receptor (FXR) in normal and hyperlipidemic Buffalo rat liver (BRL) cells. Normal and hyperlipidemic BRL cells were divided into eight groups: normal, or normal cells treated with 50, 100, and 150 mg/L ASE, hyperlipidemic, or hyperlipidemic cells treated with 50, 100, and 150 mg/L ASE. After treatment for 24 h, Ldlr, LXRα, and FXR mRNA expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Data showed that mRNA expression of Ldlr in normal BRL cells was significantly up-regulated by ASE treatment and mRNA expressions of LXRα and FXR were significantly down-regulated both in normal and hyperlipidemic BRL cells after ASE treatment. Thus, ASE might ameliorate hepatic steatosis by regulating genes involved in cholesterol metabolism, including up-regulation of Ldlr as well as down-regulation of LXRα and FXR. PMID:26055909

  13. Plakophilins 1 and 3 Bind to FXR1 and Thereby Influence the mRNA Stability of Desmosomal Proteins

    PubMed Central

    Fischer-Kešo, Regina; Breuninger, Sonja; Hofmann, Sarah; Henn, Manuela; Röhrig, Theresa; Ströbel, Philipp; Stoecklin, Georg

    2014-01-01

    Plakophilins 1 and 3 (PKP1/3) are members of the arm repeat family of catenin proteins and serve as structural components of desmosomes, which are important for cell-cell-adhesion. In addition, PKP1/3 occur as soluble proteins outside desmosomes, yet their role in the cytoplasm is not known. We found that cytoplasmic PKP1/3 coprecipitated with the RNA-binding proteins FXR1, G3BP, PABPC1, and UPF1, and these PKP1/3 complexes also comprised desmoplakin and PKP2 mRNAs. Moreover, we showed that the interaction of PKP1/3 with G3BP, PABPC1, and UPF1 but not with FXR1 was RNase sensitive. To address the cytoplasmic function of PKP1/3, we performed gain-and-loss-of-function studies. Both PKP1 and PKP3 knockdown cell lines showed reduced protein and mRNA levels for desmoplakin and PKP2. Whereas global rates of translation were unaffected, desmoplakin and PKP2 mRNA were destabilized. Furthermore, binding of PKP1/3 to FXR1 was RNA independent, and both PKP3 and FXR1 stabilized PKP2 mRNA. Our results demonstrate that cytoplasmic PKP1/3 are components of mRNA ribonucleoprotein particles and act as posttranscriptional regulators of gene expression. PMID:25225333

  14. Activated FXR Inhibits Leptin Signaling and Counteracts Tumor-promoting Activities of Cancer-Associated Fibroblasts in Breast Malignancy.

    PubMed

    Giordano, Cinzia; Barone, Ines; Vircillo, Valentina; Panza, Salvatore; Malivindi, Rocco; Gelsomino, Luca; Pellegrino, Michele; Rago, Vittoria; Mauro, Loredana; Lanzino, Marilena; Panno, Maria Luisa; Bonofiglio, Daniela; Catalano, Stefania; Andò, Sebastiano

    2016-02-22

    Cancer-associated fibroblasts (CAFs), the principal components of the tumor stroma, play a central role in cancer development and progression. As an important regulator of the crosstalk between breast cancer cells and CAFs, the cytokine leptin has been associated to breast carcinogenesis. The nuclear Farnesoid X Receptor-(FXR) seems to exert an oncosuppressive role in different tumors, including breast cancer. Herein, we demonstrated, for the first time, that the synthetic FXR agonist GW4064, inhibiting leptin signaling, affects the tumor-promoting activities of CAFs in breast malignancy. GW4064 inhibited growth, motility and invasiveness induced by leptin as well as by CAF-conditioned media in different breast cancer cell lines. These effects rely on the ability of activated FXR to increase the expression of the suppressor of the cytokine signaling 3 (SOCS3) leading to inhibition of leptin-activated signaling and downregulation of leptin-target genes. In vivo xenograft studies, using MCF-7 cells alone or co-injected with CAFs, showed that GW4064 administration markedly reduced tumor growth. Interestingly, GW4064-treated tumors exhibited decreased levels of leptin-regulated proteins along with a strong staining intensity for SOCS3. Thus, FXR ligands might represent an emerging potential anti-cancer therapy able to block the tumor supportive role of activated fibroblasts within the breast microenvironment.

  15. Activated FXR Inhibits Leptin Signaling and Counteracts Tumor-promoting Activities of Cancer-Associated Fibroblasts in Breast Malignancy

    PubMed Central

    Giordano, Cinzia; Barone, Ines; Vircillo, Valentina; Panza, Salvatore; Malivindi, Rocco; Gelsomino, Luca; Pellegrino, Michele; Rago, Vittoria; Mauro, Loredana; Lanzino, Marilena; Panno, Maria Luisa; Bonofiglio, Daniela; Catalano, Stefania; Andò, Sebastiano

    2016-01-01

    Cancer-associated fibroblasts (CAFs), the principal components of the tumor stroma, play a central role in cancer development and progression. As an important regulator of the crosstalk between breast cancer cells and CAFs, the cytokine leptin has been associated to breast carcinogenesis. The nuclear Farnesoid X Receptor-(FXR) seems to exert an oncosuppressive role in different tumors, including breast cancer. Herein, we demonstrated, for the first time, that the synthetic FXR agonist GW4064, inhibiting leptin signaling, affects the tumor-promoting activities of CAFs in breast malignancy. GW4064 inhibited growth, motility and invasiveness induced by leptin as well as by CAF-conditioned media in different breast cancer cell lines. These effects rely on the ability of activated FXR to increase the expression of the suppressor of the cytokine signaling 3 (SOCS3) leading to inhibition of leptin-activated signaling and downregulation of leptin-target genes. In vivo xenograft studies, using MCF-7 cells alone or co-injected with CAFs, showed that GW4064 administration markedly reduced tumor growth. Interestingly, GW4064-treated tumors exhibited decreased levels of leptin-regulated proteins along with a strong staining intensity for SOCS3. Thus, FXR ligands might represent an emerging potential anti-cancer therapy able to block the tumor supportive role of activated fibroblasts within the breast microenvironment. PMID:26899873

  16. Semisynthetic bile acid FXR and TGR5 agonists: physicochemical properties, pharmacokinetics, and metabolism in the rat.

    PubMed

    Roda, Aldo; Pellicciari, Roberto; Gioiello, Antimo; Neri, Flavia; Camborata, Cecilia; Passeri, Daniela; De Franco, Francesca; Spinozzi, Silvia; Colliva, Carolina; Adorini, Luciano; Montagnani, Marco; Aldini, Rita

    2014-07-01

    We report on the relationship between the structure-pharmacokinetics, metabolism, and therapeutic activity of semisynthetic bile acid analogs, including 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid (a selective farnesoid X receptor [FXR] receptor agonist), 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid (a specific Takeda G protein-coupled receptor 5 [TGR5] receptor agonist), and 6α-ethyl-3α,7α-dihydroxy-24-nor-5β-cholan-23-sulfate (a dual FXR/TGR5 agonist). We measured the main physicochemical properties of these molecules, including ionization constants, water solubility, lipophilicity, detergency, and protein binding. Biliary secretion and metabolism and plasma and hepatic concentrations were evaluated by high-pressure liquid chromatography-electrospray-mass spectrometry/mass spectrometry in bile fistula rat and compared with natural analogs chenodeoxycholic, cholic acid, and taurochenodexycholic acid and intestinal bacteria metabolism was evaluated in terms of 7α-dehydroxylase substrate-specificity in anaerobic human stool culture. The semisynthetic derivatives detergency, measured in terms of their critical micellar concentration, was quite similar to the natural analogs. They were slightly more lipophilic than the corresponding natural analogs, evaluated by their 1-octanol water partition coefficient (log P), because of the ethyl group in 6 position, which makes these molecules very stable toward bacterial 7-dehydroxylation. The hepatic metabolism and biliary secretion were different: 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid, as chenodeoxycholic acid, was efficiently conjugated with taurine in the liver and, only in this form, promptly and efficiently secreted in bile. 6α-Ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid was poorly conjugated with taurine because of the steric hindrance of the methyl at C23(S) position metabolized to the C23(R) isomer and partly conjugated with taurine. Conversely, 6

  17. Semisynthetic bile acid FXR and TGR5 agonists: physicochemical properties, pharmacokinetics, and metabolism in the rat.

    PubMed

    Roda, Aldo; Pellicciari, Roberto; Gioiello, Antimo; Neri, Flavia; Camborata, Cecilia; Passeri, Daniela; De Franco, Francesca; Spinozzi, Silvia; Colliva, Carolina; Adorini, Luciano; Montagnani, Marco; Aldini, Rita

    2014-07-01

    We report on the relationship between the structure-pharmacokinetics, metabolism, and therapeutic activity of semisynthetic bile acid analogs, including 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid (a selective farnesoid X receptor [FXR] receptor agonist), 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid (a specific Takeda G protein-coupled receptor 5 [TGR5] receptor agonist), and 6α-ethyl-3α,7α-dihydroxy-24-nor-5β-cholan-23-sulfate (a dual FXR/TGR5 agonist). We measured the main physicochemical properties of these molecules, including ionization constants, water solubility, lipophilicity, detergency, and protein binding. Biliary secretion and metabolism and plasma and hepatic concentrations were evaluated by high-pressure liquid chromatography-electrospray-mass spectrometry/mass spectrometry in bile fistula rat and compared with natural analogs chenodeoxycholic, cholic acid, and taurochenodexycholic acid and intestinal bacteria metabolism was evaluated in terms of 7α-dehydroxylase substrate-specificity in anaerobic human stool culture. The semisynthetic derivatives detergency, measured in terms of their critical micellar concentration, was quite similar to the natural analogs. They were slightly more lipophilic than the corresponding natural analogs, evaluated by their 1-octanol water partition coefficient (log P), because of the ethyl group in 6 position, which makes these molecules very stable toward bacterial 7-dehydroxylation. The hepatic metabolism and biliary secretion were different: 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid, as chenodeoxycholic acid, was efficiently conjugated with taurine in the liver and, only in this form, promptly and efficiently secreted in bile. 6α-Ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid was poorly conjugated with taurine because of the steric hindrance of the methyl at C23(S) position metabolized to the C23(R) isomer and partly conjugated with taurine. Conversely, 6

  18. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts.

    PubMed

    Hu, Li; Wang, Juan; Zhou, Xin; Xiong, Zehuan; Zhao, Jiajia; Yu, Ran; Huang, Fang; Zhang, Handong; Chen, Lili

    2016-09-12

    Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell migration, proliferation and collagen synthesis in a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1, PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos can be recruited to soft tissue wound area in a mouse skin incision model and significantly accelerated cutaneous wound healing. Histological analysis showed increased collagen I and III production by systemic administration of exosomes in the early stage of wound healing, while in the late stage, exosomes might inhibit collagen expression to reduce scar formation. Collectively, our findings indicate that ASCs-Exos can facilitate cutaneous wound healing via optimizing the characteristics of fibroblasts. Our results provide a new perspective and therapeutic strategy for the use of ASCs-Exos in soft tissue repair.

  19. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts.

    PubMed

    Hu, Li; Wang, Juan; Zhou, Xin; Xiong, Zehuan; Zhao, Jiajia; Yu, Ran; Huang, Fang; Zhang, Handong; Chen, Lili

    2016-01-01

    Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell migration, proliferation and collagen synthesis in a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1, PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos can be recruited to soft tissue wound area in a mouse skin incision model and significantly accelerated cutaneous wound healing. Histological analysis showed increased collagen I and III production by systemic administration of exosomes in the early stage of wound healing, while in the late stage, exosomes might inhibit collagen expression to reduce scar formation. Collectively, our findings indicate that ASCs-Exos can facilitate cutaneous wound healing via optimizing the characteristics of fibroblasts. Our results provide a new perspective and therapeutic strategy for the use of ASCs-Exos in soft tissue repair. PMID:27615560

  20. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts

    PubMed Central

    Hu, Li; Wang, Juan; Zhou, Xin; Xiong, Zehuan; Zhao, Jiajia; Yu, Ran; Huang, Fang; Zhang, Handong; Chen, Lili

    2016-01-01

    Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell migration, proliferation and collagen synthesis in a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1, PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos can be recruited to soft tissue wound area in a mouse skin incision model and significantly accelerated cutaneous wound healing. Histological analysis showed increased collagen I and III production by systemic administration of exosomes in the early stage of wound healing, while in the late stage, exosomes might inhibit collagen expression to reduce scar formation. Collectively, our findings indicate that ASCs-Exos can facilitate cutaneous wound healing via optimizing the characteristics of fibroblasts. Our results provide a new perspective and therapeutic strategy for the use of ASCs-Exos in soft tissue repair. PMID:27615560

  1. Design of a MeV, 4kA linear induction accelerator for flash radiography

    SciTech Connect

    Kulke, B.; Brier, R.; Chapin, W.

    1981-02-10

    For verifying the hydrodynamics of nuclear weapons design it is useful to have flash x-ray machines that can deliver a maximum dose in a minimum pulse length and with very high reliability. At LLNL, such a requirement was identified some years ago as 500 roentgens at one meter, in a 60 nsec pulse length. In response to this requirement, a linear induction accelerator was proposed to and funded by DOE in 1977. The design of this machine, called FXR, has now been completed and construction has begun. The FXR design extends the parameters of a similar machine that had been built and operated at LBL, Berkeley, some ten years ago. Using a cold cathode injector followed by 48 accelerator modules rated at 400 kV each, the FXR machine will accelerate a 4 kA electron beam pulse to 20 MeV final energy. Key design features are the generation and the stable transport of a low emittance (100 mr-cm) beam from a field emitter diode, the design of reliable, compact energy storage components such as Blumleins, feedlines and accelerator modules, and a computer-assisted control system.

  2. Longitudinal laser ion acceleration in low density targets: experimental optimization on the Titan laser facility and numerical investigation of the ultra-high intensity limit

    NASA Astrophysics Data System (ADS)

    d'Humières, E.; Chen, S.; Lobet, Mathieu; Sciscio, M.; Antici, Patrizio; Bailly-Grandvaux, Mathieu; Gangolf, Thomas; Revet, Guilhem; Santos, Joao J.; Schroer, Anna-Marie; Willi, O.; Tikhonchuk, Vladimir T.; Pepin, Henri; Fuchs, Julien

    2015-05-01

    Recent theoretical and experimental studies suggest the possibility of enhancing the efficiency and ease of laser acceleration of protons and ions using underdense or near critical plasmas through electrostatic shocks. Very promising results were recently obtained in this regime. In these experiments, a first ns pulse was focused on a thin target to explode it and a second laser with a high intensity was focused on the exploded foil. The delay between two lasers allowed to control the density gradient seen by the second laser pulse. The transition between various laser ion acceleration regimes depending on the density gradient length was studied. With a laser energy of a few Joules, protons with energies close to the energies of TNSA accelerated protons were obtained for various exploded foils configurations. In the high energy regime (~180 J), protons with energies significantly higher than the ones of TNSA accelerated protons were obtained when exploding the foil while keeping a good beam quality. These results demonstrate that low-density targets are promising candidates for an efficient proton source that can be optimized by choosing appropriate plasma conditions. New experiments were also performed in this regime with gas jets. Scaling shock acceleration in the low density regime to ultra high intensities is a challenge as radiation losses and electron positron pair production change the optimization of the shock process. Using large-scale Particle-In-Cell simulations, the transition to this regime in which intense beams of relativistic ions can be produced is investigated.

  3. Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them.

    PubMed Central

    Siomi, M C; Zhang, Y; Siomi, H; Dreyfuss, G

    1996-01-01

    Fragile X syndrome, the most common form of hereditary mental retardation, usually results from lack of expression of the FMR1 gene. The FMR1 protein is a cytoplasmic RNA-binding protein. The RNA-binding activity of FMR1 is an essential feature of FMR1, as fragile X syndrome can also result from the expression of mutant FMR1 protein that is impaired in RNA binding. Recently, we described two novel cytoplasmic proteins, FXR1 and FXR2, which are both very similar in amino acid sequence to FMR1 and which also interact strongly with FMR1 and with each other. To understand the function of FMR1 and the FXR proteins, we carried out cell fractionation and sedimentation experiments with monoclonal antibodies to these proteins to characterize the complexes they form. Here, we report that the FMR1 and FXR proteins are associated with ribosomes, predominantly with 60S large ribosomal subunits. The FXR proteins are associated with 60S ribosomal subunits even in cells that lack FMR1 and that are derived from a fragile X syndrome patient, indicating that FMR1 is not required for this association. We delineated the regions of FMR1 that mediate its binding to 60S ribosomal subunits and the interactions among the FMR1-FXR family members. Both regions contain sequences predicted to have a high propensity to form coiled coil interactions, and the sequences are highly evolutionarily conserved in this protein family. The association of the FMR1, FXR1, and FXR2 proteins with ribosomes suggests they have functions in translation or mRNA stability. PMID:8668200

  4. Laser driven ion accelerator

    DOEpatents

    Tajima, Toshiki

    2006-04-18

    A system and method of accelerating ions in an accelerator to optimize the energy produced by a light source. Several parameters may be controlled in constructing a target used in the accelerator system to adjust performance of the accelerator system. These parameters include the material, thickness, geometry and surface of the target.

  5. Synthesis and evaluation of (18)F-labeled bile acid compound: a potential PET imaging agent for FXR-related diseases.

    PubMed

    Jia, Lina; Jiang, Dawei; Hu, Pengcheng; Li, Xiao; Shi, Hongcheng; Cheng, Dengfeng; Zhang, Lan

    2014-07-01

    The farnesoid-X-receptor (FXR) is a member of the nuclear hormone receptor superfamily. The FXR has critical functions in maintaining bile acid synthesis and homeostasis, liver regeneration and tumorigenesis, intestinal diseases, intestinal tumorigenesis, cholesterol gallstone disease, cholestasis, and atherosclerosis. FXR expression is strongly downregulated in liver fibrosis, hepatocellular adenoma and hepatocellular carcinoma compared to expression levels in adjacent normal tissues. Chenodeoxycholic acid (CDCA) is the most potent physiological ligand for FXR. CDCA was radiolabeled with (18)F based on the efficiency click reaction of 1,3-dipolar cycloaddition of terminal alkynes and organic azides for noninvasively evaluating the relationship between FXR and FXR-related disease. The PET tracer [(18)F]8 was produced by 'click' labeling and showed a high non-decay corrected radiochemical yield (end of synthesis (EOS) yield=42±3% (n=5) from aqueous [(18)F]fluoride), high radiochemical purity ( >99%), and high specific activity (>320GBq/μmol). [(18)F]8 had a high metabolic stability in vitro and in vivo. PET imaging studies in nude mice indicated a rapid uptake of the tracer into liver tissue with uniform distribution of radioactivity in the liver. Significant accumulation of radioactivity was found in the liver, gallbladder, and intestine, while no obvious uptake was observed in other organs, such as the bladder, heart, and brain. Thus, this PET tracer represents a novel tool for early detection of abnormalities in the liver and staging of neoplasms.

  6. Recent optimization of the beam-optical characteristics of the 6 MV van de Graaff accelerator for high brightness beams at the iThemba LABS NMP facility

    NASA Astrophysics Data System (ADS)

    Conradie, J. L.; Eisa, M. E. M.; Celliers, P. J.; Delsink, J. L. G.; Fourie, D. T.; de Villiers, J. G.; Maine, P. M.; Springhorn, K. A.; Pineda-Vargas, C. A.

    2005-04-01

    With the aim of improving the reliability and stability of the beams delivered to the nuclear microprobe at iThemba LABS, as well as optimization of the beam characteristics along the van de Graaff accelerator beamlines in general, relevant modifications were implemented since the beginning of 2003. The design and layout of the beamlines were revised. The beam-optical characteristics through the accelerator, from the ion source up to the analysing magnet directly after the accelerator, were calculated and the design optimised, using the computer codes TRANSPORT, IGUN and TOSCA. The ion source characteristics and optimal operating conditions were determined on an ion source test bench. The measured optimal emittance for 90% of the beam intensity was about 50π mm mrad for an extraction voltage of 6 kV. These changes allow operation of the Nuclear Microprobe at proton energies in the range 1 MeV-4 MeV with beam intensities of tenths of a pA at the target surface. The capabilities of the nuclear microprobe facility were evaluated in the improved beamline, with particular emphasis to bio-medical samples.

  7. Optimizing the configuration of a superconducting photonic band gap accelerator cavity to increase the maximum achievable gradients

    NASA Astrophysics Data System (ADS)

    Simakov, Evgenya I.; Kurennoy, Sergey S.; O'Hara, James F.; Olivas, Eric R.; Shchegolkov, Dmitry Yu.

    2014-02-01

    We present a design of a superconducting rf photonic band gap (SRF PBG) accelerator cell with specially shaped rods in order to reduce peak surface magnetic fields and improve the effectiveness of the PBG structure for suppression of higher order modes (HOMs). The ability of PBG structures to suppress long-range wakefields is especially beneficial for superconducting electron accelerators for high power free-electron lasers (FELs), which are designed to provide high current continuous duty electron beams. Using PBG structures to reduce the prominent beam-breakup phenomena due to HOMs will allow significantly increased beam-breakup thresholds. As a result, there will be possibilities for increasing the operation frequency of SRF accelerators and for the development of novel compact high-current accelerator modules for the FELs.

  8. Self-Organizing Hierarchical Particle Swarm Optimization with Time-Varying Acceleration Coefficients for Economic Dispatch with Valve Point Effects and Multifuel Options

    NASA Astrophysics Data System (ADS)

    Polprasert, Jirawadee; Ongsakul, Weerakorn; Dieu, Vo Ngoc

    2011-06-01

    This paper proposes a self-organizing hierarchical particle swarm optimization (SPSO) with time-varying acceleration coefficients (TVAC) for solving economic dispatch (ED) problem with non-smooth functions including multiple fuel options (MFO) and valve-point loading effects (VPLE). The proposed SPSO with TVAC is the new approach optimizer and good performance for solving ED problems. It can handle the premature convergence of the problem by re-initialization of velocity whenever particles are stagnated in the search space. To properly control both local and global explorations of the swarm during the optimization process, the performance of TVAC is included. The proposed method is tested in different ED problems with non-smooth cost functions and the obtained results are compared to those from many other methods in the literature. The results have revealed that the proposed SPSO with TVAC is effective in finding higher quality solutions for non-smooth ED problems than many other methods.

  9. TH-A-19A-12: A GPU-Accelerated and Monte Carlo-Based Intensity Modulated Proton Therapy Optimization System

    SciTech Connect

    Ma, J; Wan Chan Tseung, H; Beltran, C

    2014-06-15

    Purpose: To develop a clinically applicable intensity modulated proton therapy (IMPT) optimization system that utilizes more accurate Monte Carlo (MC) dose calculation, rather than analytical dose calculation. Methods: A very fast in-house graphics processing unit (GPU) based MC dose calculation engine was employed to generate the dose influence map for each proton spot. With the MC generated influence map, a modified gradient based optimization method was used to achieve the desired dose volume histograms (DVH). The intrinsic CT image resolution was adopted for voxelization in simulation and optimization to preserve the spatial resolution. The optimizations were computed on a multi-GPU framework to mitigate the memory limitation issues for the large dose influence maps that Result from maintaining the intrinsic CT resolution and large number of proton spots. The dose effects were studied particularly in cases with heterogeneous materials in comparison with the commercial treatment planning system (TPS). Results: For a relatively large and complex three-field bi-lateral head and neck case (i.e. >100K spots with a target volume of ∼1000 cc and multiple surrounding critical structures), the optimization together with the initial MC dose influence map calculation can be done in a clinically viable time frame (i.e. less than 15 minutes) on a GPU cluster consisting of 24 Nvidia GeForce GTX Titan cards. The DVHs of the MC TPS plan compare favorably with those of a commercial treatment planning system. Conclusion: A GPU accelerated and MC-based IMPT optimization system was developed. The dose calculation and plan optimization can be performed in less than 15 minutes on a hardware system costing less than 45,000 dollars. The fast calculation and optimization makes the system easily expandable to robust and multi-criteria optimization. This work was funded in part by a grant from Varian Medical Systems, Inc.

  10. Effects of bile acids and the bile acid receptor FXR agonist on the respiratory rhythm in the in vitro brainstem medulla slice of neonatal Sprague-Dawley rats.

    PubMed

    Zhao, Cong; Wang, Xianbao; Cong, Yuling; Deng, Yi; Xu, Yijun; Chen, Aihua; Yin, Yanru

    2014-01-01

    Intrahepatic cholestasis of pregnancy is always accompanied by adverse fetal outcomes such as malfunctions of respiration. Farnesoid X receptor (FXR) plays a critical role in the homeostasis of bile acids. Thus, we are determined to explore the effects of farnesoid X receptor (FXR) and five bile acids on respiratory rhythm generation and modulation of neonatal rats. Spontaneous periodic respiratory-related rhythmical discharge activity (RRDA) was recorded from hypoglossal nerves during the perfusion of modified Krebs solution. Group 1-6 was each given GW4064 and five bile acids of chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), cholic acid (CA) as well as ursodeoxycholic acid (UDCA) at different concentrations to identify their specific functions on respiratory rhythm modulations. Group 7 was applied to receive FXR blocker Z-guggulsterone and Z-guggulsterone with the above bile acids separately to explore the role of FXR in the respiratory rhythm modulation. Group 8 was given dimethyl sulfoxide (DMSO) as controls. Apart from UDCA, CDCA, DCA LCA and CA all exerted effects on RRDA recorded from hypoglossal nerves in a concentration-dependent manner. Respiratory cycle (RC), Inspiratory time (TI), Expiratory Time (TE) and Integral Amplitude (IA) were influenced and such effects could be reversed by Z-guggulsterone. FXR may contribute to the effects on the modulation of respiratory rhythm exerted by bile acids.

  11. Are Transition Periods the Optimal Time for Acceleration? The Training of a First Order Conservation in Young Children.

    ERIC Educational Resources Information Center

    Biskin, Donald S.; Rice, Deborah

    The effectiveness of acceleration training with children who were in a transition period was examined. Forty-eight kindergarten children were separated into four groups on the basis of their status (Preoperational vs. Transitional) and whether or not they received three sessions of inversion-negation training. The results of the immediate and…

  12. Pyrazinamide Induced Rat Cholestatic Liver Injury through Inhibition of FXR Regulatory Effect on Bile Acid Synthesis and Transport.

    PubMed

    Guo, Hong-Li; Hassan, Hozeifa M; Zhang, Yun; Dong, Si-Zhe; Ding, Ping-Ping; Wang, Tao; Sun, Li-Xin; Zhang, Lu-Yong; Jiang, Zhen-Zhou

    2016-08-01

    Pyrazinamide (PZA) is an indispensable first-line drug used for the treatment of tuberculosis which may cause serious hepatotoxicity; however, the mechanisms underlying these toxicities are poorly understood. Cholestasis plays an important role in drug-induced liver injury. Since there were no previous published works reported cholestasis and PZA hepatotoxicity relationship, this study aimed to identify whether PZA can induce liver injury with characterized evidences of cholestasis and to clarify expression changes of proteins related to both bile acid synthesis and transport in PZA-induced liver injury. PZA (2 g/kg) was administered for 7 consecutive days by oral gavage. Results showed there were 2-fold elevation in both ALT and AST serum levels in PZA-treated rats. In addition, a 10-fold increment in serum total bile acid was observed after PZA administration. The mRNA and protein expressions of bile acid synthesis and transport parameters were markedly altered, in which FXR, Bsep, Mrp2, Mdr2, Ostα/β, Oatp1a1, Oatp1b2, and Cyp8b1 were decreased (P < .05), while Mrp3, Ntcp, Oatp1a4, and Cyp7a1 were increased (P < .05). Moreover, treatment with the FXR agonist obeticholic acid (OCA) generated obvious reductions in serum ALT, AST, and TBA levels in PZA-treated rats. Those effects were due to transcriptional regulation of pre-mentioned target genes by OCA. Taken together, these results suggested that PZA-induced cholestatic liver injury was related to FXR inhibition, leading to the dysfunction in bile acid synthesis and transport. PMID:27255380

  13. Optimal Model-Based Fault Estimation and Correction for Particle Accelerators and Industrial Plants Using Combined Support Vector Machines and First Principles Models

    SciTech Connect

    Sayyar-Rodsari, Bijan; Schweiger, Carl; /SLAC /Pavilion Technologies, Inc., Austin, TX

    2010-08-25

    parameters of the beam lifetime model) are physically meaningful. (3) Numerical Efficiency of the Training - We investigated the numerical efficiency of the SVM training. More specifically, for the primal formulation of the training, we have developed a problem formulation that avoids the linear increase in the number of the constraints as a function of the number of data points. (4) Flexibility of Software Architecture - The software framework for the training of the support vector machines was designed to enable experimentation with different solvers. We experimented with two commonly used nonlinear solvers for our simulations. The primary application of interest for this project has been the sustained optimal operation of particle accelerators at the Stanford Linear Accelerator Center (SLAC). Particle storage rings are used for a variety of applications ranging from 'colliding beam' systems for high-energy physics research to highly collimated x-ray generators for synchrotron radiation science. Linear accelerators are also used for collider research such as International Linear Collider (ILC), as well as for free electron lasers, such as the Linear Coherent Light Source (LCLS) at SLAC. One common theme in the operation of storage rings and linear accelerators is the need to precisely control the particle beams over long periods of time with minimum beam loss and stable, yet challenging, beam parameters. We strongly believe that beyond applications in particle accelerators, the high fidelity and cost benefits of a combined model-based fault estimation/correction system will attract customers from a wide variety of commercial and scientific industries. Even though the acquisition of Pavilion Technologies, Inc. by Rockwell Automation Inc. in 2007 has altered the small business status of the Pavilion and it no longer qualifies for a Phase II funding, our findings in the course of the Phase I research have convinced us that further research will render a workable model

  14. Laser-assisted skin closure (LASC) using a 815-nm diode laser system: determination of an optimal dose to accelerate wound healing

    NASA Astrophysics Data System (ADS)

    Capon, Alexandre; Mitchell, Valerie A.; Sumian, Chryslain C.; Gauthier, Beatrice; Mordon, Serge R.

    1999-01-01

    This study aimed to evaluate a 815 nm diode-laser system to assist wound closure. It was proposed to determine an optimal fluence being able to accelerate and improve heating process without thermal damage after laser irradiation. Male hairless rats with dorsal skin incisions were used for the study. Different fluences were screened (76 to 346 J/cm2) in a first phase with clinical examination at 3, 7, 15 and 21 days after surgery. Best results were obtained for a fluence of 145 J/cm2 and 3 sec time of exposure. A second phase was conducted to valid these parameters with histological study and determination of tensile strength at 3, 7, 15 and 21 days after surgery. LASC was 4 times faster to process than conventional suture. In the laser group with an optimal fluence of 145 J/cm2, healing was accelerated. The resulting scar was more indiscernible than in the control groups. Histological aspect was better with continuous epidermis and dermis at 3 days in most cases. Tensile strength was 30 to 58% greater than in control groups (1141 g/cm2 at 7 days in the laser group versus 856 g/cm2 and 724 g/cm2 in the control groups, p < 0.001).

  15. A novel role for the RNA-binding protein FXR1P in myoblasts cell-cycle progression by modulating p21/Cdkn1a/Cip1/Waf1 mRNA stability.

    PubMed

    Davidovic, Laetitia; Durand, Nelly; Khalfallah, Olfa; Tabet, Ricardo; Barbry, Pascal; Mari, Bernard; Sacconi, Sabrina; Moine, Hervé; Bardoni, Barbara

    2013-03-01

    The Fragile X-Related 1 gene (FXR1) is a paralog of the Fragile X Mental Retardation 1 gene (FMR1), whose absence causes the Fragile X syndrome, the most common form of inherited intellectual disability. FXR1P plays an important role in normal muscle development, and its absence causes muscular abnormalities in mice, frog, and zebrafish. Seven alternatively spliced FXR1 transcripts have been identified and two of them are skeletal muscle-specific. A reduction of these isoforms is found in myoblasts from Facio-Scapulo Humeral Dystrophy (FSHD) patients. FXR1P is an RNA-binding protein involved in translational control; however, so far, no mRNA target of FXR1P has been linked to the drastic muscular phenotypes caused by its absence. In this study, gene expression profiling of C2C12 myoblasts reveals that transcripts involved in cell cycle and muscular development pathways are modulated by Fxr1-depletion. We observed an increase of p21--a regulator of cell-cycle progression--in Fxr1-knocked-down mouse C2C12 and FSHD human myoblasts. Rescue of this molecular phenotype is possible by re-expressing human FXR1P in Fxr1-depleted C2C12 cells. FXR1P muscle-specific isoforms bind p21 mRNA via direct interaction with a conserved G-quadruplex located in its 3' untranslated region. The FXR1P/G-quadruplex complex reduces the half-life of p21 mRNA. In the absence of FXR1P, the upregulation of p21 mRNA determines the elevated level of its protein product that affects cell-cycle progression inducing a premature cell-cycle exit and generating a pool of cells blocked at G0. Our study describes a novel role of FXR1P that has crucial implications for the understanding of its role during myogenesis and muscle development, since we show here that in its absence a reduced number of myoblasts will be available for muscle formation/regeneration, shedding new light into the pathophysiology of FSHD.

  16. Curcumin protects ANIT-induced cholestasis through signaling pathway of FXR-regulated bile acid and inflammation.

    PubMed

    Yang, Fan; Tang, Xiaowen; Ding, Lili; Zhou, Yue; Yang, Qiaoling; Gong, Junting; Wang, Guangyun; Wang, Zhengtao; Yang, Li

    2016-01-01

    Cholestasis is a clinically significant symptom and widely associated with liver diseases, however, there are very few effective therapies for cholestasis. Danning tablet (DNT, a Chinese patent medicine preparation) has been clinically used to treat human liver and gallbladder diseases for more than 20 years in China. However, which ingredients of DNT contributed to this beneficial effect and their mechanistic underpinnings have been largely unknown. In the present study, we discovered that DNT not only demonstrated greater benefits for cholecystitis patients after cholecystectomy surgery in clinic but also showed protective effect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis model in rodent. Curcumin, one major compound derived from DNT, exerted the protective effect against cholestasis through farnesoid X receptor (FXR), which has been focused as potential therapeutic targets for treating cholestasis. The underlying mechanism of curcumin against cholestasis was restoring bile acid homeostasis and antagonizing inflammatory responses in a FXR-dependent manner and in turn contributed to overall cholestasis attenuation. Collectively, curcumin can be served as a potential treatment option for liver injury with cholestasis. PMID:27624003

  17. A Specialized Mechanism of Translation Mediated by FXR1a-Associated MicroRNP in Cellular Quiescence.

    PubMed

    Bukhari, Syed I A; Truesdell, Samuel S; Lee, Sooncheol; Kollu, Swapna; Classon, Anthony; Boukhali, Myriam; Jain, Esha; Mortensen, Richard D; Yanagiya, Akiko; Sadreyev, Ruslan I; Haas, Wilhelm; Vasudevan, Shobha

    2016-03-01

    MicroRNAs predominantly decrease gene expression; however, specific mRNAs are translationally upregulated in quiescent (G0) mammalian cells and immature Xenopus laevis oocytes by an FXR1a-associated microRNA-protein complex (microRNP) that lacks the microRNP repressor, GW182. Their mechanism in these conditions of decreased mTOR signaling, and therefore reduced canonical (cap-and-poly(A)-tail-mediated) translation, remains undiscovered. Our data reveal that mTOR inhibition in human THP1 cells enables microRNA-mediated activation. Activation requires shortened/no poly(A)-tail targets; polyadenylated mRNAs are partially activated upon PAIP2 overexpression, which interferes with poly(A)-bound PABP, precluding PABP-enhanced microRNA-mediated inhibition and canonical translation. Consistently, inhibition of PARN deadenylase prevents activation. P97/DAP5, a homolog of canonical translation factor, eIF4G, which lacks PABP- and cap binding complex-interacting domains, is required for activation, and thereby for the oocyte immature state. P97 interacts with 3' UTR-binding FXR1a-associated microRNPs and with PARN, which binds mRNA 5' caps, forming a specialized complex to translate recruited mRNAs in these altered canonical translation conditions.

  18. FXR Agonist INT-747 Upregulates DDAH Expression and Enhances Insulin Sensitivity in High-Salt Fed Dahl Rats

    PubMed Central

    Ghebremariam, Yohannes T.; Yamada, Keisuke; Lee, Jerry C.; Johnson, Christine L. C.; Atzler, Dorothee; Anderssohn, Maike; Agrawal, Rani; Higgins, John P.; Patterson, Andrew J.; Böger, Rainer H.; Cooke, John P

    2013-01-01

    Aims Genetic and pharmacological studies have shown that impairment of the nitric oxide (NO) synthase (NOS) pathway is associated with hypertension and insulin-resistance (IR). In addition, inhibition of NOS by the endogenous inhibitor, asymmetric dimethylarginine (ADMA), may also result in hypertension and IR. On the other hand, overexpression of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes ADMA, in mice is associated with lower ADMA, increased NO and enhanced insulin sensitivity. Since DDAH carries a farnesoid X receptor (FXR)-responsive element, we aimed to upregulate its expression by an FXR-agonist, INT-747, and evaluate its effect on blood pressure and insulin sensitivity. Methods and Results In this study, we evaluated the in vivo effect of INT-747 on tissue DDAH expression and insulin sensitivity in the Dahl rat model of salt-sensitive hypertension and IR (Dahl-SS). Our data indicates that high salt (HS) diet significantly increased systemic blood pressure. In addition, HS diet downregulated tissue DDAH expression while INT-747 protected the loss in DDAH expression and enhanced insulin sensitivity compared to vehicle controls. Conclusion Our study may provide the basis for a new therapeutic approach for IR by modulating DDAH expression and/or activity using small molecules. PMID:23593273

  19. Curcumin protects ANIT-induced cholestasis through signaling pathway of FXR-regulated bile acid and inflammation

    PubMed Central

    Yang, Fan; Tang, Xiaowen; Ding, Lili; zhou, Yue; Yang, Qiaoling; Gong, Junting; Wang, Guangyun; Wang, Zhengtao; Yang, Li

    2016-01-01

    Cholestasis is a clinically significant symptom and widely associated with liver diseases, however, there are very few effective therapies for cholestasis. Danning tablet (DNT, a Chinese patent medicine preparation) has been clinically used to treat human liver and gallbladder diseases for more than 20 years in China. However, which ingredients of DNT contributed to this beneficial effect and their mechanistic underpinnings have been largely unknown. In the present study, we discovered that DNT not only demonstrated greater benefits for cholecystitis patients after cholecystectomy surgery in clinic but also showed protective effect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis model in rodent. Curcumin, one major compound derived from DNT, exerted the protective effect against cholestasis through farnesoid X receptor (FXR), which has been focused as potential therapeutic targets for treating cholestasis. The underlying mechanism of curcumin against cholestasis was restoring bile acid homeostasis and antagonizing inflammatory responses in a FXR-dependent manner and in turn contributed to overall cholestasis attenuation. Collectively, curcumin can be served as a potential treatment option for liver injury with cholestasis. PMID:27624003

  20. Optimism

    PubMed Central

    Carver, Charles S.; Scheier, Michael F.; Segerstrom, Suzanne C.

    2010-01-01

    Optimism is an individual difference variable that reflects the extent to which people hold generalized favorable expectancies for their future. Higher levels of optimism have been related prospectively to better subjective well-being in times of adversity or difficulty (i.e., controlling for previous well-being). Consistent with such findings, optimism has been linked to higher levels of engagement coping and lower levels of avoidance, or disengagement, coping. There is evidence that optimism is associated with taking proactive steps to protect one's health, whereas pessimism is associated with health-damaging behaviors. Consistent with such findings, optimism is also related to indicators of better physical health. The energetic, task-focused approach that optimists take to goals also relates to benefits in the socioeconomic world. Some evidence suggests that optimism relates to more persistence in educational efforts and to higher later income. Optimists also appear to fare better than pessimists in relationships. Although there are instances in which optimism fails to convey an advantage, and instances in which it may convey a disadvantage, those instances are relatively rare. In sum, the behavioral patterns of optimists appear to provide models of living for others to learn from. PMID:20170998

  1. FXR agonists enhance the sensitivity of biliary tract cancer cells to cisplatin via SHP dependent inhibition of Bcl-xL expression

    PubMed Central

    Wang, Wei; Zhan, Ming; Li, Qi; Chen, Wei; Chu, Huiling; Huang, Qihong; Hou, Zhaoyuan; Man, Mohan; Wang, Jian

    2016-01-01

    Chemoresistance is common in patients with biliary tract cancer (BTC) including gallbladder cancer (GBC) and cholangiocarcinoma (CC). Therefore, it is necessary to identify effective chemotherapeutic agents for BTC. In the present study, we for the first time tested the effect of farnesoid X receptor (FXR) agonists GW4064 and CDCA (chenodeoxycholic acid) in combination with cisplatin (CDDP) on increasing the chemosensitivity in BTC. Our results show that co-treatment of CDDP with FXR agonists remarkably enhance chemosensitivity of BTC cells. Mechanistically, we found that activation of FXR induced expression of small heterodimer partner (SHP), which in turn inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation and resulted in down-regulation of Bcl-xL expression in BTC cells, leading to increased susceptibility to CDDP. Moreover, the experiments on tumor-bearing mice showed that GW4064/CDDP co-treatment inhibited the tumor growth in vivo by up-regulating SHP expression and down-regulating STAT3 phosphorylation. These results suggest CDDP in combination with FXR agonists could be a potential new therapeutic strategy for BTC. PMID:27127878

  2. FXR1P limits long-term memory, long-lasting synaptic potentiation, and de novo GluA2 translation.

    PubMed

    Cook, Denise; Nuro, Erin; Jones, Emma V; Altimimi, Haider F; Farmer, W Todd; Gandin, Valentina; Hanna, Edith; Zong, Ruiting; Barbon, Alessandro; Nelson, David L; Topisirovic, Ivan; Rochford, Joseph; Stellwagen, David; Béïque, Jean-Claude; Murai, Keith K

    2014-11-20

    Translational control of mRNAs allows for rapid and selective changes in synaptic protein expression that are required for long-lasting plasticity and memory formation in the brain. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein that controls mRNA translation in nonneuronal cells and colocalizes with translational machinery in neurons. However, its neuronal mRNA targets and role in the brain are unknown. Here, we demonstrate that removal of FXR1P from the forebrain of postnatal mice selectively enhances long-term storage of spatial memories, hippocampal late-phase long-term potentiation (L-LTP), and de novo GluA2 synthesis. Furthermore, FXR1P binds specifically to the 5' UTR of GluA2 mRNA to repress translation and limit the amount of GluA2 that is incorporated at potentiated synapses. This study uncovers a mechanism for regulating long-lasting synaptic plasticity and spatial memory formation and reveals an unexpected divergent role of FXR1P among Fragile X proteins in brain plasticity.

  3. Optimization-driven identification of genetic perturbations accelerates the convergence of model parameters in ensemble modeling of metabolic networks.

    PubMed

    Zomorrodi, Ali R; Lafontaine Rivera, Jimmy G; Liao, James C; Maranas, Costas D

    2013-09-01

    The ensemble modeling (EM) approach has shown promise in capturing kinetic and regulatory effects in the modeling of metabolic networks. Efficacy of the EM procedure relies on the identification of model parameterizations that adequately describe all observed metabolic phenotypes upon perturbation. In this study, we propose an optimization-based algorithm for the systematic identification of genetic/enzyme perturbations to maximally reduce the number of models retained in the ensemble after each round of model screening. The key premise here is to design perturbations that will maximally scatter the predicted steady-state fluxes over the ensemble parameterizations. We demonstrate the applicability of this procedure for an Escherichia coli metabolic model of central metabolism by successively identifying single, double, and triple enzyme perturbations that cause the maximum degree of flux separation between models in the ensemble. Results revealed that optimal perturbations are not always located close to reaction(s) whose fluxes are measured, especially when multiple perturbations are considered. In addition, there appears to be a maximum number of simultaneous perturbations beyond which no appreciable increase in the divergence of flux predictions is achieved. Overall, this study provides a systematic way of optimally designing genetic perturbations for populating the ensemble of models with relevant model parameterizations.

  4. Linear Accelerators

    SciTech Connect

    Sidorin, Anatoly

    2010-01-05

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  5. Factors Associated With Optimal Long-Term Cosmetic Results in Patients Treated With Accelerated Partial Breast Irradiation Using Balloon-Based Brachytherapy

    SciTech Connect

    Vicini, Frank A.; Keisch, Martin; Shah, Chirag; Goyal, Sharad; Khan, Atif J.; Beitsch, Peter D.; Lyden, Maureen; Haffty, Bruce G.

    2012-06-01

    Purpose: To evaluate factors associated with optimal cosmetic results at 72 months for early-stage breast cancer patients treated with Mammosite balloon-based accelerated partial breast irradiation (APBI). Methods and Materials: A total of 1,440 patients (1,449 cases) with early-stage breast cancer undergoing breast-conserving therapy were treated with balloon-based brachytherapy to deliver APBI (34 Gy in 3.4-Gy fractions). Cosmetic outcome was evaluated at each follow-up visit and dichotomized as excellent/good (E/G) or fair/poor (F/P). Follow-up was evaluated at 36 and 72 months to establish long-term cosmesis, stability of cosmesis, and factors associated with optimal results. Results: The percentage of evaluable patients with excellent/good (E/G) cosmetic results at 36 months and more than 72 months were 93.3% (n = 708/759) and 90.4% (n = 235/260). Factors associated with optimal cosmetic results at 72 months included: larger skin spacing (p = 0.04) and T1 tumors (p = 0.02). Using multiple regression analysis, the only factors predictive of worse cosmetic outcome at 72 months were smaller skin spacing (odds ratio [OR], 0.89; confidence interval [CI], 0.80-0.99) and tumors greater than 2 cm (OR, 4.96, CI, 1.53-16.07). In all, 227 patients had both a 36-month and a 72-month cosmetic evaluation. The number of patients with E/G cosmetic results decreased only slightly from 93.4% at 3 years to 90.8% (p = 0.13) at 6 years, respectively. Conclusions: APBI delivered with balloon-based brachytherapy produced E/G cosmetic results in 90.4% of cases at 6 years. Larger tumors (T2) and smaller skin spacing were found to be the two most important independent predictors of cosmesis.

  6. 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.

  7. Can Accelerators Accelerate Learning?

    SciTech Connect

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-10

    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.

  8. Optimization and validation of an accelerated laboratory extraction method to estimate nitrogen release patterns of slow- and controlled-release fertilizers.

    PubMed

    Medina, L Carolina; Sartain, Jerry B; Obreza, Thomas A; Hall, William L; Thiex, Nancy J

    2014-01-01

    Several technologies have been proposed to characterize the nutrient release and availability patterns of enhanced-efficiency fertilizers (EEFs), especially slow-release fertilizers (SRFs) and controlled-release fertilizers (CRFs) during the last few decades. These technologies have been developed mainly by manufacturers and are product-specific based on the regulation and analysis of each EEF product. Despite previous efforts to characterize EEF materials, no validated method exists to assess their nutrient release patterns. However, the increased use of EEFs in specialty and nonspecialty markets requires an appropriate method to verify nutrient claims and material performance. A series of experiments were conducted to evaluate the effect of temperature, fertilizer test portion size, and extraction time on the performance of a 74 h accelerated laboratory extraction method to measure SRF and CRF nutrient release profiles. Temperature was the only factor that influenced nutrient release rate, with a highly marked effect for phosphorus and to a lesser extent for nitrogen (N) and potassium. Based on the results, the optimal extraction temperature set was: Extraction No. 1-2:00 h at 25 degrees C; Extraction No. 2-2:00 h at 50 degrees C; Extraction No. 3-20:00 h at 55 degrees C; and Extraction No. 4-50:00 h at 60 degrees C. Ruggedness of the method was tested by evaluating the effect of small changes in seven selected factors on method behavior using a fractional multifactorial design. Overall, the method showed ruggedness for measuring N release rates of coated CRFs.

  9. The Gut Microbiota as a Therapeutic Target in IBD and Metabolic Disease: A Role for the Bile Acid Receptors FXR and TGR5

    PubMed Central

    Baars, Annemarie; Oosting, Annemarie; Knol, Jan; Garssen, Johan; van Bergenhenegouwen, Jeroen

    2015-01-01

    The gut microbiota plays a crucial role in regulating many physiological systems of the host, including the metabolic and immune system. Disturbances in microbiota composition are increasingly correlated with disease; however, the underlying mechanisms are not well understood. Recent evidence suggests that changes in microbiota composition directly affect the metabolism of bile salts. Next to their role in digestion of dietary fats, bile salts function as signaling molecules for bile salt receptors such as Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor (TGR5). Complementary to their role in metabolism, FXR and TGR5 are shown to play a role in intestinal homeostasis and immune regulation. This review presents an overview of evidence showing that changes in bile salt pool and composition due to changes in gut microbial composition contribute to the pathogenesis of inflammatory bowel disease and metabolic disease, possibly through altered activation of TGR5 and FXR. We further discuss how dietary interventions, such as pro- and synbiotics, may be used to treat metabolic disease and inflammatory bowel disease (IBD) through normalization of bile acid dysregulation directly or indirectly through normalization of the intestinal microbiota.

  10. Lowering bile acid pool size with a synthetic farnesoid X receptor (FXR) agonist induces obesity and diabetes through reduced energy expenditure.

    PubMed

    Watanabe, Mitsuhiro; Horai, Yasushi; Houten, Sander M; Morimoto, Kohkichi; Sugizaki, Taichi; Arita, Eri; Mataki, Chikage; Sato, Hiroyuki; Tanigawara, Yusuke; Schoonjans, Kristina; Itoh, Hiroshi; Auwerx, Johan

    2011-07-29

    We evaluated the metabolic impact of farnesoid X receptor (FXR) activation by administering a synthetic FXR agonist (GW4064) to mice in which obesity was induced by a high fat diet. Administration of GW4064 accentuated body weight gain and glucose intolerance induced by the high fat diet and led to a pronounced worsening of the changes in liver and adipose tissue. Mechanistically, treatment with GW4064 decreased bile acid (BA) biosynthesis, BA pool size, and energy expenditure, whereas reconstitution of the BA pool in these GW4064-treated animals by BA administration dose-dependently reverted the metabolic abnormalities. Our data therefore suggest that activation of FXR with synthetic agonists is not useful for long term management of the metabolic syndrome, as it reduces the BA pool size and subsequently decreases energy expenditure, translating as weight gain and insulin resistance. In contrast, expansion of the BA pool size, which can be achieved by BA administration, could be an interesting strategy to manage the metabolic syndrome.

  11. The Gut Microbiota as a Therapeutic Target in IBD and Metabolic Disease: A Role for the Bile Acid Receptors FXR and TGR5

    PubMed Central

    Baars, Annemarie; Oosting, Annemarie; Knol, Jan; Garssen, Johan; van Bergenhenegouwen, Jeroen

    2015-01-01

    The gut microbiota plays a crucial role in regulating many physiological systems of the host, including the metabolic and immune system. Disturbances in microbiota composition are increasingly correlated with disease; however, the underlying mechanisms are not well understood. Recent evidence suggests that changes in microbiota composition directly affect the metabolism of bile salts. Next to their role in digestion of dietary fats, bile salts function as signaling molecules for bile salt receptors such as Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor (TGR5). Complementary to their role in metabolism, FXR and TGR5 are shown to play a role in intestinal homeostasis and immune regulation. This review presents an overview of evidence showing that changes in bile salt pool and composition due to changes in gut microbial composition contribute to the pathogenesis of inflammatory bowel disease and metabolic disease, possibly through altered activation of TGR5 and FXR. We further discuss how dietary interventions, such as pro- and synbiotics, may be used to treat metabolic disease and inflammatory bowel disease (IBD) through normalization of bile acid dysregulation directly or indirectly through normalization of the intestinal microbiota. PMID:27682110

  12. Optimal moderator materials at various proton energies considering photon dose rate after irradiation for an accelerator-driven ⁹Be(p, n) boron neutron capture therapy neutron source.

    PubMed

    Hashimoto, Y; Hiraga, F; Kiyanagi, Y

    2015-12-01

    We evaluated the accelerator beam power and the neutron-induced radioactivity of (9)Be(p, n) boron neutron capture therapy (BNCT) neutron sources having a MgF2, CaF2, or AlF3 moderator and driven by protons with energy from 8 MeV to 30 MeV. The optimal moderator materials were found to be MgF2 for proton energies less than 10 MeV because of lower required accelerator beam power and CaF2 for higher proton energies because of lower photon dose rate at the treatment position after neutron irradiation. PMID:26272165

  13. Optimal moderator materials at various proton energies considering photon dose rate after irradiation for an accelerator-driven ⁹Be(p, n) boron neutron capture therapy neutron source.

    PubMed

    Hashimoto, Y; Hiraga, F; Kiyanagi, Y

    2015-12-01

    We evaluated the accelerator beam power and the neutron-induced radioactivity of (9)Be(p, n) boron neutron capture therapy (BNCT) neutron sources having a MgF2, CaF2, or AlF3 moderator and driven by protons with energy from 8 MeV to 30 MeV. The optimal moderator materials were found to be MgF2 for proton energies less than 10 MeV because of lower required accelerator beam power and CaF2 for higher proton energies because of lower photon dose rate at the treatment position after neutron irradiation.

  14. Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis

    SciTech Connect

    Meng, Qiang; Chen, Xin-li; Wang, Chang-yuan; Liu, Qi; Sun, Hui-jun; Sun, Peng-yuan; Huo, Xiao-kui; Liu, Zhi-hao; Yao, Ji-hong; Liu, Ke-xin

    2015-03-15

    Intrahepatic cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Appropriate regulation of bile acids in hepatocytes is critically important for protection against liver injury. In the present study, we characterized the protective effect of alisol B 23-acetate (AB23A), a natural triterpenoid, on alpha-naphthylisothiocyanate (ANIT)-induced liver injury and intrahepatic cholestasis in mice and further elucidated the mechanisms in vivo and in vitro. AB23A treatment dose-dependently protected against liver injury induced by ANIT through reducing hepatic uptake and increasing efflux of bile acid via down-regulation of hepatic uptake transporters (Ntcp) and up-regulation of efflux transporter (Bsep, Mrp2 and Mdr2) expression. Furthermore, AB23A reduced bile acid synthesis through repressing Cyp7a1 and Cyp8b1, increased bile acid conjugation through inducing Bal, Baat and bile acid metabolism through an induction in gene expression of Sult2a1. We further demonstrate the involvement of farnesoid X receptor (FXR) in the hepatoprotective effect of AB23A. The changes in transporters and enzymes, as well as ameliorative liver histology in AB23A-treated mice were abrogated by FXR antagonist guggulsterone in vivo. In vitro evidences also directly demonstrated the effect of AB23A on FXR activation in a dose-dependent manner using luciferase reporter assay in HepG2 cells. In conclusion, AB23A produces protective effect against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes. - Highlights: • AB23A has at least three roles in protection against ANIT-induced liver injury. • AB23A decreases Ntcp, and increases Bsep, Mrp2 and Mdr2 expression. • AB23A represses Cyp7a1 and Cyp8b1 through inducing Shp and Fgf15 expression. • AB23A increases bile acid metabolism through inducing Sult2a1 expression. • FXR activation is involved

  15. Optimization and validation of an accelerated laboratory extraction method to estimate nitrogen release patterns of slow- and controlled-release fertilizers.

    PubMed

    Medina, L Carolina; Sartain, Jerry B; Obreza, Thomas A; Hall, William L; Thiex, Nancy J

    2014-01-01

    Several technologies have been proposed to characterize the nutrient release and availability patterns of enhanced-efficiency fertilizers (EEFs), especially slow-release fertilizers (SRFs) and controlled-release fertilizers (CRFs) during the last few decades. These technologies have been developed mainly by manufacturers and are product-specific based on the regulation and analysis of each EEF product. Despite previous efforts to characterize EEF materials, no validated method exists to assess their nutrient release patterns. However, the increased use of EEFs in specialty and nonspecialty markets requires an appropriate method to verify nutrient claims and material performance. A series of experiments were conducted to evaluate the effect of temperature, fertilizer test portion size, and extraction time on the performance of a 74 h accelerated laboratory extraction method to measure SRF and CRF nutrient release profiles. Temperature was the only factor that influenced nutrient release rate, with a highly marked effect for phosphorus and to a lesser extent for nitrogen (N) and potassium. Based on the results, the optimal extraction temperature set was: Extraction No. 1-2:00 h at 25 degrees C; Extraction No. 2-2:00 h at 50 degrees C; Extraction No. 3-20:00 h at 55 degrees C; and Extraction No. 4-50:00 h at 60 degrees C. Ruggedness of the method was tested by evaluating the effect of small changes in seven selected factors on method behavior using a fractional multifactorial design. Overall, the method showed ruggedness for measuring N release rates of coated CRFs. PMID:25051611

  16. Breakthrough: Fermilab Accelerator Technology

    ScienceCinema

    None

    2016-07-12

    There are more than 30,000 particle accelerators in operation around the world. At Fermilab, scientists are collaborating with other laboratories and industry to optimize the manufacturing processes for a new type of powerful accelerator that uses superconducting niobium cavities. Experimenting with unique polishing materials, a Fermilab team has now developed an efficient and environmentally friendly way of creating cavities that can propel particles with more than 30 million volts per meter.

  17. 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.

  18. FXR-induced lysine-specific histone demethylase, LSD1, reduces hepatic bile acid levels and protects the liver against bile acid toxicity

    PubMed Central

    Kim, Young-Chae; Fang, Sungsoon; Byun, Sangwon; Seok, Sunmi; Kemper, Byron; Kemper, Jongsook Kim

    2015-01-01

    Bile acids (BAs) function as endocrine signaling molecules that activate multiple nuclear and membrane receptor signaling pathways to control fed-state metabolism. Since the detergent-like property of BAs causes liver damage at high concentrations, hepatic BA levels must be tightly regulated. BA homeostasis is regulated largely at the level of transcription by nuclear receptors, particularly the primary bile acid receptor, farnesoid X receptor (FXR), and small heterodimer partner (SHP) that inhibits BA synthesis by recruiting repressive histone-modifying enzymes. Although histone modifiers have been shown to regulate BA-responsive genes, their in vivo functions remain unclear. Here we show that lysine-specific histone demethylase1 (LSD1) is directly induced by BA-activated FXR, is recruited to BA synthetic genes, Cyp7a1 and Cyp8b1, and the BA uptake transporter gene, Ntcp, and removes a gene-activation mark, tri-methylated histone H3 lysine-4, leading to gene repression. LSD1 recruitment was dependent on SHP, and LSD1-mediated demethylation of H3K4-me3 was required for additional repressive histone modifications, H3K9/K14 deacetylation and H3K9 methylation. BA overload, feeding 0.5% cholic acid chow for 6 days, resulted in adaptive responses of altered expression of hepatic genes involved in BA synthesis, transport, and detoxification/conjugation. In contrast, adenoviral-mediated downregulation of hepatic LSD1 blunted these responses, which led to substantial increases in liver and serum BA levels, serum AST/ALT levels, and hepatic inflammation. This study identifies LSD1 as a novel histone-modifying enzyme in the orchestrated regulation mediated by the FXR and SHP that reduces hepatic BA levels and protects the liver against BA toxicity. PMID:25545350

  19. Research on computed tomography reconstructions from one or two radiographs: A report and the application to FXR radiography

    SciTech Connect

    Back, N.; Schneberk, D.; McMillan, C.; Azevedo, S.; Gorvad, M.

    1995-01-26

    This report documents some cooperative research into volumetric image reconstruction from single radiographs. Imaging dynamic events is the most important application for this type of work, but the techniques have possible extensions. Two general objectives guide this work. The first objective is to gain an understanding of the assumptions and limitations of single-view methods for representing internal features. Second, we endeavor to obtain and/or develop techniques for performing image reconstructions with FXR radiographs. If possible, we seek to obtain some quantitative measure of the accuracy of this class of image reconstructions in two respects: (i) in terms of the dimensional accuracy of feature boundaries, and (ii) as pertains to the accuracy of the voxel intensities. Dynamic events are not always self-calibrating, and it is important to establish the reconstruction accuracy of single-view methods for placing bounds on the kinds of conclusions which can be advanced from single-view reconstructed images. Computed tomographic image reconstructions provide dimensional detail of internal structures of objects and provide a measure of the per-voxel attenuation of material in the object. When assumptions behind a reconstruction algorithm are not satisfied, or are satisfied in a limited way, the accuracy of the reconstructed image is compromised. It is the goal of Cr analysis to discern the {open_quotes}real{close_quotes} features of the internals of an object in the midst of a certain level of artifactual content in the image. By understanding the ways in which CT reconstructions from a single radiograph can produce misleading results we hope to develop some measure of the benefits and limitations of single view techniques. 31 refs., 20 figs.

  20. 'Light Sail' Acceleration Reexamined

    SciTech Connect

    Macchi, Andrea; Veghini, Silvia; Pegoraro, Francesco

    2009-08-21

    The dynamics of the acceleration of ultrathin foil targets by the radiation pressure of superintense, circularly polarized laser pulses is investigated by analytical modeling and particle-in-cell simulations. By addressing self-induced transparency and charge separation effects, it is shown that for 'optimal' values of the foil thickness only a thin layer at the rear side is accelerated by radiation pressure. The simple 'light sail' model gives a good estimate of the energy per nucleon, but overestimates the conversion efficiency of laser energy into monoenergetic ions.

  1. Muon Acceleration - RLA and FFAG

    SciTech Connect

    Bogacz, Alex

    2011-10-01

    Various acceleration schemes for muons are presented. The overall goal of the acceleration systems: large acceptance acceleration to 25 GeV and 'beam shaping' can be accomplished by various fixed field accelerators at different stages. They involve three superconducting linacs: a single pass linear Pre-accelerator followed by a pair of multi-pass Recirculating Linear Accelerators (RLA) and finally a non-scaling FFAG ring. The present baseline acceleration scenario has been optimized to take maximum advantage of appropriate acceleration scheme at a given stage. The solenoid based Pre-accelerator offers very large acceptance and facilitates correction of energy gain across the bunch and significant longitudinal compression trough induced synchrotron motion. However, far off-crest acceleration reduces the effective acceleration gradient and adds complexity through the requirement of individual RF phase control for each cavity. The RLAs offer very efficient usage of high gradient superconducting RF and ability to adjust path-length after each linac pass through individual return arcs with uniformly periodic FODO optics suitable for chromatic compensation of emittance dilution with sextupoles. However, they require spreaders/recombiners switchyards at both linac ends and significant total length of the arcs. The non-scaling Fixed Field Alternating Gradient (FFAG) ring combines compactness with very large chromatic acceptance (twice the injection energy) and it allows for large number of passes through the RF (at least eight, possibly as high as 15).

  2. Wakefield accelerators

    SciTech Connect

    Simpson, J.D.

    1990-01-01

    The search for new methods to accelerate particle beams to high energy using high gradients has resulted in a number of candidate schemes. One of these, wakefield acceleration, has been the subject of considerable R D in recent years. This effort has resulted in successful proof of principle experiments and in increased understanding of many of the practical aspects of the technique. Some wakefield basics plus the status of existing and proposed experimental work is discussed, along with speculations on the future of wake field acceleration. 10 refs., 6 figs.

  3. 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.

  4. Optimization of an accelerated solvent extraction dispersive liquid-liquid microextraction method for the separation and determination of essential oil from Ligusticum chuanxiong Hort by gas chromatography with mass spectrometry.

    PubMed

    Yang, Guang; Sun, Qiushi; Hu, Zhiyan; Liu, Hua; Zhou, Tingting; Fan, Guorong

    2015-10-01

    In this study, an accelerated solvent extraction dispersive liquid-liquid microextraction coupled with gas chromatography and mass spectrometry was established and employed for the extraction, concentration and analysis of essential oil constituents from Ligusticum chuanxiong Hort. Response surface methodology was performed to optimize the key parameters in accelerated solvent extraction on the extraction efficiency, and key parameters in dispersive liquid-liquid microextraction were discussed as well. Two representative constituents in Ligusticum chuanxiong Hort, (Z)-ligustilide and n-butylphthalide, were quantitatively analyzed. It was shown that the qualitative result of the accelerated solvent extraction dispersive liquid-liquid microextraction approach was in good agreement with that of hydro-distillation, whereas the proposed approach took far less extraction time (30 min), consumed less plant material (usually <1 g, 0.01 g for this study) and solvent (<20 mL) than the conventional system. To sum up, the proposed method could be recommended as a new approach in the extraction and analysis of essential oil. PMID:26304788

  5. Optimization of an accelerated solvent extraction dispersive liquid-liquid microextraction method for the separation and determination of essential oil from Ligusticum chuanxiong Hort by gas chromatography with mass spectrometry.

    PubMed

    Yang, Guang; Sun, Qiushi; Hu, Zhiyan; Liu, Hua; Zhou, Tingting; Fan, Guorong

    2015-10-01

    In this study, an accelerated solvent extraction dispersive liquid-liquid microextraction coupled with gas chromatography and mass spectrometry was established and employed for the extraction, concentration and analysis of essential oil constituents from Ligusticum chuanxiong Hort. Response surface methodology was performed to optimize the key parameters in accelerated solvent extraction on the extraction efficiency, and key parameters in dispersive liquid-liquid microextraction were discussed as well. Two representative constituents in Ligusticum chuanxiong Hort, (Z)-ligustilide and n-butylphthalide, were quantitatively analyzed. It was shown that the qualitative result of the accelerated solvent extraction dispersive liquid-liquid microextraction approach was in good agreement with that of hydro-distillation, whereas the proposed approach took far less extraction time (30 min), consumed less plant material (usually <1 g, 0.01 g for this study) and solvent (<20 mL) than the conventional system. To sum up, the proposed method could be recommended as a new approach in the extraction and analysis of essential oil.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Genetic algorithms and their applications in accelerator physics

    SciTech Connect

    Hofler, Alicia S.

    2013-12-01

    Multi-objective optimization techniques are widely used in an extremely broad range of fields. Genetic optimization for multi-objective optimization was introduced in the accelerator community in relatively recent times and quickly spread becoming a fundamental tool in multi-dimensional optimization problems. This discussion introduces the basics of the technique and reviews applications in accelerator problems.

  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. Atorvastatin induces bile acid-synthetic enzyme Cyp7a1 by suppressing FXR signaling in both liver and intestine in mice.

    PubMed

    Fu, Zidong Donna; Cui, Julia Yue; Klaassen, Curtis D

    2014-12-01

    Statins are effective cholesterol-lowering drugs to treat CVDs. Bile acids (BAs), the end products of cholesterol metabolism in the liver, are important nutrient and energy regulators. The present study aims to investigate how statins affect BA homeostasis in the enterohepatic circulation. Male C57BL/6 mice were treated with atorvastatin (100 mg/kg/day po) for 1 week, followed by BA profiling by ultra-performance LC-MS/MS. Atorvastatin decreased BA pool size, mainly due to less BA in the intestine. Surprisingly, atorvastatin did not alter total BAs in the serum or liver. Atorvastatin increased the ratio of 12α-OH/non12α-OH BAs. Atorvastatin increased the mRNAs of the BA-synthetic enzymes cholesterol 7α-hydroxylase (Cyp7a1) (over 10-fold) and cytochrome P450 27a1, the BA uptake transporters Na⁺/taurocholate cotransporting polypeptide and organic anion transporting polypeptide 1b2, and the efflux transporter multidrug resistance-associated protein 2 in the liver. Noticeably, atorvastatin suppressed the expression of BA nuclear receptor farnesoid X receptor (FXR) target genes, namely small heterodimer partner (liver) and fibroblast growth factor 15 (ileum). Furthermore, atorvastatin increased the mRNAs of the organic cation uptake transporter 1 and cholesterol efflux transporters Abcg5 and Abcg8 in the liver. The increased expression of BA-synthetic enzymes and BA transporters appear to be a compensatory response to maintain BA homeostasis after atorvastatin treatment. The Cyp7a1 induction by atorvastatin appears to be due to suppressed FXR signaling in both the liver and intestine.

  13. Atorvastatin induces bile acid-synthetic enzyme Cyp7a1 by suppressing FXR signaling in both liver and intestine in mice[S

    PubMed Central

    Fu, Zidong Donna; Cui, Julia Yue; Klaassen, Curtis D.

    2014-01-01

    Statins are effective cholesterol-lowering drugs to treat CVDs. Bile acids (BAs), the end products of cholesterol metabolism in the liver, are important nutrient and energy regulators. The present study aims to investigate how statins affect BA homeostasis in the enterohepatic circulation. Male C57BL/6 mice were treated with atorvastatin (100 mg/kg/day po) for 1 week, followed by BA profiling by ultra-performance LC-MS/MS. Atorvastatin decreased BA pool size, mainly due to less BA in the intestine. Surprisingly, atorvastatin did not alter total BAs in the serum or liver. Atorvastatin increased the ratio of 12α-OH/non12α-OH BAs. Atorvastatin increased the mRNAs of the BA-synthetic enzymes cholesterol 7α-hydroxylase (Cyp7a1) (over 10-fold) and cytochrome P450 27a1, the BA uptake transporters Na+/taurocholate cotransporting polypeptide and organic anion transporting polypeptide 1b2, and the efflux transporter multidrug resistance-associated protein 2 in the liver. Noticeably, atorvastatin suppressed the expression of BA nuclear receptor farnesoid X receptor (FXR) target genes, namely small heterodimer partner (liver) and fibroblast growth factor 15 (ileum). Furthermore, atorvastatin increased the mRNAs of the organic cation uptake transporter 1 and cholesterol efflux transporters Abcg5 and Abcg8 in the liver. The increased expression of BA-synthetic enzymes and BA transporters appear to be a compensatory response to maintain BA homeostasis after atorvastatin treatment. The Cyp7a1 induction by atorvastatin appears to be due to suppressed FXR signaling in both the liver and intestine. PMID:25278499

  14. New World and Old World Alphaviruses Have Evolved to Exploit Different Components of Stress Granules, FXR and G3BP Proteins, for Assembly of Viral Replication Complexes

    PubMed Central

    Kim, Dal Young; Reynaud, Josephine M.; Rasalouskaya, Aliaksandra; Akhrymuk, Ivan; Mobley, James A.; Frolov, Ilya; Frolova, Elena I.

    2016-01-01

    The positive-strand RNA viruses initiate their amplification in the cell from a single genome delivered by virion. This single RNA molecule needs to become involved in replication process before it is recognized and degraded by cellular machinery. In this study, we show that distantly related New World and Old World alphaviruses have independently evolved to utilize different cellular stress granule-related proteins for assembly of complexes, which recruit viral genomic RNA and facilitate formation of viral replication complexes (vRCs). Venezuelan equine encephalitis virus (VEEV) utilizes all members of the Fragile X syndrome (FXR) family, while chikungunya and Sindbis viruses exploit both members of the G3BP family. Despite being in different families, these proteins share common characteristics, which determine their role in alphavirus replication, namely, the abilities for RNA-binding and for self-assembly into large structures. Both FXR and G3BP proteins interact with virus-specific, repeating amino acid sequences located in the C-termini of hypervariable, intrinsically disordered domains (HVDs) of viral nonstructural protein nsP3. We demonstrate that these host factors orchestrate assembly of vRCs and play key roles in RNA and virus replication. Only knockout of all of the homologs results in either pronounced or complete inhibition of replication of different alphaviruses. The use of multiple homologous proteins with redundant functions mediates highly efficient recruitment of viral RNA into the replication process. This independently evolved acquisition of different families of cellular proteins by the disordered protein fragment to support alphavirus replication suggests that other RNA viruses may utilize a similar mechanism of host factor recruitment for vRC assembly. The use of different host factors by alphavirus species may be one of the important determinants of their pathogenesis. PMID:27509095

  15. 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.

  16. 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…

  17. 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.

  18. 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.

  19. Optimizations of a GPU accelerated heat conduction equation by a programming of CUDA Fortran from an analysis of a PTX file

    NASA Astrophysics Data System (ADS)

    Satake, Shin-ichi; Yoshimori, Hajime; Suzuki, Takayuki

    2012-11-01

    The Fortran language has been commonly used for many kinds of scientific computation. In this paper, we focus on the solution of an unsteady heat conduction equation, which is one of the simplest problems for thermal dynamics. Recently, a GPU (graphics processing unit) has been enhanced with a Fortran programming language capability employing CUDA (compute unified device architecture), known as CUDA Fortran. We find that the speed performance of a system using an ordinary program coding of CUDA Fortran is lower than that of systems using a program coding of CUDA C. We also find that intermediate assembly files PTX (parallel thread execution) of the two languages are not coincident. Therefore, by comparing the PTX files from the two coding programs we could detect the bottleneck that causes the speed reduction. We propose three optimization techniques that can enable the calculated speeds using CUDA Fortran and CUDA C to be coincident. The optimizations can be performed by the Fortran language when improved by an analyzed PTX file. It is thus possible to improve the performance of CUDA Fortran by adding a correction to it, which happens to be at a programming language level.

  20. Compact accelerator

    DOEpatents

    Caporaso, George J.; Sampayan, Stephen E.; Kirbie, Hugh C.

    2007-02-06

    A compact linear accelerator having at least one strip-shaped Blumlein module which guides a propagating wavefront between first and second ends and controls the output pulse at the second end. Each Blumlein module has first, second, and third planar conductor strips, with a first dielectric strip between the first and second conductor strips, and a second dielectric strip between the second and third conductor strips. Additionally, the compact linear accelerator includes a high voltage power supply connected to charge the second conductor strip to a high potential, and a switch for switching the high potential in the second conductor strip to at least one of the first and third conductor strips so as to initiate a propagating reverse polarity wavefront(s) in the corresponding dielectric strip(s).

  1. BICEP's acceleration

    SciTech Connect

    Contaldi, Carlo R.

    2014-10-01

    The recent Bicep2 [1] detection of, what is claimed to be primordial B-modes, opens up the possibility of constraining not only the energy scale of inflation but also the detailed acceleration history that occurred during inflation. In turn this can be used to determine the shape of the inflaton potential V(φ) for the first time — if a single, scalar inflaton is assumed to be driving the acceleration. We carry out a Monte Carlo exploration of inflationary trajectories given the current data. Using this method we obtain a posterior distribution of possible acceleration profiles ε(N) as a function of e-fold N and derived posterior distributions of the primordial power spectrum P(k) and potential V(φ). We find that the Bicep2 result, in combination with Planck measurements of total intensity Cosmic Microwave Background (CMB) anisotropies, induces a significant feature in the scalar primordial spectrum at scales k∼ 10{sup -3} Mpc {sup -1}. This is in agreement with a previous detection of a suppression in the scalar power [2].

  2. Community Petascale Project for Accelerator Science and Simulation: Advancing Computational Science for Future Accelerators and Accelerator Technologies

    SciTech Connect

    Spentzouris, P.; Cary, J.; McInnes, L.C.; Mori, W.; Ng, C.; Ng, E.; Ryne, R.; /LBL, Berkeley

    2011-11-14

    The design and performance optimization of particle accelerators are essential for the success of the DOE scientific program in the next decade. Particle accelerators are very complex systems whose accurate description involves a large number of degrees of freedom and requires the inclusion of many physics processes. Building on the success of the SciDAC-1 Accelerator Science and Technology project, the SciDAC-2 Community Petascale Project for Accelerator Science and Simulation (ComPASS) is developing a comprehensive set of interoperable components for beam dynamics, electromagnetics, electron cooling, and laser/plasma acceleration modelling. ComPASS is providing accelerator scientists the tools required to enable the necessary accelerator simulation paradigm shift from high-fidelity single physics process modeling (covered under SciDAC1) to high-fidelity multiphysics modeling. Our computational frameworks have been used to model the behavior of a large number of accelerators and accelerator R&D experiments, assisting both their design and performance optimization. As parallel computational applications, the ComPASS codes have been shown to make effective use of thousands of processors. ComPASS is in the first year of executing its plan to develop the next-generation HPC accelerator modeling tools. ComPASS aims to develop an integrated simulation environment that will utilize existing and new accelerator physics modules with petascale capabilities, by employing modern computing and solver technologies. The ComPASS vision is to deliver to accelerator scientists a virtual accelerator and virtual prototyping modeling environment, with the necessary multiphysics, multiscale capabilities. The plan for this development includes delivering accelerator modeling applications appropriate for each stage of the ComPASS software evolution. Such applications are already being used to address challenging problems in accelerator design and optimization. The ComPASS organization

  3. Advanced concepts for acceleration

    SciTech Connect

    Keefe, D.

    1986-07-01

    Selected examples of advanced accelerator concepts are reviewed. Such plasma accelerators as plasma beat wave accelerator, plasma wake field accelerator, and plasma grating accelerator are discussed particularly as examples of concepts for accelerating relativistic electrons or positrons. Also covered are the pulsed electron-beam, pulsed laser accelerator, inverse Cherenkov accelerator, inverse free-electron laser, switched radial-line accelerators, and two-beam accelerator. Advanced concepts for ion acceleration discussed include the electron ring accelerator, excitation of waves on intense electron beams, and two-wave combinations. (LEW)

  4. Accelerators and the Accelerator Community

    SciTech Connect

    Malamud, Ernest; Sessler, Andrew

    2008-06-01

    In this paper, standing back--looking from afar--and adopting a historical perspective, the field of accelerator science is examined. How it grew, what are the forces that made it what it is, where it is now, and what it is likely to be in the future are the subjects explored. Clearly, a great deal of personal opinion is invoked in this process.

  5. Suppressing Thermal Energy Drift In The LLNL Flash X-Ray Accelerator Using Linear Disk Resistor Stacks

    SciTech Connect

    Kreitzer, B R; Houck, T L; Luchterhand, O C

    2011-07-19

    This paper addresses thermal drift in sodium thiosulfate liquid resistors and their replacement with linear disk resistors from HVR Advanced Power Components. Sodium thiosulfate resistors in the FXR induction linear accelerator application have a temperature coefficient of {approx}1.8%/C. The FXR Marx banks send an 8kJ pulse through eight 524 cm{sup 3} liquid resistors at a repetition rate of up to 1 every 45 seconds. Every pulse increases the temperature of the solution by {approx}0.4 C which produces a 0.7% change in resistance. The typical cooling rate is {approx}0.4 C per minute which results in {approx}0.1% energy drop per pulse during continuous pulsed operations. A radiographic accelerator is extraordinarily sensitive to energy variations. Changes in beam energy produce movement in beam transport, changes in spot size, and large dose variations. If self-heating were the only problem, we could predict the increase in input voltage required to compensate for the energy loss. However, there are other variables that influence the temperature of the resistors such as focus magnet heating, changes in room temperature, changes in cooling water, where the cell is located, etc. Additionally not all of the resistors have equivalent cooling rates and as many as 32 resistors are driven from a single power source. The FXR accelerator group elected to replace the sodium thiosulfate resistors with HVR Linear Disk Resistors in a stack type configuration. With data limited for these resistors when used in oil and at low resistance values, a full characterization needed to be performed. High currents (up to 15kA), high voltages (up to 400kV), and Fast Rise times (<10ns) made a resistor choice difficult. Other solid resistors have been tried and had problems at the connection points and with the fact that the resistivity changed as they absorbed oil. The selected HVR resistors have the advantage of being manufactured with the oil impregnated in to them so this characteristic

  6. Accelerating Commercial Remote Sensing

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Through the Visiting Investigator Program (VIP) at Stennis Space Center, Community Coffee was able to use satellites to forecast coffee crops in Guatemala. Using satellite imagery, the company can produce detailed maps that separate coffee cropland from wild vegetation and show information on the health of specific crops. The data can control coffee prices and eventually may be used to optimize application of fertilizers, pesticides and irrigation. This would result in maximal crop yields, minimal pollution and lower production costs. VIP is a mechanism involving NASA funding designed to accelerate the growth of commercial remote sensing by promoting general awareness and basic training in the technology.

  7. Electron acceleration in a two-stage laser wakefield accelerator

    NASA Astrophysics Data System (ADS)

    Li, Ruxin; Liu, Jiansheng; Xia, Changquan; Wang, Wentao; Lu, Haiyang; Wang, Cheng; Deng, Aihua; Li, Wentao; Zhang, Hui; Liang, Xiaoyan; Leng, Yuxin; Lu, Xiaoming; Wang, Cheng; Wang, Jianzhou; Shen, Baifei; Nakajima, Kazuhisa; Xu, Zhizhan

    2012-07-01

    Near-GeV electron beam generation from a two-stage laser wakefield accelerator (LWFA) is reported. Electron injection and acceleration are separated into two distinct LWFA stages and controlled independently from each other by employing two gas cells filled with a He/O2 mixture and pure He gas, respectively. Electrons with a Maxwellian spectrum, generated from the injection stage assisted by ionization-induced injection, are seeded into the acceleration stage with a 3-mm long gas cell and accelerated to produce a 0.8-GeV quasimonoenergetic electron beam for a 45 TW 40 fs laser pulse, corresponding to an acceleration gradient of 187 GV/m. In the injection stage, the produced electron beam properties can be optimized by adjusting the input laser intensity and the plasma density so that quasimonoenergetic electron beams are obtained owing to the self-focusing effects of the laser beam. The ionization-induced injection scheme has been extensively employed for a capillary discharge plasma waveguide to demonstrate channel-guided LWFA beyond 1 GeV. Using a 4-cm capillary made of oxygen containing acrylic resin results in optically guiding 130 TW 55 fs laser pulse that accelerates electrons up to 1.8 GeV in contrast with no electron acceleration in a polyethylene capillary free of oxygen.

  8. Multiple time step molecular dynamics in the optimized isokinetic ensemble steered with the molecular theory of solvation: Accelerating with advanced extrapolation of effective solvation forces

    SciTech Connect

    Omelyan, Igor E-mail: omelyan@icmp.lviv.ua; Kovalenko, Andriy

    2013-12-28

    We develop efficient handling of solvation forces in the multiscale method of multiple time step molecular dynamics (MTS-MD) of a biomolecule steered by the solvation free energy (effective solvation forces) obtained from the 3D-RISM-KH molecular theory of solvation (three-dimensional reference interaction site model complemented with the Kovalenko-Hirata closure approximation). To reduce the computational expenses, we calculate the effective solvation forces acting on the biomolecule by using advanced solvation force extrapolation (ASFE) at inner time steps while converging the 3D-RISM-KH integral equations only at large outer time steps. The idea of ASFE consists in developing a discrete non-Eckart rotational transformation of atomic coordinates that minimizes the distances between the atomic positions of the biomolecule at different time moments. The effective solvation forces for the biomolecule in a current conformation at an inner time step are then extrapolated in the transformed subspace of those at outer time steps by using a modified least square fit approach applied to a relatively small number of the best force-coordinate pairs. The latter are selected from an extended set collecting the effective solvation forces obtained from 3D-RISM-KH at outer time steps over a broad time interval. The MTS-MD integration with effective solvation forces obtained by converging 3D-RISM-KH at outer time steps and applying ASFE at inner time steps is stabilized by employing the optimized isokinetic Nosé-Hoover chain (OIN) ensemble. Compared to the previous extrapolation schemes used in combination with the Langevin thermostat, the ASFE approach substantially improves the accuracy of evaluation of effective solvation forces and in combination with the OIN thermostat enables a dramatic increase of outer time steps. We demonstrate on a fully flexible model of alanine dipeptide in aqueous solution that the MTS-MD/OIN/ASFE/3D-RISM-KH multiscale method of molecular dynamics

  9. Multiple time step molecular dynamics in the optimized isokinetic ensemble steered with the molecular theory of solvation: Accelerating with advanced extrapolation of effective solvation forces

    NASA Astrophysics Data System (ADS)

    Omelyan, Igor; Kovalenko, Andriy

    2013-12-01

    We develop efficient handling of solvation forces in the multiscale method of multiple time step molecular dynamics (MTS-MD) of a biomolecule steered by the solvation free energy (effective solvation forces) obtained from the 3D-RISM-KH molecular theory of solvation (three-dimensional reference interaction site model complemented with the Kovalenko-Hirata closure approximation). To reduce the computational expenses, we calculate the effective solvation forces acting on the biomolecule by using advanced solvation force extrapolation (ASFE) at inner time steps while converging the 3D-RISM-KH integral equations only at large outer time steps. The idea of ASFE consists in developing a discrete non-Eckart rotational transformation of atomic coordinates that minimizes the distances between the atomic positions of the biomolecule at different time moments. The effective solvation forces for the biomolecule in a current conformation at an inner time step are then extrapolated in the transformed subspace of those at outer time steps by using a modified least square fit approach applied to a relatively small number of the best force-coordinate pairs. The latter are selected from an extended set collecting the effective solvation forces obtained from 3D-RISM-KH at outer time steps over a broad time interval. The MTS-MD integration with effective solvation forces obtained by converging 3D-RISM-KH at outer time steps and applying ASFE at inner time steps is stabilized by employing the optimized isokinetic Nosé-Hoover chain (OIN) ensemble. Compared to the previous extrapolation schemes used in combination with the Langevin thermostat, the ASFE approach substantially improves the accuracy of evaluation of effective solvation forces and in combination with the OIN thermostat enables a dramatic increase of outer time steps. We demonstrate on a fully flexible model of alanine dipeptide in aqueous solution that the MTS-MD/OIN/ASFE/3D-RISM-KH multiscale method of molecular dynamics

  10. A Survey of Hadron Therapy Accelerator Technologies.

    SciTech Connect

    PEGGS,S.; SATOGATA, T.; FLANZ, J.

    2007-06-25

    Hadron therapy has entered a new age [1]. The number of facilities grows steadily, and 'consumer' interest is high. Some groups are working on new accelerator technology, while others optimize existing designs by reducing capital and operating costs, and improving performance. This paper surveys the current requirements and directions in accelerator technology for hadron therapy.

  11. Preliminary tests of the electrostatic plasma accelerator

    NASA Technical Reports Server (NTRS)

    Aston, G.; Acker, T.

    1990-01-01

    This report describes the results of a program to verify an electrostatic plasma acceleration concept and to identify those parameters most important in optimizing an Electrostatic Plasma Accelerator (EPA) thruster based upon this thrust mechanism. Preliminary performance measurements of thrust, specific impulse and efficiency were obtained using a unique plasma exhaust momentum probe. Reliable EPA thruster operation was achieved using one power supply.

  12. Accelerator system and method of accelerating particles

    NASA Technical Reports Server (NTRS)

    Wirz, Richard E. (Inventor)

    2010-01-01

    An accelerator system and method that utilize dust as the primary mass flux for generating thrust are provided. The accelerator system can include an accelerator capable of operating in a self-neutralizing mode and having a discharge chamber and at least one ionizer capable of charging dust particles. The system can also include a dust particle feeder that is capable of introducing the dust particles into the accelerator. By applying a pulsed positive and negative charge voltage to the accelerator, the charged dust particles can be accelerated thereby generating thrust and neutralizing the accelerator system.

  13. Vacuum Brazing of Accelerator Components

    NASA Astrophysics Data System (ADS)

    Singh, Rajvir; Pant, K. K.; Lal, Shankar; Yadav, D. P.; Garg, S. R.; Raghuvanshi, V. K.; Mundra, G.

    2012-11-01

    Commonly used materials for accelerator components are those which are vacuum compatible and thermally conductive. Stainless steel, aluminum and copper are common among them. Stainless steel is a poor heat conductor and not very common in use where good thermal conductivity is required. Aluminum and copper and their alloys meet the above requirements and are frequently used for the above purpose. The accelerator components made of aluminum and its alloys using welding process have become a common practice now a days. It is mandatory to use copper and its other grades in RF devices required for accelerators. Beam line and Front End components of the accelerators are fabricated from stainless steel and OFHC copper. Fabrication of components made of copper using welding process is very difficult and in most of the cases it is impossible. Fabrication and joining in such cases is possible using brazing process especially under vacuum and inert gas atmosphere. Several accelerator components have been vacuum brazed for Indus projects at Raja Ramanna Centre for Advanced Technology (RRCAT), Indore using vacuum brazing facility available at RRCAT, Indore. This paper presents details regarding development of the above mentioned high value and strategic components/assemblies. It will include basics required for vacuum brazing, details of vacuum brazing facility, joint design, fixturing of the jobs, selection of filler alloys, optimization of brazing parameters so as to obtain high quality brazed joints, brief description of vacuum brazed accelerator components etc.

  14. Commnity Petascale Project for Accelerator Science and Simulation: Advancing Computational Science for Future Accelerators and Accelerator Technologies

    SciTech Connect

    Spentzouris, Panagiotis; Cary, John; Mcinnes, Lois Curfman; Mori, Warren; Ng, Cho; Ng, Esmond; Ryne, Robert; /LBL, Berkeley

    2008-07-01

    The design and performance optimization of particle accelerators is essential for the success of the DOE scientific program in the next decade. Particle accelerators are very complex systems whose accurate description involves a large number of degrees of freedom and requires the inclusion of many physics processes. Building on the success of the SciDAC1 Accelerator Science and Technology project, the SciDAC2 Community Petascale Project for Accelerator Science and Simulation (ComPASS) is developing a comprehensive set of interoperable components for beam dynamics, electromagnetics, electron cooling, and laser/plasma acceleration modeling. ComPASS is providing accelerator scientists the tools required to enable the necessary accelerator simulation paradigm shift from high-fidelity single physics process modeling (covered under SciDAC1) to high-fidelity multi-physics modeling. Our computational frameworks have been used to model the behavior of a large number of accelerators and accelerator R&D experiments, assisting both their design and performance optimization. As parallel computational applications, the ComPASS codes have been shown to make effective use of thousands of processors.

  15. Community petascale project for accelerator science and simulation : Advancing computational science for future accelerators and accelerator technologies.

    SciTech Connect

    Spentzouris, P.; Cary, J.; McInnes, L. C.; Mori, W.; Ng, C.; Ng, E.; Ryne, R.

    2008-01-01

    The design and performance optimization of particle accelerators are essential for the success of the DOE scientific program in the next decade. Particle accelerators are very complex systems whose accurate description involves a large number of degrees of freedom and requires the inclusion of many physics processes. Building on the success of the SciDAC-1 Accelerator Science and Technology project, the SciDAC-2 Community Petascale Project for Accelerator Science and Simulation (ComPASS) is developing a comprehensive set of interoperable components for beam dynamics, electromagnetics, electron cooling, and laser/plasma acceleration modelling. ComPASS is providing accelerator scientists the tools required to enable the necessary accelerator simulation paradigm shift from high-fidelity single physics process modeling (covered under SciDAC1) to high-fidelity multiphysics modeling. Our computational frameworks have been used to model the behavior of a large number of accelerators and accelerator R & D experiments, assisting both their design and performance optimization. As parallel computational applications, the ComPASS codes have been shown to make effective use of thousands of processors.

  16. Commnity Petascale Project for Accelerator Science And Simulation: Advancing Computational Science for Future Accelerators And Accelerator Technologies

    SciTech Connect

    Spentzouris, Panagiotis; Cary, John; Mcinnes, Lois Curfman; Mori, Warren; Ng, Cho; Ng, Esmond; Ryne, Robert; /LBL, Berkeley

    2011-10-21

    The design and performance optimization of particle accelerators are essential for the success of the DOE scientific program in the next decade. Particle accelerators are very complex systems whose accurate description involves a large number of degrees of freedom and requires the inclusion of many physics processes. Building on the success of the SciDAC-1 Accelerator Science and Technology project, the SciDAC-2 Community Petascale Project for Accelerator Science and Simulation (ComPASS) is developing a comprehensive set of interoperable components for beam dynamics, electromagnetics, electron cooling, and laser/plasma acceleration modelling. ComPASS is providing accelerator scientists the tools required to enable the necessary accelerator simulation paradigm shift from high-fidelity single physics process modeling (covered under SciDAC1) to high-fidelity multiphysics modeling. Our computational frameworks have been used to model the behavior of a large number of accelerators and accelerator R&D experiments, assisting both their design and performance optimization. As parallel computational applications, the ComPASS codes have been shown to make effective use of thousands of processors.

  17. Multiple pulse resonantly enhanced laser plasma wakefield acceleration

    SciTech Connect

    Corner, L.; Walczak, R.; Nevay, L. J.; Dann, S.; Hooker, S. M.; Bourgeois, N.; Cowley, J.

    2012-12-21

    We present an outline of experiments being conducted at Oxford University on multiple-pulse, resonantly-enhanced laser plasma wakefield acceleration. This method of laser plasma acceleration uses trains of optimally spaced low energy short pulses to drive plasma oscillations and may enable laser plasma accelerators to be driven by compact and efficient fibre laser sources operating at high repetition rates.

  18. Pulsed Plasma Accelerator Modeling

    NASA Technical Reports Server (NTRS)

    Goodman, M.; Kazeminezhad, F.; Owens, T.

    2009-01-01

    This report presents the main results of the modeling task of the PPA project. The objective of this task is to make major progress towards developing a new computational tool with new capabilities for simulating cylindrically symmetric 2.5 dimensional (2.5 D) PPA's. This tool may be used for designing, optimizing, and understanding the operation of PPA s and other pulsed power devices. The foundation for this task is the 2-D, cylindrically symmetric, magnetohydrodynamic (MHD) code PCAPPS (Princeton Code for Advanced Plasma Propulsion Simulation). PCAPPS was originally developed by Sankaran (2001, 2005) to model Lithium Lorentz Force Accelerators (LLFA's), which are electrode based devices, and are typically operated in continuous magnetic field to the model, and implementing a first principles, self-consistent algorithm to couple the plasma and power circuit that drives the plasma dynamics.

  19. Pros and Cons of the Acceleration Scheme (NF-IDS)

    SciTech Connect

    Bogacz, Alex; Bogacz, Slawomir

    2008-07-01

    The overall goal of the acceleration systems: large acceptance acceleration to 25 GeV and beam shaping can be accomplished by various fixed field accelerators at different stages. They involve three superconducting linacs: a single pass linear Pre-accelerator followed by a pair of multi-pass Recirculating Linear Accelerators (RLA) and finally a nonâ scaling FFAG ring. The present baseline acceleration scenario has been optimized to take maximum advantage of appropriate acceleration scheme at a given stage. Pros and cons of various stages are discussed here in detail. The solenoid based Pre-accelerator offers very large acceptance and facilitates correction of energy gain across the bunch and significant longitudinal compression trough induced synchrotron motion. However, far off-crest acceleration reduces the effective acceleration gradient and adds complexity through the requirement of individual RF phase control for each cavity. Close proximity of strong solenoids and superc

  20. Computational Tools for Accelerating Carbon Capture Process Development

    SciTech Connect

    Miller, David; Sahinidis, N V; Cozad, A; Lee, A; Kim, H; Morinelly, J; Eslick, J; Yuan, Z

    2013-06-04

    This presentation reports development of advanced computational tools to accelerate next generation technology development. These tools are to develop an optimized process using rigorous models. They include: Process Models; Simulation-Based Optimization; Optimized Process; Uncertainty Quantification; Algebraic Surrogate Models; and Superstructure Optimization (Determine Configuration).

  1. EDITORIAL: Laser and plasma accelerators Laser and plasma accelerators

    NASA Astrophysics Data System (ADS)

    Bingham, Robert

    2009-02-01

    by Chen et al where the driver, instead of being a laser, is a whistler wave known as the magnetowave plasma accelerator. The application to electron--positron plasmas that are found around pulsars is studied in the paper by Shukla, and to muon acceleration by Peano et al. Electron wakefield experiments are now concentrating on control and optimisation of high-quality beams that can be used as drivers for novel radiation sources. Studies by Thomas et al show that filamentation has a deleterious effect on the production of high quality mono-energetic electron beams and is caused by non-optimal choice of focusing geometry and/or electron density. It is crucial to match the focusing with the right plasma parameters and new types of plasma channels are being developed, such as the magnetically controlled plasma waveguide reported by Froula et al. The magnetic field provides a pressure profile shaping the channel to match the guiding conditions of the incident laser, resulting in predicted electron energies of 3GeV. In the forced laser-wakefield experiment Fang et al show that pump depletion reduces or inhibits the acceleration of electrons. One of the earlier laser acceleration concepts known as the beat wave may be revived due to the work by Kalmykov et al who report on all-optical control of nonlinear focusing of laser beams, allowing for stable propagation over several Rayleigh lengths with pre-injected electrons accelerated beyond 100 MeV. With the increasing number of petawatt lasers, attention is being focused on different acceleration regimes such as stochastic acceleration by counterpropagating laser pulses, the relativistic mirror, or the snow-plough effect leading to single-step acceleration reported by Mendonca. During wakefield acceleration the leading edge of the pulse undergoes frequency downshifting and head erosion as the laser energy is transferred to the wake while the trailing edge of the laser pulse undergoes frequency up-shift. This is commonly known

  2. Medium Beta Superconducting Accelerating Structures

    SciTech Connect

    Jean Delayen

    2001-09-01

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

  3. Modeling Ion Acceleration Using LSP

    NASA Astrophysics Data System (ADS)

    McMahon, Matthew

    This thesis presents the development of simulations modeling ion acceleration using the particle-in-cell code LSP. A new technique was developed to model the Target Normal Sheath Acceleration (TNSA) mechanism. Multiple simulations are performed, each optimized for a certain part of the TNSA process with appropriate information being passed from one to the next. The technique allows for tradeoffs between accuracy and speed. Physical length and timescales are met when necessary and different physical models are employed as needed. This TNSA modeling technique is used to perform a study on the effect front-surface structures have on the resulting ion acceleration. The front-surface structures tested have been shown to either modify the electron kinetic energy spectrum by increasing the maximum energy obtained or by increasing the overall coupling of laser energy to electron energy. Both of these types of front-surface structures are tested for their potential benefits for the accelerated ions. It is shown that optimizing the coupling of laser energy to electron energy is more important than producing extremely energetic electrons in the case of the TNSA ions. Simulations modeling the interaction of an intense laser with very thin (<100 nm thick) liquid crystal targets, modeled for the first time, are presented. Modeling this interaction is difficult and the effect of different simulation design choices is explored in depth. In particular, it is shown that the initial electron temperature used in the simulation has a significant effect on the resulting ion acceleration and light transmitted through the target. This behavior is explored through numerous 1D simulations.

  4. Self-shielded electron linear accelerators designed for radiation technologies

    NASA Astrophysics Data System (ADS)

    Belugin, V. M.; Rozanov, N. E.; Pirozhenko, V. M.

    2009-09-01

    This paper describes self-shielded high-intensity electron linear accelerators designed for radiation technologies. The specific property of the accelerators is that they do not apply an external magnetic field; acceleration and focusing of electron beams are performed by radio-frequency fields in the accelerating structures. The main characteristics of the accelerators are high current and beam power, but also reliable operation and a long service life. To obtain these characteristics, a number of problems have been solved, including a particular optimization of the accelerator components and the application of a variety of specific means. The paper describes features of the electron beam dynamics, accelerating structure, and radio-frequency power supply. Several compact self-shielded accelerators for radiation sterilization and x-ray cargo inspection have been created. The introduced methods made it possible to obtain a high intensity of the electron beam and good performance of the accelerators.

  5. TURBULENT SHEAR ACCELERATION

    SciTech Connect

    Ohira, Yutaka

    2013-04-10

    We consider particle acceleration by large-scale incompressible turbulence with a length scale larger than the particle mean free path. We derive an ensemble-averaged transport equation of energetic charged particles from an extended transport equation that contains the shear acceleration. The ensemble-averaged transport equation describes particle acceleration by incompressible turbulence (turbulent shear acceleration). We find that for Kolmogorov turbulence, the turbulent shear acceleration becomes important on small scales. Moreover, using Monte Carlo simulations, we confirm that the ensemble-averaged transport equation describes the turbulent shear acceleration.

  6. The direction of acceleration

    NASA Astrophysics Data System (ADS)

    Wilhelm, Thomas; Burde, Jan-Philipp; Lück, Stephan

    2015-11-01

    Acceleration is a physical quantity that is difficult to understand and hence its complexity is often erroneously simplified. Many students think of acceleration as equivalent to velocity, a ˜ v. For others, acceleration is a scalar quantity, which describes the change in speed Δ|v| or Δ|v|/Δt (as opposed to the change in velocity). The main difficulty with the concept of acceleration therefore lies in developing a correct understanding of its direction. The free iOS app AccelVisu supports students in acquiring a correct conception of acceleration by showing acceleration arrows directly at moving objects.

  7. Accelerating Particles with Plasma

    SciTech Connect

    Litos, Michael; Hogan, Mark

    2014-11-05

    Researchers at SLAC explain how they use plasma wakefields to accelerate bunches of electrons to very high energies over only a short distance. Their experiments offer a possible path for the future of particle accelerators.

  8. Accelerator Technology Division

    NASA Astrophysics Data System (ADS)

    1992-04-01

    In fiscal year (FY) 1991, the Accelerator Technology (AT) division continued fulfilling its mission to pursue accelerator science and technology and to develop new accelerator concepts for application to research, defense, energy, industry, and other areas of national interest. This report discusses the following programs: The Ground Test Accelerator Program; APLE Free-Electron Laser Program; Accelerator Transmutation of Waste; JAERI, OMEGA Project, and Intense Neutron Source for Materials Testing; Advanced Free-Electron Laser Initiative; Superconducting Super Collider; The High-Power Microwave Program; (Phi) Factory Collaboration; Neutral Particle Beam Power System Highlights; Accelerator Physics and Special Projects; Magnetic Optics and Beam Diagnostics; Accelerator Design and Engineering; Radio-Frequency Technology; Free-Electron Laser Technology; Accelerator Controls and Automation; Very High-Power Microwave Sources and Effects; and GTA Installation, Commissioning, and Operations.

  9. Linear accelerator: A concept

    NASA Technical Reports Server (NTRS)

    Mutzberg, J.

    1972-01-01

    Design is proposed for inexpensive accelerometer which would work by applying pressure to fluid during acceleration. Pressure is used to move shuttle, and shuttle movement is sensed and calibrated to give acceleration readings.

  10. Improved plasma accelerator

    NASA Technical Reports Server (NTRS)

    Cheng, D. Y.

    1971-01-01

    Converging, coaxial accelerator electrode configuration operates in vacuum as plasma gun. Plasma forms by periodic injections of high pressure gas that is ionized by electrical discharges. Deflagration mode of discharge provides acceleration, and converging contours of plasma gun provide focusing.

  11. MEQALAC rf accelerating structure

    SciTech Connect

    Keane, J.; Brodowski, J.

    1981-01-01

    A prototype MEQALAC capable of replacing the Cockcroft Walton pre-injector at BNL is being fabricated. Ten milliamperes of H/sup -/ beam supplied from a source sitting at a potential of -40 kilovolt is to be accelerated to 750 keV. This energy gain is provided by a 200 Megahertz accelerating system rather than the normal dc acceleration. Substantial size and cost reduction would be realized by such a system over conventional pre-accelerator systems.

  12. EDITORIAL: Laser and plasma accelerators Laser and plasma accelerators

    NASA Astrophysics Data System (ADS)

    Bingham, Robert

    2009-02-01

    by Chen et al where the driver, instead of being a laser, is a whistler wave known as the magnetowave plasma accelerator. The application to electron--positron plasmas that are found around pulsars is studied in the paper by Shukla, and to muon acceleration by Peano et al. Electron wakefield experiments are now concentrating on control and optimisation of high-quality beams that can be used as drivers for novel radiation sources. Studies by Thomas et al show that filamentation has a deleterious effect on the production of high quality mono-energetic electron beams and is caused by non-optimal choice of focusing geometry and/or electron density. It is crucial to match the focusing with the right plasma parameters and new types of plasma channels are being developed, such as the magnetically controlled plasma waveguide reported by Froula et al. The magnetic field provides a pressure profile shaping the channel to match the guiding conditions of the incident laser, resulting in predicted electron energies of 3GeV. In the forced laser-wakefield experiment Fang et al show that pump depletion reduces or inhibits the acceleration of electrons. One of the earlier laser acceleration concepts known as the beat wave may be revived due to the work by Kalmykov et al who report on all-optical control of nonlinear focusing of laser beams, allowing for stable propagation over several Rayleigh lengths with pre-injected electrons accelerated beyond 100 MeV. With the increasing number of petawatt lasers, attention is being focused on different acceleration regimes such as stochastic acceleration by counterpropagating laser pulses, the relativistic mirror, or the snow-plough effect leading to single-step acceleration reported by Mendonca. During wakefield acceleration the leading edge of the pulse undergoes frequency downshifting and head erosion as the laser energy is transferred to the wake while the trailing edge of the laser pulse undergoes frequency up-shift. This is commonly known

  13. Convex accelerated maximum entropy reconstruction

    NASA Astrophysics Data System (ADS)

    Worley, Bradley

    2016-04-01

    Maximum entropy (MaxEnt) spectral reconstruction methods provide a powerful framework for spectral estimation of nonuniformly sampled datasets. Many methods exist within this framework, usually defined based on the magnitude of a Lagrange multiplier in the MaxEnt objective function. An algorithm is presented here that utilizes accelerated first-order convex optimization techniques to rapidly and reliably reconstruct nonuniformly sampled NMR datasets using the principle of maximum entropy. This algorithm - called CAMERA for Convex Accelerated Maximum Entropy Reconstruction Algorithm - is a new approach to spectral reconstruction that exhibits fast, tunable convergence in both constant-aim and constant-lambda modes. A high-performance, open source NMR data processing tool is described that implements CAMERA, and brief comparisons to existing reconstruction methods are made on several example spectra.

  14. Elementary principles of linear accelerators

    SciTech Connect

    Loew, G.A.; Talman, R.

    1983-09-01

    These lectures come in five sections. The first is this introduction. The second is a short chronology of what are viewed as important milestones in the field. The third covers proton linacs. It introduces elementary concepts such as transit time, shunt impedance, and Q. Critical issues such as phase stability and transverse forces are discussed. The fourth section contains an elementary discussion of waveguide accelerating structures. It can be regarded as an introduction to some of the more advanced treatments of the subject. The final section is devoted to electron accelerators. Taking SLAC as an example, various topics are discussed such as structure design, choice of parameters, frequency optimization, beam current, emittance, bunch length and beam loading. Recent developments and future challenges are mentioned briefly. 41 figures, 4 tables.

  15. Acceleration gradient of a plasma wakefield accelerator

    SciTech Connect

    Uhm, Han S.

    2008-02-25

    The phase velocity of the wakefield waves is identical to the electron beam velocity. A theoretical analysis indicates that the acceleration gradient of the wakefield accelerator normalized by the wave breaking amplitude is K{sub 0}({xi})/K{sub 1}({xi}), where K{sub 0}({xi}) and K{sub 1}({xi}) are the modified Bessel functions of the second kind of order zero and one, respectively and {xi} is the beam parameter representing the beam intensity. It is also shown that the beam density must be considerably higher than the diffuse plasma density for the large radial velocity of plasma electrons that are required for a high acceleration gradient.

  16. Acceleration: It's Elementary

    ERIC Educational Resources Information Center

    Willis, Mariam

    2012-01-01

    Acceleration is one tool for providing high-ability students the opportunity to learn something new every day. Some people talk about acceleration as taking a student out of step. In actuality, what one is doing is putting a student in step with the right curriculum. Whole-grade acceleration, also called grade-skipping, usually happens between…

  17. Far field acceleration

    SciTech Connect

    Fernow, R.C.

    1995-07-01

    Far fields are propagating electromagnetic waves far from their source, boundary surfaces, and free charges. The general principles governing the acceleration of charged particles by far fields are reviewed. A survey of proposed field configurations is given. The two most important schemes, Inverse Cerenkov acceleration and Inverse free electron laser acceleration, are discussed in detail.

  18. Angular Acceleration without Torque?

    ERIC Educational Resources Information Center

    Kaufman, Richard D.

    2012-01-01

    Hardly. Just as Robert Johns qualitatively describes angular acceleration by an internal force in his article "Acceleration Without Force?" here we will extend the discussion to consider angular acceleration by an internal torque. As we will see, this internal torque is due to an internal force acting at a distance from an instantaneous center.

  19. Optimized planning of in-service inspections of local flow-accelerated corrosion of pipeline elements used in the secondary coolant circuit of the VVER-440-based units at the Novovoronezh NPP

    NASA Astrophysics Data System (ADS)

    Tomarov, G. V.; Povarov, V. P.; Shipkov, A. A.; Gromov, A. F.; Budanov, V. A.; Golubeva, T. N.

    2015-03-01

    Matters concerned with making efficient use of the information-analytical system on the flow-accelerated corrosion problem in setting up in-service examination of the metal of pipeline elements operating in the secondary coolant circuit of the VVER-440-based power units at the Novovoronezh NPP are considered. The principles used to select samples of pipeline elements in planning ultrasonic thickness measurements for timely revealing metal thinning due to flow-accelerated corrosion along with reducing the total amount of measurements in the condensate-feedwater path are discussed.

  20. RF Gun Optimization Study

    SciTech Connect

    Alicia Hofler; Pavel Evtushenko

    2007-07-03

    Injector gun design is an iterative process where the designer optimizes a few nonlinearly interdependent beam parameters to achieve the required beam quality for a particle accelerator. Few tools exist to automate the optimization process and thoroughly explore the parameter space. The challenging beam requirements of new accelerator applications such as light sources and electron cooling devices drive the development of RF and SRF photo injectors. A genetic algorithm (GA) has been successfully used to optimize DC photo injector designs at Cornell University [1] and Jefferson Lab [2]. We propose to apply GA techniques to the design of RF and SRF gun injectors. In this paper, we report on the initial phase of the study where we model and optimize a system that has been benchmarked with beam measurements and simulation.

  1. RF Gun Optimization Study

    SciTech Connect

    A. S. Hofler; P. Evtushenko; M. Krasilnikov

    2007-08-01

    Injector gun design is an iterative process where the designer optimizes a few nonlinearly interdependent beam parameters to achieve the required beam quality for a particle accelerator. Few tools exist to automate the optimization process and thoroughly explore the parameter space. The challenging beam requirements of new accelerator applications such as light sources and electron cooling devices drive the development of RF and SRF photo injectors. RF and SRF gun design is further complicated because the bunches are space charge dominated and require additional emittance compensation. A genetic algorithm has been successfully used to optimize DC photo injector designs for Cornell* and Jefferson Lab**, and we propose studying how the genetic algorithm techniques can be applied to the design of RF and SRF gun injectors. In this paper, we report on the initial phase of the study where we model and optimize gun designs that have been benchmarked with beam measurements and simulation.

  2. Summary report: working group 2 on 'Plasma Based AccelerationConcepts'

    SciTech Connect

    Esarey, E.; Leemans, Wim

    1998-09-01

    A summary of the talks, papers and discussion sessions presented in the Working Group on Plasma Based Acceleration Concepts is given within the context of the progress towards a 1 GeV laser driven accelerator module. The topics covered within the Working Group were self-modulated laser wakefield acceleration, standard laser wakefield acceleration, plasma beatwave acceleration, laser guiding and wake excitation in plasma channels, plasma wakefield acceleration, plasma lenses and optical injection techniques for laser wakefield accelerators. An overview will be given of the present status of experimental and theoretical progress as well as an outlook towards the future physics and technological challenges for the development of an optimized accelerator module.

  3. Compact Plasma Accelerator

    NASA Technical Reports Server (NTRS)

    Foster, John E.

    2004-01-01

    A plasma accelerator has been conceived for both material-processing and spacecraft-propulsion applications. This accelerator generates and accelerates ions within a very small volume. Because of its compactness, this accelerator could be nearly ideal for primary or station-keeping propulsion for spacecraft having masses between 1 and 20 kg. Because this accelerator is designed to generate beams of ions having energies between 50 and 200 eV, it could also be used for surface modification or activation of thin films.

  4. High brightness electron accelerator

    DOEpatents

    Sheffield, Richard L.; Carlsten, Bruce E.; Young, Lloyd M.

    1994-01-01

    A compact high brightness linear accelerator is provided for use, e.g., in a free electron laser. The accelerator has a first plurality of acclerating cavities having end walls with four coupling slots for accelerating electrons to high velocities in the absence of quadrupole fields. A second plurality of cavities receives the high velocity electrons for further acceleration, where each of the second cavities has end walls with two coupling slots for acceleration in the absence of dipole fields. The accelerator also includes a first cavity with an extended length to provide for phase matching the electron beam along the accelerating cavities. A solenoid is provided about the photocathode that emits the electons, where the solenoid is configured to provide a substantially uniform magnetic field over the photocathode surface to minimize emittance of the electons as the electrons enter the first cavity.

  5. 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.

  6. Acceleration in astrophysics

    SciTech Connect

    Colgate, S.A.

    1993-12-31

    The origin of cosmic rays and applicable laboratory experiments are discussed. Some of the problems of shock acceleration for the production of cosmic rays are discussed in the context of astrophysical conditions. These are: The presumed unique explanation of the power law spectrum is shown instead to be a universal property of all lossy accelerators; the extraordinary isotropy of cosmic rays and the limited diffusion distances implied by supernova induced shock acceleration requires a more frequent and space-filling source than supernovae; the near perfect adiabaticity of strong hydromagnetic turbulence necessary for reflecting the accelerated particles each doubling in energy roughly 10{sup 5} to {sup 6} scatterings with negligible energy loss seems most unlikely; the evidence for acceleration due to quasi-parallel heliosphere shocks is weak. There is small evidence for the expected strong hydromagnetic turbulence, and instead, only a small number of particles accelerate after only a few shock traversals; the acceleration of electrons in the same collisionless shock that accelerates ions is difficult to reconcile with the theoretical picture of strong hydromagnetic turbulence that reflects the ions. The hydromagnetic turbulence will appear adiabatic to the electrons at their much higher Larmor frequency and so the electrons should not be scattered incoherently as they must be for acceleration. Therefore the electrons must be accelerated by a different mechanism. This is unsatisfactory, because wherever electrons are accelerated these sites, observed in radio emission, may accelerate ions more favorably. The acceleration is coherent provided the reconnection is coherent, in which case the total flux, as for example of collimated radio sources, predicts single charge accelerated energies much greater than observed.

  7. GPU-Accelerated Text Mining

    SciTech Connect

    Cui, Xiaohui; Mueller, Frank; Zhang, Yongpeng; Potok, Thomas E

    2009-01-01

    Accelerating hardware devices represent a novel promise for improving the performance for many problem domains but it is not clear for which domains what accelerators are suitable. While there is no room in general-purpose processor design to significantly increase the processor frequency, developers are instead resorting to multi-core chips duplicating conventional computing capabilities on a single die. Yet, accelerators offer more radical designs with a much higher level of parallelism and novel programming environments. This present work assesses the viability of text mining on CUDA. Text mining is one of the key concepts that has become prominent as an effective means to index the Internet, but its applications range beyond this scope and extend to providing document similarity metrics, the subject of this work. We have developed and optimized text search algorithms for GPUs to exploit their potential for massive data processing. We discuss the algorithmic challenges of parallelization for text search problems on GPUs and demonstrate the potential of these devices in experiments by reporting significant speedups. Our study may be one of the first to assess more complex text search problems for suitability for GPU devices, and it may also be one of the first to exploit and report on atomic instruction usage that have recently become available in NVIDIA devices.

  8. The Dielectric Wall Accelerator

    SciTech Connect

    Caporaso, George J.; Chen, Yu-Jiuan; Sampayan, Stephen E.

    2009-01-01

    The Dielectric Wall Accelerator (DWA), a class of induction accelerators, employs a novel insulating beam tube to impress a longitudinal electric field on a bunch of charged particles. The surface flashover characteristics of this tube may permit the attainment of accelerating gradients on the order of 100 MV/m for accelerating pulses on the order of a nanosecond in duration. A virtual traveling wave of excitation along the tube is produced at any desired speed by controlling the timing of pulse generating modules that supply a tangential electric field to the tube wall. Because of the ability to control the speed of this virtual wave, the accelerator is capable of handling any charge to mass ratio particle; hence it can be used for electrons, protons and any ion. The accelerator architectures, key technologies and development challenges will be described.

  9. Switched matrix accelerator

    SciTech Connect

    Whittum, David H.; Tantawi, Sami G.

    2001-01-01

    We describe a new concept for a microwave circuit functioning as a charged-particle accelerator at mm wavelengths, permitting an accelerating gradient higher than conventional passive circuits can withstand consistent with cyclic fatigue. The device provides acceleration for multiple bunches in parallel channels, and permits a short exposure time for the conducting surface of the accelerating cavities. Our analysis includes scalings based on a smooth transmission line model and a complementary treatment with a coupled-cavity simulation. We also provide an electromagnetic design for the accelerating structure, arriving at rough dimensions for a seven-cell accelerator matched to standard waveguide and suitable for bench tests at low power in air at 91.392 GHz. A critical element in the concept is a fast mm-wave switch suitable for operation at high power, and we present the considerations for implementation in an H-plane tee. We discuss the use of diamond as the photoconductor switch medium.

  10. Switched Matrix Accelerator

    SciTech Connect

    Whittum, David H

    2000-10-04

    We describe a new concept for a microwave circuit functioning as a charged-particle accelerator at mm-wavelengths, permitting an accelerating gradient higher than conventional passive circuits can withstand consistent with cyclic fatigue. The device provides acceleration for multiple bunches in parallel channels, and permits a short exposure time for the conducting surface of the accelerating cavities. Our analysis includes scalings based on a smooth transmission line model and a complementary treatment with a coupled-cavity simulation. We provide also an electromagnetic design for the accelerating structure, arriving at rough dimensions for a seven-cell accelerator matched to standard waveguide and suitable for bench tests at low power in air at 91.392. GHz. A critical element in the concept is a fast mm-wave switch suitable for operation at high-power, and we present the considerations for implementation in an H-plane tee. We discuss the use of diamond as the photoconductor switch medium.

  11. Wake field accelerators

    SciTech Connect

    Wilson, P.B.

    1986-02-01

    In a wake field accelerator a high current driving bunch injected into a structure or plasma produces intense induced fields, which are in turn used to accelerate a trailing charge or bunch. The basic concepts of wake field acceleration are described. Wake potentials for closed cavities and periodic structures are derived, as are wake potentials on a collinear path with a charge distribution. Cylindrically symmetric structures excited by a beam in the form of a ring are considered. (LEW)

  12. ACCELERATION RESPONSIVE SWITCH

    DOEpatents

    Chabrek, A.F.; Maxwell, R.L.

    1963-07-01

    An acceleration-responsive device with dual channel capabilities whereby a first circuit is actuated upon attainment of a predetermined maximum acceleration level and when the acceleration drops to a predetermined minimum acceleriltion level another circuit is actuated is described. A fluid-damped sensing mass slidably mounted in a relatively frictionless manner on a shaft through the intermediation of a ball bushing and biased by an adjustable compression spring provides inertially operated means for actuating the circuits. (AEC)

  13. Optically pulsed electron accelerator

    DOEpatents

    Fraser, John S.; Sheffield, Richard L.

    1987-01-01

    An optically pulsed electron accelerator can be used as an injector for a free electron laser and comprises a pulsed light source, such as a laser, for providing discrete incident light pulses. A photoemissive electron source emits electron bursts having the same duration as the incident light pulses when impinged upon by same. The photoemissive electron source is located on an inside wall of a radio frequency powered accelerator cell which accelerates the electron burst emitted by the photoemissive electron source.

  14. Optically pulsed electron accelerator

    DOEpatents

    Fraser, J.S.; Sheffield, R.L.

    1985-05-20

    An optically pulsed electron accelerator can be used as an injector for a free electron laser and comprises a pulsed light source, such as a laser, for providing discrete incident light pulses. A photoemissive electron source emits electron bursts having the same duration as the incident light pulses when impinged upon by same. The photoemissive electron source is located on an inside wall of a radiofrequency-powered accelerator cell which accelerates the electron burst emitted by the photoemissive electron source.

  15. Induction technology optimization code

    SciTech Connect

    Caporaso, G.J.; Brooks, A.L.; Kirbie, H.C.

    1992-08-21

    A code has been developed to evaluate relative costs of induction accelerator driver systems for relativistic klystrons. The code incorporates beam generation, transport and pulsed power system constraints to provide an integrated design tool. The code generates an injector/accelerator combination which satisfies the top level requirements and all system constraints once a small number of design choices have been specified (rise time of the injector voltage and aspect ratio of the ferrite induction cores, for example). The code calculates dimensions of accelerator mechanical assemblies and values of all electrical components. Cost factors for machined parts, raw materials and components are applied to yield a total system cost. These costs are then plotted as a function of the two design choices to enable selection of an optimum design based on various criteria. The Induction Technology Optimization Study (ITOS) was undertaken to examine viable combinations of a linear induction accelerator and a relativistic klystron (RK) for high power microwave production. It is proposed, that microwaves from the RK will power a high-gradient accelerator structure for linear collider development. Previous work indicates that the RK will require a nominal 3-MeV, 3-kA electron beam with a 100-ns flat top. The proposed accelerator-RK combination will be a high average power system capable of sustained microwave output at a 300-Hz pulse repetition frequency. The ITOS code models many combinations of injector, accelerator, and pulse power designs that will supply an RK with the beam parameters described above.

  16. Acceleration of polarized protons in circular accelerators

    SciTech Connect

    Courant, E.D.; Ruth, R.D.

    1980-09-12

    The theory of depolarization in circular accelerators is presented. The spin equation is first expressed in terms of the particle orbit and then converted to the equivalent spinor equation. The spinor equation is then solved for three different situations: (1) a beam on a flat top near a resonance, (2) uniform acceleration through an isolated resonance, and (3) a model of a fast resonance jump. Finally, the depolarization coefficient, epsilon, is calculated in terms of properties of the particle orbit and the results are applied to a calculation of depolarization in the AGS.

  17. Charged particle accelerator grating

    DOEpatents

    Palmer, Robert B.

    1986-01-01

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams into the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  18. Particle acceleration in flares

    NASA Technical Reports Server (NTRS)

    Benz, Arnold O.; Kosugi, Takeo; Aschwanden, Markus J.; Benka, Steve G.; Chupp, Edward L.; Enome, Shinzo; Garcia, Howard; Holman, Gordon D.; Kurt, Victoria G.; Sakao, Taro

    1994-01-01

    Particle acceleration is intrinsic to the primary energy release in the impulsive phase of solar flares, and we cannot understand flares without understanding acceleration. New observations in soft and hard X-rays, gamma-rays and coherent radio emissions are presented, suggesting flare fragmentation in time and space. X-ray and radio measurements exhibit at least five different time scales in flares. In addition, some new observations of delayed acceleration signatures are also presented. The theory of acceleration by parallel electric fields is used to model the spectral shape and evolution of hard X-rays. The possibility of the appearance of double layers is further investigated.

  19. Accelerator-based BNCT.

    PubMed

    Kreiner, A J; Baldo, M; Bergueiro, J R; Cartelli, D; Castell, W; Thatar Vento, V; Gomez Asoia, J; Mercuri, D; Padulo, J; Suarez Sandin, J C; Erhardt, J; Kesque, J M; Valda, A A; Debray, M E; Somacal, H R; Igarzabal, M; Minsky, D M; Herrera, M S; Capoulat, M E; Gonzalez, S J; del Grosso, M F; Gagetti, L; Suarez Anzorena, M; Gun, M; Carranza, O

    2014-06-01

    The activity in accelerator development for accelerator-based BNCT (AB-BNCT) both worldwide and in Argentina is described. Projects in Russia, UK, Italy, Japan, Israel, and Argentina to develop AB-BNCT around different types of accelerators are briefly presented. In particular, the present status and recent progress of the Argentine project will be reviewed. The topics will cover: intense ion sources, accelerator tubes, transport of intense beams, beam diagnostics, the (9)Be(d,n) reaction as a possible neutron source, Beam Shaping Assemblies (BSA), a treatment room, and treatment planning in realistic cases.

  20. Accelerator-based BNCT.

    PubMed

    Kreiner, A J; Baldo, M; Bergueiro, J R; Cartelli, D; Castell, W; Thatar Vento, V; Gomez Asoia, J; Mercuri, D; Padulo, J; Suarez Sandin, J C; Erhardt, J; Kesque, J M; Valda, A A; Debray, M E; Somacal, H R; Igarzabal, M; Minsky, D M; Herrera, M S; Capoulat, M E; Gonzalez, S J; del Grosso, M F; Gagetti, L; Suarez Anzorena, M; Gun, M; Carranza, O

    2014-06-01

    The activity in accelerator development for accelerator-based BNCT (AB-BNCT) both worldwide and in Argentina is described. Projects in Russia, UK, Italy, Japan, Israel, and Argentina to develop AB-BNCT around different types of accelerators are briefly presented. In particular, the present status and recent progress of the Argentine project will be reviewed. The topics will cover: intense ion sources, accelerator tubes, transport of intense beams, beam diagnostics, the (9)Be(d,n) reaction as a possible neutron source, Beam Shaping Assemblies (BSA), a treatment room, and treatment planning in realistic cases. PMID:24365468

  1. Charged particle accelerator grating

    DOEpatents

    Palmer, Robert B.

    1986-09-02

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams into the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  2. SSTO design optimization

    NASA Astrophysics Data System (ADS)

    Furniss, S. G.

    1989-10-01

    While an SSTO with airbreathing propulsion for initial acceleration may greatly reduce future payload launch costs, such vehicles exhibit extreme sensitivity to design assumptions; the process of vehicle optimization is, accordingly, a difficult one. Attention is presently given to the role in optimization of the design mission, fuselage geometry, and the means employed to furnish adequate pitch and directional control. The requirements influencing wing design and scaling are also discussed. The Saenger and Hotol designs are the illustrative cases noted in this generalizing consideration of the SSTO-optimization process.

  3. Laser Guiding for GeV Laser-Plasma Accelerators

    SciTech Connect

    Leemans, Wim; Esarey, Eric; Geddes, Cameron; Schroeder, C.B.; Toth, Csaba

    2005-06-06

    Guiding of relativistically intense laser beams in preformed plasma channels is discussed for development of GeV-class laser accelerators. Experiments using a channel guided laser wakefield accelerator (LWFA) at LBNL have demonstrated that near mono-energetic 100 MeV-class electron beams can be produced with a 10 TW laser system. Analysis, aided by particle-in-cell simulations, as well as experiments with various plasma lengths and densities, indicate that tailoring the length of the accelerator, together with loading of the accelerating structure with beam, is the key to production of mono-energetic electron beams. Increasing the energy towards a GeV and beyond will require reducing the plasma density and design criteria are discussed for an optimized accelerator module. The current progress and future directions are summarized through comparison with conventional accelerators, highlighting the unique short term prospects for intense radiation sources based on laser-driven plasma accelerators.

  4. Angular velocities, angular accelerations, and coriolis accelerations

    NASA Technical Reports Server (NTRS)

    Graybiel, A.

    1975-01-01

    Weightlessness, rotating environment, and mathematical analysis of Coriolis acceleration is described for man's biological effective force environments. Effects on the vestibular system are summarized, including the end organs, functional neurology, and input-output relations. Ground-based studies in preparation for space missions are examined, including functional tests, provocative tests, adaptive capacity tests, simulation studies, and antimotion sickness.

  5. Four-body trajectory optimization

    NASA Technical Reports Server (NTRS)

    Pu, C. L.; Edelbaum, T. N.

    1974-01-01

    A comprehensive optimization program has been developed for computing fuel-optimal trajectories between the earth and a point in the sun-earth-moon system. It presents methods for generating fuel optimal two-impulse trajectories which may originate at the earth or a point in space and fuel optimal three-impulse trajectories between two points in space. The extrapolation of the state vector and the computation of the state transition matrix are accomplished by the Stumpff-Weiss method. The cost and constraint gradients are computed analytically in terms of the terminal state and the state transition matrix. The 4-body Lambert problem is solved by using the Newton-Raphson method. An accelerated gradient projection method is used to optimize a 2-impulse trajectory with terminal constraint. The Davidon's Variance Method is used both in the accelerated gradient projection method and the outer loop of a 3-impulse trajectory optimization problem.

  6. Accelerators Beyond The Tevatron?

    SciTech Connect

    Lach, Joseph; /Fermilab

    2010-07-01

    Following the successful operation of the Fermilab superconducting accelerator three new higher energy accelerators were planned. They were the UNK in the Soviet Union, the LHC in Europe, and the SSC in the United States. All were expected to start producing physics about 1995. They did not. Why?

  7. Accelerators Beyond The Tevatron?

    SciTech Connect

    Lach, Joseph

    2010-07-29

    Following the successful operation of the Fermilab superconducting accelerator three new higher energy accelerators were planned. They were the UNK in the Soviet Union, the LHC in Europe, and the SSC in the United States. All were expected to start producing physics about 1995. They did not. Why?.

  8. Accelerators (4/5)

    ScienceCinema

    None

    2016-07-12

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  9. 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.

  10. Accelerators (3/5)

    ScienceCinema

    None

    2016-07-12

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  11. Accelerators (5/5)

    ScienceCinema

    None

    2016-07-12

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  12. Accelerators (5/5)

    SciTech Connect

    2009-07-09

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  13. Accelerators (4/5)

    SciTech Connect

    2009-07-08

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  14. Accelerators (3/5)

    SciTech Connect

    2009-07-07

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  15. Ion Induction Accelerators

    NASA Astrophysics Data System (ADS)

    Barnard, John J.; Horioka, Kazuhiko

    The description of beams in RF and induction accelerators share many common features. Likewise, there is considerable commonality between electron induction accelerators (see Chap. 7) and ion induction accelerators. However, in contrast to electron induction accelerators, there are fewer ion induction accelerators that have been operated as application-driven user facilities. Ion induction accelerators are envisioned for applications (see Chap. 10) such as Heavy Ion Fusion (HIF), High Energy Density Physics (HEDP), and spallation neutron sources. Most ion induction accelerators constructed to date have been limited scale facilities built for feasibility studies for HIF and HEDP where a large numbers of ions are required on target in short pulses. Because ions are typically non-relativistic or weakly relativistic in much of the machine, space-charge effects can be of crucial importance. This contrasts the situation with electron machines, which are usually strongly relativistic leading to weaker transverse space-charge effects and simplified longitudinal dynamics. Similarly, the bunch structure of ion induction accelerators relative to RF machines results in significant differences in the longitudinal physics.

  16. Particle Acceleration in Jets

    NASA Technical Reports Server (NTRS)

    Nishikawa, Ken-Ichi

    2005-01-01

    Nonthermal radiation observed from astrophysical systems containing relativistic jets and shocks, e.g., active galactic nuclei (AGNs), gamma ray burst (GRBs), and Galactic microquasar systems usually have power-law emission spectra. Fermi acceleration is the mechanism usually assumed for the acceleration of particles in astrophysical environments.

  17. Microscale acceleration history discriminators

    DOEpatents

    Polosky, Marc A.; Plummer, David W.

    2002-01-01

    A new class of micromechanical acceleration history discriminators is claimed. These discriminators allow the precise differentiation of a wide range of acceleration-time histories, thereby allowing adaptive events to be triggered in response to the severity (or lack thereof) of an external environment. Such devices have applications in airbag activation, and other safety and surety applications.

  18. Diagnostics for induction accelerators

    SciTech Connect

    Fessenden, T.J.

    1996-04-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at LLNL from the early 1960`s to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400 ns pulses. The Advanced Test Accelerator (ATA) built at Livermore`s Site 300 produced 10,000 Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and LBNL. This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high current, short pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail.

  19. KEK digital accelerator

    NASA Astrophysics Data System (ADS)

    Iwashita, T.; Adachi, T.; Takayama, K.; Leo, K. W.; Arai, T.; Arakida, Y.; Hashimoto, M.; Kadokura, E.; Kawai, M.; Kawakubo, T.; Kubo, Tomio; Koyama, K.; Nakanishi, H.; Okazaki, K.; Okamura, K.; Someya, H.; Takagi, A.; Tokuchi, A.; Wake, M.

    2011-07-01

    The High Energy Accelerator Research Organization KEK digital accelerator (KEK-DA) is a renovation of the KEK 500 MeV booster proton synchrotron, which was shut down in 2006. The existing 40 MeV drift tube linac and rf cavities have been replaced by an electron cyclotron resonance (ECR) ion source embedded in a 200 kV high-voltage terminal and induction acceleration cells, respectively. A DA is, in principle, capable of accelerating any species of ion in all possible charge states. The KEK-DA is characterized by specific accelerator components such as a permanent magnet X-band ECR ion source, a low-energy transport line, an electrostatic injection kicker, an extraction septum magnet operated in air, combined-function main magnets, and an induction acceleration system. The induction acceleration method, integrating modern pulse power technology and state-of-art digital control, is crucial for the rapid-cycle KEK-DA. The key issues of beam dynamics associated with low-energy injection of heavy ions are beam loss caused by electron capture and stripping as results of the interaction with residual gas molecules and the closed orbit distortion resulting from relatively high remanent fields in the bending magnets. Attractive applications of this accelerator in materials and biological sciences are discussed.

  20. Controllable Laser Ion Acceleration

    NASA Astrophysics Data System (ADS)

    Kawata, S.; Kamiyama, D.; Ohtake, Y.; Takano, M.; Barada, D.; Kong, Q.; Wang, P. X.; Gu, Y. J.; Wang, W. M.; Limpouch, J.; Andreev, A.; Bulanov, S. V.; Sheng, Z. M.; Klimo, O.; Psikal, J.; Ma, Y. Y.; Li, X. F.; Yu, Q. S.

    2016-02-01

    In this paper a future laser ion accelerator is discussed to make the laser-based ion accelerator compact and controllable. Especially a collimation device is focused in this paper. The future laser ion accelerator should have an ion source, ion collimators, ion beam bunchers, and ion post acceleration devices [Laser Therapy 22, 103(2013)]: the ion particle energy and the ion energy spectrum are controlled to meet requirements for a future compact laser ion accelerator for ion cancer therapy or for other purposes. The energy efficiency from the laser to ions is improved by using a solid target with a fine sub-wavelength structure or a near-critical density gas plasma. The ion beam collimation is performed by holes behind the solid target or a multi-layered solid target. The control of the ion energy spectrum and the ion particle energy, and the ion beam bunching would be successfully realized by a multistage laser-target interaction.

  1. Cascaded radiation pressure acceleration

    SciTech Connect

    Pei, Zhikun; Shen, Baifei E-mail: zhxm@siom.ac.cn; Zhang, Xiaomei E-mail: zhxm@siom.ac.cn; Wang, Wenpeng; Zhang, Lingang; Yi, Longqing; Shi, Yin; Xu, Zhizhan

    2015-07-15

    A cascaded radiation-pressure acceleration scheme is proposed. When an energetic proton beam is injected into an electrostatic field moving at light speed in a foil accelerated by light pressure, protons can be re-accelerated to much higher energy. An initial 3-GeV proton beam can be re-accelerated to 7 GeV while its energy spread is narrowed significantly, indicating a 4-GeV energy gain for one acceleration stage, as shown in one-dimensional simulations and analytical results. The validity of the method is further confirmed by two-dimensional simulations. This scheme provides a way to scale proton energy at the GeV level linearly with laser energy and is promising to obtain proton bunches at tens of gigaelectron-volts.

  2. Accelerators, Beams And Physical Review Special Topics - Accelerators And Beams

    SciTech Connect

    Siemann, R.H.; /SLAC

    2011-10-24

    Accelerator science and technology have evolved as accelerators became larger and important to a broad range of science. Physical Review Special Topics - Accelerators and Beams was established to serve the accelerator community as a timely, widely circulated, international journal covering the full breadth of accelerators and beams. The history of the journal and the innovations associated with it are reviewed.

  3. Large electrostatic accelerators

    SciTech Connect

    Jones, C.M.

    1984-01-01

    The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of large electrostatic accelerators designed to operate at terminal potentials of 20 MV or above. In this paper, the author briefly discusses the status of these new accelerators and also discusses several recent technological advances which may be expected to further improve their performance. The paper is divided into four parts: (1) a discussion of the motivation for the construction of large electrostatic accelerators, (2) a description and discussion of several large electrostatic accelerators which have been recently completed or are under construction, (3) a description of several recent innovations which may be expected to improve the performance of large electrostatic accelerators in the future, and (4) a description of an innovative new large electrostatic accelerator whose construction is scheduled to begin next year. Due to time and space constraints, discussion is restricted to consideration of only tandem accelerators.

  4. Analyzing radial acceleration with a smartphone acceleration sensor

    NASA Astrophysics Data System (ADS)

    Vogt, Patrik; Kuhn, Jochen

    2013-03-01

    This paper continues the sequence of experiments using the acceleration sensor of smartphones (for description of the function and the use of the acceleration sensor, see Ref. 1) within this column, in this case for analyzing the radial acceleration.

  5. Accelerating Scientific Computations using FPGAs

    NASA Astrophysics Data System (ADS)

    Pell, O.; Atasu, K.; Mencer, O.

    Field Programmable Gate Arrays (FPGAs) are semiconductor devices that contain a grid of programmable cells, which the user configures to implement any digital circuit of up to a few million gates. Modern FPGAs allow the user to reconfigure these circuits many times each second, making FPGAs fully programmable and general purpose. Recent FPGA technology provides sufficient resources to tackle scientific applications on large-scale parallel systems. As a case study, we implement the Fast Fourier Transform [1] in a flexible floating point implementation. We utilize A Stream Compiler [2] (ASC) which combines C++ syntax with flexible floating point support by providing a 'HWfloat' data-type. The resulting FFT can be targeted to a variety of FPGA platforms in FFTW-style, though not yet completely automatically. The resulting FFT circuit can be adapted to the particular resources available on the system. The optimal implementation of an FFT accelerator depends on the length and dimensionality of the FFT, the available FPGA area, the available hard DSP blocks, the FPGA board architecture, and the precision and range of the application [3]. Software-style object-orientated abstractions allow us to pursue an accelerated pace of development by maximizing re-use of design patterns. ASC allows a few core hardware descriptions to generate hundreds of different circuit variants to meet particular speed, area and precision goals. The key to achieving maximum acceleration of FFT computation is to match memory and compute bandwidths so that maximum use is made of computational resources. Modern FPGAs contain up to hundreds of independent SRAM banks to store intermediate results, providing ample scope for optimizing memory parallelism. At 175Mhz, one of Maxeler's Radix-4 FFT cores computes 4x as many 1024pt FFTs per second as a dual Pentium-IV Xeon machine running FFTW. Eight such parallel cores fit onto the largest FPGA in the Xilinx Virtex-4 family, providing a 32x speed-up over

  6. Confronting Twin Paradox Acceleration

    NASA Astrophysics Data System (ADS)

    Murphy, Thomas W.

    2016-05-01

    The resolution to the classic twin paradox in special relativity rests on the asymmetry of acceleration. Yet most students are not exposed to a satisfactory analysis of what exactly happens during the acceleration phase that results in the nonaccelerated observer's more rapid aging. The simple treatment presented here offers both graphical and quantitative solutions to the problem, leading to the correct result that the acceleration-induced age gap is 2Lβ years when the one-way distance L is expressed in light-years and velocity β ≡v/c .

  7. Twisted waveguide accelerating structure.

    SciTech Connect

    Kang, Y. W.

    2000-08-15

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

  8. Ion beam accelerator system

    NASA Technical Reports Server (NTRS)

    Aston, Graeme (Inventor)

    1984-01-01

    A system is described that combines geometrical and electrostatic focusing to provide high ion extraction efficiency and good focusing of an accelerated ion beam. The apparatus includes a pair of curved extraction grids (16, 18) with multiple pairs of aligned holes positioned to direct a group of beamlets (20) along converging paths. The extraction grids are closely spaced and maintained at a moderate potential to efficiently extract beamlets of ions and allow them to combine into a single beam (14). An accelerator electrode device (22) downstream from the extraction grids, is at a much lower potential than the grids to accelerate the combined beam.

  9. Ion beam accelerator system

    NASA Technical Reports Server (NTRS)

    Aston, G. (Inventor)

    1981-01-01

    A system is described that combines geometrical and electrostatic focusing to provide high ion extraction efficiency and good focusing of an accelerated ion beam. The apparatus includes a pair of curved extraction grids with multiple pairs of aligned holes positioned to direct a group of beamlets along converging paths. The extraction grids are closely spaced and maintained at a moderate potential to efficiently extract beamlets of ions and allow them to combine into a single beam. An accelerator electrode device downstream from the extraction grids is at a much lower potential than the grids to accelerate the combined beam. The application of the system to ion implantation is mentioned.

  10. Accelerator on a Chip

    ScienceCinema

    England, Joel

    2016-07-12

    SLAC's Joel England explains how the same fabrication techniques used for silicon computer microchips allowed their team to create the new laser-driven particle accelerator chips. (SLAC Multimedia Communications)

  11. Charged particle accelerator grating

    DOEpatents

    Palmer, R.B.

    1985-09-09

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator is described. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams onto the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  12. Non-accelerator experiments

    SciTech Connect

    Goldhaber, M.

    1986-01-01

    This report discusses several topics which can be investigated without the use of accelerators. Topics covered are: (1) proton decay, (2) atmospheric neutrinos, (3) neutrino detection, (4) muons from Cygnus X-3, and (5) the double-beta decay.

  13. 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.

  14. 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.

  15. Rare Isotope Accelerators

    NASA Astrophysics Data System (ADS)

    Savard, Guy

    2002-04-01

    The next frontier for low-energy nuclear physics involves experimentation with accelerated beams of short-lived radioactive isotopes. A new facility, the Rare Isotope Accelerator (RIA), is proposed to produce large amount of these rare isotopes and post-accelerate them to energies relevant for studies in nuclear physics, astrophysics and the study of fundamental interactions at low energy. The basic science motivation for this facility will be introduced. The general facility layout, from the 400 kW heavy-ion superconducting linac used for production of the required isotopes to the novel production and extraction schemes and the highly efficient post-accelerator, will be presented. Special emphasis will be put on a number of technical breakthroughs and recent R&D results that enable this new facility.

  16. Accelerator on a Chip

    SciTech Connect

    England, Joel

    2014-06-30

    SLAC's Joel England explains how the same fabrication techniques used for silicon computer microchips allowed their team to create the new laser-driven particle accelerator chips. (SLAC Multimedia Communications)

  17. HEAVY ION LINEAR ACCELERATOR

    DOEpatents

    Van Atta, C.M.; Beringer, R.; Smith, L.

    1959-01-01

    A linear accelerator of heavy ions is described. The basic contributions of the invention consist of a method and apparatus for obtaining high energy particles of an element with an increased charge-to-mass ratio. The method comprises the steps of ionizing the atoms of an element, accelerating the resultant ions to an energy substantially equal to one Mev per nucleon, stripping orbital electrons from the accelerated ions by passing the ions through a curtain of elemental vapor disposed transversely of the path of the ions to provide a second charge-to-mass ratio, and finally accelerating the resultant stripped ions to a final energy of at least ten Mev per nucleon.

  18. Wake field acceleration experiments

    SciTech Connect

    Simpson, J.D.

    1988-01-01

    Where and how will wake field acceleration devices find use for other than, possibly, accelerators for high energy physics. I don't know that this can be responsibly answered at this time. What I can do is describe some recent results from an ongoing experimental program at Argonne which support the idea that wake field techniques and devices are potentially important for future accelerators. Perhaps this will spawn expanded interest and even new ideas for the use of this new technology. The Argonne program, and in particular the Advanced Accelerator Test Facility (AATF), has been reported in several fairly recent papers and reports. But because this is a substantially new audience for the subject, I will include a brief review of the program and the facility before describing experiments. 10 refs., 7 figs.

  19. 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.

  20. Multileaf collimator for Coline medical accelerators

    NASA Astrophysics Data System (ADS)

    Harasimowicz, Janusz; Plebański, Grzegorz; Sajna, Krzysztof

    2008-01-01

    Multileaf collimator (MLC) allows advanced field shaping for radiation therapy delivered with medical accelerators. In this paper theoretical considerations and scientific studies of a new MLC design are described. Considered multileaf collimator model comprises of a multiplicity of tungsten leaves of 1 cm width projected at isocenter plane. To ensure compatibility of a new MLC solution with different accelerator types as well as to assure high reliability in irradiated environment and presence of strong magnetic field, a complex and independent control system had to be developed. It comprises of two modules - one placed in the accelerator treatment head and the other one placed in the control room. Both of them ensure high reliability and treatment quality while working in harsh conditions. Mechanical design and leaf shape optimization algorithm based on a ray tracing method are also described in details. Adapted solutions allowed providing minimized and uniform radiation penumbrae in the full range of leaves positions which is crucial for modern advanced radiotherapy.

  1. Collective field accelerator

    DOEpatents

    Luce, John S.

    1978-01-01

    A collective field accelerator which operates with a vacuum diode and utilizes a grooved cathode and a dielectric anode that operates with a relativistic electron beam with a .nu./.gamma. of .about. 1, and a plurality of dielectric lenses having an axial magnetic field thereabout to focus the collectively accelerated electrons and ions which are ejected from the anode. The anode and lenses operate as unoptimized r-f cavities which modulate and focus the beam.

  2. Rolamite acceleration sensor

    DOEpatents

    Abbin, Joseph P.; Briner, Clifton F.; Martin, Samuel B.

    1993-01-01

    A rolamite acceleration sensor which has a failsafe feature including a housing, a pair of rollers, a tension band wrapped in an S shaped fashion around the rollers, wherein the band has a force-generation cut out and a failsafe cut out or weak portion. The failsafe cut out or weak portion breaks when the sensor is subjected to an excessive acceleration so that the sensor fails in an open circuit (non-conducting) state permanently.

  3. Microgravity Acceleration Measurement System

    NASA Technical Reports Server (NTRS)

    Foster, William

    2009-01-01

    Microgravity Acceleration Measurement System (MAMS) is an ongoing study of the small forces (vibrations and accelerations) on the ISS that result from the operation of hardware, crew activities, as well as dockings and maneuvering. Results will be used to generalize the types of vibrations affecting vibration-sensitive experiments. Investigators seek to better understand the vibration environment on the space station to enable future research.

  4. Rolamite acceleration sensor

    DOEpatents

    Abbin, J.P.; Briner, C.F.; Martin, S.B.

    1993-12-21

    A rolamite acceleration sensor is described which has a failsafe feature including a housing, a pair of rollers, a tension band wrapped in an S shaped fashion around the rollers, wherein the band has a force-generation cut out and a failsafe cut out or weak portion. The failsafe cut out or weak portion breaks when the sensor is subjected to an excessive acceleration so that the sensor fails in an open circuit (non-conducting) state permanently. 6 figures.

  5. Microwave inverse Cerenkov accelerator

    NASA Astrophysics Data System (ADS)

    Zhang, T. B.; Marshall, T. C.; LaPointe, M. A.; Hirshfield, J. L.

    1997-03-01

    A Microwave Inverse Cerenkov Accelerator (MICA) is currently under construction at the Yale Beam Physics Laboratory. The accelerating structure in MICA consists of an axisymmetric dielectrically lined waveguide. For the injection of 6 MeV microbunches from a 2.856 GHz RF gun, and subsequent acceleration by the TM01 fields, particle simulation studies predict that an acceleration gradient of 6.3 MV/m can be achieved with a traveling-wave power of 15 MW applied to the structure. Synchronous injection into a narrow phase window is shown to allow trapping of all injected particles. The RF fields of the accelerating structure are shown to provide radial focusing, so that longitudinal and transverse emittance growth during acceleration is small, and that no external magnetic fields are required for focusing. For 0.16 nC, 5 psec microbunches, the normalized emittance of the accelerated beam is predicted to be less than 5πmm-mrad. Experiments on sample alumina tubes have been conducted that verify the theoretical dispersion relation for the TM01 mode over a two-to-one range in frequency. No excitation of axisymmetric or non-axisymmetric competing waveguide modes was observed. High power tests showed that tangential electric fields at the inner surface of an uncoated sample of alumina pipe could be sustained up to at least 8.4 MV/m without breakdown. These considerations suggest that a MICA test accelerator can be built to examine these predictions using an available RF power source, 6 MeV RF gun and associated beam line.

  6. Amps particle accelerator definition study

    NASA Technical Reports Server (NTRS)

    Sellen, J. M., Jr.

    1975-01-01

    The Particle Accelerator System of the AMPS (Atmospheric, Magnetospheric, and Plasmas in Space) payload is a series of charged particle accelerators to be flown with the Space Transportation System Shuttle on Spacelab missions. In the configuration presented, the total particle accelerator system consists of an energetic electron beam, an energetic ion accelerator, and both low voltage and high voltage plasma acceleration devices. The Orbiter is illustrated with such a particle accelerator system.

  7. Laser Plasma Accelerators

    NASA Astrophysics Data System (ADS)

    Malka, Victor

    The continuing development of powerful laser systems has permitted to extend the interaction of laser beams with matter far into the relativistic domain, and to demonstrate new approaches for producing energetic particle beams. The extremely large electric fields, with amplitudes exceeding the TV/m level, that are produced in plasma medium are of relevance particle acceleration. Since the value of this longitudinal electric field, 10,000 times larger than those produced in conventional radio-frequency cavities, plasma accelerators appear to be very promising for the development of compact accelerators. The incredible progresses in the understanding of laser plasma interaction physic, allows an excellent control of electron injection and acceleration. Thanks to these recent achievements, laser plasma accelerators deliver today high quality beams of energetic radiation and particles. These beams have a number of interesting properties such as shortness, brightness and spatial quality, and could lend themselves to applications in many fields, including medicine, radio-biology, chemistry, physics and material science,security (material inspection), and of course in accelerator science.

  8. Biomedical accelerator mass spectrometry

    NASA Astrophysics Data System (ADS)

    Freeman, Stewart P. H. T.; Vogel, John S.

    1995-05-01

    Ultrasensitive SIMS with accelerator based spectrometers has recently begun to be applied to biomedical problems. Certain very long-lived radioisotopes of very low natural abundances can be used to trace metabolism at environmental dose levels ( [greater-or-equal, slanted] z mol in mg samples). 14C in particular can be employed to label a myriad of compounds. Competing technologies typically require super environmental doses that can perturb the system under investigation, followed by uncertain extrapolation to the low dose regime. 41Ca and 26Al are also used as elemental tracers. Given the sensitivity of the accelerator method, care must be taken to avoid contamination of the mass spectrometer and the apparatus employed in prior sample handling including chemical separation. This infant field comprises the efforts of a dozen accelerator laboratories. The Center for Accelerator Mass Spectrometry has been particularly active. In addition to collaborating with groups further afield, we are researching the kinematics and binding of genotoxins in-house, and we support innovative uses of our capability in the disciplines of chemistry, pharmacology, nutrition and physiology within the University of California. The field can be expected to grow further given the numerous potential applications and the efforts of several groups and companies to integrate more the accelerator technology into biomedical research programs; the development of miniaturized accelerator systems and ion sources capable of interfacing to conventional HPLC and GMC, etc. apparatus for complementary chemical analysis is anticipated for biomedical laboratories.

  9. 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

  10. GPU Accelerated Vector Median Filter

    NASA Technical Reports Server (NTRS)

    Aras, Rifat; Shen, Yuzhong

    2011-01-01

    Noise reduction is an important step for most image processing tasks. For three channel color images, a widely used technique is vector median filter in which color values of pixels are treated as 3-component vectors. Vector median filters are computationally expensive; for a window size of n x n, each of the n(sup 2) vectors has to be compared with other n(sup 2) - 1 vectors in distances. General purpose computation on graphics processing units (GPUs) is the paradigm of utilizing high-performance many-core GPU architectures for computation tasks that are normally handled by CPUs. In this work. NVIDIA's Compute Unified Device Architecture (CUDA) paradigm is used to accelerate vector median filtering. which has to the best of our knowledge never been done before. The performance of GPU accelerated vector median filter is compared to that of the CPU and MPI-based versions for different image and window sizes, Initial findings of the study showed 100x improvement of performance of vector median filter implementation on GPUs over CPU implementations and further speed-up is expected after more extensive optimizations of the GPU algorithm .

  11. Accelerator Physics Working Group Summary

    NASA Astrophysics Data System (ADS)

    Li, D.; Uesugi, T.; Wildnerc, E.

    2010-03-01

    The Accelerator Physics Working Group addressed the worldwide R&D activities performed in support of future neutrino facilities. These studies cover R&D activities for Super Beam, Beta Beam and muon-based Neutrino Factory facilities. Beta Beam activities reported the important progress made, together with the research activity planned for the coming years. Discussion sessions were also organized jointly with other working groups in order to define common ground for the optimization of a future neutrino facility. Lessons learned from already operating neutrino facilities provide key information for the design of any future neutrino facility, and were also discussed in this meeting. Radiation damage, remote handling for equipment maintenance and exchange, and primary proton beam stability and monitoring were among the important subjects presented and discussed. Status reports for each of the facility subsystems were presented: proton drivers, targets, capture systems, and muon cooling and acceleration systems. The preferred scenario for each type of possible future facility was presented, together with the challenges and remaining issues. The baseline specification for the muon-based Neutrino Factory was reviewed and updated where required. This report will emphasize new results and ideas and discuss possible changes in the baseline scenarios of the facilities. A list of possible future steps is proposed that should be followed up at NuFact10.

  12. Diffusive Shock Acceleration and Reconnection Acceleration Processes

    NASA Astrophysics Data System (ADS)

    Zank, G. P.; Hunana, P.; Mostafavi, P.; Le Roux, J. A.; Li, Gang; Webb, G. M.; Khabarova, O.; Cummings, A.; Stone, E.; Decker, R.

    2015-12-01

    Shock waves, as shown by simulations and observations, can generate high levels of downstream vortical turbulence, including magnetic islands. We consider a combination of diffusive shock acceleration (DSA) and downstream magnetic-island-reconnection-related processes as an energization mechanism for charged particles. Observations of electron and ion distributions downstream of interplanetary shocks and the heliospheric termination shock (HTS) are frequently inconsistent with the predictions of classical DSA. We utilize a recently developed transport theory for charged particles propagating diffusively in a turbulent region filled with contracting and reconnecting plasmoids and small-scale current sheets. Particle energization associated with the anti-reconnection electric field, a consequence of magnetic island merging, and magnetic island contraction, are considered. For the former only, we find that (i) the spectrum is a hard power law in particle speed, and (ii) the downstream solution is constant. For downstream plasmoid contraction only, (i) the accelerated spectrum is a hard power law in particle speed; (ii) the particle intensity for a given energy peaks downstream of the shock, and the distance to the peak location increases with increasing particle energy, and (iii) the particle intensity amplification for a particular particle energy, f(x,c/{c}0)/f(0,c/{c}0), is not 1, as predicted by DSA, but increases with increasing particle energy. The general solution combines both the reconnection-induced electric field and plasmoid contraction. The observed energetic particle intensity profile observed by Voyager 2 downstream of the HTS appears to support a particle acceleration mechanism that combines both DSA and magnetic-island-reconnection-related processes.

  13. Emittance measurements from the LLUMC proton accelerator

    NASA Astrophysics Data System (ADS)

    Coutrakon, G.; Gillespie, G. H.; Hubbard, J.; Sanders, E.

    2005-12-01

    A new method of calculating beam emittances at the extraction point of a particle accelerator is presented. The technique uses the optimization programs NPSOL and MINOS developed at Stanford University in order to determine the initial values of beam size, divergence and correlation parameters (i.e. beam sigma matrix, σij) that best fit measured beam parameters. These σij elements are then used to compute the Twiss parameters α, β, and the phase space area, ε, of the beam at the extraction point. Beam size measurements in X and Y throughout the transport line were input to the optimizer along with the magnetic elements of bends, quads, and drifts. The σij parameters were optimized at the accelerator's extraction point by finding the best agreement between these measured beam sizes and those predicted by TRANSPORT. This expands upon a previous study in which a "trial and error" technique was used instead of the optimizer software, and which yielded similar results. The Particle Beam Optics Laboratory (PBO Lab™) program used for this paper integrates particle beam optics and other codes into a single intuitive graphically-based computing environment. This new software provides a seamless interface between the NPSOL and MINOS optimizer and TRANSPORT calculations. The results of these emittance searches are presented here for the eight clinical energies between 70 and 250 MeV currently being used at LLUMC.

  14. New Advanced Dielectric Materials for Accelerator Applications

    SciTech Connect

    Kanareykin, A.

    2010-11-04

    We present our recent results on the development and experimental testing of advanced dielectric materials that are capable of supporting the high RF electric fields generated by electron beams or pulsed high power microwaves. These materials have been optimized or specially designed for accelerator applications. The materials discussed here include low loss microwave ceramics, quartz, Chemical Vapor Deposition diamonds and nonlinear Barium Strontium Titanate based ferroelectrics.

  15. Ion acceleration enhanced by target ablation

    SciTech Connect

    Zhao, S.; Lin, C. Wang, H. Y.; Lu, H. Y.; He, X. T.; Yan, X. Q.; Chen, J. E.; Cowan, T. E.

    2015-07-15

    Laser proton acceleration can be enhanced by using target ablation, due to the energetic electrons generated in the ablation preplasma. When the ablation pulse matches main pulse, the enhancement gets optimized because the electrons' energy density is highest. A scaling law between the ablation pulse and main pulse is confirmed by the simulation, showing that for given CPA pulse and target, proton energy improvement can be achieved several times by adjusting the target ablation.

  16. New Advanced Dielectric Materials for Accelerator Applications

    NASA Astrophysics Data System (ADS)

    Kanareykin, A.

    2010-11-01

    We present our recent results on the development and experimental testing of advanced dielectric materials that are capable of supporting the high RF electric fields generated by electron beams or pulsed high power microwaves. These materials have been optimized or specially designed for accelerator applications. The materials discussed here include low loss microwave ceramics, quartz, Chemical Vapor Deposition diamonds and nonlinear Barium Strontium Titanate based ferroelectrics.

  17. Terascale Optimal PDE Simulations

    SciTech Connect

    David Keyes

    2009-07-28

    The Terascale Optimal PDE Solvers (TOPS) Integrated Software Infrastructure Center (ISIC) was created to develop and implement algorithms and support scientific investigations performed by DOE-sponsored researchers. These simulations often involve the solution of partial differential equations (PDEs) on terascale computers. The TOPS Center researched, developed and deployed an integrated toolkit of open-source, optimal complexity solvers for the nonlinear partial differential equations that arise in many DOE application areas, including fusion, accelerator design, global climate change and reactive chemistry. The algorithms created as part of this project were also designed to reduce current computational bottlenecks by orders of magnitude on terascale computers, enabling scientific simulation on a scale heretofore impossible.

  18. Surfzone alongshore advective accelerations: observations and modeling

    NASA Astrophysics Data System (ADS)

    Hansen, J.; Raubenheimer, B.; Elgar, S.

    2014-12-01

    The sources, magnitudes, and impacts of non-linear advective accelerations on alongshore surfzone currents are investigated with observations and a numerical model. Previous numerical modeling results have indicated that advective accelerations are an important contribution to the alongshore force balance, and are required to understand spatial variations in alongshore currents (which may result in spatially variable morphological change). However, most prior observational studies have neglected advective accelerations in the alongshore force balance. Using a numerical model (Delft3D) to predict optimal sensor locations, a dense array of 26 colocated current meters and pressure sensors was deployed between the shoreline and 3-m water depth over a 200 by 115 m region near Duck, NC in fall 2013. The array included 7 cross- and 3 alongshore transects. Here, observational and numerical estimates of the dominant forcing terms in the alongshore balance (pressure and radiation-stress gradients) and the advective acceleration terms will be compared with each other. In addition, the numerical model will be used to examine the force balance, including sources of velocity gradients, at a higher spatial resolution than possible with the instrument array. Preliminary numerical results indicate that at O(10-100 m) alongshore scales, bathymetric variations and the ensuing alongshore variations in the wave field and subsequent forcing are the dominant sources of the modeled velocity gradients and advective accelerations. Additional simulations and analysis of the observations will be presented. Funded by NSF and ASDR&E.

  19. Induction accelerator development for heavy ion fusion

    SciTech Connect

    Reginato, L.L.

    1993-05-01

    For approximately a decade, the Heavy Ion Fusion Accelerator Research (HIFAR) group at LBL has been exploring the use of induction accelerators with multiple beams as the driver for inertial fusion targets. Scaled experiments have investigated the transport of space charge dominated beams (SBTE), and the current amplification and transverse emittance control in induction linacs (MBE-4) with very encouraging results. In order to study many of the beam manipulations required by a driver and to further develop economically competitive technology, a proposal has been made in partnership with LLNL to build a 10 MeV accelerator and to conduct a series of experiments collectively called the Induction Linac System Experiments (ILSE). The major components critical to the ILSE accelerator are currently under development. We have constructed a full scale induction module and we have tested a number of amorphous magnetic materials developed by Allied Signal to establish an overall optimal design. The electric and magnetic quadrupoles critical to the transport and focusing of heavy ion beams are also under development The hardware is intended to be economically competitive for a driver without sacrificing any of the physics or performance requirements. This paper will concentrate on the recent developments and tests of the major components required by the ILSE accelerator.

  20. AESS: Accelerated Exact Stochastic Simulation

    NASA Astrophysics Data System (ADS)

    Jenkins, David D.; Peterson, Gregory D.

    2011-12-01

    The Stochastic Simulation Algorithm (SSA) developed by Gillespie provides a powerful mechanism for exploring the behavior of chemical systems with small species populations or with important noise contributions. Gene circuit simulations for systems biology commonly employ the SSA method, as do ecological applications. This algorithm tends to be computationally expensive, so researchers seek an efficient implementation of SSA. In this program package, the Accelerated Exact Stochastic Simulation Algorithm (AESS) contains optimized implementations of Gillespie's SSA that improve the performance of individual simulation runs or ensembles of simulations used for sweeping parameters or to provide statistically significant results. Program summaryProgram title: AESS Catalogue identifier: AEJW_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEJW_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: University of Tennessee copyright agreement No. of lines in distributed program, including test data, etc.: 10 861 No. of bytes in distributed program, including test data, etc.: 394 631 Distribution format: tar.gz Programming language: C for processors, CUDA for NVIDIA GPUs Computer: Developed and tested on various x86 computers and NVIDIA C1060 Tesla and GTX 480 Fermi GPUs. The system targets x86 workstations, optionally with multicore processors or NVIDIA GPUs as accelerators. Operating system: Tested under Ubuntu Linux OS and CentOS 5.5 Linux OS Classification: 3, 16.12 Nature of problem: Simulation of chemical systems, particularly with low species populations, can be accurately performed using Gillespie's method of stochastic simulation. Numerous variations on the original stochastic simulation algorithm have been developed, including approaches that produce results with statistics that exactly match the chemical master equation (CME) as well as other approaches that approximate the CME. Solution

  1. Electrostatic Plasma Accelerator (EPA)

    NASA Technical Reports Server (NTRS)

    Brophy, John R.; Aston, Graeme

    1989-01-01

    The Electrostatic Plasma Accelerator (EPA) is a thruster concept which promises specific impulse levels between low power arcjets and those of the ion engine while retaining the relative simplicity of the arcjet. The EPA thruster produces thrust through the electrostatic acceleration of a moderately dense plasma. No accelerating electrodes are used and the specific impulse is a direct function of the applied discharge voltage and the propellant atomic mass. The goal of the present program is to demonstrate feasibility of the EPA thruster concept through experimental and theoretical investigations of the EPA acceleration mechanism and discharge chamber performance. Experimental investigations will include operating the test bed ion (TBI) engine as an EPA thruster and parametrically varying the thruster geometry and operating conditions to quantify the electrostatic plasma acceleration effect. The theoretical investigations will include the development of a discharge chamber model which describes the relationships between the engine size, plasma properties, and overall performance. For the EPA thruster to be a viable propulsion concept, overall thruster efficiencies approaching 30% with specific impulses approaching 1000 s must be achieved.

  2. 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.

  3. Beamlets from stochastic acceleration.

    PubMed

    Perri, Silvia; Carbone, Vincenzo

    2008-09-01

    We investigate the dynamics of a realization of the stochastic Fermi acceleration mechanism. The model consists of test particles moving between two oscillating magnetic clouds and differs from the usual Fermi-Ulam model in two ways. (i) Particles can penetrate inside clouds before being reflected. (ii) Particles can radiate a fraction of their energy during the process. Since the Fermi mechanism is at work, particles are stochastically accelerated, even in the presence of the radiated energy. Furthermore, due to a kind of resonance between particles and oscillating clouds, the probability density function of particles is strongly modified, thus generating beams of accelerated particles rather than a translation of the whole distribution function to higher energy. This simple mechanism could account for the presence of beamlets in some space plasma physics situations.

  4. Perturbations for transient acceleration

    SciTech Connect

    Vargas, Cristofher Zuñiga; Zimdahl, Winfried; Hipólito-Ricaldi, Wiliam S. E-mail: hipolito@ceunes.ufes.br

    2012-04-01

    According to the standard ΛCDM model, the accelerated expansion of the Universe will go on forever. Motivated by recent observational results, we explore the possibility of a finite phase of acceleration which asymptotically approaches another period of decelerated expansion. Extending an earlier study on a corresponding homogeneous and isotropic dynamics, in which interactions between dark matter and dark energy are crucial, the present paper also investigates the dynamics of the matter perturbations both on the Newtonian and General Relativistic (GR) levels and quantifies the potential relevance of perturbations of the dark-energy component. In the background, the model is tested against the Supernova type Ia (SNIa) data of the Constitution set and on the perturbative level against growth rate data, among them those of the WiggleZ survey, and the data of the 2dFGRS project. Our results indicate that a transient phase of accelerated expansion is not excluded by current observations.

  5. Acceleration radioisotope production simulations

    SciTech Connect

    Waters, L.S.; Wilson, W.B.

    1996-12-31

    We have identified 96 radionuclides now being used or under consideration for use in medical applications. Previously, we calculated the production of {sup 99}Mo from enriched and depleted uranium targets at the 800-MeV energy used in the LAMPF accelerator at Los Alamos. We now consider the production of isotopes using lower energy beams, which may become available as a result of new high-intensity spallation target accelerators now being planned. The production of four radionuclides ({sup 7}Be, {sup 67}Cu, {sup 99}Mo, and {sup 195m}Pt) in a simplified proton accelerator target design is being examined. The LAHET, MCNP, and CINDER90 codes were used to model the target, transport a beam of protons and secondary produced particles through the system, and compute the nuclide production from spallation and low-energy neutron interactions. Beam energies of 200 and 400 MeV were used, and several targets were considered for each nuclide.

  6. Laser acceleration with open waveguides

    SciTech Connect

    Xie, Ming

    1999-03-01

    A unified framework based on solid-state open waveguides is developed to overcome all three major limitations on acceleration distance and hence on the feasibility of two classes of laser acceleration. The three limitations are due to laser diffraction, acceleration phase slippage, and damage of waveguide structure by high power laser. The two classes of laser acceleration are direct-field acceleration and ponderomotive-driven acceleration. Thus the solutions provided here encompass all mainstream approaches for laser acceleration, either in vacuum, gases or plasmas.

  7. Uniform acceleration in general relativity

    NASA Astrophysics Data System (ADS)

    Friedman, Yaakov; Scarr, Tzvi

    2015-10-01

    We extend de la Fuente and Romero's (Gen Relativ Gravit 47:33, 2015) defining equation for uniform acceleration in a general curved spacetime from linear acceleration to the full Lorentz covariant uniform acceleration. In a flat spacetime background, we have explicit solutions. We use generalized Fermi-Walker transport to parallel transport the Frenet basis along the trajectory. In flat spacetime, we obtain velocity and acceleration transformations from a uniformly accelerated system to an inertial system. We obtain the time dilation between accelerated clocks. We apply our acceleration transformations to the motion of a charged particle in a constant electromagnetic field and recover the Lorentz-Abraham-Dirac equation.

  8. Diffusive Shock Acceleration

    NASA Astrophysics Data System (ADS)

    Baring, Matthew

    2003-04-01

    The process of diffusive acceleration of charged particles in shocked plasmas is widely invoked in astrophysics to account for the ubiquitous presence of signatures of non-thermal relativistic electrons and ions in the universe. This statistical energization mechanism, manifested in turbulent media, was first posited by Enrico Fermi in 1949 to explain the observed cosmic ray population, which exhibits an almost power-law distribution in rigidity. The absence of a momentum scale is a key characteristic of diffusive shock acceleration, and astrophysical systems generally only impose scales at the injection (low energy) and loss (high energy) ends of the particle spectrum. The existence of structure in the cosmic ray spectrum (the "knee") at around 3000 TeV has promoted contentions that there are at least two origins for cosmic rays, a galactic one supplying those up to the knee, and perhaps an extragalactic one that can explain even the ultra-high energy cosmic rays (UHECRs) seen at 1-300 EeV. Accounting for the UHECRs with familiar astrophysical sites of acceleration has historically proven difficult due to the need to assume high magnetic fields in order to reduce the shortest diffusive acceleration timescale, the ion gyroperiod, to meaningful values. Yet active galaxies and gamma-ray bursts remain strong and interesting candidate sources for UHECRs, turning the theoretical focus to relativistic shocks. This review summarizes properties of diffusive shock acceleration that are salient to the issue of UHECR generation. These include spectral indices, anisotropies, acceleration efficencies and timescales, as functions of the shock speed and mean field orientation, and also the degree of field turbulence. Astrophysical sites for UHECR production are also critiqued.

  9. Microelectromechanical acceleration-sensing apparatus

    DOEpatents

    Lee, Robb M.; Shul, Randy J.; Polosky, Marc A.; Hoke, Darren A.; Vernon, George E.

    2006-12-12

    An acceleration-sensing apparatus is disclosed which includes a moveable shuttle (i.e. a suspended mass) and a latch for capturing and holding the shuttle when an acceleration event is sensed above a predetermined threshold level. The acceleration-sensing apparatus provides a switch closure upon sensing the acceleration event and remains latched in place thereafter. Examples of the acceleration-sensing apparatus are provided which are responsive to an acceleration component in a single direction (i.e. a single-sided device) or to two oppositely-directed acceleration components (i.e. a dual-sided device). A two-stage acceleration-sensing apparatus is also disclosed which can sense two acceleration events separated in time. The acceleration-sensing apparatus of the present invention has applications, for example, in an automotive airbag deployment system.

  10. HIGH GRADIENT INDUCTION ACCELERATOR

    SciTech Connect

    Caporaso, G J; Sampayan, S; Chen, Y; Blackfield, D; Harris, J; Hawkins, S; Holmes, C; Krogh, M; Nelson, S; Nunnally, W; Paul, A; Poole, B; Rhodes, M; Sanders, D; Selenes, K; Sullivan, J; Wang, L; Watson, J

    2007-06-21

    A new type of compact induction accelerator is under development at the Lawrence Livermore National Laboratory that promises to increase the average accelerating gradient by at least an order of magnitude over that of existing induction machines. The machine is based on the use of high gradient vacuum insulators, advanced dielectric materials and switches and is stimulated by the desire for compact flash x-ray radiography sources. Research describing an extreme variant of this technology aimed at proton therapy for cancer will be described. Progress in applying this technology to several applications will be reviewed.

  11. Photocathodes in accelerator applications

    SciTech Connect

    Fraser, J.S.; Sheffield, R.L.; Gray, E.R.; Giles, P.M.; Springer, R.W.; Loebs, V.A.

    1987-01-01

    Some electron accelerator applications require bursts of short pulses at high microscopic repetition rates and high peak brightness. A photocathode, illuminated by a mode-locked laser, is well suited to filling this need. The intrinsic brightness of a photoemitter beam is high; experiments are under way at Los Alamos to study the brightness of short bunches with high space charge after acceleration. A laser-illuminated Cs/sub 3/Sb photoemitter is located in the first rf cavity of an injector linac. Diagnostics include a pepper-pot emittance analyzer, a magnetic spectrometer, and a streak camera.

  12. Interfacing to accelerator instrumentation

    SciTech Connect

    Shea, T.J.

    1995-12-31

    As the sensory system for an accelerator, the beam instrumentation provides a tremendous amount of diagnostic information. Access to this information can vary from periodic spot checks by operators to high bandwidth data acquisition during studies. In this paper, example applications will illustrate the requirements on interfaces between the control system and the instrumentation hardware. A survey of the major accelerator facilities will identify the most popular interface standards. The impact of developments such as isochronous protocols and embedded digital signal processing will also be discussed.

  13. Accelerated molecular dynamics methods

    SciTech Connect

    Perez, Danny

    2011-01-04

    The molecular dynamics method, although extremely powerful for materials simulations, is limited to times scales of roughly one microsecond or less. On longer time scales, dynamical evolution typically consists of infrequent events, which are usually activated processes. This course is focused on understanding infrequent-event dynamics, on methods for characterizing infrequent-event mechanisms and rate constants, and on methods for simulating long time scales in infrequent-event systems, emphasizing the recently developed accelerated molecular dynamics methods (hyperdynamics, parallel replica dynamics, and temperature accelerated dynamics). Some familiarity with basic statistical mechanics and molecular dynamics methods will be assumed.

  14. Critical assessment of accelerating trypsination methods.

    PubMed

    Hustoft, Hanne Kolsrud; Reubsaet, Leon; Greibrokk, Tyge; Lundanes, Elsa; Malerod, Helle

    2011-12-15

    In LC-MS based proteomics, several accelerating trypsination methods have been introduced in order to speed up the protein digestion, which is often considered a bottleneck. Traditionally and most commonly, due to sample heterogeneity, overnight digestion at 37 °C is performed in order to digest both easily and more resistant proteins. High efficiency protein identification is important in proteomics, hours with LC-MS/MS analysis is needless if the majority of the proteins are not digested. Based on preliminary experiments utilizing some of the suggested accelerating methods, the question of whether accelerating digestion methods really provide the same protein identification efficiency as the overnight digestion was asked. In the present study we have evaluated four different accelerating trypsination methods (infrared (IR) and microwave assisted, solvent aided and immobilized trypsination). The methods were compared with conventional digestion at 37 °C in the same time range using a four protein mixture. Sequence coverage and peak area of intact proteins were used for the comparison. The accelerating methods were able to digest the proteins, but none of the methods appeared to be more efficient than the conventional digestion method at 37 °C. The conventional method at 37 °C is easy to perform using commercially available instrumentation and appears to be the digestion method to use. The digestion time in targeted proteomics can be optimized for each protein, while in comprehensive proteomics the digestion time should be extended due to sample heterogeneity and influence of other proteins present. Recommendations regarding optimizing and evaluating the tryptic digestion for both targeted and comprehensive proteomics are given, and a digestion method suitable as the first method for newcomers in comprehensive proteomics is suggested.

  15. Prospects for Accelerator Technology

    NASA Astrophysics Data System (ADS)

    Todd, Alan

    2011-02-01

    Accelerator technology today is a greater than US$5 billion per annum business. Development of higher-performance technology with improved reliability that delivers reduced system size and life cycle cost is expected to significantly increase the total accelerator technology market and open up new application sales. Potential future directions are identified and pitfalls in new market penetration are considered. Both of the present big market segments, medical radiation therapy units and semiconductor ion implanters, are approaching the "maturity" phase of their product cycles, where incremental development rather than paradigm shifts is the norm, but they should continue to dominate commercial sales for some time. It is anticipated that large discovery-science accelerators will continue to provide a specialty market beset by the unpredictable cycles resulting from the scale of the projects themselves, coupled with external political and economic drivers. Although fraught with differing market entry difficulties, the security and environmental markets, together with new, as yet unrealized, industrial material processing applications, are expected to provide the bulk of future commercial accelerator technology growth.

  16. Radioisotope Dating with Accelerators.

    ERIC Educational Resources Information Center

    Muller, Richard A.

    1979-01-01

    Explains a new method of detecting radioactive isotopes by counting their accelerated ions rather than the atoms that decay during the counting period. This method increases the sensitivity by several orders of magnitude, and allows one to find the ages of much older and smaller samples. (GA)

  17. The neutrino electron accelerator

    SciTech Connect

    Shukla, P.K.; Stenflo, L.; Bingham, R.; Bethe, H.A.; Dawson, J.M.; Mendonca, J.T.

    1998-01-01

    It is shown that a wake of electron plasma oscillations can be created by the nonlinear ponderomotive force of an intense neutrino flux. The electrons trapped in the plasma wakefield will be accelerated to high energies. Such processes may be important in supernovas and pulsars. {copyright} {ital 1998 American Institute of Physics.}

  18. FPGA Verification Accelerator (FVAX)

    NASA Technical Reports Server (NTRS)

    Oh, Jane; Burke, Gary

    2008-01-01

    Is Verification Acceleration Possible? - Increasing the visibility of the internal nodes of the FPGA results in much faster debug time - Forcing internal signals directly allows a problem condition to be setup very quickly center dot Is this all? - No, this is part of a comprehensive effort to improve the JPL FPGA design and V&V process.

  19. Pulsed electromagnetic gas acceleration

    NASA Technical Reports Server (NTRS)

    Jahn, R. G.; Vonjaskowsky, W. F.; Clark, K. E.

    1974-01-01

    Detailed measurements of the axial velocity profile and electromagnetic structure of a high power, quasi-steady MPD discharge are used to formulate a gasdynamic model of the acceleration process. Conceptually dividing the accelerated plasma into an inner flow and an outer flow, it is found that more than two-thirds of the total power in the plasma is deposited in the inner flow, accelerating it to an exhaust velocity of 12.5 km/sec. The outer flow, which is accelerated to a velocity of only 6.2 km/sec, appears to provide a current conduction path between the inner flow and the anode. Related cathode studies have shown that the critical current for the onset of terminal voltage fluctuations, which was recently shown to be a function of the cathode area, appears to reach an asymptote for cathodes of very large surface area. Detailed floating potential measurements show that the fluctuations are confined to the vicinity of the cathode and hence reflect a cathode emission process rather than a fundamental limit on MPD performance.

  20. Combined generating-accelerating buncher for compact linear accelerators

    NASA Astrophysics Data System (ADS)

    Savin, E. A.; Matsievskiy, S. V.; Sobenin, N. P.; Sokolov, I. D.; Zavadtsev, A. A.

    2016-09-01

    Described in the previous article [1] method of the power extraction from the modulated electron beam has been applied to the compact standing wave electron linear accelerator feeding system, which doesnt require any connection waveguides between the power source and the accelerator itself [2]. Generating and accelerating bunches meet in the hybrid accelerating cell operating at TM020 mode, thus the accelerating module is placed on the axis of the generating module, which consists from the pulsed high voltage electron sources and electrons dumps. This combination makes the accelerator very compact in size which is very valuable for the modern applications such as portable inspection sources. Simulations and geometry cold tests are presented.

  1. Menopause accelerates biological aging.

    PubMed

    Levine, Morgan E; Lu, Ake T; Chen, Brian H; Hernandez, Dena G; Singleton, Andrew B; Ferrucci, Luigi; Bandinelli, Stefania; Salfati, Elias; Manson, JoAnn E; Quach, Austin; Kusters, Cynthia D J; Kuh, Diana; Wong, Andrew; Teschendorff, Andrew E; Widschwendter, Martin; Ritz, Beate R; Absher, Devin; Assimes, Themistocles L; Horvath, Steve

    2016-08-16

    Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the "epigenetic clock"), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further. PMID:27457926

  2. Dynamics of a current bridge in a coaxial plasma accelerator

    NASA Astrophysics Data System (ADS)

    Voronin, A. V.; Gusev, V. K.; Kobyakov, S. V.

    2011-07-01

    The pioneering investigation of the behavior of a current bridge in a coaxial accelerator with pulsed delivery of a working gas liberated from titanium hydride by an electrical discharge is reported. A new method to trace the motion of the current bridge using LEDs is suggested. The behavior of the current bridge in accelerators with axial and radial gas injection is studied. The parameters of an accelerator generating a pure plasma jet with a high kinetic energy (such as the size and polarity of electrodes, gas flow direction, and time delay between the delivery of the gas to the accelerator and its ionization) are optimized. The applicability of an electrodynamic model to this type of accelerator is discussed. Good agreement between experimental data and calculation results is obtained.

  3. Theory of electron-cyclotron-resonance laser accelerators

    SciTech Connect

    Chen, C. )

    1992-11-15

    The cyclotron-resonance laser (CRL) accelerator is a novel concept of accelerating continuous charged-particle beams to moderately or highly relativistic energies. This paper discusses prospects and limitations of this concept. In particular, the nonlinear coupling of an intense traveling electromagnetic wave with an electron beam in a guide magnetic field is studied, and the effects of wave dispersion on particle acceleration are analyzed. For a tenuous beam, it is shown in a single-particle theory that the maximum energy gain and the maximum acceleration distance for the beam electrons in CRL accelerators with optimal magnetic taper exhibit power-law scaling on the degree of wave dispersion (measured by the parameter [omega]/[ital ck][sub [parallel

  4. Efficient Optical Energy Harvesting in Self-Accelerating Beams

    PubMed Central

    Bongiovanni, Domenico; Hu, Yi; Wetzel, Benjamin; Robles, Raul A.; Mendoza González, Gregorio; Marti-Panameño, Erwin A.; Chen, Zhigang; Morandotti, Roberto

    2015-01-01

    We report the experimental observation of energetically confined self-accelerating optical beams propagating along various convex trajectories. We show that, under an appropriate transverse compression of their spatial spectra, these self-accelerating beams can exhibit a dramatic enhancement of their peak intensity and a significant decrease of their transverse expansion, yet retaining both the expected acceleration profile and the intrinsic self-healing properties. We found our experimental results to be in excellent agreement with the numerical simulations. We expect further applications in such contexts where power budget and optimal spatial confinement can be important limiting factors. PMID:26299360

  5. A New Cavity Design For Medium Beta Acceleration

    SciTech Connect

    He, Feisi; Wang, Haipeng; Rimmer, Robert A.

    2014-02-01

    Heavy duty or cw, superconducting proton and heavy ion accelerators are being proposed and constructed worldwide. The total length of the machine is one of the main drivers in terms of cost. Thus hwr and spoke cavities at medium beta are usually optimized to achieve low surface field and high gradient. A novel accelerating structure at beta=0.5 evolved from spoke cavity is proposed, with lower surface fields but slightly higher heat load. It would be an interesting option for pulsed and cw accelerators with beam energy of more than 200mev/u.

  6. Staging acceleration and cooling in a Neutrino Factory

    NASA Astrophysics Data System (ADS)

    Johnstone, C.; Berz, M.; Makino, K.

    2006-03-01

    All schemes to produce intense sources of high-energy muons—Neutrino factories, beta beams, Colliders—require collection, RF capture, and transport of particle beams with unprecedented emittances, both longitudinally and transversely. These large initial emittances must be reduced or "cooled" both in size and in energy spread before the muons can be efficiently accelerated to multi-GeV energies. The acceleration stage becomes critical in formulating and optimizing muon beams; individual stages are strongly interlinked and not independent as is the case in most conventional acceleration systems. Most importantly, the degree of cooling, or cooling channel, depends on the choice of acceleration. In the current US baseline scenario, the cooling required for acceleration is about a factor of 10 in transverse emittance per plane. Longitudinal cooling is also required. In the proposed Japanese scenario, using an alternative acceleration scheme, no cooling is presumed. This work discusses two basic, but different approaches to a Neutrino Factory and how the optimal strategy depends on beam parameters and method of acceleration.

  7. Tapered plasma channels to phase-lock accelerating and focusing forces in laser-plasma accelerators

    SciTech Connect

    Rittershofer, W.; Schroeder, C.B.; Esarey, E.; Gruner, F.J.; Leemans, W.P.

    2010-05-17

    Tapered plasma channels are considered for controlling dephasing of a beam with respect to a plasma wave driven by a weakly-relativistic, short-pulse laser. Tapering allows for enhanced energy gain in a single laser plasma accelerator stage. Expressions are derived for the taper, or longitudinal plasma density variation, required to maintain a beam at a constant phase in the longitudinal and/or transverse fields of the plasma wave. In a plasma channel, the phase velocities of the longitudinal and transverse fields differ, and, hence, the required tapering differs. The length over which the tapered plasma density becomes singular is calculated. Linear plasma tapering as well as discontinuous plasma tapering, which moves beams to adjacent plasma wave buckets, are also considered. The energy gain of an accelerated electron in a tapered laser-plasma accelerator is calculated and the laser pulse length to optimize the energy gain is determined.

  8. Mass spectrometry with accelerators.

    PubMed

    Litherland, A E; Zhao, X-L; Kieser, W E

    2011-01-01

    As one in a series of articles on Canadian contributions to mass spectrometry, this review begins with an outline of the history of accelerator mass spectrometry (AMS), noting roles played by researchers at three Canadian AMS laboratories. After a description of the unique features of AMS, three examples, (14)C, (10)Be, and (129)I are given to illustrate the methods. The capabilities of mass spectrometry have been extended by the addition of atomic isobar selection, molecular isobar attenuation, further ion acceleration, followed by ion detection and ion identification at essentially zero dark current or ion flux. This has been accomplished by exploiting the techniques and accelerators of atomic and nuclear physics. In 1939, the first principles of AMS were established using a cyclotron. In 1977 the selection of isobars in the ion source was established when it was shown that the (14)N(-) ion was very unstable, or extremely difficult to create, making a tandem electrostatic accelerator highly suitable for assisting the mass spectrometric measurement of the rare long-lived radioactive isotope (14)C in the environment. This observation, together with the large attenuation of the molecular isobars (13)CH(-) and (12)CH 2(-) during tandem acceleration and the observed very low background contamination from the ion source, was found to facilitate the mass spectrometry of (14)C to at least a level of (14)C/C ~ 6 × 10(-16), the equivalent of a radiocarbon age of 60,000 years. Tandem Accelerator Mass Spectrometry, or AMS, has now made possible the accurate radiocarbon dating of milligram-sized carbon samples by ion counting as well as dating and tracing with many other long-lived radioactive isotopes such as (10)Be, (26)Al, (36)Cl, and (129)I. The difficulty of obtaining large anion currents with low electron affinities and the difficulties of isobar separation, especially for the heavier mass ions, has prompted the use of molecular anions and the search for alternative

  9. Accelerator research studies

    SciTech Connect

    Not Available

    1992-01-01

    The Accelerator Research Studies program at the University of Maryland, sponsored by the Department of Energy under grant number DE-FG05-91ER40642, is currently in the first year of a three-year funding cycle. The program consists of the following three tasks: TASK A, Study of Transport and Longitudinal Compression of Intense, High-Brightness Beams, TASK B, Study of Collective Ion Acceleration by Intense Electron Beams and Pseudospark Produced High Brightness Electron Beams; TASK C, Study of a Gyroklystron High-power Microwave Source for Linear Colliders. In this report we document the progress that has been made during the past year for each of the three tasks.

  10. Accelerators for Cancer Therapy

    DOE R&D Accomplishments Database

    Lennox, Arlene J.

    2000-05-30

    The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy.

  11. SUPERDIFFUSIVE SHOCK ACCELERATION

    SciTech Connect

    Perri, S.; Zimbardo, G.

    2012-05-10

    The theory of diffusive shock acceleration is extended to the case of superdiffusive transport, i.e., when the mean square deviation grows proportionally to t{sup {alpha}}, with {alpha} > 1. Superdiffusion can be described by a statistical process called Levy random walk, in which the propagator is not a Gaussian but it exhibits power-law tails. By using the propagator appropriate for Levy random walk, it is found that the indices of energy spectra of particles are harder than those obtained where a normal diffusion is envisaged, with the spectral index decreasing with the increase of {alpha}. A new scaling for the acceleration time is also found, allowing substantially shorter times than in the case of normal diffusion. Within this framework we can explain a number of observations of flat spectra in various astrophysical and heliospheric contexts, for instance, for the Crab Nebula and the termination shock of the solar wind.

  12. Hardware Accelerated Simulated Radiography

    SciTech Connect

    Laney, D; Callahan, S; Max, N; Silva, C; Langer, S; Frank, R

    2005-04-12

    We present the application of hardware accelerated volume rendering algorithms to the simulation of radiographs as an aid to scientists designing experiments, validating simulation codes, and understanding experimental data. The techniques presented take advantage of 32 bit floating point texture capabilities to obtain validated solutions to the radiative transport equation for X-rays. An unsorted hexahedron projection algorithm is presented for curvilinear hexahedra that produces simulated radiographs in the absorption-only regime. A sorted tetrahedral projection algorithm is presented that simulates radiographs of emissive materials. We apply the tetrahedral projection algorithm to the simulation of experimental diagnostics for inertial confinement fusion experiments on a laser at the University of Rochester. We show that the hardware accelerated solution is faster than the current technique used by scientists.

  13. Accelerated expansion through interaction

    SciTech Connect

    Zimdahl, Winfried

    2009-05-01

    Interactions between dark matter and dark energy with a given equation of state are known to modify the cosmic dynamics. On the other hand, the strength of these interactions is subject to strong observational constraints. Here we discuss a model in which the transition from decelerated to accelerated expansion of the Universe arises as a pure interaction phenomenon. Various cosmological scenarios that describe a present stage of accelerated expansion, like the {lambda}CDM model or a (generalized) Chaplygin gas, follow as special cases for different interaction rates. This unifying view on the homogeneous and isotropic background level is accompanied by a non-adiabatic perturbation dynamics which can be seen as a consequence of a fluctuating interaction rate.

  14. Hypervelocity plate acceleration

    SciTech Connect

    Marsh, S.P.; Tan, T.H.

    1991-01-01

    Shock tubes have been used to accelerate 1.5-mm-thick stainless steel plates to high velocity while retaining their integrity. The fast shock tubes are 5.1-cm-diameter, 15.2-cm-long cylinders of PBX-9501 explosive containing a 1.1-cm-diameter cylindrical core of low-density polystyrene foam. The plates have been placed directly in contact with one face of the explosive system. Plane-wave detonation was initiated on the opposite face. A Mach disk was formed in the imploding styrofoam core, which provided the impulse required to accelerate the metal plate to high velocity. Parametric studies were made on this system to find the effect of varying plate metal, plate thickness, foam properties, and addition of a barrel. A maximum plate velocity of 9.0 km/s has been observed. 6 refs., 17 figs.

  15. Pulsed electromagnetic gas acceleration

    NASA Technical Reports Server (NTRS)

    Jahn, R. G.; Vonjaskowsky, W. F.; Clark, K. E.

    1971-01-01

    Experimental data were combined with one-dimensional conservation relations to yield information on the energy deposition ratio in a parallel-plate accelerator, where the downstream flow was confined to a constant area channel. Approximately 70% of the total input power was detected in the exhaust flow, of which only about 20% appeared as directed kinetic energy, thus implying that a downstream expansion to convert chamber enthalpy into kinetic energy must be an important aspect of conventional high power MPD arcs. Spectroscopic experiments on a quasi-steady MPD argon accelerator verified the presence of A(III) and the absence of A(I), and indicated an azimuthal structure in the jet related to the mass injection locations. Measurements of pressure in the arc chamber and impact pressure in the exhaust jet using a piezocrystal backed by a Plexiglas rod were in good agreement with the electromagnetic thrust model.

  16. Commissioning the GTA accelerator

    SciTech Connect

    Sander, O.R.; Atkins, W.H.; Bolme, G.O.; Bowling, S.; Brown, S.; Cole, R.; Gilpatrick, J.D.; Garnett, R.; Guy, F.W.; Ingalls, W.B.; Johnson, K.F.; Kerstiens, D.; Little, C.; Lohsen, R.A.; Lloyd, S.; Lysenko, W.P.; Mottershead, C.T.; Neuschaefer, G.; Power, J.; Rusthoi, D.P.; Sandoval, D.P. Stevens, R.R. Jr.; Vaughn, G.; Wadlinger, E.A.; Yuan, V.; Connolly, R.; Weiss, R.; Saadatmand, K.

    1992-09-01

    The Ground Test Accelerator (GTA) is supported by the Strategic Defense command as part of their Neutral Particle Beam (NPB) program. Neutral particles have the advantage that in space they are unaffected by the earth`s magnetic field and travel in straight lines unless they enter the earth`s atmosphere and become charged by stripping. Heavy particles are difficult to stop and can probe the interior of space vehicles; hence, NPB can function as a discriminator between warheads and decoys. We are using GTA to resolve the physics and engineering issues related to accelerating, focusing, and steering a high-brightness, high-current H{sup -} beam and then neutralizing it. Our immediate goal is to produce a 24-MeV, 50mA device with a 2% duty factor.

  17. Adaptive control for accelerators

    DOEpatents

    Eaton, Lawrie E.; Jachim, Stephen P.; Natter, Eckard F.

    1991-01-01

    An adaptive feedforward control loop is provided to stabilize accelerator beam loading of the radio frequency field in an accelerator cavity during successive pulses of the beam into the cavity. A digital signal processor enables an adaptive algorithm to generate a feedforward error correcting signal functionally determined by the feedback error obtained by a beam pulse loading the cavity after the previous correcting signal was applied to the cavity. Each cavity feedforward correcting signal is successively stored in the digital processor and modified by the feedback error resulting from its application to generate the next feedforward error correcting signal. A feedforward error correcting signal is generated by the digital processor in advance of the beam pulse to enable a composite correcting signal and the beam pulse to arrive concurrently at the cavity.

  18. Modulational effects in accelerators

    SciTech Connect

    Satogata, T.

    1997-12-01

    We discuss effects of field modulations in accelerators, specifically those that can be used for operational beam diagnostics and beam halo control. In transverse beam dynamics, combined effects of nonlinear resonances and tune modulations influence diffusion rates with applied tune modulation has been demonstrated. In the longitudinal domain, applied RF phase and voltage modulations provide mechanisms for parasitic halo transport, useful in slow crystal extraction. Experimental experiences with transverse tune and RF modulations are also discussed.

  19. Linear induction accelerator

    DOEpatents

    Buttram, M.T.; Ginn, J.W.

    1988-06-21

    A linear induction accelerator includes a plurality of adder cavities arranged in a series and provided in a structure which is evacuated so that a vacuum inductance is provided between each adder cavity and the structure. An energy storage system for the adder cavities includes a pulsed current source and a respective plurality of bipolar converting networks connected thereto. The bipolar high-voltage, high-repetition-rate square pulse train sets and resets the cavities. 4 figs.

  20. Accelerated plate tectonics.

    PubMed

    Anderson, D L

    1975-03-21

    The concept of a stressed elastic lithospheric plate riding on a viscous asthenosphere is used to calculate the recurrence interval of great earthquakes at convergent plate boundaries, the separation of decoupling and lithospheric earthquakes, and the migration pattern of large earthquakes along an arc. It is proposed that plate motions accelerate after great decoupling earthquakes and that most of the observed plate motions occur during short periods of time, separated by periods of relative quiescence.

  1. ION ACCELERATION SYSTEM

    DOEpatents

    Luce, J.S.; Martin, J.A.

    1960-02-23

    Well focused, intense ion beams are obtained by providing a multi- apertured source grid in front of an ion source chamber and an accelerating multi- apertured grid closely spaced from and in alignment with the source grid. The longest dimensions of the elongated apertures in the grids are normal to the direction of the magnetic field used with the device. Large ion currents may be withdrawn from the source, since they do not pass through any small focal region between the grids.

  2. Computer assisted accelerator tuning

    SciTech Connect

    Boyd, J.K.

    1993-04-14

    The challenge of tuning an induction accelerator in real time has been addressed with the new TUNE GUIDE code. The code initializes a beam at a particular position using a tracer particle representation of the phase space. The particles are transported, using a matrix formulation, element by element along the beamline assuming that the field of a solenoid, or steering element is constant over its length. The other allowed elements are gaps and drift sections. A great deal of effort has been spent programming TUNE GUIDE to operate under the IBMPC Windows 3.1 system. This system features an intuitive, menu driven interface, which provides an ability to rapidly change beamline component parameter values. Consequently various accelerator setups can be explored and new values determined in real time while the accelerator is operating. In addition the code has the capability of varying a capability value over a range and then plotting the resulting beam properties, such as radius or centroid position, at a down stream position. Element parameter editing is also included along with an on-line hyper text oriented help package.

  3. TRACKING ACCELERATOR SETTINGS.

    SciTech Connect

    D OTTAVIO,T.; FU, W.; OTTAVIO, D.P.

    2007-10-15

    Recording setting changes within an accelerator facility provides information that can be used to answer questions about when, why, and how changes were made to some accelerator system. This can be very useful during normal operations, but can also aid with security concerns and in detecting unusual software behavior. The Set History System (SHS) is a new client-server system developed at the Collider-Accelerator Department of Brookhaven National Laboratory to provide these capabilities. The SHS has been operational for over two years and currently stores about IOOK settings per day into a commercial database management system. The SHS system consists of a server written in Java, client tools written in both Java and C++, and a web interface for querying the database of setting changes. The design of the SHS focuses on performance, portability, and a minimal impact on database resources. In this paper, we present an overview of the system design along with benchmark results showing the performance and reliability of the SHS over the last year.

  4. Accelerator mass spectrometry.

    PubMed

    Hellborg, Ragnar; Skog, Göran

    2008-01-01

    In this overview the technique of accelerator mass spectrometry (AMS) and its use are described. AMS is a highly sensitive method of counting atoms. It is used to detect very low concentrations of natural isotopic abundances (typically in the range between 10(-12) and 10(-16)) of both radionuclides and stable nuclides. The main advantages of AMS compared to conventional radiometric methods are the use of smaller samples (mg and even sub-mg size) and shorter measuring times (less than 1 hr). The equipment used for AMS is almost exclusively based on the electrostatic tandem accelerator, although some of the newest systems are based on a slightly different principle. Dedicated accelerators as well as older "nuclear physics machines" can be found in the 80 or so AMS laboratories in existence today. The most widely used isotope studied with AMS is 14C. Besides radiocarbon dating this isotope is used in climate studies, biomedicine applications and many other fields. More than 100,000 14C samples are measured per year. Other isotopes studied include 10Be, 26Al, 36Cl, 41Ca, 59Ni, 129I, U, and Pu. Although these measurements are important, the number of samples of these other isotopes measured each year is estimated to be less than 10% of the number of 14C samples.

  5. Electrostatic Plasma Accelerator (EPA)

    NASA Technical Reports Server (NTRS)

    Brophy, John R.; Aston, Graeme

    1995-01-01

    The application of electric propulsion to communications satellites, however, has been limited to the use of hydrazine thrusters with electric heaters for thrust and specific impulse augmentation. These electrothermal thrusters operate at specific impulse levels of approximately 300 s with heater powers of about 500 W. Low power arcjets (1-3 kW) are currently being investigated as a way to increase specific impulse levels to approximately 500 s. Ion propulsion systems can easily produce specific impulses of 3000 s or greater, but have yet to be applied to communications satellites. The reasons most often given for not using ion propulsion systems are their high level of overall complexity, low thrust with long burn times, and the difficulty of integrating the propulsion system into existing commercial spacecraft busses. The Electrostatic Plasma Accelerator (EPA) is a thruster concept which promises specific impulse levels between low power arcjets and those of the ion engine while retaining the relative simplicity of the arcjet. The EPA thruster produces thrust through the electrostatic acceleration of a moderately dense plasma. No accelerating electrodes are used and the specific impulse is a direct function of the applied discharge voltage and the propellant atomic mass.

  6. ACCELERATION INTEGRATING MEANS

    DOEpatents

    Wilkes, D.F.

    1961-08-29

    An acceleration responsive device is described. A housing has at one end normally open electrical contacts and contains a piston system with a first part of non-magnetic material having metering orifices in the side walls for forming an air bearing between it and the walls of the housing; this first piston part is normally held against the other end of the housing from the noted contacts by a second piston or reset part. The reset part is of partly magnetic material, is separable from the flrst piston part, and is positioned within the housing intermediate the contacts and the first piston part. A magnet carried by the housing imposes a retaining force upon the reset part, along with a helical compression spring that is between the reset part and the end with the contacts. When a predetermined acceleration level is attained, the reset part overcomes the bias or retaining force provided by the magnet and the spring'' snaps'' into a depression in the housing adjacent the contacts. The first piston part is then free to move toward the contacts with its movement responsive tc acceleration forces and the metering orifices. (AEC)

  7. Acceleration during magnetic reconnection

    SciTech Connect

    Beresnyak, Andrey; Li, Hui

    2015-07-16

    The presentation begins with colorful depictions of solar x-ray flares and references to pulsar phenomena. Plasma reconnection is complex, could be x-point dominated or turbulent, field lines could break due to either resistivity or non-ideal effects, such as electron pressure anisotropy. Electron acceleration is sometimes observed, and sometimes not. One way to study this complex problem is to have many examples of the process (reconnection) and compare them; the other way is to simplify and come to something robust. Ideal MHD (E=0) turbulence driven by magnetic energy is assumed, and the first-order acceleration is sought. It is found that dissipation in big (length >100 ion skin depths) current sheets is universal and independent on microscopic resistivity and the mean imposed field; particles are regularly accelerated while experiencing curvature drift in flows driven by magnetic tension. One example of such flow is spontaneous reconnection. This explains hot electrons with a power-law tail in solar flares, as well as ultrashort time variability in some astrophysical sources.

  8. Berkeley Proton Linear Accelerator

    DOE R&D Accomplishments Database

    Alvarez, L. W.; Bradner, H.; Franck, J.; Gordon, H.; Gow, J. D.; Marshall, L. C.; Oppenheimer, F. F.; Panofsky, W. K. H.; Richman, C.; Woodyard, J. R.

    1953-10-13

    A linear accelerator, which increases the energy of protons from a 4 Mev Van de Graaff injector, to a final energy of 31.5 Mev, has been constructed. The accelerator consists of a cavity 40 feet long and 39 inches in diameter, excited at resonance in a longitudinal electric mode with a radio-frequency power of about 2.2 x 10{sup 6} watts peak at 202.5 mc. Acceleration is made possible by the introduction of 46 axial "drift tubes" into the cavity, which is designed such that the particles traverse the distance between the centers of successive tubes in one cycle of the r.f. power. The protons are longitudinally stable as in the synchrotron, and are stabilized transversely by the action of converging fields produced by focusing grids. The electrical cavity is constructed like an inverted airplane fuselage and is supported in a vacuum tank. Power is supplied by 9 high powered oscillators fed from a pulse generator of the artificial transmission line type.

  9. Overview of accelerators in medicine

    SciTech Connect

    Lennox, A.J. |

    1993-06-01

    Accelerators used for medicine include synchrotrons, cyclotrons, betatrons, microtrons, and electron, proton, and light ion linacs. Some accelerators which were formerly found only at physics laboratories are now being considered for use in hospital-based treatment and diagnostic facilities. This paper presents typical operating parameters for medical accelerators and gives specific examples of clinical applications for each type of accelerator, with emphasis on recent developments in the field.

  10. Tritium target manufacturing for use in accelerators

    NASA Astrophysics Data System (ADS)

    Bach, P.; Monnin, C.; Van Rompay, M.; Ballanger, A.

    2001-07-01

    As a neutron tube manufacturer, SODERN is now in charge of manufacturing tritium targets for accelerators, in cooperation with CEA/DAM/DTMN in Valduc. Specific deuterium and tritium targets are manufactured on request, according to the requirements of the users, starting from titanium target on copper substrate, and going to more sophisticated devices. A wide range of possible uses is covered, including thin targets for neutron calibration, thick targets with controlled loading of deuterium and tritium, rotating targets for higher lifetimes, or large size rotating targets for accelerators used in boron neutron therapy. Activity of targets lies in the 1 to 1000 Curie, diameter of targets being up to 30 cm. Special targets are also considered, including surface layer targets for lowering tritium desorption under irradiation, or those made from different kinds of occluders such as titanium, zirconium, erbium, scandium, with different substrates. It is then possible to optimize either neutron output, or lifetime and stability, or thermal behavior.

  11. Controlled Microwave Heating Accelerates Rolling Circle Amplification.

    PubMed

    Yoshimura, Takeo; Suzuki, Takamasa; Mineki, Shigeru; Ohuchi, Shokichi

    2015-01-01

    Rolling circle amplification (RCA) generates single-stranded DNAs or RNA, and the diverse applications of this isothermal technique range from the sensitive detection of nucleic acids to analysis of single nucleotide polymorphisms. Microwave chemistry is widely applied to increase reaction rate as well as product yield and purity. The objectives of the present research were to apply microwave heating to RCA and indicate factors that contribute to the microwave selective heating effect. The microwave reaction temperature was strictly controlled using a microwave applicator optimized for enzymatic-scale reactions. Here, we showed that microwave-assisted RCA reactions catalyzed by either of the four thermostable DNA polymerases were accelerated over 4-folds compared with conventional RCA. Furthermore, the temperatures of the individual buffer components were specifically influenced by microwave heating. We concluded that microwave heating accelerated isothermal RCA of DNA because of the differential heating mechanisms of microwaves on the temperatures of reaction components, although the overall reaction temperatures were the same.

  12. EIDOSCOPE: particle acceleration at plasma boundaries

    NASA Astrophysics Data System (ADS)

    Vaivads, A.; Andersson, G.; Bale, S. D.; Cully, C. M.; De Keyser, J.; Fujimoto, M.; Grahn, S.; Haaland, S.; Ji, H.; Khotyaintsev, Yu. V.; Lazarian, A.; Lavraud, B.; Mann, I. R.; Nakamura, R.; Nakamura, T. K. M.; Narita, Y.; Retinò, A.; Sahraoui, F.; Schekochihin, A.; Schwartz, S. J.; Shinohara, I.; Sorriso-Valvo, L.

    2012-04-01

    We describe the mission concept of how ESA can make a major contribution to the Japanese Canadian multi-spacecraft mission SCOPE by adding one cost-effective spacecraft EIDO (Electron and Ion Dynamics Observatory), which has a comprehensive and optimized plasma payload to address the physics of particle acceleration. The combined mission EIDOSCOPE will distinguish amongst and quantify the governing processes of particle acceleration at several important plasma boundaries and their associated boundary layers: collisionless shocks, plasma jet fronts, thin current sheets and turbulent boundary layers. Particle acceleration and associated cross-scale coupling is one of the key outstanding topics to be addressed in the Plasma Universe. The very important science questions that only the combined EIDOSCOPE mission will be able to tackle are: 1) Quantitatively, what are the processes and efficiencies with which both electrons and ions are selectively injected and subsequently accelerated by collisionless shocks? 2) How does small-scale electron and ion acceleration at jet fronts due to kinetic processes couple simultaneously to large scale acceleration due to fluid (MHD) mechanisms? 3) How does multi-scale coupling govern acceleration mechanisms at electron, ion and fluid scales in thin current sheets? 4) How do particle acceleration processes inside turbulent boundary layers depend on turbulence properties at ion/electron scales? EIDO particle instruments are capable of resolving full 3D particle distribution functions in both thermal and suprathermal regimes and at high enough temporal resolution to resolve the relevant scales even in very dynamic plasma processes. The EIDO spin axis is designed to be sun-pointing, allowing EIDO to carry out the most sensitive electric field measurements ever accomplished in the outer magnetosphere. Combined with a nearby SCOPE Far Daughter satellite, EIDO will form a second pair (in addition to SCOPE Mother-Near Daughter) of closely

  13. Particle acceleration on Galactic scales

    NASA Astrophysics Data System (ADS)

    Axford, W. I.

    The history of and current ideas concerning the origin of cosmic rays in the Galaxy and in extragalactic sources are surveyed. The observed properties of Galactic cosmic rays and shock acceleration are discussed. It is argued that shock acceleration in various guises is an essential and conceptually the most economical acceleration mechanism.

  14. Multicriterial approach to beam dynamics optimization problem

    NASA Astrophysics Data System (ADS)

    Vladimirova, L. V.

    2016-09-01

    The problem of optimization of particle beam dynamics in accelerating system is considered in the case when control process quality is estimated by several functionals. Multicriterial approach is used. When there are two criteria, compromise curve may be obtained. If the number of criteria is three or more, one can select some criteria to be main and impose the constraints on the remaining criteria. The optimization result is the set of efficient controls; a user has an opportunity to select the most appropriate control among them. The paper presents the results of multicriteria optimization of beam dynamics in linear accelerator LEA-15-M.

  15. Dynamic Optimization

    NASA Technical Reports Server (NTRS)

    Laird, Philip

    1992-01-01

    We distinguish static and dynamic optimization of programs: whereas static optimization modifies a program before runtime and is based only on its syntactical structure, dynamic optimization is based on the statistical properties of the input source and examples of program execution. Explanation-based generalization is a commonly used dynamic optimization method, but its effectiveness as a speedup-learning method is limited, in part because it fails to separate the learning process from the program transformation process. This paper describes a dynamic optimization technique called a learn-optimize cycle that first uses a learning element to uncover predictable patterns in the program execution and then uses an optimization algorithm to map these patterns into beneficial transformations. The technique has been used successfully for dynamic optimization of pure Prolog.

  16. APT accelerator. Topical report

    SciTech Connect

    Lawrence, G.; Rusthoi, D.

    1995-03-01

    The Accelerator Production of Tritium (APT) project, sponsored by Department of Energy Defense Programs (DOE/DP), involves the preconceptual design of an accelerator system to produce tritium for the nation`s stockpile of nuclear weapons. Tritium is an isotope of hydrogen used in nuclear weapons, and must be replenished because of radioactive decay (its half-life is approximately 12 years). Because the annual production requirements for tritium has greatly decreased since the end of the Cold War, an alternative approach to reactors for tritium production, based on a linear accelerator, is now being seriously considered. The annual tritium requirement at the time this study was undertaken (1992-1993) was 3/8 that of the 1988 goal, usually stated as 3/8-Goal. Continued reduction in the number of weapons in the stockpile has led to a revised (lower) production requirement today (March, 1995). The production requirement needed to maintain the reduced stockpile, as stated in the recent Nuclear Posture Review (summer 1994) is approximately 3/16-Goal, half the previous level. The Nuclear Posture Review also requires that the production plant be designed to accomodate a production increase (surge) to 3/8-Goal capability within five years, to allow recovery from a possible extended outage of the tritium plant. A multi-laboratory team, collaborating with several industrial partners, has developed a preconceptual APT design for the 3/8-Goal, operating at 75% capacity. The team has presented APT as a promising alternative to the reactor concepts proposed for Complex-21. Given the requirements of a reduced weapons stockpile, APT offers both significant safety, environmental, and production-fexibility advantages in comparison with reactor systems, and the prospect of successful development in time to meet the US defense requirements of the 21st Century.

  17. VLHC accelerator physics

    SciTech Connect

    Michael Blaskiewicz et al.

    2001-11-01

    A six-month design study for a future high energy hadron collider was initiated by the Fermilab director in October 2000. The request was to study a staged approach where a large circumference tunnel is built that initially would house a low field ({approx}2 T) collider with center-of-mass energy greater than 30 TeV and a peak (initial) luminosity of 10{sup 34} cm{sup -2}s{sup -1}. The tunnel was to be scoped, however, to support a future upgrade to a center-of-mass energy greater than 150 TeV with a peak luminosity of 2 x 10{sup 34} cm{sup -2} sec{sup -1} using high field ({approx} 10 T) superconducting magnet technology. In a collaboration with Brookhaven National Laboratory and Lawrence Berkeley National Laboratory, a report of the Design Study was produced by Fermilab in June 2001. 1 The Design Study focused on a Stage 1, 20 x 20 TeV collider using a 2-in-1 transmission line magnet and leads to a Stage 2, 87.5 x 87.5 TeV collider using 10 T Nb{sub 3}Sn magnet technology. The article that follows is a compilation of accelerator physics designs and computational results which contributed to the Design Study. Many of the parameters found in this report evolved during the study, and thus slight differences between this text and the Design Study report can be found. The present text, however, presents the major accelerator physics issues of the Very Large Hadron Collider as examined by the Design Study collaboration and provides a basis for discussion and further studies of VLHC accelerator parameters and design philosophies.

  18. Flattening Earth acceleration in atomic fountains

    SciTech Connect

    Bertoldi, Andrea

    2010-07-15

    A method to compensate for Earth's gravity tide over an extended axial region is reported. Flattening acceleration is important in experiments where the coupling of the dynamics of free-falling probes to the gravity gradient generates stochastic noise on the measurement. Optimized cylindrically symmetric mass distributions lower Earth's tidal effect over 10 cm by a factor 10{sup 3}. A multimass compensation system with comparable performance is devised for tall atom interferometers. Reducing the gravity gradient is essential in terrestrial experiments based on atom fountain configurations being developed to precisely test general relativity or the neutrality of matter.

  19. Accelerated Innovation Pilot

    NASA Technical Reports Server (NTRS)

    Davis, Jeffrey

    2012-01-01

    Opportunities: I. Engage NASA team (examples) a) Research and technology calls . provide suggestions to AES, HRP, OCT. b) Use NASA@Work to solicit other ideas; (possibly before R+D calls). II. Stimulate collaboration (examples) a) NHHPC. b) Wharton Mack Center for Technological Innovation (Feb 2013). c) International ] DLR ] :envihab (July 2013). d) Accelerated research models . NSF, Myelin Repair Foundation. III. Engage public Prizes (open platform: InnoCentive, yet2.com, NTL; Rice Business Plan, etc.) IV. Use same methods to engage STEM.

  20. Ion wave breaking acceleration

    NASA Astrophysics Data System (ADS)

    Liu, B.; Meyer-ter-Vehn, J.; Bamberg, K.-U.; Ma, W. J.; Liu, J.; He, X. T.; Yan, X. Q.; Ruhl, H.

    2016-07-01

    Laser driven ion wave breaking acceleration (IWBA) in plasma wakefields is investigated by means of a one-dimensional (1D) model and 1D/3D particle-in-cell (PIC) simulations. IWBA operates in relativistic transparent plasma for laser intensities in the range of 1020- 1023 W /cm2 . The threshold for IWBA is identified in the plane of plasma density and laser amplitude. In the region just beyond the threshold, self-injection takes place only for a fraction of ions and in a limited time period. This leads to well collimated ion pulses with peaked energy spectra, in particular for 3D geometry.

  1. Optimized design for PIGMI

    SciTech Connect

    Hansborough, L.; Hamm, R.; Stovall, J.; Swenson, D.

    1980-01-01

    PIGMI (Pion Generator for Medical Irradiations) is a compact linear proton accelerator design, optimized for pion production and cancer treatment use in a hospital environment. Technology developed during a four-year PIGMI Prototype experimental program allows the design of smaller, less expensive, and more reliable proton linacs. A new type of low-energy accelerating structure, the radio-frequency quadrupole (RFQ) has been tested; it produces an exceptionally good-quality beam and allows the use of a simple 30-kV injector. Average axial electric-field gradients of over 9 MV/m have been demonstrated in a drift-tube linac (DTL) structure. Experimental work is underway to test the disk-and-washer (DAW) structure, another new type of accelerating structure for use in the high-energy coupled-cavity linac (CCL). Sufficient experimental and developmental progress has been made to closely define an actual PIGMI. It will consist of a 30-kV injector, and RFQ linac to a proton energy of 2.5 MeV, a DTL linac to 125 MeV, and a CCL linac to the final energy of 650 MeV. The total length of the accelerator is 133 meters. The RFQ and DTL will be driven by a single 440-MHz klystron; the CCL will be driven by six 1320-MHz klystrons. The peak beam current is 28 mA. The beam pulse length is 60 ..mu..s at a 60-Hz repetition rate, resulting in a 100-..mu..A average beam current. The total cost of the accelerator is estimated to be approx. $10 million.

  2. Accelerating the loop expansion

    SciTech Connect

    Ingermanson, R.

    1986-07-29

    This thesis introduces a new non-perturbative technique into quantum field theory. To illustrate the method, I analyze the much-studied phi/sup 4/ theory in two dimensions. As a prelude, I first show that the Hartree approximation is easy to obtain from the calculation of the one-loop effective potential by a simple modification of the propagator that does not affect the perturbative renormalization procedure. A further modification then susggests itself, which has the same nice property, and which automatically yields a convex effective potential. I then show that both of these modifications extend naturally to higher orders in the derivative expansion of the effective action and to higher orders in the loop-expansion. The net effect is to re-sum the perturbation series for the effective action as a systematic ''accelerated'' non-perturbative expansion. Each term in the accelerated expansion corresponds to an infinite number of terms in the original series. Each term can be computed explicitly, albeit numerically. Many numerical graphs of the various approximations to the first two terms in the derivative expansion are given. I discuss the reliability of the results and the problem of spontaneous symmetry-breaking, as well as some potential applications to more interesting field theories. 40 refs.

  3. Laser acceleration in vacuum

    SciTech Connect

    Hsu, J.L.; Katsouleas, T.; Mori, W.B.; Schroeder, C.B.; Wurtele, J.S.

    1997-02-01

    This paper explores the use of the large electric fields of high-brightness lasers (e.g., up to order TV/cm) to accelerate particles. Unfortunately, as is well known, it is difficult to couple the vacuum field of the laser to particles so as to achieve a net energy gain. In principle, the energy gain near the focus of the laser can be quite high, i.e., on the order of the work done in crossing the focus {Delta}{gamma}={radical}({pi})eEw{approximately}30MeV{radical}(P/1TW), where P is the laser power. In order to retain this energy, the particles must be in the highly nonlinear regime (Vosc/c{gt}1) or must be separated from the laser within a distance on the order of a Rayleigh length from the focus. In this work, we explore the acceleration and output energy distribution of an electron beam injected at various angles and injection energies into a focused laser beam. Insight into the physical mechanism of energy gain is obtained by separating the contributions from the longitudinal and transverse laser field components. {copyright} {ital 1997 American Institute of Physics.}

  4. PARMELA simulations of RF linear accelerators for ion implantation

    SciTech Connect

    Swenson, D. R.; Wan Zhimin; Di Vergilio, W. F.; Saadatmand, K.

    1999-06-10

    RF linear accelerators (LINACs) offer the highest beam energies and currents available to the high-energy segment of the ion-implantation industry. We are using the computer code PARMELA to simulate a variety of beam parameters. The simulations are used to generate beam tunes, optimize LINAC performance, and to design new LINACs.

  5. The Student Course Experience among Online, Accelerated, and Traditional Courses

    ERIC Educational Resources Information Center

    Bielitz, Colleen L.

    2016-01-01

    The demand by the public for a wider variety of course formats has led to complexity in determining a course's optimal delivery format as many faculty members still believe that online and accelerated courses do not offer students an equivalent experience to traditional face to face instruction. The purpose of this quantitative, comparative study…

  6. Introduction to Korean Accelerator Science and Activities in Industrial Accelerators

    NASA Astrophysics Data System (ADS)

    Namkung, Won

    2012-03-01

    After 20 years of the first large-scale accelerator in Korea, the Pohang Light Source (PLS) of 2.0 GeV at POSTECH, its upgrade (PLS-II) is now under commissioning with energy of 3.0 GeV. The users' service for synchrotron radiation is scheduled in April 2012. There are five big accelerator projects in various stages of construction, namely a high-intensity proton linac of 100 MeV, the PAL-XFEL of 10-GeV, a carbon therapy cyclotron of 400 MeV/u, and rare isotope accelerators for isotope separator on-line (ISOL) and In-flight Fragmentation (IFF). There are also strong demands for industrial uses of accelerators, especially in sterilization applications. In this paper, we report the current status of accelerator projects and its science in Korea, along with a brief review of accelerator R&D going back to the early 1960s at universities.

  7. Numerical Investigation and Experimental Reproduction of Fermi Acceleration in Laboratory Scale

    NASA Astrophysics Data System (ADS)

    Zhou, M.; Zhai, C.

    2015-12-01

    Fermi acceleration is widely accepted as the mechanism to explain power law of cosmic ray spectrum. Now this mechanism has been developed to first order Fermi acceleration and second order Fermi acceleration. In first order Fermi acceleration, also known as diffusive shock acceleration, particles are confined around the shock through scattering and accelerated by repeatedly crossing shock front. In second order Fermi acceleration, particles gain energy through statistical collisions with interstellar clouds. In this proposed work, we plan to carefully study these two kinds of acceleration numerically and experimentally. We first consider a single relativistic particle and investigate how it gains energy in Fermi-Ulam model and shock wave acceleration model respectively. We investigate collective behavior of particles with different kinds of wall-oscillation functions and try to find an optimal one in terms of efficiency of acceleration. Then, we plan to go further and consider a group of particles statistically, during which we borrow the correct generalization of Maxwell's velocity distribution in special relativity and compare the results with those in cases where we simply use Maxwell-Boltzmann distribution. To this end, we try to provide a scheme to build an accelerator applying both laser technology and mirror effect in Laboratory to reproduce Fermi acceleration, which might be a promising source to obtain high energy particles and further study the mechanism of cosmic rays acceleration.

  8. Acceleration in Linear and Circular Motion

    ERIC Educational Resources Information Center

    Kellington, S. H.; Docherty, W.

    1975-01-01

    Describes the construction of a simple accelerometer and explains its use in demonstrating acceleration, deceleration, constant speed, measurement of acceleration, acceleration and the inclined plane and angular and radial acceleration. (GS)

  9. Nonlinear dynamics of autonomous vehicles with limits on acceleration

    NASA Astrophysics Data System (ADS)

    Davis, L. C.

    2014-07-01

    The stability of autonomous vehicle platoons with limits on acceleration and deceleration is determined. If the leading-vehicle acceleration remains within the limits, all vehicles in the platoon remain within the limits when the relative-velocity feedback coefficient is equal to the headway time constant [k=1/h]. Furthermore, if the sensitivity α>1/h, no collisions occur. String stability for small perturbations is assumed and the initial condition is taken as the equilibrium state. Other values of k and α that give stability with no collisions are found from simulations. For vehicles with non-negligible mechanical response, simulations indicate that the acceleration-feedback-control gain might have to be dynamically adjusted to obtain optimal performance as the response time changes with engine speed. Stability is demonstrated for some perturbations that cause initial acceleration or deceleration greater than the limits, yet do not cause collisions.

  10. Optimizing proton therapy at the LBL medical accelerator

    SciTech Connect

    Alonso, J.

    1992-03-01

    This Grant has marked the beginning of a multi-year study process expected to lead to design and construction of at least one, possibly several hospital-based proton therapy facilities in the United States.

  11. Optimizing proton therapy at the LBL medical accelerator. Final report

    SciTech Connect

    Alonso, J.

    1992-03-01

    This Grant has marked the beginning of a multi-year study process expected to lead to design and construction of at least one, possibly several hospital-based proton therapy facilities in the United States.

  12. Optimal coupler and power setting for superconductive linear accelerators

    SciTech Connect

    Branlard, J.; Chase, B,; Nagaitsev, S.; Nezhevenko, O.; Reid, J.; /Fermilab

    2008-09-01

    The modeling analysis presented in this paper addresses the question of how to achieve the highest vector sum gradient for all beam currents when individual cavities operate at different gradients due to their inherent quenching limitations. The analytical method explained here constitutes a step forward toward the operability of the International Linear Collider (ILC), Project X [8], or XFEL [7]. Unlike previously proposed methods [1, 2], this approach prevents cavities from quenching should the beam current be lower than its maximum value.

  13. Breeding nuclear fuels with accelerators — replacement for breeder reactors

    NASA Astrophysics Data System (ADS)

    Grand, P.; Takahashi, H.

    1985-05-01

    High-current, high-energy linear accelerators are potential competitors to breeder reactors and fusion devices for the production of fissile fuel. Accelerator breeder studies, conducted at Chalk River (Canada) and Brookhaven National Laboratory during the last decade, indicate that the technology is available and system's costs competitive with that of the LMFBR and Fusion-Hybrid systems. This paper addresses the technical issues to be faced in an accelerator specifically designed for commercial operation of this kind, the neutronics and engineering feasibility of target systems, and related fuel-cycle cost/benefit analysis. A nearly optimized accelerator breeder concept consisting of a 1.5 GeV, 300 mA linear accelerator, and of a H 2O-cooled, U-metal target (or thorium) has been designed and costed. Accelerator efficiency, beam-to-plug, is estimated at 50% and target power generation efficiency, beam-to-thermal output, at about 600% (U-metal case). Fuel costs produced by the facility are practically entirely driven by capital investment costs. This is also true for any competing system. On the basis, the accelerator breeder is economically competitive with the LMFBR while offering real advantages in terms of safety, fuel cycle flexibility, and resource independence.

  14. The Accelerating Universe

    SciTech Connect

    Blandford, Roger

    2013-05-15

    From keV electrons in terrestrial aurorae to Ultra High Energy Cosmic Rays from unidentified "Zevatrons", the cosmos shows a plutocratic proclivity to concentrate energy in a tiny minority of suprathermal particles. The mechanisms involved can be traced back to the ideas of Faraday, Fermi and Alfvén though we are learning that the details are idiosyncratic to the many environments that we have observed and that much can be learned from comparing and contrasting particle acceleration in laboratory and diverse astronomical locations. It will be argued that new mechanisms are required to account for recent observations of galactic nuclei, pulsar wind nebulae and interplanetary, interstellar and intergalactic media and some candidates will be discussed.

  15. HIGH ENERGY PARTICLE ACCELERATOR

    DOEpatents

    Courant, E.D.; Livingston, M.S.; Snyder, H.S.

    1959-04-14

    An improved apparatus is presented for focusing charged particles in an accelerator. In essence, the invention includes means for establishing a magnetic field in discrete sectors along the path of moving charged particles, the magnetic field varying in each sector in accordance with the relation. B = B/ sub 0/ STAln (r-r/sub 0/)/r/sub 0/!, where B/sub 0/ is the value of the magnetic field at the equilibrium orbit of radius r/sub 0/ of the path of the particles, B equals the magnetic field at the radius r of the chamber and n equals the magnetic field gradient index, the polarity of n being abruptly reversed a plurality of times as the particles travel along their arcuate path. With this arrangement, the particles are alternately converged towards the axis of their equillbrium orbit and diverged therefrom in successive sectors with a resultant focusing effect.

  16. Lectures in accelerator theory

    SciTech Connect

    Month, M

    1980-01-01

    Lecture I deals with the behavior of particles in the nonlinear field arising from the electromagnetic interaction of colliding beams. The case treated, that of counter-rotating proton beams crossing each other at a non-zero angle, has the simple feature that the force between the beam is one dimensional. In lecture II, an analysis of the development of traveling waves on particle beams is presented. The situation studied is that of a uniform beam current in a circular accelerator and the excitation for the coherent motion is induced by the resistivity of the vacuum chamber wall. Finally, in lecture III, a description of the current accumulation process used at the proton storage rings at CERN (The ISR) is given. Particle pulses of rather low average current are injected and stored along the length and width of the vacuum chamber. The efficiency is very high and large currents (over 40 amperes) have been achieved.

  17. Network acceleration techniques

    NASA Technical Reports Server (NTRS)

    Crowley, Patricia (Inventor); Awrach, James Michael (Inventor); Maccabe, Arthur Barney (Inventor)

    2012-01-01

    Splintered offloading techniques with receive batch processing are described for network acceleration. Such techniques offload specific functionality to a NIC while maintaining the bulk of the protocol processing in the host operating system ("OS"). The resulting protocol implementation allows the application to bypass the protocol processing of the received data. Such can be accomplished this by moving data from the NIC directly to the application through direct memory access ("DMA") and batch processing the receive headers in the host OS when the host OS is interrupted to perform other work. Batch processing receive headers allows the data path to be separated from the control path. Unlike operating system bypass, however, the operating system still fully manages the network resource and has relevant feedback about traffic and flows. Embodiments of the present disclosure can therefore address the challenges of networks with extreme bandwidth delay products (BWDP).

  18. Accelerator mass spectrometry

    SciTech Connect

    Vogel, J.S.; Turteltaub, K.W.; Finkel, R.; Nelson, D.E.

    1995-06-01

    Accelerator mass spectroscopy (AMS) can be used for efficient detection of long-lived isotopes at part-per-quadrillion sensitivities with good precision. In this article we present an overview of AMS and its recent use in archaeology, geochemistry and biomolecular tracing. All AMS systems use cesium sputter ion sources to produce negative ions from a small button of a solid sample containing the element of interest, such as graphite, metal halide, or metal oxide, often mixed with a metal powder as binder and thermal conductor. Experience shows that both natural and biomedical samples are compatible in a single AMS system, but few other AMS sites make routine {sup 14}C measurements for both dating and tracing. AMS is, in one sense, just `a very sensitive decay counter`, but if AMS sensitivity is creatively coupled to analytical chemistry of certain isotopes, whole new areas of geosciences, archaeology, and life sciences can be explored. 29 refs., 2 figs., 1 tab.

  19. Accelerating Spectrum Sharing Technologies

    SciTech Connect

    Juan D. Deaton; Lynda L. Brighton; Rangam Subramanian; Hussein Moradi; Jose Loera

    2013-09-01

    Spectrum sharing potentially holds the promise of solving the emerging spectrum crisis. However, technology innovators face the conundrum of developing spectrum sharing technologies without the ability to experiment and test with real incumbent systems. Interference with operational incumbents can prevent critical services, and the cost of deploying and operating an incumbent system can be prohibitive. Thus, the lack of incumbent systems and frequency authorization for technology incubation and demonstration has stymied spectrum sharing research. To this end, industry, academia, and regulators all require a test facility for validating hypotheses and demonstrating functionality without affecting operational incumbent systems. This article proposes a four-phase program supported by our spectrum accountability architecture. We propose that our comprehensive experimentation and testing approach for technology incubation and demonstration will accelerate the development of spectrum sharing technologies.

  20. Pulsed electromagnetic acceleration

    NASA Technical Reports Server (NTRS)

    Jahn, R. G.; Vonjaskowsky, W. F.; Clark, K. E.

    1973-01-01

    Direct measurements of the power deposited in the anode of a multimegawatt MPD accelerator using thermocouples attached to a thin shell anode reveal a dramatic decrease in the fractional anode power from 50% at 200 KW input power to less than 10% at 20 MW power. The corresponding local power flux peak at a value of 10,000 W/sq cm at the lip of the anode exhaust orifice, a distribution traced to a corresponding peak in the local current density at the anode. A comparison of voltage-current characteristics and spectral photographs of the MPD discharge using quartz, boron nitride and plexiglas insulators with various mass injection configurations led to the identification of different voltage modes and regions of ablation free operation. The technique of piezoelectric impact pressure measurement in the MPD exhaust flow was refined to account for the effects due to probe yaw angle.

  1. Paraelectric gas flow accelerator

    NASA Technical Reports Server (NTRS)

    Sherman, Daniel M. (Inventor); Wilkinson, Stephen P. (Inventor); Roth, J. Reece (Inventor)

    2001-01-01

    A substrate is configured with first and second sets of electrodes, where the second set of electrodes is positioned asymmetrically between the first set of electrodes. When a RF voltage is applied to the electrodes sufficient to generate a discharge plasma (e.g., a one-atmosphere uniform glow discharge plasma) in the gas adjacent to the substrate, the asymmetry in the electrode configuration results in force being applied to the active species in the plasma and in turn to the neutral background gas. Depending on the relative orientation of the electrodes to the gas, the present invention can be used to accelerate or decelerate the gas. The present invention has many potential applications, including increasing or decreasing aerodynamic drag or turbulence, and controlling the flow of active and/or neutral species for such uses as flow separation, altering heat flow, plasma cleaning, sterilization, deposition, etching, or alteration in wettability, printability, and/or adhesion.

  2. Dynamics of pyroelectric accelerators

    SciTech Connect

    Ghaderi, R.; Davani, F. Abbasi

    2015-01-26

    Pyroelectric crystals are used to produce high energy electron beams. We have derived a method to model electric potential generation on LiTaO{sub 3} crystal during heating cycle. In this method, effect of heat transfer on the potential generation is investigated by some experiments. In addition, electron emission from the crystal surface is modeled by measurements and analysis. These spectral data are used to present a dynamic equation of electric potential with respect to thickness of the crystal and variation of its temperature. The dynamic equation's results for different thicknesses are compared with measured data. As a result, to attain more energetic electrons, best thickness of the crystals could be extracted from the equation. This allows for better understanding of pyroelectric crystals and help to study about current and energy of accelerated electrons.

  3. Hadron accelerators for radiotherapy

    NASA Astrophysics Data System (ADS)

    Owen, Hywel; MacKay, Ranald; Peach, Ken; Smith, Susan

    2014-04-01

    Over the last twenty years the treatment of cancer with protons and light nuclei such as carbon ions has moved from being the preserve of research laboratories into widespread clinical use. A number of choices now exist for the creation and delivery of these particles, key amongst these being the adoption of pencil beam scanning using a rotating gantry; attention is now being given to what technologies will enable cheaper and more effective treatment in the future. In this article the physics and engineering used in these hadron therapy facilities is presented, and the research areas likely to lead to substantive improvements. The wider use of superconducting magnets is an emerging trend, whilst further ahead novel high-gradient acceleration techniques may enable much smaller treatment systems. Imaging techniques to improve the accuracy of treatment plans must also be developed hand-in-hand with future sources of particles, a notable example of which is proton computed tomography.

  4. Laser acceleration and its future

    PubMed Central

    Tajima, Toshiki

    2010-01-01

    Laser acceleration is based on the concept to marshal collective fields that may be induced by laser. In order to exceed the material breakdown field by a large factor, we employ the broken-down matter of plasma. While the generated wakefields resemble with the fields in conventional accelerators in their structure (at least qualitatively), it is their extreme accelerating fields that distinguish the laser wakefield from others, amounting to tiny emittance and compact accelerator. The current research largely falls on how to master the control of acceleration process in spatial and temporal scales several orders of magnitude smaller than the conventional method. The efforts over the last several years have come to a fruition of generating good beam properties with GeV energies on a table top, leading to many applications, such as ultrafast radiolysis, intraoperative radiation therapy, injection to X-ray free electron laser, and a candidate for future high energy accelerators. PMID:20228616

  5. Particle acceleration in pulsar magnetospheres

    NASA Technical Reports Server (NTRS)

    Baker, K. B.

    1978-01-01

    The structure of pulsar magnetospheres and the acceleration mechanism for charged particles in the magnetosphere was studied using a pulsar model which required large acceleration of the particles near the surface of the star. A theorem was developed which showed that particle acceleration cannot be expected when the angle between the magnetic field lines and the rotation axis is constant (e.g. radial field lines). If this angle is not constant, however, acceleration must occur. The more realistic model of an axisymmetric neutron star with a strong dipole magnetic field aligned with the rotation axis was investigated. In this case, acceleration occurred at large distances from the surface of the star. The magnitude of the current can be determined using the model presented. In the case of nonaxisymmetric systems, the acceleration is expected to occur nearer to the surface of the star.

  6. Accelerator simulation of astrophysical processes

    NASA Technical Reports Server (NTRS)

    Tombrello, T. A.

    1983-01-01

    Phenomena that involve accelerated ions in stellar processes that can be simulated with laboratory accelerators are described. Stellar evolutionary phases, such as the CNO cycle, have been partially explored with accelerators, up to the consumption of He by alpha particle radiative capture reactions. Further experimentation is indicated on reactions featuring N-13(p,gamma)O-14, O-15(alpha, gamma)Ne-19, and O-14(alpha,p)F-17. Accelerated beams interacting with thin foils produce reaction products that permit a determination of possible elemental abundances in stellar objects. Additionally, isotopic ratios observed in chondrites can be duplicated with accelerator beam interactions and thus constraints can be set on the conditions producing the meteorites. Data from isotopic fractionation from sputtering, i.e., blasting surface atoms from a material using a low energy ion beam, leads to possible models for processes occurring in supernova explosions. Finally, molecules can be synthesized with accelerators and compared with spectroscopic observations of stellar winds.

  7. A Framework for a General Purpose Intelligent Control System for Particle Accelerators. Phase II Final Report

    SciTech Connect

    Dr. Robert Westervelt; Dr. William Klein; Dr. Michael Kroupa; Eric Olsson; Rick Rothrock

    1999-06-28

    Vista Control Systems, Inc. has developed a portable system for intelligent accelerator control. The design is general in scope and is thus configurable to a wide range of accelerator facilities and control problems. The control system employs a multi-layer organization in which knowledge-based decision making is used to dynamically configure lower level optimization and control algorithms.

  8. Muon Collider Progress: Accelerators

    SciTech Connect

    Zisman, Michael S.

    2011-09-10

    A muon collider would be a powerful tool for exploring the energy-frontier with leptons, and would complement the studies now under way at the LHC. Such a device would offer several important benefits. Muons, like electrons, are point particles so the full center-of-mass energy is available for particle production. Moreover, on account of their higher mass, muons give rise to very little synchrotron radiation and produce very little beamstrahlung. The first feature permits the use of a circular collider that can make efficient use of the expensive rf system and whose footprint is compatible with an existing laboratory site. The second feature leads to a relatively narrow energy spread at the collision point. Designing an accelerator complex for a muon collider is a challenging task. Firstly, the muons are produced as a tertiary beam, so a high-power proton beam and a target that can withstand it are needed to provide the required luminosity of ~1 × 10{sup 34} cm{sup –2}s{sup –1}. Secondly, the beam is initially produced with a large 6D phase space, which necessitates a scheme for reducing the muon beam emittance (“cooling”). Finally, the muon has a short lifetime so all beam manipulations must be done very rapidly. The Muon Accelerator Program, led by Fermilab and including a number of U.S. national laboratories and universities, has undertaken design and R&D activities aimed toward the eventual construction of a muon collider. Design features of such a facility and the supporting R&D program are described.

  9. Particle acceleration in solar flares

    NASA Technical Reports Server (NTRS)

    Ramaty, R.; Forman, M. A.

    1987-01-01

    The most direct signatures of particle acceleration in flares are energetic particles detected in interplanetary space and in the Earth atmosphere, and gamma rays, neutrons, hard X-rays, and radio emissions produced by the energetic particles in the solar atmosphere. The stochastic and shock acceleration theories in flares are reviewed and the implications of observations on particle energy spectra, particle confinement and escape, multiple acceleration phases, particle anistropies, and solar atmospheric abundances are discussed.

  10. Cast dielectric composite linear accelerator

    DOEpatents

    Sanders, David M.; Sampayan, Stephen; Slenes, Kirk; Stoller, H. M.

    2009-11-10

    A linear accelerator having cast dielectric composite layers integrally formed with conductor electrodes in a solventless fabrication process, with the cast dielectric composite preferably having a nanoparticle filler in an organic polymer such as a thermosetting resin. By incorporating this cast dielectric composite the dielectric constant of critical insulating layers of the transmission lines of the accelerator are increased while simultaneously maintaining high dielectric strengths for the accelerator.

  11. Accelerating Science Driven System Design With RAMP

    SciTech Connect

    Wawrzynek, John

    2015-05-01

    Researchers from UC Berkeley, in collaboration with the Lawrence Berkeley National Lab, are engaged in developing an Infrastructure for Synthesis with Integrated Simulation (ISIS). The ISIS Project was a cooperative effort for “application-driven hardware design” that engages application scientists in the early parts of the hardware design process for future generation supercomputing systems. This project served to foster development of computing systems that are better tuned to the application requirements of demanding scientific applications and result in more cost-effective and efficient HPC system designs. In order to overcome long conventional design-cycle times, we leveraged reconfigurable devices to aid in the design of high-efficiency systems, including conventional multi- and many-core systems. The resulting system emulation/prototyping environment, in conjunction with the appropriate intermediate abstractions, provided both a convenient user programming experience and retained flexibility, and thus efficiency, of a reconfigurable platform. We initially targeted the Berkeley RAMP system (Research Accelerator for Multiple Processors) as that hardware emulation environment to facilitate and ultimately accelerate the iterative process of science-driven system design. Our goal was to develop and demonstrate a design methodology for domain-optimized computer system architectures. The tangible outcome is a methodology and tools for rapid prototyping and design-space exploration, leading to highly optimized and efficient HPC systems.

  12. High field gradient particle accelerator

    DOEpatents

    Nation, J.A.; Greenwald, S.

    1989-05-30

    A high electric field gradient electron accelerator utilizing short duration, microwave radiation, and capable of operating at high field gradients for high energy physics applications or at reduced electric field gradients for high average current intermediate energy accelerator applications is disclosed. Particles are accelerated in a smooth bore, periodic undulating waveguide, wherein the period is so selected that the particles slip an integral number of cycles of the r.f. wave every period of the structure. This phase step of the particles produces substantially continuous acceleration in a traveling wave without transverse magnetic or other guide means for the particle. 10 figs.

  13. High field gradient particle accelerator

    DOEpatents

    Nation, John A.; Greenwald, Shlomo

    1989-01-01

    A high electric field gradient electron accelerator utilizing short duration, microwave radiation, and capable of operating at high field gradients for high energy physics applications or at reduced electric field gradients for high average current intermediate energy accelerator applications. Particles are accelerated in a smooth bore, periodic undulating waveguide, wherein the period is so selected that the particles slip an integral number of cycles of the r.f. wave every period of the structure. This phase step of the particles produces substantially continuous acceleration in a traveling wave without transverse magnetic or other guide means for the particle.

  14. Accelerators for research and applications

    SciTech Connect

    Alonso, J.R.

    1990-06-01

    The newest particle accelerators are almost always built for extending the frontiers of research, at the cutting edge of science and technology. Once these machines are operating and these technologies mature, new applications are always found, many of which touch our lives in profound ways. The evolution of accelerator technologies will be discussed, with descriptions of accelerator types and characteristics. The wide range of applications of accelerators will be discussed, in fields such as nuclear science, medicine, astrophysics and space-sciences, power generation, airport security, materials processing and microcircuit fabrication. 13 figs.

  15. Compact accelerator for medical therapy

    DOEpatents

    Caporaso, George J.; Chen, Yu-Jiuan; Hawkins, Steven A.; Sampayan, Stephen E.; Paul, Arthur C.

    2010-05-04

    A compact accelerator system having an integrated particle generator-linear accelerator with a compact, small-scale construction capable of producing an energetic (.about.70-250 MeV) proton beam or other nuclei and transporting the beam direction to a medical therapy patient without the need for bending magnets or other hardware often required for remote beam transport. The integrated particle generator-accelerator is actuable as a unitary body on a support structure to enable scanning of a particle beam by direction actuation of the particle generator-accelerator.

  16. An accelerated ordered subsets reconstruction algorithm using an accelerating power factor for emission tomography

    NASA Astrophysics Data System (ADS)

    Hsiao, Ing-Tsung; Huang, Hsuan-Ming

    2010-02-01

    We proposed a speed-enhanced tomographic reconstruction algorithm, ACOSEM (accelerated complete-data ordered-subset expectation-maximization), to accelerate a convergent OS-type algorithm (COSEM). The ACOSEM algorithm was based on modification of the COSEM update by applying an accelerating power factor or a bigger step size. Unlike the limited enhancement of the other speed-enhanced algorithm (E-COSEM), the proposed ACOSEM with an appropriate power factor can lead to a much faster reconstruction speed than COSEM and ECOSEM. Similar to COSEM, there is no free user-entered relaxation parameter needed for ACOSEM to ensure the convergent performance as required in the other type of fast convergent algorithms such as RAMLA. We derived the ACOSEM algorithm, and compared its performance to those of other fast convergent algorithms including COSEM, ECOSEM and RAMLA with optimized relaxation parameters. Though not convergent, OSEM is the current state-of-the-art reconstruction method used in the clinics, and thus included in the noise performance comparison. The results showed that ACOSEM reached the same image quality as in COSEM but two times faster when a power factor of 2.0 was used. An upper limit of 5 for the power factor with monotonically increasing log-likelihood in ACOSEM was observed under various conditions. Although the convergence proof is not available now, the results of log-likelihood values and noise studies showed that ACOSEM performed consistently with COSEM but with an accelerating reconstruction speed.

  17. Superdiffusive shock acceleration and short acceleration times at interplanetary shocks

    NASA Astrophysics Data System (ADS)

    Perri, Silvia; Zimbardo, Gaetano

    2016-04-01

    The analysis of time profiles of particles accelerated at interplanetary shock waves has shown evidence for superdiffusive transport in the upstream region. Superdiffusive transport is characterized by a mean square displacement that grows faster than linearly in time and by non Gaussian statistics for the distribution of the particle jump lengths. In the superdiffusive framework it has been shown that particle time profiles upstream of a planar shock decay as power laws, at variance with exponential particle time profiles predicted in the case of diffusive transport. A large number of interplanetary shocks, including coronal mass ejection driven shocks, exhibit energetic particle time profiles that decay as power laws far upstream. In order to take this evidence into account, we have extended the standard theory of diffusive shock acceleration to the case of particle superdiffusive transport (superdiffusive shock acceleration). This has allowed us to derive both hard energy spectral indices and short acceleration times. This new theory has been tested for a number of interplanetary shock waves, observed by the Ulysses and the ACE spacecraft, and for the termination shock. The superdiffusive shock acceleration leads to a strong reduction of the acceleration times (even of about one order of magnitude) with respect to the diffusive shock acceleration. Thus, this new framework provides a substantial advancement in the understanding of the processes of particle acceleration and particle transport, which are among the main objectives of the new Solar Probe and Solar Orbiter space missions.

  18. SHORT ACCELERATION TIMES FROM SUPERDIFFUSIVE SHOCK ACCELERATION IN THE HELIOSPHERE

    SciTech Connect

    Perri, S.; Zimbardo, G.

    2015-12-10

    The analysis of time profiles of particles accelerated at interplanetary shocks allows particle transport properties to be inferred. The frequently observed power-law decay upstream, indeed, implies a superdiffusive particle transport when the level of magnetic field variance does not change as the time interval from the shock front increases. In this context, a superdiffusive shock acceleration (SSA) theory has been developed, allowing us to make predictions of the acceleration times. In this work we estimate for a number of interplanetary shocks, including the solar wind termination shock, the acceleration times for energetic protons in the framework of SSA and we compare the results with the acceleration times predicted by standard diffusive shock acceleration. The acceleration times due to SSA are found to be much shorter than in the classical model, and also shorter than the interplanetary shock lifetimes. This decrease of the acceleration times is due to the scale-free nature of the particle displacements in the framework of superdiffusion. Indeed, very long displacements are possible, increasing the probability for particles far from the front of the shock to return, and short displacements have a high probability of occurrence, increasing the chances for particles close to the front to cross the shock many times.

  19. Feedback in Flow for Accelerated Reaction Development.

    PubMed

    Reizman, Brandon J; Jensen, Klavs F

    2016-09-20

    The pharmaceutical industry is investing in continuous flow and high-throughput experimentation as tools for rapid process development accelerated scale-up. Coupled with automation, these technologies offer the potential for comprehensive reaction characterization and optimization, but with the cost of conducting exhaustive multifactor screens. Automated feedback in flow offers researchers an alternative strategy for efficient characterization of reactions based on the use of continuous technology to control chemical reaction conditions and optimize in lieu of screening. Optimization with feedback allows experiments to be conducted where the most information can be gained from the chemistry, enabling product yields to be maximized and kinetic models to be generated while the total number of experiments is minimized. This Account opens by reviewing select examples of feedback optimization in flow and applications to chemical research. Systems in the literature are classified into (i) deterministic "black box" optimization systems that do not model the reaction system and are therefore limited in the utility of results for scale-up, (ii) deterministic model-based optimization systems from which reaction kinetics and/or mechanisms can be automatically evaluated, and (iii) stochastic systems. Though diverse in application, flow feedback systems have predominantly focused upon the optimization of continuous variables, i.e., variables such as time, temperature, and concentration that can be ramped from one experiment to the next. Unfortunately, this implies that the screening of discrete variables such as catalyst, ligand, or solvent generally does not factor into automated flow optimization, resulting in incomplete process knowledge. Herein, we present a system and strategy developed for optimizing discrete and continuous variables of a chemical reaction simultaneously. The approach couples automated feedback with high-throughput reaction screening in droplet flow

  20. Feedback in Flow for Accelerated Reaction Development.

    PubMed

    Reizman, Brandon J; Jensen, Klavs F

    2016-09-20

    The pharmaceutical industry is investing in continuous flow and high-throughput experimentation as tools for rapid process development accelerated scale-up. Coupled with automation, these technologies offer the potential for comprehensive reaction characterization and optimization, but with the cost of conducting exhaustive multifactor screens. Automated feedback in flow offers researchers an alternative strategy for efficient characterization of reactions based on the use of continuous technology to control chemical reaction conditions and optimize in lieu of screening. Optimization with feedback allows experiments to be conducted where the most information can be gained from the chemistry, enabling product yields to be maximized and kinetic models to be generated while the total number of experiments is minimized. This Account opens by reviewing select examples of feedback optimization in flow and applications to chemical research. Systems in the literature are classified into (i) deterministic "black box" optimization systems that do not model the reaction system and are therefore limited in the utility of results for scale-up, (ii) deterministic model-based optimization systems from which reaction kinetics and/or mechanisms can be automatically evaluated, and (iii) stochastic systems. Though diverse in application, flow feedback systems have predominantly focused upon the optimization of continuous variables, i.e., variables such as time, temperature, and concentration that can be ramped from one experiment to the next. Unfortunately, this implies that the screening of discrete variables such as catalyst, ligand, or solvent generally does not factor into automated flow optimization, resulting in incomplete process knowledge. Herein, we present a system and strategy developed for optimizing discrete and continuous variables of a chemical reaction simultaneously. The approach couples automated feedback with high-throughput reaction screening in droplet flow

  1. Accelerating molecular docking calculations using graphics processing units.

    PubMed

    Korb, Oliver; Stützle, Thomas; Exner, Thomas E

    2011-04-25

    The generation of molecular conformations and the evaluation of interaction potentials are common tasks in molecular modeling applications, particularly in protein-ligand or protein-protein docking programs. In this work, we present a GPU-accelerated approach capable of speeding up these tasks considerably. For the evaluation of interaction potentials in the context of rigid protein-protein docking, the GPU-accelerated approach reached speedup factors of up to over 50 compared to an optimized CPU-based implementation. Treating the ligand and donor groups in the protein binding site as flexible, speedup factors of up to 16 can be observed in the evaluation of protein-ligand interaction potentials. Additionally, we introduce a parallel version of our protein-ligand docking algorithm PLANTS that can take advantage of this GPU-accelerated scoring function evaluation. We compared the GPU-accelerated parallel version to the same algorithm running on the CPU and also to the highly optimized sequential CPU-based version. In terms of dependence of the ligand size and the number of rotatable bonds, speedup factors of up to 10 and 7, respectively, can be observed. Finally, a fitness landscape analysis in the context of rigid protein-protein docking was performed. Using a systematic grid-based search methodology, the GPU-accelerated version outperformed the CPU-based version with speedup factors of up to 60. PMID:21434638

  2. New directions in linear accelerators

    SciTech Connect

    Jameson, R.A.

    1984-01-01

    Current work on linear particle accelerators is placed in historical and physics contexts, and applications driving the state of the art are discussed. Future needs and the ways they may force development are outlined in terms of exciting R and D challenges presented to today's accelerator designers. 23 references, 7 figures.

  3. Thomas Edison Accelerated Elementary School.

    ERIC Educational Resources Information Center

    Levin, Henry M.; Chasin, Gene

    This paper describes early outcomes of a Sacramento, California, elementary school that participated in the Accelerated Schools Project. The school, which serves many minority and poor students, began training for the project in 1992. Accelerated Schools were designed to advance the learning rate of students through a gifted and talented approach,…

  4. General purpose programmable accelerator board

    DOEpatents

    Robertson, Perry J.; Witzke, Edward L.

    2001-01-01

    A general purpose accelerator board and acceleration method comprising use of: one or more programmable logic devices; a plurality of memory blocks; bus interface for communicating data between the memory blocks and devices external to the board; and dynamic programming capabilities for providing logic to the programmable logic device to be executed on data in the memory blocks.

  5. Natural Acceleration: Supporting Creative Trajectories

    ERIC Educational Resources Information Center

    Cohen, LeoNora M.

    2011-01-01

    "Natural acceleration" happens through an internal fire that burns to learn and may transcend school boundaries. Based on their passionate interests and connections with a domain, children who hunger for domain understandings outside school curricula require different types of acceleration, motivated by these interests. The lifeworks, domains, and…

  6. The Brookhaven Accelerator Test Facility

    SciTech Connect

    Batchelor, K.; Ben-Zvi, I.; Fernow, R.C.; Fischer, J.; Fisher, A.S.; Gallardo, J.; Jialin, Xie; Kirk, H.G.; Parsa, Z.; Palmer, R.B.; Rao, T.; Rogers, J.; Sheehan, J.; Tsang, T.Y.F.; Ulc, S.; Van Steenbergen, A.; Woodle, M.; Zhang, R.S. ); McDonald, K.T.; Russell, D.P. ); Jiang, Z.Y. (State Univ. of New York, Stony Brook, NY (Un

    1990-01-01

    The Accelerator Test Facility (ATF), presently under construction at Brookhaven National laboratory, is described. It consists of a 50-MeV electron beam synchronizable to a high-peak power CO{sub 2} laser. The interaction of electrons with the laser field will be probed, with some emphasis on exploring laser-based acceleration techniques. 5 refs., 2 figs.

  7. Data Understanding Applied to Optimization

    NASA Technical Reports Server (NTRS)

    Buntine, Wray; Shilman, Michael

    1998-01-01

    The goal of this research is to explore and develop software for supporting visualization and data analysis of search and optimization. Optimization is an ever-present problem in science. The theory of NP-completeness implies that the problems can only be resolved by increasingly smarter problem specific knowledge, possibly for use in some general purpose algorithms. Visualization and data analysis offers an opportunity to accelerate our understanding of key computational bottlenecks in optimization and to automatically tune aspects of the computation for specific problems. We will prototype systems to demonstrate how data understanding can be successfully applied to problems characteristic of NASA's key science optimization tasks, such as central tasks for parallel processing, spacecraft scheduling, and data transmission from a remote satellite.

  8. Accelerating incoherent dedispersion

    NASA Astrophysics Data System (ADS)

    Barsdell, B. R.; Bailes, M.; Barnes, D. G.; Fluke, C. J.

    2012-05-01

    Incoherent dedispersion is a computationally intensive problem that appears frequently in pulsar and transient astronomy. For current and future transient pipelines, dedispersion can dominate the total execution time, meaning its computational speed acts as a constraint on the quality and quantity of science results. It is thus critical that the algorithm be able to take advantage of trends in commodity computing hardware. With this goal in mind, we present an analysis of the 'direct', 'tree' and 'sub-band' dedispersion algorithms with respect to their potential for efficient execution on modern graphics processing units (GPUs). We find all three to be excellent candidates, and proceed to describe implementations in C for CUDA using insight gained from the analysis. Using recent CPU and GPU hardware, the transition to the GPU provides a speed-up of nine times for the direct algorithm when compared to an optimized quad-core CPU code. For realistic recent survey parameters, these speeds are high enough that further optimization is unnecessary to achieve real-time processing. Where further speed-ups are desirable, we find that the tree and sub-band algorithms are able to provide three to seven times better performance at the cost of certain smearing, memory consumption and development time trade-offs. We finish with a discussion of the implications of these results for future transient surveys. Our GPU dedispersion code is publicly available as a C library at .

  9. Dispositional optimism.

    PubMed

    Carver, Charles S; Scheier, Michael F

    2014-06-01

    Optimism is a cognitive construct (expectancies regarding future outcomes) that also relates to motivation: optimistic people exert effort, whereas pessimistic people disengage from effort. Study of optimism began largely in health contexts, finding positive associations between optimism and markers of better psychological and physical health. Physical health effects likely occur through differences in both health-promoting behaviors and physiological concomitants of coping. Recently, the scientific study of optimism has extended to the realm of social relations: new evidence indicates that optimists have better social connections, partly because they work harder at them. In this review, we examine the myriad ways this trait can benefit an individual, and our current understanding of the biological basis of optimism.

  10. Remote handling and accelerators

    NASA Astrophysics Data System (ADS)

    Wilson, M. T.

    The high-current levels of contemporary and proposed accelerator facilities induce radiation levels into components, requiring consideration be given to maintenance techniques that reduce personnel exposure. Typical components involved include beamstops, targets, collimators, windows, and instrumentation that intercepts the direct beam. Also included are beam extraction, injection, splitting, and kicking regions, as well as purposeful spill areas where beam tails are trimmed and neutral particles are deposited. Scattered beam and secondary particles activate components all along a beamline such as vacuum pipes, magnets, and shielding. Maintenance techniques vary from hands-on to TV-viewed operation using state-of-the-art servomanipulators. Bottom- or side-entry casks are used with thimble-type target and diagnostic assemblies. Long-handled tools are operated from behind shadow shields. Swinging shield doors, unstacking block, and horizontally rolling shield roofs are all used to provide access. Common to all techniques is the need to make operations simple and to provide a means of seeing and reaching the area.

  11. Hot Spot Cosmic Accelerators

    NASA Astrophysics Data System (ADS)

    2002-11-01

    length of more than 3 million light-years, or no less than one-and-a-half times the distance from the Milky Way to the Andromeda galaxy, this structure is indeed gigantic. The region where the jets collide with the intergalactic medium are known as " hot spots ". Superposing the intensity contours of the radio emission from the southern "hot spot" on a near-infrared J-band (wavelength 1.25 µm) VLT ISAAC image ("b") shows three distinct emitting areas; they are even better visible on the I-band (0.9 µm) FORS1 image ("c"). This emission is obviously associated with the shock front visible on the radio image. This is one of the first times it has been possible to obtain an optical/near-IR image of synchrotron emission from such an intergalactic shock and, thanks to the sensitivity and image sharpness of the VLT, the most detailed view of its kind so far . The central area (with the strongest emission) is where the plasma jet from the galaxy centre hits the intergalactic medium. The light from the two other "knots", some 10 - 15,000 light-years away from the central "hot spot", is also interpreted as synchrotron emission. However, in view of the large distance, the astronomers are convinced that it must be caused by electrons accelerated in secondary processes at those sites . The new images thus confirm that electrons are being continuously accelerated in these "knots" - hence called "cosmic accelerators" - far from the galaxy and the main jets, and in nearly empty space. The exact physical circumstances of this effect are not well known and will be the subject of further investigations. The present VLT-images of the "hot spots" near 3C 445 may not have the same public appeal as some of those beautiful images that have been produced by the same instruments during the past years. But they are not less valuable - their unusual importance is of a different kind, as they now herald the advent of fundamentally new insights into the mysteries of this class of remote and active

  12. EXOTIC MAGNETS FOR ACCELERATORS.

    SciTech Connect

    WANDERER, P.

    2005-09-18

    Over the last few years, several novel magnet designs have been introduced to meet the requirements of new, high performance accelerators and beam lines. For example, the FAIR project at GSI requires superconducting magnets ramped at high rates ({approx} 4 T/s) in order to achieve the design intensity. Magnets for the RIA and FAIR projects and for the next generation of LHC interaction regions will need to withstand high doses of radiation. Helical magnets are required to maintain and control the polarization of high energy protons at RHIC. In other cases, novel magnets have been designed in response to limited budgets and space. For example, it is planned to use combined function superconducting magnets for the 50 GeV proton transport line at J-PARC to satisfy both budget and performance requirements. Novel coil winding methods have been developed for short, large aperture magnets such as those used in the insertion region upgrade at BEPC. This paper will highlight the novel features of these exotic magnets.

  13. Pulsars and Acceleration Sites

    NASA Technical Reports Server (NTRS)

    Harding, Alice

    2008-01-01

    Rotation-powered pulsars are excellent laboratories for the studying particle acceleration as well as fundamental physics of strong gravity, strong magnetic fields and relativity. But even forty years after their discovery, we still do not understand their pulsed emission at any wavelength. I will review both the basic physics of pulsars as well as the latest developments in understanding their high-energy emission. Special and general relativistic effects play important roles in pulsar emission, from inertial frame-dragging near the stellar surface to aberration, time-of-flight and retardation of the magnetic field near the light cylinder. Understanding how these effects determine what we observe at different wavelengths is critical to unraveling the emission physics. Fortunately the Gamma-Ray Large Area Space Telescope (GLAST), with launch in May 2008 will detect many new gamma-ray pulsars and test the predictions of these models with unprecedented sensitivity and energy resolution for gamma-rays in the range of 30 MeV to 300 GeV.

  14. Actinides, accelerators and erosion

    NASA Astrophysics Data System (ADS)

    Tims, S. G.; Fifield, L. K.

    2012-10-01

    Fallout isotopes can be used as artificial tracers of soil erosion and sediment accumulation. The most commonly used isotope to date has been 137Cs. Concentrations of 137Cs are, however, significantly lower in the Southern Hemisphere, and furthermore have now declined to 35% of original values due to radioactive decay. As a consequence the future utility of 137Cs is limited in Australia, with many erosion applications becoming untenable within the next 20 years, and there is a need to replace it with another tracer. Plutonium could fill this role, and has the advantages that there were six times as many atoms of Pu as of 137Cs in fallout, and any loss to decay has been negligible due to the long half-lives of the plutonium isotopes. Uranium-236 is another long-lived fallout isotope with significant potential for exploitation as a tracer of soil and sediment movement. Uranium is expected to be more mobile in soils than plutonium (or caesium), and hence the 236U/Pu ratio will vary with soil depth, and so could provide an independent measure of the amount of soil loss. In this paper we discuss accelerator based ultra-sensitive measurements of plutonium and 236U isotopes and their advantages over 137Cs as tracers of soil erosion and sediment movement.

  15. Is Global Warming Accelerating?

    NASA Astrophysics Data System (ADS)

    Shukla, J.; Delsole, T. M.; Tippett, M. K.

    2009-12-01

    A global pattern that fluctuates naturally on decadal time scales is identified in climate simulations and observations. This newly discovered component, called the Global Multidecadal Oscillation (GMO), is related to the Atlantic Meridional Oscillation and shown to account for a substantial fraction of decadal fluctuations in the observed global average sea surface temperature. IPCC-class climate models generally underestimate the variance of the GMO, and hence underestimate the decadal fluctuations due to this component of natural variability. Decomposing observed sea surface temperature into a component due to anthropogenic and natural radiative forcing plus the GMO, reveals that most multidecadal fluctuations in the observed global average sea surface temperature can be accounted for by these two components alone. The fact that the GMO varies naturally on multidecadal time scales implies that it can be predicted with some skill on decadal time scales, which provides a scientific rationale for decadal predictions. Furthermore, the GMO is shown to account for about half of the warming in the last 25 years and hence a substantial fraction of the recent acceleration in the rate of increase in global average sea surface temperature. Nevertheless, in terms of the global average “well-observed” sea surface temperature, the GMO can account for only about 0.1° C in transient, decadal-scale fluctuations, not the century-long 1° C warming that has been observed during the twentieth century.

  16. RFQ accelerator tuning system

    DOEpatents

    Bolie, Victor W.

    1990-01-01

    A cooling system is provided for maintaining a preselected operating temperature in a device, which may be an RFQ accelerator, having a variable heat removal requirement, by circulating a cooling fluid through a cooling system remote from the device. Internal sensors in the device enable an estimated error signal to be generated from parameters which are indicative of the heat removal requirement from the device. Sensors are provided at predetermined locations in the cooling system for outputting operational temperature signals. Analog and digital computers define a control signal functionally related to the temperature signals and the estimated error signal, where the control signal is defined effective to return the device to the preselected operating temperature in a stable manner. The cooling system includes a first heat sink responsive to a first portion of the control signal to remove heat from a major portion of the circulating fluid. A second heat sink is responsive to a second portion of the control signal to remove heat from a minor portion of the circulating fluid. The cooled major and minor portions of the circulating fluid are mixed in response to a mixing portion of the control signal, which is effective to proportion the major and minor portions of the circulating fluid to establish a mixed fluid temperature which is effective to define the preselected operating temperature for the remote device. In an RFQ environment the stable temperature control enables the resonant frequency of the device to be maintained at substantially a predetermined value during transient operations.

  17. RFQ accelerator tuning system

    DOEpatents

    Bolie, V.W.

    1990-07-03

    A cooling system is provided for maintaining a preselected operating temperature in a device, which may be an RFQ accelerator, having a variable heat removal requirement, by circulating a cooling fluid through a cooling system remote from the device. Internal sensors in the device enable an estimated error signal to be generated from parameters which are indicative of the heat removal requirement from the device. Sensors are provided at predetermined locations in the cooling system for outputting operational temperature signals. Analog and digital computers define a control signal functionally related to the temperature signals and the estimated error signal, where the control signal is defined effective to return the device to the preselected operating temperature in a stable manner. The cooling system includes a first heat sink responsive to a first portion of the control signal to remove heat from a major portion of the circulating fluid. A second heat sink is responsive to a second portion of the control signal to remove heat from a minor portion of the circulating fluid. The cooled major and minor portions of the circulating fluid are mixed in response to a mixing portion of the control signal, which is effective to proportion the major and minor portions of the circulating fluid to establish a mixed fluid temperature which is effective to define the preselected operating temperature for the remote device. In an RFQ environment the stable temperature control enables the resonant frequency of the device to be maintained at substantially a predetermined value during transient operations. 3 figs.

  18. Compact plasma accelerator

    NASA Technical Reports Server (NTRS)

    Foster, John E. (Inventor)

    2004-01-01

    A compact plasma accelerator having components including a cathode electron source, an anodic ionizing gas source, and a magnetic field that is cusped. The components are held by an electrically insulating body having a central axis, a top axial end, and a bottom axial end. The cusped magnetic field is formed by a cylindrical magnet having an axis of rotation that is the same as the axis of rotation of the insulating body, and magnetized with opposite poles at its two axial ends; and an annular magnet coaxially surrounding the cylindrical magnet, magnetized with opposite poles at its two axial ends such that a top axial end has a magnetic polarity that is opposite to the magnetic polarity of a top axial end of the cylindrical magnet. The ionizing gas source is a tubular plenum that has been curved into a substantially annular shape, positioned above the top axial end of the annular magnet such that the plenum is centered in a ring-shaped cusp of the magnetic field generated by the magnets. The plenum has one or more capillary-like orifices spaced around its top such that an ionizing gas supplied through the plenum is sprayed through the one or more orifices. The plenum is electrically conductive and is positively charged relative to the cathode electron source such that the plenum functions as the anode; and the cathode is positioned above and radially outward relative to the plenum.

  19. Accelerating momentum for change!

    PubMed

    Wenzel, S; Panetta, J

    1995-05-01

    As we develop strategies to compete globally, we are challenged with integrating our resources to execute these strategies effectively. Many companies are in the midst of dramatic shifts in corporate cultures, giving more responsibility to employees while raising expectations for their performance. The extent of these changes is far reaching and brings significant challenges to both employees and corporations. This article is a continuation of the evolution (over five years) of a corrective action/continuous improvement process implemented at Exide Electronics. It discusses organizational structures, including steering committees, corrective action teams, task teams, and work cells. Specific expectations, goals, and results of the teams are presented, along with ground rules for functioning within the organization. After structuring the organization and coordinating the resources effectively, the next challenge is accelerating momentum for change. The presentation also discusses the evolutionary process required to make a culture focused on change, including ongoing communication and feedback, constant evaluation and direction of the process, and measuring and paying for performance.

  20. Maximal acceleration and radiative processes

    NASA Astrophysics Data System (ADS)

    Papini, Giorgio

    2015-08-01

    We derive the radiation characteristics of an accelerated, charged particle in a model due to Caianiello in which the proper acceleration of a particle of mass m has the upper limit 𝒜m = 2mc3/ℏ. We find two power laws, one applicable to lower accelerations, the other more suitable for accelerations closer to 𝒜m and to the related physical singularity in the Ricci scalar. Geometrical constraints and power spectra are also discussed. By comparing the power laws due to the maximal acceleration (MA) with that for particles in gravitational fields, we find that the model of Caianiello allows, in principle, the use of charged particles as tools to distinguish inertial from gravitational fields locally.

  1. The ISAC post-accelerator

    NASA Astrophysics Data System (ADS)

    Laxdal, R. E.; Marchetto, M.

    2014-01-01

    The acceleration chain of the ISAC facility boosts the energy of both radioactive and stable light and heavy ions for beam delivery to both a medium energy area in ISAC-I and a high energy area in ISAC-II. The post-accelerator comprises a 35.4 MHz RFQ to accelerate beams of A/q ≤ 30 from 2 keV/u to 150 keV/u and a post stripper, 106.1 MHz variable energy drift tube linac (DTL) to accelerate ions of A/q ≤ 6 to a final energy between 0.15 MeV/u to 1.5 MeV/u. A 40 MV superconducting linac further accelerates beam from 1.5 MeV/u to energies above the Coulomb barrier. All linacs operate cw to preserve beam intensity.

  2. Electron cyclotron harmonic wave acceleration

    NASA Technical Reports Server (NTRS)

    Karimabadi, H.; Menyuk, C. R.; Sprangle, P.; Vlahos, L.

    1987-01-01

    A nonlinear analysis of particle acceleration in a finite bandwidth, obliquely propagating electromagnetic cyclotron wave is presented. It has been suggested by Sprangle and Vlahos in 1983 that the narrow bandwidth cyclotron radiation emitted by the unstable electron distribution inside a flaring solar loop can accelerate electrons outside the loop by the interaction of a monochromatic wave propagating along the ambient magnetic field with the ambient electrons. It is shown here that electrons gyrating and streaming along a uniform, static magnetic field can be accelerated by interacting with the fundamental or second harmonic of a monochromatic, obliquely propagating cyclotron wave. It is also shown that the acceleration is virtually unchanged when a wave with finite bandwidth is considered. This acceleration mechanism can explain the observed high-energy electrons in type III bursts.

  3. FINAL REPORT DE-FG02-04ER41317 Advanced Computation and Chaotic Dynamics for Beams and Accelerators

    SciTech Connect

    Cary, John R

    2014-09-08

    During the year ending in August 2013, we continued to investigate the potential of photonic crystal (PhC) materials for acceleration purposes. We worked to characterize acceleration ability of simple PhC accelerator structures, as well as to characterize PhC materials to determine whether current fabrication techniques can meet the needs of future accelerating structures. We have also continued to design and optimize PhC accelerator structures, with the ultimate goal of finding a new kind of accelerator structure that could offer significant advantages over current RF acceleration technology. This design and optimization of these requires high performance computation, and we continue to work on methods to make such computation faster and more efficient.

  4. Optimization of Cylindrical Hall Thrusters

    SciTech Connect

    Yevgeny Raitses, Artem Smirnov, Erik Granstedt, and Nathaniel J. Fi

    2007-07-24

    The cylindrical Hall thruster features high ionization efficiency, quiet operation, and ion acceleration in a large volume-to-surface ratio channel with performance comparable with the state-of-the-art annular Hall thrusters. These characteristics were demonstrated in low and medium power ranges. Optimization of miniaturized cylindrical thrusters led to performance improvements in the 50-200W input power range, including plume narrowing, increased thruster efficiency, reliable discharge initiation, and stable operation. __________________________________________________

  5. Optimization of Cylindrical Hall Thrusters

    SciTech Connect

    Yevgeny Raitses, Artem Smirnov, Erik Granstedt, and Nathaniel J. Fisch

    2007-11-27

    The cylindrical Hall thruster features high ionization efficiency, quiet operation, and ion acceleration in a large volume-to-surface ratio channel with performance comparable with the state-of-the-art annular Hall thrusters. These characteristics were demonstrated in low and medium power ranges. Optimization of miniaturized cylindrical thrusters led to performance improvements in the 50-200W input power range, including plume narrowing, increased thruster efficiency, reliable discharge initiation, and stable operation.

  6. Helium refrigeration systems for super-conducting accelerators

    SciTech Connect

    Ganni, V.

    2015-12-04

    Many of the present day accelerators are based on superconducting technology which requires 4.5-K or 2-K helium refrigeration systems. These systems utilize superconducting radio frequency (SRF) cavities and/or superconducting magnets which are packaged into vacuum vessels known as cryo-modules (CM’s). Many of the present day accelerators are optimized to operate primarily at around 2-K, requiring specialized helium refrigeration systems which are cost intensive to produce and to operate. Some of the cryogenic refrigeration system design considerations for these challenging applications are discussed.

  7. Acceleration units for the Induction Linac Systems Experiment (ILSE)

    SciTech Connect

    Faltens, A.; Brady, V.; Brodzik, D.; Hansen, L.; Laslett, L.J.; Mukherjee, S.; Bubp, D.; Ravenscroft, D.; Reginato, L.

    1989-03-01

    The design of a high current heavy ion induction linac driver for inertial confinement fusion is optimized by adjusting the acceleration units along the length of the accelerator to match the beam current, energy, and pulse duration at any location. At the low energy end of the machine the optimum is a large number of electrostatically focused parallel beamlets, whereas at higher energies the optimum is a smaller number of magnetically focused beams. ILSE parallels this strategy by using 16 electrostatically focused beamlets at the low end followed by 4 magnetically focused beams after beam combining. 3 refs., 2 figs.

  8. Beam acceleration through proton radio frequency quadrupole accelerator in BARC

    NASA Astrophysics Data System (ADS)

    Bhagwat, P. V.; Krishnagopal, S.; Mathew, J. V.; Singh, S. K.; Jain, P.; Rao, S. V. L. S.; Pande, M.; Kumar, R.; Roychowdhury, P.; Kelwani, H.; Rama Rao, B. V.; Gupta, S. K.; Agarwal, A.; Kukreti, B. M.; Singh, P.

    2016-05-01

    A 3 MeV proton Radio Frequency Quadrupole (RFQ) accelerator has been designed at the Bhabha Atomic Research Centre, Mumbai, India, for the Low Energy High Intensity Proton Accelerator (LEHIPA) programme. The 352 MHz RFQ is built in 4 segments and in the first phase two segments of the LEHIPA RFQ were commissioned, accelerating a 50 keV, 1 mA pulsed proton beam from the ion source, to an energy of 1.24 MeV. The successful operation of the RFQ gave confidence in the physics understanding and technology development that have been achieved, and indicate that the road forward can now be traversed rather more quickly.

  9. Electron beam accelerator with magnetic pulse compression and accelerator switching

    DOEpatents

    Birx, Daniel L.; Reginato, Louis L.

    1988-01-01

    An electron beam accelerator comprising an electron beam generator-injector to produce a focused beam of .gtoreq.0.1 MeV energy electrons; a plurality of substantially identical, aligned accelerator modules to sequentially receive and increase the kinetic energies of the beam electrons by about 0.1-1 MeV per module. Each accelerator module includes a pulse-forming network that delivers a voltage pulse to the module of substantially .gtoreq.0.1-1 MeV maximum energy over a time duration of .ltoreq.1 .mu.sec.

  10. Electron beam accelerator with magnetic pulse compression and accelerator switching

    DOEpatents

    Birx, Daniel L.; Reginato, Louis L.

    1987-01-01

    An electron beam accelerator comprising an electron beam generator-injector to produce a focused beam of .gtoreq.0.1 MeV energy electrons; a plurality of substantially identical, aligned accelerator modules to sequentially receive and increase the kinetic energies of the beam electrons by about 0.1-1 MeV per module. Each accelerator module includes a pulse-forming network that delivers a voltage pulse to the module of substantially 0.1-1 MeV maximum energy over a time duration of .ltoreq.1 .mu.sec.

  11. Electron beam accelerator with magnetic pulse compression and accelerator switching

    DOEpatents

    Birx, D.L.; Reginato, L.L.

    1984-03-22

    An electron beam accelerator is described comprising an electron beam generator-injector to produce a focused beam of greater than or equal to .1 MeV energy electrons; a plurality of substantially identical, aligned accelerator modules to sequentially receive and increase the kinetic energies of the beam electron by about .1-1 MeV per module. Each accelerator module includes a pulse-forming network that delivers a voltage pulse to the module of substantially .1-1 MeV maximum energy over a time duration of less than or equal to 1 ..mu..sec.

  12. Further analysis of MHD acceleration for a hypersonic wind tunnel

    SciTech Connect

    Christiansen, M.J.; Schmidt, H.J.; Chapman, J.N.

    1995-12-31

    A previously completed MHD study of the use of an MHD accelerator with seeded air from a state-of-the-art arc heater, was generally hailed as showing that the system studied has some promise of meeting the most critical hypersonic testing requirements. However, some concerns existed about certain aspects of the results. This paper discusses some of these problems and presents analysis of potential solutions. Specifically the problems addressed are; reducing the amount of seed in the flow, reducing test chamber temperatures, and reducing the oxygen dissociation. Modeling techniques are used to study three design variables of the MHD accelerator. The accelerator channel inlet Mach number, the accelerator channel divergence angle, and the magnetic field strength are all studied. These variables are all optimized to meet the goals for seed, temperature, and dissociated oxygen reduction. The results of this paper are encouraging, showing that all three goals can be met. General relationships are observed as to how the design variables affect the performance of the MHD accelerator facility. This paper expands on the results presented in the UTSI report and further supports the feasibility of MHD acceleration as a means to provide hypersonic flight simulation.

  13. Operation of the accelerator

    SciTech Connect

    Pardo, R.C.; Batzka, B.; Billquist, P.J.

    1995-08-01

    Fiscal Year 1994 was the first year of seven-day operation since ATLAS became a national user facility in 1985. ATLAS made the most of the opportunity this year by providing 5200 hours of beam on-target to the research program. A record number of 60 experiments were completed and the {open_quotes}facility reliability{close_quotes} remained near the 90% level. Seven-day operation was made possible with the addition to the staff of two operator positions providing single-operator coverage during the weekend period. The normally scheduled coverage was augmented by an on-call list of system experts who respond to emergencies with phone-in advice and return to the Laboratory when necessary. This staffing approach continues but we rearranged our staffing patterns so that we now have one cryogenics engineer working a shift pattern which includes 8-hour daily coverage during the weekend. ATLAS provided a beam mix to users consisting of 26 different isotopic species, 23% of which were for A>100 in FY 1994. Approximately 60% of the beam time was provided by the Positive Ion Injector, slightly less than the usage rate of FY 1993. Experiments using uranium or lead beams accounted for 16.4% of the total beam time. The ECR ion source and high-voltage platform functioned well throughout the year. A new technique for solid material production in the source was developed which uses a sputtering process wherein the sample of material placed near the plasma chamber wall is biased negatively. Plasma ions are accelerated into the sample and material is sputtered from the surface into the plasma. This technique is now used routinely for many elements. Runs of calcium, germanium, nickel, lead, tellurium, and uranium were carried out with this technique.

  14. Accelerating DSMC data extraction.

    SciTech Connect

    Gallis, Michail A.; Piekos, Edward Stanley

    2006-10-01

    In many direct simulation Monte Carlo (DSMC) simulations, the majority of computation time is consumed after the flowfield reaches a steady state. This situation occurs when the desired output quantities are small compared to the background fluctuations. For example, gas flows in many microelectromechanical systems (MEMS) have mean speeds more than two orders of magnitude smaller than the thermal speeds of the molecules themselves. The current solution to this problem is to collect sufficient samples to achieve the desired resolution. This can be an arduous process because the error is inversely proportional to the square root of the number of samples so we must, for example, quadruple the samples to cut the error in half. This work is intended to improve this situation by employing more advanced techniques, from fields other than solely statistics, for determining the output quantities. Our strategy centers on exploiting information neglected by current techniques, which collect moments in each cell without regard to one another, values in neighboring cells, nor their evolution in time. Unlike many previous acceleration techniques that modify the method itself, the techniques examined in this work strictly post-process so they may be applied to any DSMC code without affecting its fidelity or generality. Many potential methods are drawn from successful applications in a diverse range of areas, from ultrasound imaging to financial market analysis. The most promising methods exploit relationships between variables in space, which always exist in DSMC due to the absence of shocks. Disparate techniques were shown to produce similar error reductions, suggesting that the results shown in this report may be typical of what is possible using these methods. Sample count reduction factors of approximately three to five were found to be typical, although factors exceeding ten were shown on some variables under some techniques.

  15. Accelerated coffee pulp composting.

    PubMed

    Sánchez, G; Olguín, E J; Mercado, G

    1999-02-01

    The effect of two abundant, easily available and very low-cost agro-industrial organic residues, i.e., filter cake from the sugar industry and poultry litter, on the composting stabilization time of coffee pulp and on the quality of the produced compost, was evaluated. Piles of one cubic meter were built and monitored within the facilities of a coffee processing plant in the Coatepec region of the State of Veracruz, Mexico. Manual aeration was carried out once a week. A longer thermophilic period (28 days) and a much lower C/N ratio (in the range of 6.9-9.1) were observed in the piles containing the amendments, as compared to the control pile containing only coffee pulp (14 days and a C/N ratio of 14.4, respectively). The maximum assimilation rate of the reducing sugars was 1.6 g kg-1 d-1 (from 7.5 to 5.3%) during the first two weeks when accelerators were present in the proportion of 20% filter cake plus 20% poultry litter, while they accumulated at a rate of 1.2 g kg-1 d-1 (from 7.4 to 9.13%) during the same period in the control pile. The best combination of amendments was 30% filter cake with 20% poultry litter, resulting in a final nitrogen content as high as 4.81%. The second best combination was 20% filter cake with 10% poultry litter, resulting in a compost which also contained a high level of total nitrogen (4.54%). It was concluded that the use of these two residues enhanced the composting process of coffee pulp, promoting a shorter stabilization period and yielding a higher quality of compost.

  16. Laser Acceleration of Quasi-Monoenergetic Protons via Radiation Pressure Driven Thin Foil

    SciTech Connect

    Liu, Chuan S.; Shao Xi; Liu, T. C.; Dudnikova, Galina; Sagdeev, Roald Z.; Eliasson, Bengt

    2011-01-04

    We present a theoretical and simulation study of laser acceleration of quasi-monoenergetic protons in a thin foil irradiated by high intensity laser light. The underlying physics of radiation pressure acceleration (RPA) is discussed, including the importance of optimal thickness and circularly polarized light for efficient acceleration of ions to quasi-monoenergetic beams. Preliminary two-dimensional simulation studies show that certain parameter regimes allow for stabilization of the Rayleigh-Taylor instability and possibility of acceleration of monoenergetic ions to an excess of 200 MeV, making them suitable for important applications such as medical cancer therapy and fast ignition.

  17. Ascent optimization of an airbreathing space vehicle

    NASA Astrophysics Data System (ADS)

    Bulirsch, R.; Chudej, K.

    In the present paper the optimized ascent of a Saenger type lower stage is studied. The controls and the time of changing from turbo to ramjet acceleration are optimized simultaneously. Valuable information concerning the design of the vehicle due to the optimized flight path can be gained. The optimal control problem is reduced to a multipoint boundary value problem which is solved by the multiple shooting algorithm. A good first estimate of state and especially adjoint variables for starting the multiple shooting algorithm is computed via a direct colocation method. Very accurate solutions including the switching structure are obtained through this hybrid approach.

  18. A Fundamental Theorem on Particle Acceleration

    SciTech Connect

    Xie, Ming

    2003-05-01

    A fundamental theorem on particle acceleration is derived from the reciprocity principle of electromagnetism and a rigorous proof of the theorem is presented. The theorem establishes a relation between acceleration and radiation, which is particularly useful for insightful understanding of and practical calculation about the first order acceleration in which energy gain of the accelerated particle is linearly proportional to the accelerating field.

  19. Acceleration: Still an Option for the Gifted.

    ERIC Educational Resources Information Center

    Heinbokel, Annette

    2002-01-01

    In response to an article (Hany, 2001) discouraging the practice of acceleration through grade skipping for gifted students, this article defends acceleration as one option for gifted students, describes use of acceleration in Germany including early school entrance, individual grade skipping, acceleration in one subject, and acceleration in…

  20. Is the Universe's Acceleration Eternal?

    NASA Astrophysics Data System (ADS)

    Bean, Rachel; Magueijo, Joao; Barrow, John

    2002-12-01

    We present a new interpretation of recent observations suggesting that the expansion of the Universe has recently started to accelerate. First we introduce a cosmological model with a minimally coupled quintessence field driven by a potential motivated by M-theory. We find that late-time acceleration does not have to lead to the usual predictions of perpetual acceleration. The model allows another broad class of scenarios in which today's acceleration is a transient phenomenon which is succeeded by a return to matter domination and decelerating expansion. Quintessence scenarios provide a simple explanation for the observed acceleration of the Universe. Yet, explaining why acceleration did not start a long time ago remains a challenge. The idea that the transition from radiation to matter domination played a dynamical role in triggering acceleration has been put forward in various guises. We, secondly, propose a simple dilaton-derived quintessence model in which temporary vacuum domination is naturally triggered by the radiation to matter transition. In this model Einstein's gravity is preserved but quintessence couples non-minimally to the cold dark matter, but not to "visible" matter. Such couplings have been attributed to the dilaton in the low-energy limit of string theory beyond tree level.