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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. FLASH X-RAY (FXR) LINEAR INDUCTION ACCELERATOR (LIA) OPTIMIZATION Sensor Delay Correction

    SciTech Connect

    Ong, M M; Houck, T L; Kreitzer, B R; Paris, R D; Vogtlin, G E; Zentler, J M

    2006-05-01

    The radiographic goal of the FXR Optimization Project is to generate an x-ray pulse with peak energy of 19 MeV, spot-size of 1.5 mm, a dose of 500 rad, and duration of 60 ns. The electrical objectives are to generate a 3 kA electron-beam and refine our 16 MV accelerator so that the voltage does not vary more than 1%-rms. In a multi-cell linear induction accelerator, like FXR, the timing of the acceleration pulses relative to the beam is critical. The pulses must be timed optimally so that a cell is at full voltage before the beam arrives and does not drop until the beam passes. In order to stay within the energy-variation budget, the synchronization between the cells and beam arrival must be controlled to a couple of nanoseconds. Therefore, temporal measurements must be accurate to a fraction of a nanosecond. FXR Optimization Project developed a one-giga-sample per second (gs/s) data acquisition system to record beam sensor data. Signal processing algorithms were written to determine cell timing with an uncertainty of a fraction of a nanosecond. However, the uncertainty in the sensor delay was still a few nanoseconds. This error had to be reduced if we are to improve the quality of the electron beam. Two types of sensors are used to align the cell voltage pulse against the beam current. The beam current is measured with resistive-wall sensors. The cell voltages are read with capacitive voltage monitors. Sensor delays can be traced to two mechanisms: (1) the sensors are not co-located at the beam and cell interaction points, and (2) the sensors have different length jumper cables and other components that connect them to the standard-length coaxial cables of the data acquisition system. Using the physical locations and dimensions of the sensor components, and the dielectric constant of the materials, delay times were computed. Relative to the cell voltage, the beam current was theoretically reporting late by 7.7 ns. Two experiments were performed to verify and

  3. FXR accelerator cavity impedance experiments

    SciTech Connect

    Avalle, C.A.

    1998-01-05

    One of the goals of the present Flash X-Ray (FXR) accelerator upgrade effort [1][2] at Lawrence Livermore National Laboratory (LLNL) is to reduce the cavity transverse impedance, since it has been shown that beam stability is significantly affected by this parameter [3]. Recently, we have evaluated various techniques and cell modifications to accomplish that, both through lab measurements and computer models. A spare cell, identical in every way to cells in the accelerator, was specially modified for the experiments. The impedance measurements were done without the beam, by applying twin-wire techniques. This report describes the results of these experiments and suggests possible cell modifications to improve their performance. The techniques and modifications which are suggested might also be applicable to AHF and DARHT-2 long-pulse accelerator development.

  4. Flash X-Ray (FXR) Accelerator Optimization Electronic Time-Resolved Measurement of X-Ray Source Size

    SciTech Connect

    Jacob, J; Ong, M; Wargo, P

    2005-07-21

    Lawrence Livermore National Laboratory (LLNL) is currently investigating various approaches to minimize the x-ray source size on the Flash X-Ray (FXR) linear induction accelerator in order to improve x-ray flux and increase resolution for hydrodynamic radiography experiments. In order to effectively gauge improvements to final x-ray source size, a fast, robust, and accurate system for measuring the spot size is required. Timely feedback on x-ray source size allows new and improved accelerator tunes to be deployed and optimized within the limited run-time constraints of a production facility with a busy experimental schedule; in addition, time-resolved measurement capability allows the investigation of not only the time-averaged source size, but also the evolution of the source size, centroid position, and x-ray dose throughout the 70 ns beam pulse. Combined with time-resolved measurements of electron beam parameters such as emittance, energy, and current, key limiting factors can be identified, modeled, and optimized for the best possible spot size. Roll-bar techniques are a widely used method for x-ray source size measurement, and have been the method of choice at FXR for many years. A thick bar of tungsten or other dense metal with a sharp edge is inserted into the path of the x-ray beam so as to heavily attenuate the lower half of the beam, resulting in a half-light, half-dark image as seen downstream of the roll-bar; by measuring the width of the transition from light to dark across the edge of the roll-bar, the source size can be deduced. For many years, film has been the imaging medium of choice for roll-bar measurements thanks to its high resolution, linear response, and excellent contrast ratio. Film measurements, however, are fairly cumbersome and require considerable setup and analysis time; moreover, with the continuing trend towards all-electronic measurement systems, film is becoming increasingly difficult and expensive to procure. Here, we shall

  5. 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.

  6. 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.

  7. The LLNL flash x-ray induction linear accelerator (FXR)

    NASA Astrophysics Data System (ADS)

    Multhauf, Lloyd G.; Back, Norman L.; Simmons, Larry F.; Zentler, Jan-Mark; Scarpetti, Raymond D.

    2003-07-01

    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.

  8. Loss of FXR protects against diet-induced obesity and accelerates liver carcinogenesis in ob/ob mice.

    PubMed

    Zhang, Yanqiao; Ge, Xuemei; Heemstra, Lydia A; Chen, Wei-Dong; Xu, Jiesi; Smith, Joseph L; Ma, Huiyan; Kasim, Neda; Edwards, Peter A; Novak, Colleen M

    2012-02-01

    Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr(-/-) mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr(-/-)) mice, the Ldlr(-/-)Fxr(-/-) double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr(-/-) background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr(-/-) mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr(-/-) mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob(-/-)Fxr(-/-) mice that were deficient in both Leptin and Fxr. On a chow diet, ob(-/-)Fxr(-/-) mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young (<11 months old) Ob(-/-)Fxr(-/-) mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions. PMID:22261820

  9. Loss of FXR Protects against Diet-Induced Obesity and Accelerates Liver Carcinogenesis in ob/ob Mice

    PubMed Central

    Ge, Xuemei; Heemstra, Lydia A.; Chen, Wei-Dong; Xu, Jiesi; Smith, Joseph L.; Ma, Huiyan; Kasim, Neda; Edwards, Peter A.; Novak, Colleen M.

    2012-01-01

    Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr−/− mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr−/−) mice, the Ldlr−/−Fxr−/− double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr−/− background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr−/− mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr−/− mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob−/−Fxr−/− mice that were deficient in both Leptin and Fxr. On a chow diet, ob−/−Fxr−/− mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young (<11 months old) Ob−/−Fxr−/− mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions. PMID:22261820

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

    PubMed

    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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. Recent performance improvements on FXR

    SciTech Connect

    Kulke, B.; Kihara, R.

    1983-01-01

    The FXR machine is a nominal 4-kA, 20-MeV, linear-induction, electron accelerator for flash radiography at LLNL. The machine met its baseline requirements in March 1982. Since then, the performance has been greatly improved. We have achieved stable and repeatable beam acceleration and transport, with over 80% transmission to the tungsten bremsstrahlung target located some 35 m downstream. For best stability, external-beam steering has been eliminated almost entirely. We regularly produce over 500 Roentgen at 1 m from the target (TLD measurement), with a radiographic spot size of 3 to 5 mm. Present efforts are directed towards the development of a 4-kA tune, working interactively with particle-field and beam transport code models. A remaining uncertainty is the possible onset of RF instabilities at the higher current levels.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Optimization of laser wakefield accelerator parameters

    SciTech Connect

    Pogorelsky, I.V.

    1998-02-01

    The author reveals the dependencies of the laser wakefield accelerator (LWFA) performance upon such basic parameters as laser wavelength, power, and pulse duration and apply them for optimization of the plasma-channeled standard LWFA operating in a linear regime. The maximum energy gain over the dephasing distance scales proportionally to the laser peak power, while the allowed minimum laser pulse duration is proportional to the square root of the energy gain. Electron beam energy spread, emittance and luminosity tend to improve with the laser wavelength increase. These considerations, supported by quantitative examples for the S GeV LWFA stage, favor picosecond CO{sub 2} laser as the optimum choice for future advanced accelerator projects.

  3. Initial performance parameters on FXR

    SciTech Connect

    Kulke, B.; Innes, T.G.; Kihara, R.; Scarpetti, R.D.

    1982-06-11

    Construction of the new flash x-ray induction LINAC (FXR) at Lawrence Livermore National Laboratory has been completed. Initial tuning of the machine has produced stable current pulses in excess of 2 kA at the design energy of 20 MeV, with an 80 ns FWHM pulse width, producing single-pulse radiation doses near 500 Roentgen at one meter from the target. The electronic spot size on the bremsstrahlung target is estimated at 3 to 5 mm. In this paper we will discuss the basic FXR design; running-in and tuning of the machine; emittance measurements; beam stability; switch gap synchronization; and measurements of the radiation dose and angular distribution.

  4. 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.

  5. FXR signaling in the enterohepatic system

    PubMed Central

    Matsubara, Tsutomu; Li, Fei; Gonzalez, Frank J.

    2012-01-01

    Enterohepatic circulation serves to capture bile acids and other steroid metabolites produced in the liver and secreted to the intestine, for reabsorption back into the circulation and reuptake to the liver. This process is under tight regulation by nuclear receptor signaling. Bile acids, produced from cholesterol, can alter gene expression in the liver and small intestine via activating the nuclear receptors farnesoid X receptor (FXR; NR1H4), pregnane X receptor (PXR; NR1I2), vitamin D receptor (VDR; NR1I1), G protein coupled receptor TGR5, and other cell signaling pathways (JNK1/2, AKT and ERK1/2). Among these controls, FXR is known to be a major bile acid-responsive ligand-activated transcription factor and a crucial control element for maintaining bile acid homeostasis. FXR has a high affinity for several major endogenous bile acids, notably cholic acid, deoxycholic acid, chenodeoxycholic acid, and lithocholic acid. By responding to excess bile acids, FXR is a bridge between the liver and small intestine to control bile acid levels and regulate bile acid synthesis and enterohepatic flow. FXR is highly expressed in the liver and gut, relative to other tissues, and contributes to the maintenance of cholesterol/bile acid homeostasis by regulating a variety of metabolic enzymes and transporters. FXR activation also affects lipid and glucose metabolism, and can influence drug metabolism. PMID:22609541

  6. Anthranilic acid derivatives as nuclear receptor modulators--development of novel PPAR selective and dual PPAR/FXR ligands.

    PubMed

    Merk, Daniel; Lamers, Christina; Weber, Julia; Flesch, Daniel; Gabler, Matthias; Proschak, Ewgenij; Schubert-Zsilavecz, Manfred

    2015-02-01

    Nuclear receptors, especially the peroxisome proliferator activated receptors (PPARs) and the farnesoid X receptor (FXR) fulfill crucial roles in metabolic balance. Their activation offers valuable therapeutic potential which has high clinical relevance with the fibrates and glitazones as PPAR agonistic drugs. With growing knowledge about the various functions of nuclear receptors in many disorders, new selective or dual ligands of these pharmaceutical targets are however still required. Here we report the class of anthranilic acid derivatives as novel selective PPAR or dual FXR/PPAR ligands. We identified distinct molecular determinants that govern selectivity for each PPAR subtype or FXR as well as the amplitude of activation of the respective receptors. We thereby discovered several lead compounds for further optimization and developed a highly potent dual PPARα/FXR partial agonist that might have a beneficial synergistic effect on lipid homeostasis by simultaneous activation of two nuclear receptors involved in lipid metabolism. PMID:25583100

  7. 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.

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

    PubMed

    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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Optimization of a Small Scale Linear Reluctance Accelerator

    NASA Astrophysics Data System (ADS)

    Barrera, Thor; Beard, Robby

    2011-11-01

    Reluctance accelerators are extremely promising future methods of transportation. Several problems still plague these devices, most prominently low efficiency. Variables to overcoming efficiency problems are many and difficult to correlate how they affect our accelerator. The study examined several differing variables that present potential challenges in optimizing the efficiency of reluctance accelerators. These include coil and projectile design, power supplies, switching, and the elusive gradient inductance problem. Extensive research in these areas has been performed from computational and theoretical to experimental. Findings show that these parameters share significant similarity to transformer design elements, thus general findings show current optimized parameters the research suggests as a baseline for further research and design. Demonstration of these current findings will be offered at the time of presentation.

  16. 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.

  17. 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. PMID:26416445

  18. Is the FXR the fix for cholesterol gallstone disease?

    PubMed

    Juran, Brian D; Lazaridis, Konstantinos N

    2005-07-01

    Cholesterol gallstone disease is characterized by several events, including cholesterol precipitation in bile, increased bile salt hydrophobicity and gallbladder inflammation. Here, we describe the same phenotype in mice lacking the bile acid receptor, FXR. Furthermore, in susceptible wild-type mice that recapitulate human cholesterol gallstone disease, treatment with a synthetic FXR agonist prevented sequelae of the disease. These effects were mediated by FXR-dependent increases in biliary bile salt and phospholipid concentrations, which restored cholesterol solubility and thereby prevented gallstone formation. Taken together, these results indicate that FXR is a promising therapeutic target for treating or preventing cholesterol gallstone disease. PMID:15962294

  19. Plasma jet accelerator optimization with supple membrane model

    NASA Astrophysics Data System (ADS)

    Galkin, S. A.; Bogatu, I. N.; Kim, J. S.

    2006-10-01

    High density (>=3x10^17cm-3) and high Mach number (M>10) plasma jets have important applications such as plasma rotation, refueling and disruption mitigation in tokamaks. The most deleterious blow-by instability occurs in coaxial plasma accelerators; hence electrode shape optimization is required to accelerate plasmas to ˜200 km/s [1]. A full 3D particle simulation takes a huge computational time. We have developed a membrane model to provide a good starting point and further physical insight for a full 3D optimization. Our model approximates the axisymmetrical plasma by a thin supple conducting membrane with a distributed mass, located between the electrodes, and connects them to model dynamics of the blow-by instability and to conduct the optimization. The supple membrane is allowed to slip along the conductors freely or with some friction as affected by Lorenz force, generated by magnetic field inside the chamber and current on membrane. The total mass and the density distribution represent the initial plasma. The density is redistributed adiabatically during the acceleration. An external electrical circuit with capacitance, inductance and resistivity is a part of the model. The membrane model simulation results will be compared to the 2D fluid MACH2 results and then will be used to guide a full 3D optimization by the LSP code. 1. http://hyperv.com/projects/pic/

  20. 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. PMID:25982493

  1. Optimizing direct intense-field laser acceleration of ions

    SciTech Connect

    Harman, Zoltan; Salamin, Yousef I.; Galow, Benjamin J.; Keitel, Christoph H.

    2011-11-15

    The dynamics of ion acceleration in tightly focused laser beams is investigated in relativistic simulations. Studies are performed to find the optimal parameters which maximize the energy gain, beam quality, and flux. The exit ionic kinetic energy and its uncertainty are improved and the number of accelerated particles is increased by orders of magnitude over our earlier results, especially when working with a longer laser wavelength. Laser beams of powers of 0.1-10 petawatts and focused to subwavelength spot radii are shown to directly accelerate protons and bare nuclei of helium, carbon, and oxygen from a few to several hundred MeV/nucleon. Variation of the volume of the initial ionic ensemble, as well as the introduction of a pulse shape on the laser fields, have been investigated and are shown to influence the exit particle kinetic energies only slightly.

  2. 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.

  3. Advanced metaheuristic algorithms for laser optimization in optical accelerator technologies

    NASA Astrophysics Data System (ADS)

    Tomizawa, Hiromitsu

    2011-10-01

    Lasers are among the most important experimental tools for user facilities, including synchrotron radiation and free electron lasers (FEL). In the synchrotron radiation field, lasers are widely used for experiments with Pump-Probe techniques. Especially for X-ray-FELs, lasers play important roles as seed light sources or photocathode-illuminating light sources to generate a high-brightness electron bunch. For future accelerators, laser-based techonologies such as electro-optic (EO) sampling to measure ultra-short electron bunches and optical-fiber-based femtosecond timing systems have been intensively developed in the last decade. Therefore, controls and optimizations of laser pulse characteristics are strongly required for many kinds of experiments and improvement of accelerator systems. However, people believe that lasers should be tuned and customized for each requirement manually by experts. This makes it difficult for laser systems to be part of the common accelerator infrastructure. Automatic laser tuning requires sophisticated algorithms, and the metaheuristic algorithm is one of the best solutions. The metaheuristic laser tuning system is expected to reduce the human effort and time required for laser preparations. I have shown some successful results on a metaheuristic algorithm based on a genetic algorithm to optimize spatial (transverse) laser profiles, and a hill-climbing method extended with a fuzzy set theory to choose one of the best laser alignments automatically for each machine requirement.

  4. FXR: Big fish or small fry for drug-induced liver injury?

    PubMed

    Ballet, François

    2016-02-01

    By integrating network analysis and molecular modeling, a "system pharmacology" approach identified FXR as a potential off-target protein mediating non-steroidal anti-inflammatory drugs (NSAID)-induced liver injury. In vitro assays showed that NSAID are potent FXR antagonists that inhibit FXR transcriptional activity. Given the role of FXR in bile acid homeostasis, liver inflammation and cell proliferation, the data suggest that FXR antagonism could mediate, at least in part, NSAID-induced liver injury. PMID:26797115

  5. Hybrid photoneutron source optimization for electron accelerator-based BNCT

    NASA Astrophysics Data System (ADS)

    Rahmani, F.; Shahriari, M.

    2010-06-01

    Boron Neutron Capture Therapy (BNCT) is being studied as a possible radiotherapic treatment for some cancer types. Neutron energy for penetrating into tissue should be in the epithermal range. Different methods are used for neutron production. Electron accelerators are an alternative way for producing neutrons in electron-photon-neutron processes. Optimization of electron/photon and photoneutron targets calculations with respect to electron energy, dimension (radius and thickness) and neutron yield were done by MCNPX Monte Carlo code. According to the results, a hybrid photoneutron source including BeD 2 and Tungsten has been introduced.

  6. 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.

  7. Deciphering the nuclear bile acid receptor FXR paradigm

    PubMed Central

    Modica, Salvatore; Gadaleta, Raffaella M.; Moschetta, Antonio

    2010-01-01

    Originally called retinoid X receptor interacting protein 14 (RIP14), the farnesoid X receptor (FXR) was renamed after the ability of its rat form to bind supra-physiological concentrations of farnesol. In 1999 FXR was de-orphanized since primary bile acids were identified as natural ligands. Strongly expressed in the liver and intestine, FXR has been shown to be the master transcriptional regulator of several entero-hepatic metabolic pathways with relevance to the pathophysiology of conditions such as cholestasis, fatty liver disease, cholesterol gallstone disease, intestinal inflammation and tumors. Furthermore, given the importance of FXR in the gut-liver axis feedbacks regulating lipid and glucose homeostasis, FXR modulation appears to have great input in diseases such as metabolic syndrome and diabetes. Exciting results from several cellular and animal models have provided the impetus to develop synthetic FXR ligands as novel pharmacological agents. Fourteen years from its discovery, FXR has gone from bench to bedside; a novel nuclear receptor ligand is going into clinical use. PMID:21383957

  8. Structural Studies of the Tandem Tudor Domains of Fragile X Mental Retardation Related Proteins FXR1 and FXR2

    SciTech Connect

    Adams-Cioaba, Melanie A.; Guo, Yahong; Bian, ChuanBing; Amaya, Maria F.; Lam, Robert; Wasney, Gregory A.; Vedadi, Masoud; Xu, Chao; Min, Jinrong

    2011-11-23

    Expansion of the CGG trinucleotide repeat in the 5'-untranslated region of the FMR1, fragile X mental retardation 1, gene results in suppression of protein expression for this gene and is the underlying cause of Fragile X syndrome. In unaffected individuals, the FMRP protein, together with two additional paralogues (Fragile X Mental Retardation Syndrome-related Protein 1 and 2), associates with mRNA to form a ribonucleoprotein complex in the nucleus that is transported to dendrites and spines of neuronal cells. It is thought that the fragile X family of proteins contributes to the regulation of protein synthesis at sites where mRNAs are locally translated in response to stimuli. Here, we report the X-ray crystal structures of the non-canonical nuclear localization signals of the FXR1 and FXR2 autosomal paralogues of FMRP, which were determined at 2.50 and 1.92 {angstrom}, respectively. The nuclear localization signals of the FXR1 and FXR2 comprise tandem Tudor domain architectures, closely resembling that of UHRF1, which is proposed to bind methylated histone H3K9. The FMRP, FXR1 and FXR2 proteins comprise a small family of highly conserved proteins that appear to be important in translational regulation, particularly in neuronal cells. The crystal structures of the N-terminal tandem Tudor domains of FXR1 and FXR2 revealed a conserved architecture with that of FMRP. Biochemical analysis of the tandem Tudor doamins reveals their ability to preferentially recognize trimethylated peptides in a sequence-specific manner.

  9. Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk.

    PubMed

    Lien, Fleur; Berthier, Alexandre; Bouchaert, Emmanuel; Gheeraert, Céline; Alexandre, Jeremy; Porez, Geoffrey; Prawitt, Janne; Dehondt, Hélène; Ploton, Maheul; Colin, Sophie; Lucas, Anthony; Patrice, Alexandre; Pattou, François; Diemer, Hélène; Van Dorsselaer, Alain; Rachez, Christophe; Kamilic, Jelena; Groen, Albert K; Staels, Bart; Lefebvre, Philippe

    2014-03-01

    The nuclear bile acid receptor farnesoid X receptor (FXR) is an important transcriptional regulator of bile acid, lipid, and glucose metabolism. FXR is highly expressed in the liver and intestine and controls the synthesis and enterohepatic circulation of bile acids. However, little is known about FXR-associated proteins that contribute to metabolic regulation. Here, we performed a mass spectrometry-based search for FXR-interacting proteins in human hepatoma cells and identified AMPK as a coregulator of FXR. FXR interacted with the nutrient-sensitive kinase AMPK in the cytoplasm of target cells and was phosphorylated in its hinge domain. In cultured human and murine hepatocytes and enterocytes, pharmacological activation of AMPK inhibited FXR transcriptional activity and prevented FXR coactivator recruitment to promoters of FXR-regulated genes. Furthermore, treatment with AMPK activators, including the antidiabetic biguanide metformin, inhibited FXR agonist induction of FXR target genes in mouse liver and intestine. In a mouse model of intrahepatic cholestasis, metformin treatment induced FXR phosphorylation, perturbed bile acid homeostasis, and worsened liver injury. Together, our data indicate that AMPK directly phosphorylates and regulates FXR transcriptional activity to precipitate liver injury under conditions favoring cholestasis. PMID:24531544

  10. Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk

    PubMed Central

    Lien, Fleur; Berthier, Alexandre; Bouchaert, Emmanuel; Gheeraert, Céline; Alexandre, Jeremy; Porez, Geoffrey; Prawitt, Janne; Dehondt, Hélène; Ploton, Maheul; Colin, Sophie; Lucas, Anthony; Patrice, Alexandre; Pattou, François; Diemer, Hélène; Van Dorsselaer, Alain; Rachez, Christophe; Kamilic, Jelena; Groen, Albert K.; Staels, Bart; Lefebvre, Philippe

    2014-01-01

    The nuclear bile acid receptor farnesoid X receptor (FXR) is an important transcriptional regulator of bile acid, lipid, and glucose metabolism. FXR is highly expressed in the liver and intestine and controls the synthesis and enterohepatic circulation of bile acids. However, little is known about FXR-associated proteins that contribute to metabolic regulation. Here, we performed a mass spectrometry–based search for FXR-interacting proteins in human hepatoma cells and identified AMPK as a coregulator of FXR. FXR interacted with the nutrient-sensitive kinase AMPK in the cytoplasm of target cells and was phosphorylated in its hinge domain. In cultured human and murine hepatocytes and enterocytes, pharmacological activation of AMPK inhibited FXR transcriptional activity and prevented FXR coactivator recruitment to promoters of FXR-regulated genes. Furthermore, treatment with AMPK activators, including the antidiabetic biguanide metformin, inhibited FXR agonist induction of FXR target genes in mouse liver and intestine. In a mouse model of intrahepatic cholestasis, metformin treatment induced FXR phosphorylation, perturbed bile acid homeostasis, and worsened liver injury. Together, our data indicate that AMPK directly phosphorylates and regulates FXR transcriptional activity to precipitate liver injury under conditions favoring cholestasis. PMID:24531544

  11. 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.

  12. 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.

  13. 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.

  14. Optimization of electrodynamic acceleration regimes for cylindrical conductors

    NASA Astrophysics Data System (ADS)

    Kalikhman, S. A.

    1985-11-01

    At the present time electromagnetic accelerators which use the action of an impulsive electromagnetic field on a current-carrying conductor appear to be promising devices for the study of high-speed collisions. In the regime using separate sources for the accelerating magnetic field and the current in the conductor being accelerated it is possible to bring cylindrical conductors up to velocities exceeding 12 km/sec [1]. Acceleration regimes have been calculated previously [2] assuming independence of the current density in the conductor from the accelerating magnetic field. However, as analysis of transient electromagnetic processes occurring in the interaction of an impulsive electromagnetic field with a cylindrical conductor shows [3], the maximum current density, limited by heating conditions, depends significantly on the induction of the accelerating magnetic field. In the present study we will analyze regimes for electrodynamic acceleration of cylindrical conductors with consideration of diffusion of both the intrinsic and the external impulsive magnetic field within the conductor.

  15. 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

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

    PubMed

    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

  17. 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.

  18. 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.

  19. Mechanisms of STAT3 activation in the liver of FXR knockout mice.

    PubMed

    Li, Guodong; Zhu, Yan; Tawfik, Ossama; Kong, Bo; Williams, Jessica A; Zhan, Le; Kassel, Karen M; Luyendyk, James P; Wang, Li; Guo, Grace L

    2013-12-01

    Farnesoid X receptor (FXR, Nr1h4) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. FXR is essential in maintaining bile acid (BA) homeostasis, and FXR(-/-) mice develop cholestasis, inflammation, and spontaneous liver tumors. The signal transducer and activator of transcription 3 (STAT3) is well known to regulate liver growth, and STAT3 is feedback inhibited by its target gene, the suppressor of cytokine signaling 3 (SOCS3). Strong activation of STAT3 was detected in FXR(-/-) mouse livers. However, the mechanism of STAT3 activation with FXR deficiency remains elusive. Wild-type (WT) and FXR(-/-) mice were used to detect STAT3 pathway activation in the liver. In vivo BA feeding or deprivation was used to determine the role of BAs in STAT3 activation, and in vitro molecular approaches were used to determine the direct transcriptional regulation of SOCS3 by FXR. STAT3 was activated in FXR(-/-) but not WT mice. BA feeding increased, but deprivation by cholestyramine reduced, serum inflammatory markers and STAT3 activation. Furthermore, the Socs3 gene was determined as a direct FXR target gene. The elevated BAs and inflammation, along with reduced SOCS3, collectively contribute to the activation of the STAT3 signaling pathway in the liver of FXR(-/-) mice. This study suggests that the constitutive activation of STAT3 may be a mechanism of liver carcinogenesis in FXR(-/-) mice. PMID:24091600

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

    PubMed

    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

    2014-02-11

    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

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. Optimization of accelerator-driven technology for LWR waste transmutation

    SciTech Connect

    Bowman, C.D.

    1996-12-31

    The role of accelerator-driven transmutation technology is examined in the context of the destruction of actinide waste from commercial light water reactors. It is pointed out that the commercial plutonium is much easier to use for entry-level nuclear weapons than weapons plutonium. Since commercial plutonium is easier to use, since there is very much more of it already, and since it is growing rapidly, the permanent disposition of commercial plutonium is an issue of greater importance than weapons plutonium. The minor actinides inventory, which may be influenced by transmutation, is compared in terms of nuclear properties with commercial and weapons plutonium and for possible utility as weapons material. Fast and thermal spectrum systems are compared as means for destruction of plutonium and the minor actinides. it is shown that the equilibrium fast spectrum actinide inventory is about 100 times larger than for thermal spectrum systems, and that there is about 100 times more weapons-usable material in the fast spectrum system inventory compared to the thermal spectrum system. Finally it is shown that the accelerator size for transmutation can be substantially reduced by design which uses the accelerator-produced neutrons only to initiate the unsustained fission chains characteristic of the subcritical system. The analysis argues for devoting primary attention to the development of thermal spectrum transmutation technology. A thermal spectrum transmuter operating at a fission power of 750-MWth fission power, which is sufficient to destroy the actinide waste from one 3,000-MWth light water reactor, may be driven by a proton beam of 1 GeV energy and a current of 7 mA. This accelerator is within the range of realizable cyclotron technology and is also near the size contemplated for the next generation spallation neutron source under consideration by the US, Europe, and Japan.

  7. 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.

  8. 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.

  9. 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.

  10. Optimized capture section for a muon accelerator front end

    NASA Astrophysics Data System (ADS)

    Kamal Sayed, Hisham; Berg, J. Scott

    2014-07-01

    In a muon accelerator complex, a target is bombarded by a multi-MW proton beam to produce pions, which decay into the muons which are thereafter bunched, cooled, and accelerated. The front end of the complex captures those pions, then manipulates their phase space, and that of the muons into which they decay, to maximize the number of muons within the acceptance of the downstream systems. The secondary pion beam produced at the target is captured by a high field target solenoid that tapers down to a constant field throughout the rest of the front end. In this study we enhance the useful muon flux by introducing a new design of the longitudinal profile of the solenoid field at, and downstream of, the target. We find that the useful muon flux exiting the front end is larger when the field at the target is higher, the distance over which the field tapers down is shorter, and the field at the end of the taper is higher. We describe how the solenoid field profile impacts the transverse and longitudinal phase space of the beam and thereby leads to these dependencies.

  11. The nuclear bile acid receptor FXR controls the liver derived tumor suppressor histidine-rich glycoprotein.

    PubMed

    Deuschle, Ulrich; Birkel, Manfred; Hambruch, Eva; Hornberger, Martin; Kinzel, Olaf; Perović-Ottstadt, Sanja; Schulz, Andreas; Hahn, Ulrike; Burnet, Michael; Kremoser, Claus

    2015-06-01

    The nuclear bile acid receptor Farnesoid X receptor (FXR) is strongly expressed in liver and intestine, controls bile acid and lipid homeostasis and exerts tumor-protective functions in liver and intestine. Histidine-rich glycoprotein (HRG) is an abundant plasma protein produced by the liver with the proposed function as a pattern recognition molecule involved in the clearance of immune complexes, necrotic cells and pathogens, the modulation of angiogenesis, the normalization of deranged endothelial vessel structure in tumors and tumor suppression. FXR recognition sequences were identified within a human HRG promoter fragment that mediated FXR/FXR-agonist dependent reporter gene activity in vitro. We show that HRG is a novel transcriptional target gene of FXR in human hepatoma cells, human upcyte® primary hepatocytes and 3D human liver microtissues in vitro and in mouse liver in vivo. Prolonged administration of the potent nonsteroidal FXR agonist PX20606 increases HRG levels in mouse plasma. Finally, daily oral administration of this FXR agonist for seven days resulted in a significant increase of HRG levels in the plasma of healthy human male volunteers during a clinical Phase I safety study. HRG might serve as a surrogate marker indicative of liver-specific FXR activation in future human clinical studies. Furthermore, potent FXR agonists might be beneficial in serious health conditions where HRG is reduced, for example, in hepatocellular carcinoma but also other solid cancers, liver failure, sepsis and pre-eclampsia. PMID:25363753

  12. 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

  13. 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.

  14. 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.

  15. DETERMINING THE OPTIMAL LOCATIONS FOR SHOCK ACCELERATION IN MAGNETOHYDRODYNAMICAL JETS

    SciTech Connect

    Polko, Peter; Markoff, Sera; Meier, David L.

    2010-11-10

    Observations of relativistic jets from black hole systems suggest that particle acceleration often occurs at fixed locations within the flow. These sites could be associated with critical points that allow the formation of standing shock regions, such as the magnetosonic modified fast point (MFP). Using the self-similar formulation of special relativistic magnetohydrodynamics by Vlahakis and Koenigl, we derive a new class of flow solutions that are both relativistic and cross the MFP at a finite height. Our solutions span a range of Lorentz factors up to at least 10, appropriate for most jets in X-ray binaries and active galactic nuclei, and a range in injected particle internal energy. A broad range of solutions exists, which will allow the eventual matching of these scale-free models to physical boundary conditions in the analysis of observed sources.

  16. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

    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.

  18. 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

  19. 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

  20. 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.

  1. Optimization and Modeling of the Accelerator for the FERMI @ Elettra FEL

    SciTech Connect

    Di Mitri, S.; Cornacchia, M.; Craievich, P.; Emma, P.; Huang, Z.; Wu, J.; Wang, D.; Zholents, A.; /LBL, Berkeley

    2005-09-30

    Design studies are in progress to use the existing FERMI{at}Elettra linear accelerator for a seeded harmonic cascade free-electron laser (FEL) facility [1]. This accelerator will be upgraded to 1.2 GeV and equipped with a low-emittance RF photocathode gun, laser heater, two bunch compressors, and a beam delivery system. We present an optimization study of all the components downstream of the gun, aimed at achieving the high peak current, low energy spread and low emittance electron beam necessary for the FEL. Various operational scenarios are discussed. Results of accelerator simulations including effects of space charge, coherent synchrotron radiation and wakefields are reported.

  2. Optimization of an accelerator-based epithermal neutron source for neutron capture therapy

    SciTech Connect

    Kononov, O.E.; Kononov, V.N.; Bokhovko, M.V.; Korobeynikov, V.V.; Soloviev, A.N.; Chu, W.T.

    2004-02-20

    A modeling investigation was performed to choose moderator material and size for creating optimal epithermal neutron beams for BNCT based on a proton accelerator and the 7Li(p,n)7Be reaction as a neutrons source. An optimal configuration is suggested for the beam shaping assembly made from polytetrafluoroethylene and magnesium fluorine. Results of calculation were experimentally tested and are in good agreement with measurements.

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

    PubMed

    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

    2015-01-13

    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

  4. 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.

  5. 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

  6. 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

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

    PubMed

    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

    2015-02-01

    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

  8. 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. PMID:26505219

  9. 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. PMID:25599407

  10. Knocking on FXR's door: the "hammerhead"-structure series of FXR agonists - amphiphilic isoxazoles with potent in vitro and in vivo activities.

    PubMed

    Gege, Christian; Kinzel, Olaf; Steeneck, Christoph; Schulz, Andreas; Kremoser, Claus

    2014-01-01

    The Farnesoid X Receptor (FXR) was recently validated in clinical studies using the bile acid analogue Obeticholic Acid (OCA) as an attractive drug target for liver diseases such as Primary Biliary Cirrhosis (PBC) or Non-alcoholic Steatohepatitis (NASH). OCA, however, turned out to induce cholesterol- related side effects upon prolonged treatment and it shows bile acid like pharmacokinetics. The quest for synthetic non-steroidal FXR agonists with general drug likeliness and improved pharmacokinetic and - dynamic properties has started more than a decade ago: The first non-steroidal and selective FXR agonist with decent submicromolar potency, GW4064, was patented in 1998 and published in 2000. Since then, many pharmaceutical companies have taken GW4064 as a structural template for their efforts in identifying novel patentable FXR agonists with the GW-derived trisubstituted isoxazole general structure. However, so far only one compound out of these different series has made it into the early stages of clinical development: The Px-102/Px-104 from Phenex is currently tested in a phase IIa study in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). In this review we try to summarize from the patent and scientific literature the attempts to improve the GW4064 structure into different directions. Furthermore, we suggest directions for further improvements of this special class of synthetic FXR agonists which all display the typical "hammerhead"-conformation in the FXR ligand binding pocket that provides the basis for their impressive in vitro and in vivo potencies. PMID:25388536

  11. 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.

  12. Optimization of the combined proton acceleration regime with a target composition scheme

    NASA Astrophysics Data System (ADS)

    Yao, W. P.; Li, B. W.; Zheng, C. Y.; Liu, Z. J.; Yan, X. Q.; Qiao, B.

    2016-01-01

    A target composition scheme to optimize the combined proton acceleration regime is presented and verified by two-dimensional particle-in-cell simulations by using an ultra-intense circularly polarized (CP) laser pulse irradiating an overdense hydrocarbon (CH) target, instead of a pure hydrogen (H) one. The combined acceleration regime is a two-stage proton acceleration scheme combining the radiation pressure dominated acceleration (RPDA) stage and the laser wakefield acceleration (LWFA) stage sequentially together. Protons get pre-accelerated in the first stage when an ultra-intense CP laser pulse irradiating an overdense CH target. The wakefield is driven by the laser pulse after penetrating through the overdense CH target and propagating in the underdense tritium plasma gas. With the pre-accelerate stage, protons can now get trapped in the wakefield and accelerated to much higher energy by LWFA. Finally, protons with higher energies (from about 20 GeV up to about 30 GeV) and lower energy spreads (from about 18% down to about 5% in full-width at half-maximum, or FWHM) are generated, as compared to the use of a pure H target. It is because protons can be more stably pre-accelerated in the first RPDA stage when using CH targets. With the increase of the carbon-to-hydrogen density ratio, the energy spread is lower and the maximum proton energy is higher. It also shows that for the same laser intensity around 1022 W cm-2, using the CH target will lead to a higher proton energy, as compared to the use of a pure H target. Additionally, proton energy can be further increased by employing a longitudinally negative gradient of a background plasma density.

  13. PPARα-UGT axis activation represses intestinal FXR-FGF15 feedback signalling and exacerbates experimental colitis

    PubMed Central

    Zhou, Xueyan; Cao, Lijuan; Jiang, Changtao; Xie, Yang; Cheng, Xuefang; Krausz, Kristopher W.; Qi, Yunpeng; Sun, Lu; Shah, Yatrik M.; Gonzalez, Frank J.; Wang, Guangji; Hao, Haiping

    2014-01-01

    Bile acids play a pivotal role in the pathological development of inflammatory bowel disease (IBD). However, the mechanism of bile acid dysregulation in IBD remains unanswered. Here we show that intestinal peroxisome proliferator-activated receptor α (PPARα)-UDP-glucuronosyltransferases (UGTs) signalling is an important determinant of bile acid homeostasis. Dextran sulphate sodium (DSS)-induced colitis leads to accumulation of bile acids in inflamed colon tissues via activation of the intestinal peroxisome PPARα-UGTs pathway. UGTs accelerate the metabolic elimination of bile acids, and thereby decrease their intracellular levels in the small intestine. Reduced intracellular bile acids results in repressed farnesoid X receptor (FXR)-FGF15 signalling, leading to upregulation of hepatic CYP7A1, thus promoting the de novo bile acid synthesis. Both knockout of PPARα and treatment with recombinant FGF19 markedly attenuate DSS-induced colitis. Thus, we propose that intestinal PPARα-UGTs and downstream FXR-FGF15 signalling play vital roles in control of bile acid homeostasis and the pathological development of colitis. PMID:25183423

  14. 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.

  15. Novel FXR (farnesoid X receptor) modulators: Potential therapies for cholesterol gallstone disease.

    PubMed

    Yu, Donna D; Andrali, Sreenath S; Li, Hongzhi; Lin, Min; Huang, Wendong; Forman, Barry M

    2016-09-15

    Metabolic disorders such as diabetes are known risk factors for developing cholesterol gallstone disease (CGD). Cholesterol gallstone disease is one of the most prevalent digestive diseases, leading to considerable financial and social burden worldwide. Ursodeoxycholic acid (UDCA) is the only bile acid drug approved by FDA for the non-surgical treatment of gallstones. However, the molecular link between UDCA and CGD is unclear. Previous data suggest that the farnesoid X receptor (FXR), a bile acid nuclear receptor, may protect against the development of CGD. In studies aimed at identifying the role of FXR, we recently identify a novel chemical tool, 6EUDCA (6-αethyl-ursodeoxycholic acid), a synthetic derivative of UDCA, for studying FXR. We found that 6EUDCA binds FXR stronger than UDCA in a TR-FRET binding assay. This result was supported by computational docking models that suggest 6EUDCA forms a more extensive hydrogen bound network with FXR. Interestingly, neither compound could activate FXR target genes in human nor mouse liver cells, suggesting UDCA and 6EUDCA activate non-genomic signals in an FXR-dependent manner. Overall these studies may lead to the identification of a novel mechanism by which bile acids regulate cell function, and 6EUDCA may be an effective targeted CGD therapeutic. PMID:27372840

  16. The nuclear receptor FXR regulates hepatic transport and metabolism of glutamine and glutamate.

    PubMed

    Renga, Barbara; Mencarelli, Andrea; Cipriani, Sabrina; D'Amore, Claudio; Zampella, Angela; Monti, Maria Chiara; Distrutti, Eleonora; Fiorucci, Stefano

    2011-11-01

    Hepatic transport and metabolism of glutamate and glutamine are regulated by intervention of several proteins. Glutamine is taken up by periportal hepatocytes and is the major source of ammonia for urea synthesis and glutamate for N-acetylglutamate (NAG) synthesis, which is catalyzed by the N-acetylglutamate synthase (NAGS). Glutamate is taken up by perivenous hepatocytes and is the main source for the synthesis of glutamine, catalyzed by glutamine synthase (GS). Accumulation of glutamate and ammonia is a common feature of chronic liver failure, but mechanism that leads to failure of the urea cycle in this setting is unknown. The Farnesoid X Receptor (FXR) is a bile acid sensor in hepatocytes. Here, we have investigated its role in the regulation of the metabolism of both glutamine and glutamate. In vitro studies in primary cultures of hepatocytes from wild type and FXR(-/-) mice and HepG2 cells, and in vivo studies, in FXR(-/-) mice as well as in a rodent model of hepatic liver failure induced by carbon tetrachloride (CCl(4)), demonstrate a role for FXR in regulating this metabolism. Further on, promoter analysis studies demonstrate that both human and mouse NAGS promoters contain a putative FXRE, an ER8 sequence. EMSA, ChIP and luciferase experiments carried out to investigate the functionality of this sequence demonstrate that FXR is essential to induce the expression of NAGS. In conclusion, FXR activation regulates glutamine and glutamate metabolism and FXR ligands might have utility in the treatment of hyperammonemia states. PMID:21757002

  17. Splenic dendritic cell involvement in FXR-mediated amelioration of DSS colitis.

    PubMed

    Massafra, Vittoria; Ijssennagger, Noortje; Plantinga, Maud; Milona, Alexandra; Ramos Pittol, José M; Boes, Marianne; van Mil, Saskia W C

    2016-02-01

    Inflammatory Bowel Disease (IBD) is a multifactorial disorder involving dysregulation of the immune response and bacterial translocation through the intestinal mucosal barrier. Previously, we have shown that activation of the bile acid sensor Farnesoid X Receptor (FXR), which belongs to the family of nuclear receptors, improves experimental intestinal inflammation, decreasing expression of pro-inflammatory cytokines and protecting the intestinal barrier. Here, we aimed to investigate the immunological mechanisms that ameliorate colitis when FXR is activated. We analyzed by FACS immune cell populations in mesenteric lymph nodes (MLN) and in the spleen to understand whether FXR activation alters the systemic immune response. We show that FXR activation by obeticholic acid (OCA) has systemic anti-inflammatory effects that include increased levels of plasma IL-10, inhibition of both DSS-colitis associated decrease in splenic dendritic cells (DCs) and increase in Tregs. Impact of OCA on DC relative abundance was seen in spleen but not MLN, possibly related to the increased FXR expression in splenic DCs compared to MLN DCs. Moreover, FXR activation modulates the chemotactic environment in the colonic site of inflammation, as Madcam1 expression is decreased, while Ccl25 is upregulated. Together, our data suggest that OCA treatment elicits an anti-inflammatory immune status including retention of DCs in the spleen, which is associated with decreased colonic inflammation. Pharmacological FXR activation is therefore an attractive new drug target for treatment of IBD. PMID:26554605

  18. Investigation of the dominant positive effect of porcine farnesoid X receptor (FXR) splice variant 1.

    PubMed

    Gray, Matthew A; James Squires, E

    2015-04-10

    Pigs are well recognized as a model for humans in research studies due to similarities in metabolism and physiology between the two species. The potential for pigs to model humans in studying metabolic diseases is highly dependent on similarities in hepatic metabolism between the two species, including similarities in the farnesoid X receptor (FXR; NR1H4) which regulate bile acid homeostasis. During initial cloning of porcine FXR (pFXR), an alternative splice variant (pFXR-SV1) was isolated which contained a four amino acid (MYTG) insert that exerted a dominant positive effect on the wild type receptor (pFXR-WT). The current study investigated the role of this insert in the dominant positive effect. Individual point mutations were made to the first three amino acids of the MYTG insert. Mutations of the methionine (M) or threonine (T) to alanine (A) reduced the dominant positive effect, while mutation of the tyrosine (Y) to either A or phenylalanine (F) completely abolished the dominant positive effect. Treatment with the tyrosine phosphatase inhibitor sodium orthovanadate (Na3VO4) increased the dominant positive effect of pFXR-SV1 by about 30%. These results suggest that the dominant positive effect may be dependent on the phosphorylation status of the tyrosine in the MYTG insert. The human variant hFXRα+ has the same MYTG insert as pFXR-SV1, but did not cause a dominant positive effect on hFXR-WT and significantly reduced the activity of hFXR-WT. Thus, although the MYTG insert is conserved in both human and pig, the effects of this insert are different in the two species. PMID:25623328

  19. Modern Simulation and Optimization Tools for Non-Scaling FFAGs and Related Accelerators

    SciTech Connect

    C. Johnstone; M. Berz; K. Makino

    2010-11-04

    With the U.S. experimental effort in HEP largely located at laboratories supporting the operations of large, highly specialized accelerators, the understanding and prediction of high energy particle accelerators becomes critical to the overall success 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. A specific newly identified problem lies in the simulation and optimization of FFAGs and related devices, for which currently available tools originally developed for other purposes provide only approximate and inefficient simulation. We propose to develop a set of tools for this purpose based on modern techniques and simulation approaches.

  20. 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.

  1. Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers

    PubMed Central

    Siegwart, Daniel J.; Leiendecker, Matthias; Langer, Robert; Anderson, Daniel G.

    2013-01-01

    Conventional synthesis of polymers by ATRP is relatively low throughput, involving iterative optimization of conditions in an inert atmosphere. Automated, high-throughput controlled radical polymerization was developed to accelerate catalyst optimization and production of disulfide-functionalized polymers without the need of an inert gas. Using ARGET ATRP, polymerization conditions were rapidly identified for eight different monomers, including the first ARGET ATRP of 2-(diethylamino)ethyl methacrylate and di(ethylene glycol) methyl ether methacrylate. In addition, butyl acrylate, oligo(ethylene glycol) methacrylate 300 and 475, 2-(dimethylamino)ethyl methacrylate, styrene, and methyl methacrylate were polymerized using bis(2-hydroxyethyl) disulfide bis(2-bromo-2-methylpropionate) as the initiator, tris(2-pyridylmethyl)amine as the ligand, and tin(II) 2-ethylhexanoate as the reducing agent. The catalyst and reducing agent concentration was optimized specifically for each monomer, and then a library of polymers was synthesized systematically using the optimized conditions. The disulfide-functionalized chains could be cleaved to two thiol-terminated chains upon exposure to dithiothreitol, which may have utility for the synthesis of polymer bioconjugates. Finally, we demonstrated that these new conditions translated perfectly to conventional batch polymerization. We believe the methods developed here may prove generally useful to accelerate the systematic optimization of a variety of chemical reactions and polymerizations. PMID:23599541

  2. 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

  3. 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.

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

    NASA Astrophysics Data System (ADS)

    Rochepault, Etienne; Aubert, Guy; Vedrine, Pierre

    2014-07-01

    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.

  5. 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

  6. 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

  7. 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.

  8. 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).

  9. The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats.

    PubMed

    Verbeke, Len; Farre, Ricard; Verbinnen, Bert; Covens, Kris; Vanuytsel, Tim; Verhaegen, Jan; Komuta, Mina; Roskams, Tania; Chatterjee, Sagnik; Annaert, Pieter; Vander Elst, Ingrid; Windmolders, Petra; Trebicka, Jonel; Nevens, Frederik; Laleman, Wim

    2015-02-01

    Bacterial translocation (BTL) drives pathogenesis and complications of cirrhosis. Farnesoid X-activated receptor (FXR) is a key transcription regulator in hepatic and intestinal bile metabolism. We studied potential intestinal FXR dysfunction in a rat model of cholestatic liver injury and evaluated effects of obeticholic acid (INT-747), an FXR agonist, on gut permeability, inflammation, and BTL. Rats were gavaged with INT-747 or vehicle during 10 days after bile-duct ligation and then were assessed for changes in gut permeability, BTL, and tight-junction protein expression, immune cell recruitment, and cytokine expression in ileum, mesenteric lymph nodes, and spleen. Auxiliary in vitro BTL-mimicking experiments were performed with Transwell supports. Vehicle-treated bile duct-ligated rats exhibited decreased FXR pathway expression in both jejunum and ileum, in association with increased gut permeability through increased claudin-2 expression and related to local and systemic recruitment of natural killer cells resulting in increased interferon-γ expression and BTL. After INT-747 treatment, natural killer cells and interferon-γ expression markedly decreased, in association with normalized permeability selectively in ileum (up-regulated claudin-1 and occludin) and a significant reduction in BTL. In vitro, interferon-γ induced increased Escherichia coli translocation, which remained unaffected by INT-747. In experimental cholestasis, FXR agonism improved ileal barrier function by attenuating intestinal inflammation, leading to reduced BTL and thus demonstrating a crucial protective role for FXR in the gut-liver axis. PMID:25592258

  10. 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

  11. 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

  12. FXR blocks the growth of liver cancer cells through inhibiting mTOR-s6K pathway.

    PubMed

    Huang, Xiongfei; Zeng, Yeting; Wang, Xinrui; Ma, Xiaoxiao; Li, Qianqian; Li, Ningbo; Su, Hongying; Huang, Wendong

    2016-05-27

    The nuclear receptor Farnesoid X Receptor (FXR) is likely a tumor suppressor in liver tissue but its molecular mechanism of suppression is not well understood. In this study, the gene expression profile of human liver cancer cells was investigated by microarray. Bioinformatics analysis of these data revealed that FXR might regulate the mTOR/S6K signaling pathway. This was confirmed by altering the expression level of FXR in liver cancer cells. Overexpression of FXR prevented the growth of cells and induced cell cycle arrest, which was enhanced by the mTOR/S6K inhibitor rapamycin. FXR upregulation also intensified the inhibition of cell growth by rapamycin. Downregulation of FXR produced the opposite effect. Finally, we found that ectopic expression of FXR in SK-Hep-1 xenografts inhibits tumor growth and reduces expression of the phosphorylated protein S6K. Taken together, our data provide the first evidence that FXR suppresses proliferation of human liver cancer cells via the inhibition of the mTOR/S6K signaling pathway. FXR expression can be used as a biomarker of personalized mTOR inhibitor treatment assessment for liver cancer patients. PMID:27109477

  13. Optimal convolution SOR acceleration of waveform relaxation with application to semiconductor device simulation

    NASA Technical Reports Server (NTRS)

    Reichelt, Mark

    1993-01-01

    In this paper we describe a novel generalized SOR (successive overrelaxation) algorithm for accelerating the convergence of the dynamic iteration method known as waveform relaxation. A new convolution SOR algorithm is presented, along with a theorem for determining the optimal convolution SOR parameter. Both analytic and experimental results are given to demonstrate that the convergence of the convolution SOR algorithm is substantially faster than that of the more obvious frequency-independent waveform SOR algorithm. Finally, to demonstrate the general applicability of this new method, it is used to solve the differential-algebraic system generated by spatial discretization of the time-dependent semiconductor device equations.

  14. 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.

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

    NASA Astrophysics Data System (ADS)

    Fadin, A. I.

    2006-03-01

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

  16. 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.

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

    PubMed

    Gidofalvi, Gergely; Mazziotti, David A

    2014-01-16

    Molecule-optimized basis sets, based on approximate natural orbitals, are developed for accelerating the convergence of quantum calculations with strongly correlated (multireferenced) electrons. We use a low-cost approximate solution of the anti-Hermitian contracted Schrödinger equation (ACSE) for the one- and two-electron reduced density matrices (RDMs) to generate an approximate set of natural orbitals for strongly correlated quantum systems. The natural-orbital basis set is truncated to generate a molecule-optimized basis set whose rank matches that of a standard correlation-consistent basis set optimized for the atoms. We show that basis-set truncation by approximate natural orbitals can be viewed as a one-electron unitary transformation of the Hamiltonian operator and suggest an extension of approximate natural-orbital truncations through two-electron unitary transformations of the Hamiltonian operator, such as those employed in the solution of the ACSE. The molecule-optimized basis set from the ACSE improves the accuracy of the equivalent standard atom-optimized basis set at little additional computational cost. We illustrate the method with the potential energy curves of hydrogen fluoride and diatomic nitrogen. Relative to the hydrogen fluoride potential energy curve from the ACSE in a polarized triple-ζ basis set, the ACSE curve in a molecule-optimized basis set, equivalent in size to a polarized double-ζ basis, has a nonparallelity error of 0.0154 au, which is significantly better than the nonparallelity error of 0.0252 au from the polarized double-ζ basis set. PMID:24387056

  18. 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

  19. Comparative effects of 1α-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on transporters and enzymes in fxr(+/+) and fxr(-/-) mice.

    PubMed

    Chow, Edwin C Y; Durk, Matthew R; Maeng, Han-Joo; Pang, K Sandy

    2013-10-01

    Previous studies have shown that 1α,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] treatment in mice resulted in induction of intestinal and renal Cyp24a1 and Trpv6 expression, increased hepatic Cyp7a1 expression and activity, as well as higher renal Mdr1/P-gp expression. The present study compared the equimolar efficacies of 1α-hydroxyvitamin D3 [1α(OH)D3 ] (6 nmol/kg i.p. q2d × 4), a lipophilic precursor with a longer plasma half-life that is converted to 1,25(OH)2 D3 , and 1,25(OH)2 D3 on vitamin D receptor (VDR) target genes. To clarify whether changes in VDR genes was due to VDR and not secondary, farnesoid X receptor (FXR)-directed effects, namely, lower Cyp7a1 expression in rat liver due to increased bile acid absorption, wildtype [fxr(+/+)] and FXR knockout [fxr(-/-)] mice were used to distinguish between VDR and FXR effects. With the exception that hepatic Sult2a1 mRNA was increased equally well by 1α(OH)D3 and 1,25(OH)2 D3 , 1α(OH)D3 treatment led to higher increases in hepatic Cyp7a1, renal Cyp24a1, VDR, Mdr1 and Mrp4, and intestinal Cyp24a1 and Trpv6 mRNA expression in both fxr(+/+) and fxr(-/-) mice compared to 1,25(OH)2 D3 treatment. A similar induction in protein expression and microsomal activity of hepatic Cyp7a1 and renal P-gp and Mrp4 protein expression was noted for both compounds. A higher intestinal induction of Trpv6 was observed, resulting in greater hypercalcemic effect following 1α(OH)D3 treatment. The higher activity of 1α(OH)D3 was explained by its rapid conversion to 1,25(OH)2 D3 in tissue sites, furnishing higher plasma and tissue 1,25(OH)2 D3 levels compared to following 1,25(OH)2 D3 -treatment. In conclusion, 1α(OH)D3 exerts a greater effect on VDR gene induction than equimolar doses of 1,25(OH)2 D3 in mice. PMID:23897575

  20. Mechanisms of STAT3 activation in the liver of FXR knockout mice

    PubMed Central

    Li, Guodong; Zhu, Yan; Tawfik, Ossama; Kong, Bo; Williams, Jessica A.; Zhan, Le; Kassel, Karen M.; Luyendyk, James P.; Wang, Li

    2013-01-01

    Farnesoid X receptor (FXR, Nr1h4) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. FXR is essential in maintaining bile acid (BA) homeostasis, and FXR−/− mice develop cholestasis, inflammation, and spontaneous liver tumors. The signal transducer and activator of transcription 3 (STAT3) is well known to regulate liver growth, and STAT3 is feedback inhibited by its target gene, the suppressor of cytokine signaling 3 (SOCS3). Strong activation of STAT3 was detected in FXR−/− mouse livers. However, the mechanism of STAT3 activation with FXR deficiency remains elusive. Wild-type (WT) and FXR−/− mice were used to detect STAT3 pathway activation in the liver. In vivo BA feeding or deprivation was used to determine the role of BAs in STAT3 activation, and in vitro molecular approaches were used to determine the direct transcriptional regulation of SOCS3 by FXR. STAT3 was activated in FXR−/− but not WT mice. BA feeding increased, but deprivation by cholestyramine reduced, serum inflammatory markers and STAT3 activation. Furthermore, the Socs3 gene was determined as a direct FXR target gene. The elevated BAs and inflammation, along with reduced SOCS3, collectively contribute to the activation of the STAT3 signaling pathway in the liver of FXR−/− mice. This study suggests that the constitutive activation of STAT3 may be a mechanism of liver carcinogenesis in FXR−/− mice. PMID:24091600

  1. Pipe degradation investigations for optimization of flow-accelerated corrosion inspection location selection

    SciTech Connect

    Chandra, S.; Habicht, P.; Chexal, B.; Mahini, R.; McBrine, W.; Esselman, T.; Horowitz, J.

    1995-12-01

    A large amount of piping in a typical nuclear power plant is susceptible to Flow-Accelerated Corrosion (FAC) wall thinning to varying degrees. A typical PAC monitoring program includes the wall thickness measurement of a select number of components in order to judge the structural integrity of entire systems. In order to appropriately allocate resources and maintain an adequate FAC program, it is necessary to optimize the selection of components for inspection by focusing on those components which provide the best indication of system susceptibility to FAC. A better understanding of system FAC predictability and the types of FAC damage encountered can provide some of the insight needed to better focus and optimize the inspection plan for an upcoming refueling outage. Laboratory examination of FAC damaged components removed from service at Northeast Utilities` (NU) nuclear power plants provides a better understanding of the damage mechanisms involved and contributing causes. Selected results of this ongoing study are presented with specific conclusions which will help NU to better focus inspections and thus optimize the ongoing FAC inspection program.

  2. Determining optimization of the initial parameters in Monte Carlo simulation for linear accelerator radiotherapy

    NASA Astrophysics Data System (ADS)

    Chang, Kwo-Ping; Wang, Zhi-Wei; Shiau, An-Cheng

    2014-02-01

    Monte Carlo (MC) method is a well known calculation algorithm which can accurately assess the dose distribution for radiotherapy. The present study investigated all the possible regions of the depth-dose or lateral profiles which may affect the fitting of the initial parameters (mean energy and the radial intensity (full width at half maximum, FWHM) of the incident electron). EGSnrc-based BEAMnrc codes were used to generate the phase space files (SSD=100 cm, FS=40×40 cm2) for the linac (linear accelerator, Varian 21EX, 6 MV photon mode) and EGSnrc-based DOSXYZnrc code was used to calculate the dose in the region of interest. Interpolation of depth dose curves of pre-set energies was proposed as a preliminary step for optimal energy fit. A good approach for determination of the optimal mean energy is the difference comparison of the PDD curves excluding buildup region, and using D(10) as a normalization method. For FWHM fitting, due to electron disequilibrium and the larger statistical uncertainty, using horn or/and penumbra regions will give inconsistent outcomes at various depths. Difference comparisons should be performed in the flat regions of the off-axis dose profiles at various depths to optimize the FWHM parameter.

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

    NASA Astrophysics Data System (ADS)

    Meeks, Sanford L.; Bova, Frank J.; Buatti, John M.; Friedman, William A.; Eyster, Brian; Kendrick, Lance 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.

  4. A novel optimized parallelization strategy to accelerate microwave tomography for breast cancer screening.

    PubMed

    Shahzad, A; O'Halloran, M; Glavin, M; Jones, E

    2014-01-01

    Microwave tomography has been proven to successfully reconstruct the dielectric profile of a human breast when used in breast imaging applications, thereby providing an alternative to other imaging modalities. However, the method suffers from high computational requirements which restrict its use in practical imaging systems. This paper presents a novel parallelization strategy to accelerate microwave tomography for reconstruction of the dielectric properties of the human breast. A Time Domain algorithm using this parallelization strategy has been validated and benchmarked against an optimized sequential implementation on a conventional high-end desktop Central Processing Unit (CPU), and a comparison of throughput is presented in this paper. The gain in computational throughput is shown to be significantly higher compared with the sequential implementation, ranging from a factor of 26 to 58, on imaging grid sizes of up to 25 cm square at 1 mm resolution. PMID:25570487

  5. 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.

  6. Optimization of accelerator target and detector for portal imaging using Monte Carlo simulation and experiment

    NASA Astrophysics Data System (ADS)

    Flampouri, S.; Evans, P. M.; Verhaegen, F.; Nahum, A. E.; Spezi, E.; Partridge, M.

    2002-09-01

    Megavoltage portal images suffer from poor quality compared to those produced with kilovoltage x-rays. Several authors have shown that the image quality can be improved by modifying the linear accelerator to generate more low-energy photons. This work addresses the problem of using Monte Carlo simulation and experiment to optimize the beam and detector combination to maximize image quality for a given patient thickness. A simple model of the whole imaging chain was developed for investigation of the effect of the target parameters on the quality of the image. The optimum targets (6 mm thick aluminium and 1.6 mm copper) were installed in an Elekta SL25 accelerator. The first beam will be referred to as Al6 and the second as Cu1.6. A tissue-equivalent contrast phantom was imaged with the 6 MV standard photon beam and the experimental beams with standard radiotherapy and mammography film/screen systems. The arrangement with a thin Al target/mammography system improved the contrast from 1.4 cm bone in 5 cm water to 19% compared with 2% for the standard arrangement of a thick, high-Z target/radiotherapy verification system. The linac/phantom/detector system was simulated with the BEAM/EGS4 Monte Carlo code. Contrast calculated from the predicted images was in good agreement with the experiment (to within 2.5%). The use of MC techniques to predict images accurately, taking into account the whole imaging system, is a powerful new method for portal imaging system design optimization.

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

    SciTech Connect

    Snopok, Pavel; /Michigan State U.

    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

  8. Chronic activation of FXR in transgenic mice caused perinatal toxicity and sensitized mice to cholesterol toxicity.

    PubMed

    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; Xie, Wen

    2015-04-01

    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

  9. 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. PMID:24597548

  10. 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

  11. 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

  12. Optimization by response surface methodology of lutein recovery from paprika leaves using accelerated solvent extraction.

    PubMed

    Kang, Jae-Hyun; Kim, Suna; Moon, BoKyung

    2016-08-15

    In this study, we used response surface methodology (RSM) to optimize the extraction conditions for recovering lutein from paprika leaves using accelerated solvent extraction (ASE). The lutein content was quantitatively analyzed using a UPLC equipped with a BEH C18 column. A central composite design (CCD) was employed for experimental design to obtain the optimized combination of extraction temperature (°C), static time (min), and solvent (EtOH, %). The experimental data obtained from a twenty sample set were fitted to a second-order polynomial equation using multiple regression analysis. The adjusted coefficient of determination (R(2)) for the lutein extraction model was 0.9518, and the probability value (p=0.0000) demonstrated a high significance for the regression model. The optimum extraction conditions for lutein were temperature: 93.26°C, static time: 5 min, and solvent: 79.63% EtOH. Under these conditions, the predicted extraction yield of lutein was 232.60 μg/g. PMID:27006224

  13. Accelerated barrier optimization compressed sensing (ABOCS) reconstruction for cone-beam CT: Phantom studies

    PubMed Central

    Niu, Tianye; Zhu, Lei

    2012-01-01

    Purpose: Recent advances in compressed sensing (CS) enable accurate CT image reconstruction from highly undersampled and noisy projection measurements, due to the sparsifiable feature of most CT images using total variation (TV). These novel reconstruction methods have demonstrated advantages in clinical applications where radiation dose reduction is critical, such as onboard cone-beam CT (CBCT) imaging in radiation therapy. The image reconstruction using CS is formulated as either a constrained problem to minimize the TV objective within a small and fixed data fidelity error, or an unconstrained problem to minimize the data fidelity error with TV regularization. However, the conventional solutions to the above two formulations are either computationally inefficient or involved with inconsistent regularization parameter tuning, which significantly limit the clinical use of CS-based iterative reconstruction. In this paper, we propose an optimization algorithm for CS reconstruction which overcomes the above two drawbacks. Methods: The data fidelity tolerance of CS reconstruction can be well estimated based on the measured data, as most of the projection errors are from Poisson noise after effective data correction for scatter and beam-hardening effects. We therefore adopt the TV optimization framework with a data fidelity constraint. To accelerate the convergence, we first convert such a constrained optimization using a logarithmic barrier method into a form similar to that of the conventional TV regularization based reconstruction but with an automatically adjusted penalty weight. The problem is then solved efficiently by gradient projection with an adaptive Barzilai–Borwein step-size selection scheme. The proposed algorithm is referred to as accelerated barrier optimization for CS (ABOCS), and evaluated using both digital and physical phantom studies. Results: ABOCS directly estimates the data fidelity tolerance from the raw projection data. Therefore, as

  14. 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

  15. 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.

  16. 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. PMID:26608185

  17. 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.

  18. 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.

  19. 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

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

    PubMed

    Gui, Ting; Gai, Zhibo

    2015-12-01

    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

  1. Dose optimization for the MRI-accelerator: IMRT in the presence of a magnetic field

    NASA Astrophysics Data System (ADS)

    Raaijmakers, A. J. E.; Hårdemark, B.; Raaymakers, B. W.; Raaijmakers, C. P. J.; Lagendijk, J. J. W.

    2007-12-01

    A combined system of a 6 MV linear accelerator and a 1.5 T MRI scanner is currently being developed. In this system, the patient will be irradiated in the presence of a 1.5 T magnetic field. This causes a strong dose increase at tissue-air interfaces. Around air cavities in the patient, these effects may become problematic. Homogeneous dose distributions can be obtained around regularly shaped symmetrical cavities using opposing beams. However, for more irregularly shaped cavities this approach may not be sufficient. This study will investigate whether IMRT can be used to cope with magnetic field dose effects, in particular for target volumes adjacent to irregularly shaped air cavities. Therefore, an inverse treatment planning approach has been designed based on pre-calculated beamlet dose distribution kernels. Using this approach, optimized dose distributions were calculated for B = 1.5 T and for B = 0 T. Investigated target sites include a prostate cancer, a laryngeal cancer and an oropharyngeal cancer. Differences in the dose distribution between B = 0 and 1.5 T were minimal; only the skin dose increased for B = 1.5 T. Homogeneous dose distributions were obtained for target structures adjacent to air cavities without the use of opposing beams. These results show that a 1.5 T magnetic field does not compromise the ability to achieve desired dose distributions with IMRT.

  2. 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.

  3. Optimization of Beam Injection Into the First Accelerating Module at TTF With Cavity Dipole Mode Signals

    SciTech Connect

    Baboi, N.; Kreps, G.; Schlarb, H.; Wendt, M.; Frisch, J.; McCormick, D.; Ross, M.; Smith, T.; Napoly, O.; Paparella, R.G.; /DSM, DAPNIA, Saclay

    2006-04-10

    The TESLA Test Facility (TTF) is a user facility for intense VUV-FEL light. The facility is densely equipped with diagnostics, essential in obtaining the necessary beam parameters, in particular the low emittance. However there is no dedicated component for alignment of the beam in the accelerating modules, each containing eight superconducting cavities. Large beam offsets can lead to an increase of the beam emittance. The centering of the beam in these modules is therefore important, mostly at the low energy end. A misalignment of the first TTF module with respect to the gun axis has already been observed using cavity dipole modes. This paper presents the experimental results of the optimization of the beam injection into the first module, based on the monitoring of dipole modes through the couplers installed for wakefield damping. For this we use a spectrum analyzer together with a multiplexer. By scanning the beam position and tilt with two pairs of steerers, we can find the trajectory which minimizes the dipole modes amplitude. The impact of the beam steering in the module on the beam is discussed. A time domain setup is also being presented.

  4. Dihydroartemisinin restricts hepatic stellate cell contraction via an FXR-S1PR2-dependent mechanism.

    PubMed

    Xu, Wenxuan; Lu, Chunfeng; Zhang, Feng; Shao, Jiangjuan; Zheng, Shizhong

    2016-05-01

    Hepatic stellate cells (HSCs) are universally acknowledged to play a stimulative role in the pathogenesis of hepatic fibrosis and portal hypertension. HSCs when activated in response to liver injury are characterized with many changes, with HSC contraction being the most common cause of portal hypertension. Previous studies have shown that dihydroartemisinine (DHA) is a potential antifibrotic natural product by inducing HSC apoptosis, whereas the role of DHA in regulating HSC contraction and the mechanisms involved remain a riddle. Recent studies have emphasized on the importance of farnesoid X receptor (FXR) and sphingosine-1-phosphate receptor 2 (S1PR2) in controlling cell contractility. This study showed that DHA strongly induced the mRNA and protein expression of FXR in LX-2 cells in a dose- and time-dependent manner and inhibited HSC activation, implying a conceivable impact of DHA on HSC contraction. The gel contraction assays and fluorescence staining of actin cytoskeleton verified that DHA dose-dependently limited contraction of collagen lattices and reorganization of actin stress fibers in LX-2 cells. DHA also decreased the phosphorylation of myosin light chain that is responsible for the contractile force of HSCs. Furthermore, gain- or loss-of-function analyses exhibited a FXR- and S1PR2-dependent mechanism of inhibiting HSC contraction by DHA, and DHA decreased S1PR2 expression by modulating FXR activation. Subsequent work revealed that inhibition of both Ca(2+) -dependent and Ca(2+) -sensitization signaling transductions contributed to DHA-induced HSC relaxation. In summary, these findings suggest that DHA could restrict HSC contraction through modulating FXR/S1PR2 pathway-mediated Ca(2+) -dependent and Ca(2+) -sensitization signaling. Our discoveries make DHA a potential candidate for portal hypertension. © 2016 IUBMB Life 68(5):376-387, 2016. PMID:27027402

  5. FXR-dependent reduction of hepatic steatosis in a bile salt deficient mouse model.

    PubMed

    Kunne, Cindy; Acco, Alexandra; Duijst, Suzanne; de Waart, Dirk R; Paulusma, Coen C; Gaemers, Ingrid; Oude Elferink, Ronald P J

    2014-05-01

    It has been established that bile salts play a role in the regulation of hepatic lipid metabolism. Accordingly, overt signs of steatosis have been observed in mice with reduced bile salt synthesis. The aim of this study was to identify the mechanism of hepatic steatosis in mice with bile salt deficiency due to a liver specific disruption of cytochrome P450 reductase. In this study mice lacking hepatic cytochrome P450 reductase (Hrn) or wild type (WT) mice were fed a diet supplemented with or without either 0.1% cholic acid (CA) or 0.025% obeticholic acid, a specific FXR-agonist. Feeding a CA-supplemented diet resulted in a significant decrease of plasma ALT in Hrn mice. Histologically, hepatic steatosis ameliorated after CA feeding and this was confirmed by reduced hepatic triglyceride content (115.5±7.3mg/g liver and 47.9±4.6mg/g liver in control- and CA-fed Hrn mice, respectively). The target genes of FXR-signaling were restored to normal levels in Hrn mice when fed cholic acid. VLDL secretion in both control and CA-fed Hrn mice was reduced by 25% compared to that in WT mice. In order to gain insight in the mechanism behind these bile salt effects, the FXR agonist also was administered for 3weeks. This resulted in a similar decrease in liver triglycerides, indicating that the effect seen in bile salt fed Hrn animals is FXR dependent. In conclusion, steatosis in Hrn mice is ameliorated when mice are fed bile salts. This effect is FXR dependent. Triglyceride accumulation in Hrn liver may partly involve impaired VLDL secretion. PMID:24548803

  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. Optimized laser pulse profile for efficient radiation pressure acceleration of ions

    SciTech Connect

    Bulanov, S. S.; Schroeder, C. B.; Esarey, E.; Leemans, W. P.

    2012-12-21

    The radiation pressure acceleration regime of laser ion acceleration requires high intensity laser pulses to function efficiently. Moreover the foil should be opaque for incident radiation during the interaction to ensure maximum momentum transfer from the pulse to the foil, which requires proper matching of the target to the laser pulse. However, in the ultrarela-tivistic regime, this leads to large acceleration distances, over which the high laser intensity for a Gaussian laser pulse must be maintained. It is shown that proper tailoring of the laser pulse profile can significantly reduce the acceleration distance, leading to a compact laser ion accelerator, requiring less energy to operate.

  8. Optimized laser pulse profile for efficient radiation pressure acceleration of ions

    SciTech Connect

    Bulanov, S. S.; Schroeder, C. B.; Esarey, E.; Leemans, W. P.

    2012-09-15

    The radiation pressure acceleration regime of laser ion acceleration requires high intensity laser pulses to function efficiently. Moreover, the foil should be opaque for incident radiation during the interaction to ensure maximum momentum transfer from the pulse to the foil, which requires proper matching of the target to the laser pulse. However, in the ultrarelativistic regime, this leads to large acceleration distances, over which the high laser intensity for a Gaussian laser pulse must be maintained. It is shown that proper tailoring of the laser pulse profile can significantly reduce the acceleration distance, leading to a compact laser ion accelerator, requiring less energy to operate.

  9. 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. PMID:24953769

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Human FXR Regulates SHP Expression through Direct Binding to an LRH-1 Binding Site, Independent of an IR-1 and LRH-1

    PubMed Central

    Hoeke, Martijn O.; Heegsma, Janette; Hoekstra, Mark; Moshage, Han; Faber, Klaas Nico

    2014-01-01

    Background Farnesoid X receptor/retinoid X receptor-alpha (FXR/RXRα) is the master transcriptional regulator of bile salt synthesis and transport in liver and intestine. FXR is activated by bile acids, RXRα by the vitamin A–derivative 9-cis retinoic acid (9cRA). Remarkably, 9cRA inhibits binding of FXR/RXRα to its response element, an inverted repeat-1 (IR-1). Still, most FXR/RXRα target genes are maximally expressed in the presence of both ligands, including the small heterodimer partner (SHP). Here, we revisited the FXR/RXRα-mediated regulation of human SHP. Methods A 579-bp hSHP promoter element was analyzed to locate FXR/chenodeoxycholic acid (CDCA)- and RXRα/9cRA-responsive elements. hSHP promoter constructs were analyzed in FXR/RXRα-transfected DLD-1, HEK293 and HepG2 cells exposed to CDCA, GW4064 (synthetic FXR ligand) and/or 9cRA. FXR-DNA interactions were analyzed by in vitro pull down assays. Results hSHP promoter elements lacking the previously identified IR-1 (−291/−279) largely maintained their activation by FXR/CDCA, but were unresponsive to 9cRA. FXR-mediated activation of the hSHP promoter was primarily dependent on the −122/−69 region. Pull down assays revealed a direct binding of FXR to the −122/−69 sequence, which was abrogated by site-specific mutations in a binding site for the liver receptor homolog-1 (LRH-1) at −78/−70. These mutations strongly impaired the FXR/CDCA-mediated activation, even in the context of a hSHP promoter containing the IR-1. LRH-1 did not increase FXR/RXRα-mediated activation of hSHP promoter activity. Conclusion FXR/CDCA-activated expression of SHP is primarily mediated through direct binding to an LRH-1 binding site, which is not modulated by LRH-1 and unresponsive to 9cRA. 9cRA-induced expression of SHP requires the IR-1 that overlaps with a direct repeat-2 (DR-2) and DR-4. This establishes for the first time a co-stimulatory, but independent, action of FXR and RXRα agonists. PMID:24498423

  16. 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

  17. 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

  18. 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

  19. Cytosol-nucleus traffic and colocalization with FXR of conjugated bile acids in rat hepatocytes.

    PubMed

    Monte, Maria J; Rosales, Ruben; Macias, Rocio I R; Iannota, Valeria; Martinez-Fernandez, Almudena; Romero, Marta R; Hofmann, Alan F; Marin, Jose J G

    2008-07-01

    Bile acids (BAs) are natural ligands of nuclear receptors, in particular farnesoid X receptor (FXR). Whether, in addition to protein-mediated cytosolic-nuclear BA translocation, other mechanisms are involved in the access of BAs to nuclear FXR was investigated. When rat hepatocytes were incubated with radiolabeled taurocholic acid, taurodeoxycholic acid, taurochenodeoxycholic acid, and tauroursodeoxycholic acid, their nuclear accumulation was proportional to their intracellular levels. With the use of flow cytometry analysis, the accumulation by nuclei isolated from rat liver cells was found to differ for several fluorescent compounds of similar molecular weight and different charge, including fluorescein-tagged BAs [cholylglycyl amidofluorescein (CGamF), ursodeoxycholylglycyl amidofluorescein, or chenodeoxycholylglycyl amidofluorescein]. When we varied nuclear volume by incubation with different sucrose concentrations, a similar relationship between nuclear volume and content of FITC and 4-kDa FITC-dextran was found. In contrast, this relationship was markedly lower for CGamF. Confocal microscopy studies revealed that fluorescein-tagged BAs, but also FITC or 10-kDa FITC-dextran were found in the nuclear envelope and concentrated in regions where DNA was less densely packed. In contrast to the cytosolic subcellular localization of peroxisome proliferator-activated receptor-alpha, FXR and nucleolin (a marker of transcriptional active chromatin) were also localized by immunoreactivity in these intranuclear regions. In conclusion, although intranuclear levels of small organic molecules including conjugated BAs depend on their concentrations in the extranuclear space, the existence of certain molecular selectivity (not strictly dependent on molecular weight or charge) suggests that, in addition to simple diffusional exchange, other mechanisms may be also involved in determining their overall nuclear content in regions where these compounds coincide and may interact

  20. 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

  1. 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

  2. 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

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

    PubMed

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

    2014-01-01

    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

  4. 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.

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

    PubMed Central

    Alexander, David; Lange, Kenneth

    2010-01-01

    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. PMID:21359052

  6. Optimization of Dose Distribution for the System of Linear Accelerator-Based Stereotactic Radiosurgery.

    NASA Astrophysics Data System (ADS)

    Suh, Tae-Suk

    The work suggested in this paper addresses a method for obtaining an optimal dose distribution for stereotactic radiosurgery. Since stereotactic radiosurgery utilizes multiple noncoplanar arcs and a three-dimensional dose evaluation technique, many beam parameters and complex optimization criteria are included in the dose optimization. Consequently, a lengthy computation time is required to optimize even the simplest case by a trial and error method. The basic approach presented here is to use both an analytical and an experimental optimization to minimize the dose to critical organs while maintaining a dose shaped to the target. The experimental approach is based on shaping the target volumes using multiple isocenters from dose experience, or on field shaping using a beam's eye view technique. The analytical approach is to adapt computer -aided design optimization to find optimum parameters automatically. Three-dimensional approximate dose models are developed to simulate the exact dose model using a spherical or cylindrical coordinate system. Optimum parameters are found much faster with the use of computer-aided design optimization techniques. The implementation of computer-aided design algorithms with the approximate dose model and the application of the algorithms to several cases are discussed. It is shown that the approximate dose model gives dose distributions similar to those of the exact dose model, which makes the approximate dose model an attractive alternative to the exact dose model, and much more efficient in terms of computer -aided design and visual optimization.

  7. 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.

  8. Combined deletion of Fxr and Shp in mice induces Cyp17a1 and results in juvenile onset cholestasis.

    PubMed

    Anakk, Sayeepriyadarshini; Watanabe, Mitsuhiro; Ochsner, Scott A; McKenna, Neil J; Finegold, Milton J; Moore, David D

    2011-01-01

    Bile acid homeostasis is tightly regulated via a feedback loop operated by the nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP). Contrary to current models, which place FXR upstream of SHP in a linear regulatory pathway, here we show that the phenotypic consequences in mice of the combined loss of both receptors are much more severe than the relatively modest impact of the loss of either Fxr or Shp alone. Fxr-/-Shp-/- mice exhibited cholestasis and liver injury as early as 3 weeks of age, and this was linked to the dysregulation of bile acid homeostatic genes, particularly cytochrome P450, family 7, subfamily a, polypeptide 1 (Cyp7a1). In addition, double-knockout mice showed misregulation of genes in the C21 steroid biosynthesis pathway, with strong induction of cytochrome P450, family 17, subfamily a, polypeptide 1 (Cyp17a1), resulting in elevated serum levels of its enzymatic product 17-hydroxyprogesterone (17-OHP). Treatment of WT mice with 17-OHP was sufficient to induce liver injury that reproduced many of the histopathological features observed in the double-knockout mice. Therefore, our data indicate a pathologic role for increased production of 17-hydroxy steroid metabolites in liver injury and suggest that Fxr-/-Shp-/- mice could provide a model for juvenile onset cholestasis. PMID:21123943

  9. Dissociation of intestinal and hepatic activities of FXR and LXRα supports metabolic effects of terminal ileum interposition in rodents.

    PubMed

    Mencarelli, Andrea; Renga, Barbara; D'Amore, Claudio; Santorelli, Chiara; Graziosi, Luigina; Bruno, Angela; Monti, Maria Chiara; Distrutti, Eleonora; Cipriani, Sabrina; Donini, Annibale; Fiorucci, Stefano

    2013-10-01

    The farnesoid X receptor (FXR) and the liver x receptors (LXRs) are bile acid-activated receptors that are highly expressed in the enterohepatic tissues. The mechanisms that support the beneficial effects of bariatric surgery are only partially defined. We have investigated the effects of ileal interposition (IT), a surgical relocation of the distal ileum into the proximal jejunum, on FXR and LXRs in rats. Seven months after surgery, blood concentrations of total bile acids, taurocholic acid, an FXR ligand, and taurohyocholic acid, an LXRα ligand, were significantly increased by IT (P < 0.05). In contrast, liver and intestinal concentrations of conjugated and nonconjugated bile acids were decreased (P < 0.05). These changes were associated with a robust induction of FXR and FXR-regulated genes in the intestine, including Fgf15, a negative regulator of bile acid synthesis. IT repressed the liver expression of glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase (Pepck), two gluconeogenetic genes, along with the expression of LXRα and its target genes sterol regulatory element-binding protein (Srebp) 1c and fatty acid synthase (Fas) in the liver. Treating IT rats with chenodeoxycholic acid ameliorated insulin signaling in the liver. Whether confirmed in human settings, these results support the association of pharmacological therapies with bariatric surgeries to exploit the selective activation of intestinal nuclear receptors. PMID:23835330

  10. 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

  11. 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

  12. Optimal design of a standing-wave accelerating tube with a high shunt impedance based on a genetic algorithm

    NASA Astrophysics Data System (ADS)

    Tang, Zhenxing; Pei, Yuanji; Pang, Jian

    2015-08-01

    In this paper, we present an optimal design based on a genetic algorithm for a compact standing-wave (SW) accelerating tube with an operating frequency of 2998 MHz for industrial and medical applications. It consists of bi-periodic structures with a nose cone whose inter-cavity coupling is achieved through electric coupling rather than magnetic coupling. A mathematical model is established to optimize the arc at the cavity wall to reduce the microwave power loss and to optimize the nose cone to increase the electric field along the axis to achieve a high shunt impedance. The simulation results indicate that with the proper nose cone and arc, the shunt impedance of the cavity can be as high as 114 MΩ / m. Afterward, we present the tuning of the tube using SUPERFISH and the calculation of the beam dynamics using ASTRA and Parmela. The total length of the optimal tube is only 30.175 cm. Finally, a coupler is designed with a small-aperture coupling using CST MICROWAVE STUDIO.

  13. Electron cyclotron resonance 140 mA D(+) beam extraction optimization for IFMIF EVEDA accelerator.

    PubMed

    Delferrière, O; De Menezes, D; Gobin, R; Harrault, F; Tuske, O

    2008-02-01

    Based on the experience of the SILHI electron cyclotron resonance (ECR) ion source for the IPHI accelerator, which produces routinely 100-120 mA H(+) beam, the CEA-Saclay is in charge of the design and realization of the 140 mA cw deuteron source for the IFMIF project (International Fusion Materials Irradiation Facility). IFMIF is an accelerator-based neutron irradiation facility consisting of two accelerators of 125 mA D(+) beam at 40 MeV that hit in parallel a lithium target. IFMIF utilizes the deuteron-lithium (d-Li) neutron, producing a reaction to simulate the 14 MeV neutron environment in deuterium-tritium (D-T) fusion reactors. In the framework of the IFMIF EVEDA phase (Engineering Validation and Engineering Design Activities), we are studying a cw ECR ion source with a new extraction system to allow high current extraction while keeping a low divergence as well as a small emittance. Starting from SILHI five-electrode system with H(+) ions, the extracted beam characteristics as well as electric field conditions are compared with the cases of four- and three-electrode extraction systems. Experimental results made on the SILHI source with H(+) ions are briefly discussed. Extensive experimental results on the new source test bench BETSI are expected as soon as the design and fabrication of a dedicated extraction system with a new set of electrodes will be finished. PMID:18315214

  14. Novel substituted isoxazole FXR agonists with cyclopropyl, hydroxycyclobutyl and hydroxyazetidinyl linkers: Understanding and improving key determinants of pharmacological properties.

    PubMed

    Kinzel, Olaf; Steeneck, Christoph; Schlüter, Thomas; Schulz, Andreas; Gege, Christian; Hahn, Ulrike; Hambruch, Eva; Hornberger, Martin; Spalwisz, Adriana; Frick, Katharina; Perović-Ottstadt, Sanja; Deuschle, Ulrich; Burnet, Michael; Kremoser, Claus

    2016-08-01

    Several isoxazole-containing series of FXR agonists have been published over the last 15years, subsequent to the prototypical amphiphilic 'hammerhead'-type structure that was originally laid out by GW4064, the first potent synthetic FXR agonist. A set of novel compounds where the hammerhead is connected to the terminal carboxylic acid-bearing aryl or heteroaryl moiety by either a cyclopropyl, a hydroxycyclobutyl or a hydroxyazetidinyl linker was synthesized in order to improve upon the ADME properties of such isoxazoles. The resulting compounds all demonstrated high potencies at the target receptor FXR but with considerable differences in their physicochemical and in vivo profiles. The structure-activity relationships for key chemical features that have a major impact on the in vivo pharmacology of this series are discussed. PMID:27268696

  15. Insights on FXR selective modulation. Speculation on bile acid chemical space in the discovery of potent and selective agonists

    PubMed Central

    Sepe, Valentina; Festa, Carmen; Renga, Barbara; Carino, Adriana; Cipriani, Sabrina; Finamore, Claudia; Masullo, Dario; del Gaudio, Federica; Monti, Maria Chiara; Fiorucci, Stefano; Zampella, Angela

    2016-01-01

    Bile acids are the endogenous modulators of the nuclear receptor FXR and the membrane receptor GPBAR1. FXR represents a promising pharmacological target for the treatment of cholestatic liver disorders. Currently available semisynthetic bile acid derivatives cover the same chemical space of bile acids and therefore they are poorly selective toward BA receptors, increasing patient risk for adverse side effects. In this report, we have investigated around the structure of CDCA describing the synthesis and the in vitro and in vivo pharmacological characterization of a novel family of compounds modified on the steroidal tetracyclic core and on the side chain. Pharmacological characterization resulted in the identification of several potent and selective FXR agonists. These novel agents might add utility in the treatment of cholestatic disorders by potentially mitigating side effects linked to unwanted activation of GPBAR1. PMID:26740187

  16. Preliminary Structure-Activity Relationship on Theonellasterol, a New Chemotype of FXR Antagonist, from the Marine Sponge Theonella swinhoei

    PubMed Central

    Sepe, Valentina; Ummarino, Raffaella; D’Auria, Maria Valeria; Taglialatela-Scafati, Orazio; Marino, Simona De; D’Amore, Claudio; Renga, Barbara; Chini, Maria Giovanna; Bifulco, Giuseppe; Nakao, Yoichi; Fusetani, Nobuhiro; Fiorucci, Stefano; Zampella, Angela

    2012-01-01

    Using theonellasterol as a novel FXR antagonist hit, we prepared a series of semi-synthetic derivatives in order to gain insight into the structural requirements for exhibiting antagonistic activity. These derivatives are characterized by modification at the exocyclic carbon-carbon double bond at C-4 and at the hydroxyl group at C-3 and were prepared from theonellasterol using simple reactions. Pharmacological investigation showed that the introduction of a hydroxyl group at C-4 as well as the oxidation at C-3 with or without concomitant modification at the exomethylene functionality preserve the ability of theonellasterol to inhibit FXR transactivation caused by CDCA. Docking analysis showed that the placement of these molecules in the FXR-LBD is well stabilized when on ring A functional groups, able to form hydrogen bonds and π interactions, are present. PMID:23203270

  17. Insights on FXR selective modulation. Speculation on bile acid chemical space in the discovery of potent and selective agonists.

    PubMed

    Sepe, Valentina; Festa, Carmen; Renga, Barbara; Carino, Adriana; Cipriani, Sabrina; Finamore, Claudia; Masullo, Dario; Del Gaudio, Federica; Monti, Maria Chiara; Fiorucci, Stefano; Zampella, Angela

    2016-01-01

    Bile acids are the endogenous modulators of the nuclear receptor FXR and the membrane receptor GPBAR1. FXR represents a promising pharmacological target for the treatment of cholestatic liver disorders. Currently available semisynthetic bile acid derivatives cover the same chemical space of bile acids and therefore they are poorly selective toward BA receptors, increasing patient risk for adverse side effects. In this report, we have investigated around the structure of CDCA describing the synthesis and the in vitro and in vivo pharmacological characterization of a novel family of compounds modified on the steroidal tetracyclic core and on the side chain. Pharmacological characterization resulted in the identification of several potent and selective FXR agonists. These novel agents might add utility in the treatment of cholestatic disorders by potentially mitigating side effects linked to unwanted activation of GPBAR1. PMID:26740187

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

    NASA Astrophysics Data System (ADS)

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

    2009-10-01

    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 ˜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.

  19. 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.

  20. 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

  1. Optimizing a microwave gas ion source for continuous-flow accelerator mass spectrometry

    SciTech Connect

    Reden, K. F. von; Roberts, M. L.; Burton, J. R.; Beaupre, S. R.

    2012-02-15

    A 2.45 GHz microwave ion source coupled with a magnesium charge exchange canal (C x C) has been successfully adapted to a large acceptance radiocarbon accelerator mass spectrometry system at the National Ocean Sciences Accelerator Mass Spectrometry (AMS) Facility, Woods Hole Oceanographic Institution. CO{sub 2} samples from various preparation sources are injected into the source through a glass capillary at 370 {mu}l/min. Routine system parameters are about 120-140 {mu}A of negative {sup 12}C current after the C x C, leading to about 400 {sup 14}C counts per second for a modern sample and implying a system efficiency of 0.2%. While these parameters already allow us to perform high-quality AMS analyses on large samples, we are working on ways to improve the output of the ion source regarding emittance and efficiency. Modeling calculations suggest modifications in the extraction triode geometry, shape, and size of the plasma chamber could improve emittance and, hence, ion transport efficiency. Results of experimental tests of these modifications are presented.

  2. 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.

  3. 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

  4. 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.

  5. Optimization of Fusion Pellet Launch Velocity in an Electrothermal Mass Accelerator

    NASA Astrophysics Data System (ADS)

    Gebhart, T. E.; Holladay, R. T.; Esmond, M. J.; Winfrey, A. L.

    2013-10-01

    Electrothermal mass accelerators, based on capillary discharges, that form a plasma propelling force from the ablation of a low-z liner material are candidates for fuelling magnetic fusion reactors. As lithium is considered a fusion fuel and not an impurity, lithium hydride and lithium deuteride can serve as good ablating liners for plasma formation in an electrothermal plasma source to propel fusion pellets. A comprehensive study of solid lithium hydride and deuteride as liner materials to generate a plasma to propel cryogenic fuel pellets is presented here. This study was conducted using the ETFLOW capillary discharge code. Relationships between propellants, source and barrel geometry, pellet volume and aspect ratio, and pellet velocity are determined for pellets ranging in volume from 5 to 100 mm3.

  6. Optimal extraction and fingerprinting of carotenoids by accelerated solvent extraction and liquid chromatography with tandem mass spectrometry.

    PubMed

    Saha, Supradip; Walia, Suresh; Kundu, Aditi; Sharma, Khushbu; Paul, Ranjit Kumar

    2015-06-15

    Accelerated solvent extraction (ASE) is applied for the extraction of carotenoids from orange carrot and the extraction parameters were optimized. Two carotenoids, lutein and β-carotene, are selected as the validation process. Hildebrand solubility parameters and dielectric constant of solvents were taken into consideration in selecting solvent mixture. The effects of various experimental parameters, such as temperature, static time, drying agent etc., on the ASE extraction efficiency are investigated systematically. Interactions among the variables were also studied. Furthermore, two carotenoids were analyzed and characterized by LC-ESI MS. The study concluded that Hildebrand solubility parameter approach may be applicable for less polar bioactive molecules like carotenoids. The properties of solvent and extraction temperature are found to be the most important parameters affecting the ASE extraction efficiency of thermolabile natural compounds. PMID:25660899

  7. Transcriptional Regulation of the Intestinal Nuclear Bile Acid Farnesoid X Receptor (FXR) by the caudal-related Homeobox 2 (CDX2)*

    PubMed Central

    Modica, Salvatore; Cariello, Marica; Morgano, Annalisa; Gross, Isabelle; Vegliante, Maria Carmela; Murzilli, Stefania; Salvatore, Lorena; Freund, Jean-Noel; Sabbà, Carlo; Moschetta, Antonio

    2014-01-01

    Farnesoid X receptor (FXR, NR1H4) is a bile acid-activated transcription factor that belongs to the nuclear receptor superfamily. It is highly expressed in the enterohepatic system, where it senses bile acid levels to consequently reduce their synthesis while inducing their detoxification. Bile acids are intestinal tumor promoters and their concentrations have to be tightly regulated. Indeed, reduced expression of FXR in the intestine increases colorectal cancer susceptibility in mice, whereas its activation can promote apoptosis in genetically modified cells. Notably, despite the broad knowledge of the FXR enterohepatic transcriptional activity, the molecular mechanisms regulating FXR expression in the intestine are still unknown. Herein, by combining both gain and loss of function approaches and FXR promoter activity studies, we identified caudal-related homeobox 2 (CDX2) transcription factor as a positive regulator of FXR expression in the enterocytes. Our results provide a putative novel tool for modulating FXR expression against bile acid-related colorectal cancer progression. PMID:25138215

  8. 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

  9. Chenodeoxycholic acid, an endogenous FXR ligand alters adipokines and reverses insulin resistance.

    PubMed

    Shihabudeen, Mohamed Sham; Roy, Debasish; James, Joel; Thirumurugan, Kavitha

    2015-10-15

    Adipose tissue secretes adipokines that regulate insulin sensitivity in adipocytes and other peripheral tissues critical to glucose metabolism. Insulin resistance is associated with severe alterations in adipokines characterized by release of increased pro-inflammatory cytokines and decreased anti-inflammatory cytokines from adipose tissue. The role of Farnesoid X receptor (FXR) activation on adipokines in relation to adipose tissue inflammation and insulin resistance is not completely explored. For the first time, we have evaluated the ability of Chenodeoxycholic acid (CDCA), an endogenous FXR ligand, in restoring the disturbance in adipokine secretion and insulin resistance in palmitate treated 3T3-L1 cells and adipose tissues of High fat diet (HFD) rats. CDCA suppressed several of the tested pro-inflammatory adipokines (TNF-α, MCP-1, IL-6, Chemerin, PAI, RBP4, resistin, vaspin), and enhanced the major anti-inflammatory and insulin sensitizing adipokines (adiponectin, leptin). CDCA suppressed the activation of critical inflammatory regulators such as NF-κB and IKKβ which are activated by palmitate treatment in differentiated cells and HFD in rats. We show the altered adipokines in insulin resistance, its association with inflammatory regulators, and the role of CDCA in amelioration of insulin resistance by modulation of adipokines. PMID:26188168

  10. 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.

  11. Enhanced docking with the mining minima optimizer: acceleration and side-chain flexibility.

    PubMed

    Kairys, Visvaldas; Gilson, Michael K

    2002-12-01

    The ligand-protein docking algorithm based on the Mining Minima method has been substantially enhanced. First, the basic algorithm is accelerated by: (1) adaptively determining the extent of each energy well to help avoid previously discovered energy minima; (2) biasing the search away from ligand positions at the surface of the receptor to prevent the ligand from staying at the surface when large sampling regions are used; (3) quickly testing multiple different ligand positions and orientations for each ligand conformation; and (4) tuning the source code to increase computational efficiency. These changes markedly shorten the time needed to discover an accurate result, especially when large sampling regions are used. The algorithm now also allows user-selected receptor sidechains to be treated as mobile during the docking procedure. The energies associated with the mobile side chains are computed as if they belonged to the ligand, except that atoms at the boundary between side chains and the rigid backbone are treated specially. This new capability is tested for several well-known ligand/protein systems, and preliminary application to an enzyme whose substrate is unknown--the recently solved hypothetical protein YecO (HI0319) from Haemophilus influenzae--indicates that side-chains relaxations allow candidate substrates of various sizes to be accommodated. PMID:12395431

  12. 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

  13. 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

  14. Microbiota modification with probiotics induces hepatic bile acid synthesis via downregulation of the Fxr-Fgf15 axis in mice.

    PubMed

    Degirolamo, Chiara; Rainaldi, Stefania; Bovenga, Fabiola; Murzilli, Stefania; Moschetta, Antonio

    2014-04-10

    Gut microbiota influences host health status by providing trophic, protective, and metabolic functions, including bile acid (BA) biotransformation. Microbial imprinting on BA signature modifies pool size and hydrophobicity, thus contributing to BA enterohepatic circulation. Microbiota-targeted therapies are now emerging as effective strategies for preventing and/or treating gut-related diseases. Here, we show that gut microbiota modulation induced by VSL#3 probiotics enhances BA deconjugation and fecal excretion in mice. These events are associated with changes in ileal BA absorption, repression of the enterohepatic farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis, and increased hepatic BA neosynthesis. Treatment with a FXR agonist normalized fecal BA levels in probiotic-administered mice, whereas probiotic-induced alterations in BA metabolism are abolished upon FXR and FGF15 deficiency. Our data provide clear in vivo evidence that VSL#3 probiotics promote ileal BA deconjugation with subsequent fecal BA excretion and induce hepatic BA neosynthesis via downregulation of the gut-liver FXR-FGF15 axis. PMID:24656817

  15. 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

    2016-01-01

    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. Optimization of in-cell accelerated solvent extraction technique for the determination of organochlorine pesticides in river sediments.

    PubMed

    Duodu, Godfred Odame; Goonetilleke, Ashantha; Ayoko, Godwin A

    2016-04-01

    Organochlorine pesticides (OCPs) are ubiquitous environmental contaminants with adverse impacts on aquatic biota, wildlife and human health even at low concentrations. However, conventional methods for their determination in river sediments are resource intensive. This paper presents an approach that is rapid and also reliable for the detection of OCPs. Accelerated Solvent Extraction (ASE) with in-cell silica gel clean-up followed by Triple Quadrupole Gas Chromatograph Mass Spectrometry (GCMS/MS) was used to recover OCPs from sediment samples. Variables such as temperature, solvent ratio, adsorbent mass and extraction cycle were evaluated and optimized for the extraction. With the exception of Aldrin, which was unaffected by any of the variables evaluated, the recovery of OCPs from sediment samples was largely influenced by solvent ratio and adsorbent mass and, to some extent, the number of cycles and temperature. The optimized conditions for OCPs extraction in sediment with good recoveries were determined to be 4 cycles, 4.5 g of silica gel, 105 °C, and 4:3 v/v DCM: hexane mixture. With the exception of two compounds (α-BHC and Aldrin) whose recoveries were low (59.73 and 47.66% respectively), the recovery of the other pesticides were in the range 85.35-117.97% with precision <10% RSD. The method developed significantly reduces sample preparation time, the amount of solvent used, matrix interference, and is highly sensitive and selective. PMID:26838409

  17. 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

  18. 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

  19. Biological/biomedical accelerator mass spectrometry targets. 1. optimizing the CO2 reduction step using zinc dust.

    PubMed

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

    2008-10-15

    Biological and biomedical applications of accelerator mass spectrometry (AMS) use isotope ratio mass spectrometry to quantify minute amounts of long-lived radioisotopes such as (14)C. AMS target preparation involves first the oxidation of carbon (in sample of interest) to CO 2 and second the reduction of CO 2 to filamentous, fluffy, fuzzy, or firm graphite-like substances that coat a -400-mesh spherical iron powder (-400MSIP) catalyst. Until now, the quality of AMS targets has been variable; consequently, they often failed to produce robust ion currents that are required for reliable, accurate, precise, and high-throughput AMS for biological/biomedical applications. Therefore, we described our optimized method for reduction of CO 2 to high-quality uniform AMS targets whose morphology we visualized using scanning electron microscope pictures. Key features of our optimized method were to reduce CO 2 (from a sample of interest that provided 1 mg of C) using 100 +/- 1.3 mg of Zn dust, 5 +/- 0.4 mg of -400MSIP, and a reduction temperature of 500 degrees C for 3 h. The thermodynamics of our optimized method were more favorable for production of graphite-coated iron powders (GCIP) than those of previous methods. All AMS targets from our optimized method were of 100% GCIP, the graphitization yield exceeded 90%, and delta (13)C was -17.9 +/- 0.3 per thousand. The GCIP reliably produced strong (12)C (-) currents and accurate and precise F m values. The observed F m value for oxalic acid II NIST SRM deviated from its accepted F m value of 1.3407 by only 0.0003 +/- 0.0027 (mean +/- SE, n = 32), limit of detection of (14)C was 0.04 amol, and limit of quantification was 0.07 amol, and a skilled analyst can prepare as many as 270 AMS targets per day. More information on the physical (hardness/color), morphological (SEMs), and structural (FT-IR, Raman, XRD spectra) characteristics of our AMS targets that determine accurate, precise, and high-hroughput AMS measurement are in the

  20. 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.

  1. The RNA binding protein FXR1 is a new driver in the 3q26-29 amplicon and predicts poor prognosis in human cancers

    PubMed Central

    Qian, Jun; Hassanein, Mohamed; Hoeksema, Megan D.; Harris, Bradford K.; Zou, Yong; Chen, Heidi; Lu, Pengcheng; Eisenberg, Rosana; Wang, Jing; Espinosa, Allan; Ji, Xiangming; Harris, Fredrick T.; Rahman, S. M. Jamshedur; Massion, Pierre P.

    2015-01-01

    Aberrant expression of RNA-binding proteins has profound implications for cellular physiology and the pathogenesis of human diseases such as cancer. We previously identified the Fragile X-Related 1 gene (FXR1) as one amplified candidate driver gene at 3q26-29 in lung squamous cell carcinoma (SCC). FXR1 is an autosomal paralog of Fragile X mental retardation 1 and has not been directly linked to human cancers. Here we demonstrate that FXR1 is a key regulator of tumor progression and its overexpression is critical for nonsmall cell lung cancer (NSCLC) cell growth in vitro and in vivo. We identified the mechanisms by which FXR1 executes its regulatory function by forming a novel complex with two other oncogenes, protein kinase C, iota and epithelial cell transforming 2, located in the same amplicon via distinct binding mechanisms. FXR1 expression is a candidate biomarker predictive of poor survival in multiple solid tumors including NSCLCs. Because FXR1 is overexpressed and associated with poor clinical outcomes in multiple cancers, these results have implications for other solid malignancies. PMID:25733852

  2. 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

  3. 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.

  4. Identification of potential dual agonists of FXR and TGR5 using e-pharmacophore based virtual screening.

    PubMed

    Sindhu, Thangaraj; Srinivasan, Pappu

    2015-05-01

    Farnesoid X receptor and Takeda G-protein-coupled receptor-5 are well known bile acid receptors and act as promising targets for the drug development and treatment of diabetes. Agonists of both the bile acid receptors increase insulin sensitivity and control glucose, lipids and bile acid homeostasis. The current study deals with the identification of novel dual agonists using ligand and structure-based virtual screening. Initially, an experimentally proven well-known dual agonist of FXR and TGR5, namely INT-767, was docked into the binding sites of FXR and TGR5 to determine the protein residues important for ligand binding. The docked complexes FXRINT-767 and TGR5INT-767 were used to generate e-pharmacophore hypotheses. Ligand-based virtual screening was carried out using the hypothetical e-pharmacophore model against the ChemBridge database. Further, structure-based virtual screening was performed with screened hits to find potential agonists of FXR and TGR5. A total of four best agonists were identified based on their affinity and mode of interactions with the receptors. The binding mode of these compounds with both receptors was analyzed in detail. Furthermore, molecular dynamics, ADME toxicity prediction, density functional theory and binding free energy calculations were carried out to rank the compounds. Based on the above analyses, the most potent compound, ChemBridge_9149693, was selected for further in vitro studies. The results of in vitro assays suggested that ChemBridge_9149693 is a potent and promising drug for the treatment of type II diabetes. Thus, the compound could be used for further drug design and development of dual agonists of FXR and TGR5. PMID:25787676

  5. Combined modulated electron and photon beams planned by a Monte-Carlo-based optimization procedure for accelerated partial breast irradiation

    NASA Astrophysics Data System (ADS)

    Atriana Palma, Bianey; Ureba Sánchez, Ana; Salguero, Francisco Javier; Arráns, Rafael; Míguez Sánchez, Carlos; Walls Zurita, Amadeo; Romero Hermida, María Isabel; Leal, Antonio

    2012-03-01

    The purpose of this study was to present a Monte-Carlo (MC)-based optimization procedure to improve conventional treatment plans for accelerated partial breast irradiation (APBI) using modulated electron beams alone or combined with modulated photon beams, to be delivered by a single collimation device, i.e. a photon multi-leaf collimator (xMLC) already installed in a standard hospital. Five left-sided breast cases were retrospectively planned using modulated photon and/or electron beams with an in-house treatment planning system (TPS), called CARMEN, and based on MC simulations. For comparison, the same cases were also planned by a PINNACLE TPS using conventional inverse intensity modulated radiation therapy (IMRT). Normal tissue complication probability for pericarditis, pneumonitis and breast fibrosis was calculated. CARMEN plans showed similar acceptable planning target volume (PTV) coverage as conventional IMRT plans with 90% of PTV volume covered by the prescribed dose (Dp). Heart and ipsilateral lung receiving 5% Dp and 15% Dp, respectively, was 3.2-3.6 times lower for CARMEN plans. Ipsilateral breast receiving 50% Dp and 100% Dp was an average of 1.4-1.7 times lower for CARMEN plans. Skin and whole body low-dose volume was also reduced. Modulated photon and/or electron beams planned by the CARMEN TPS improve APBI treatments by increasing normal tissue sparing maintaining the same PTV coverage achieved by other techniques. The use of the xMLC, already installed in the linac, to collimate photon and electron beams favors the clinical implementation of APBI with the highest efficiency.

  6. 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.

  7. Laser driven ion accelerator

    DOEpatents

    Tajima, Toshiki

    2005-06-14

    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.

  8. 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.

  9. The mechanism of action of FXR1P-related miR-19b-3p in SH-SY5Y.

    PubMed

    Ma, Yun; Tian, Shuai; He, Shuya; Chen, Qiong; Wang, Zongbao; Xiao, Xiao; Fu, Liang; Lei, Xiaoyong

    2016-08-15

    The biological effects of microRNAs (miRNAs) in the Fragile X Syndrome (FXS) have been widely studied. Dysregulation of miRNAs plays a critical role in the progression of nervous system diseases and in cell proliferation and differentiation. Our previous study validated that miR-19b-3p was associated with FXR1 (Fragile X related gene 1), one of homologous genes of FMR1 (Fragile X mental retardation 1). The purpose of this study was to investigate the relationship of FXR1 and miR-19b-3p, and the crucial role of miR-19b-3p in FXS and to validate whether miR-19b-3p could regulate the growth of SH-SY5Y cells. We determined that miR-19b-3p could regulate the expression of not only USP32, RAB18 and Dusp6 but also FXR1, and FXR1 could in turn regulate the expression of miR-19b-3p. What's more, the overexpression of miR-19b-3p significantly inhibited the proliferation, contributed the apoptosis and slowed down the cycle of SH-SY5Y cells. Taken together, our results indicate that miR-19b-3p plays a significant role in the molecular pathology of FXS by interacting with FXR1 and influencing the growth of SH-SY5Y cells. PMID:27138803

  10. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist.

    PubMed

    Sayin, Sama I; Wahlström, Annika; Felin, Jenny; Jäntti, Sirkku; Marschall, Hanns-Ulrich; Bamberg, Krister; Angelin, Bo; Hyötyläinen, Tuulia; Orešič, Matej; Bäckhed, Fredrik

    2013-02-01

    Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (FXR) in the ileum and liver. Here we profiled the bile acid composition throughout the enterohepatic system in germ-free (GF) and conventionally raised (CONV-R) mice. We confirmed a dramatic reduction in muricholic acid, but not cholic acid, levels in CONV-R mice. Rederivation of Fxr-deficient mice as GF demonstrated that the gut microbiota regulated expression of fibroblast growth factor 15 in the ileum and cholesterol 7α-hydroxylase (CYP7A1) in the liver by FXR-dependent mechanisms. Importantly, we identified tauro-conjugated beta- and alpha-muricholic acids as FXR antagonists. These studies suggest that the gut microbiota not only regulates secondary bile acid metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum. PMID:23395169

  11. 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.

  12. 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.

  13. FXR-induced secretion of FGF15/19 inhibits CYP27 expression in cholangiocytes through p38 kinase pathway

    PubMed Central

    Jung, Dongju; York, J. Philippe; Wang, Li; Yang, Chaofeng; Zhang, Aijun; Francis, Heather L.; Webb, Paul; McKeehan, Wallace L.; Alpini, Gianfranco; LeSage, Gene D.; Moore, David D.

    2014-01-01

    Cholangiocytes, bile duct lining cells, actively adjust the amount of cholesterol and bile acids in bile through expression of enzymes and channels involved in transportation and metabolism of the cholesterol and bile acids. Herein, we report molecular mechanisms regulating bile acid biosynthesis in cholangiocytes. Among the cytochrome p450 (Cyp) enzymes involved in bile acid biosynthesis, sterol 27-hydroxylase (Cyp27) that is the rate-limiting enzyme for the acidic pathway of bile acid biosynthesis expressed in cholangiocytes. Expression of other Cyp enzymes for the basic bile acid biosynthesis was hardly detected. The Cyp27 expression was negatively regulated by a hydrophobic bile acid through farnesoid X receptor (FXR), a nuclear receptor activated by bile acid ligands. Activated FXR exerted the negative effects by inducing an expression of fibroblast growth factor 15/19 (FGF15/19). Similar to its repressive function against cholesterol 7α-hydroxylase (Cyp7a1) expression in hepatocytes, secreted FGF15/19 triggered Cyp27 repression in cholangiocytes through interaction with its cognate receptor fibroblast growth factor receptor 4 (FGFR4). The involvements of FXR and FGFR4 for the bile acid-induced Cyp27 repression were confirmed in vivo using knockout mouse models. Different from the signaling in hepatocytes, wherein the FGF15/19-induced repression signaling is mediated by c-Jun N-terminal kinase (JNK), FGF15/19-induced Cyp27 repression in cholangiocytes was mediated by p38 kinase. Thus, the results collectively suggest that cholangiocytes may be able to actively regulate bile acid biosynthesis in cholangiocytes and even hepatocyte by secreting FGF15/19. We suggest the presence of cholangiocyte-mediated intrahepatic feedback loop in addition to the enterohepatic feedback loop against bile acid biosynthesis in the liver. PMID:24068255

  14. Bile acids and derivatives, their nuclear receptors FXR, PXR and ligands: role in health and disease and their therapeutic potential.

    PubMed

    Zimber, Amazia; Gespach, Christian

    2008-06-01

    Bile acids, their physiology and metabolism, their role in carcinogenesis and other major human diseases are recently undergoing significant progress. Starting in 1999 when the orphan nuclear receptor FXR was shown to be specifically activated by bile acids, these compounds became part of the arsenal of ligands of the steroid hormone superfamily of nuclear receptors, including receptors of Vitamin D3, retinoids (RAR, RXR), and thyroid hormone. Another decisive discovery pointed later that the pregnane X-receptor (PXR) is activated by the endogenous toxic lithocholic acid, as well as several xenobiotics and drugs. Bile acids have recently emerged as key regulators of their own metabolism, and of lipid and carbohydrate metabolism. They have important role as promoters of esophageal and colon cancers, cholangiocarcinoma, as well as new implications in breast cancer development and metastasis. This Review will emphasize novel aspects of bile acids, FXR and PXR as regulators of interfaces at cell proliferation and differentiation, cell death, survival, invasion, and metastasis during normal development and cancer progression. Signaling pathways controlled by bile acids will be presented and discussed in relation to their impact on gene expression. The biological and pharmacological significance of bile acids and their recently developed synthetic derivatives and conjugates, as well as new development in the design of FXR agonists and antagonists for clinical applications in cancer prevention and therapy, will be evaluated. This part includes advances in the utilization of bile acid transporters in drug resistance, therapeutic targeting and delivery of anticancer drugs, as well as therapeutic combinations using new bile acid derivatives, sequestrating agents and reabsorption inhibitors, and their limitations. PMID:18537536

  15. 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

  16. Optimizing pulse shaping and zooming for acceleration to high velocities and fusion neutron production on the Nike laser

    NASA Astrophysics Data System (ADS)

    Karasik, Max; Weaver, J. L.; Aglitskiy, Y.; Zalesak, S. T.; Velikovich, A. L.; Oh, J.; Obenschain, S. P.; Arikawa, Y.; Watari, T.

    2010-11-01

    We will present results from follow-on experiments to the record-high velocities of 1000 km/s achieved on Nike [Karasik et al., Phys. Plasmas 17, 056317 (2010) ], in which highly accelerated planar foils of deuterated polystyrene were made to collide with a witness foil to produce extreme shock pressures and result in heating of matter to thermonuclear temperatures. Still higher velocities and higher target densities are required for impact fast ignition. The aim of these experiments is shaping the driving pulse to minimize shock heating of the accelerated target and using the focal zoom capability of Nike to achieve higher densities and velocities. Spectroscopic measurements of electron temperature achieved upon impact will complement the neutron time-of-flight ion temperature measurement. Work is supported by US DOE and Office of Naval Research.

  17. Optimization of conditions for thermal treatment of rice bran using an accelerator including an organo-iron compound.

    PubMed

    Kanno, Hikari; Tachibana, Naoya; Fukushima, Masami

    2011-02-01

    A method for thermal conversion of raw organic waste (ROW) to a compost-like material (CLM) with higher levels of unsaturated carbohydrates, nitrogen- and oxygen-containing compounds was developed, in which rice bran and an organo-iron compound were employed as a model ROW and the accelerator, respectively. To evaluate the qualities of CLMs, organic substances of an acid insoluble fraction of alkaline extracts (AIAEs) from a CLM were structurally characterized by elemental analysis, pyrolysis-gas chromatography/mass spectrometry and FT-IR. The levels of unsaturated carbohydrates, and nitrogen- and oxygen-containing compounds in the CLM samples were increased by long-term treatment (60°C for 5 days, 170°C for 3 days). In particular, the high lipid content of the AIAEs, which was indicative of inadequate digestion of CLM components, was dramatically reduced in the presence of the accelerator. PMID:21044838

  18. 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

  19. Activation of farnesoid X receptor (FXR) protects against fructose-induced liver steatosis via inflammatory inhibition and ADRP reduction.

    PubMed

    Liu, Xijun; Xue, Ruyi; Ji, Lingling; Zhang, Xingwang; Wu, Jian; Gu, Jianxin; Zhou, Meiling; Chen, She

    2014-07-18

    Fructose is a key dietary factor in the development of nonalcoholic fatty liver disease (NAFLD). Here we investigated whether WAY-362450 (WAY), a potent synthetic and orally active FXR agonist, protects against fructose-induced steatosis and the underlying mechanisms. C57BL/6J mice, fed 30% fructose for 8 weeks, were treated with or without WAY, 30 mg/kg, for 20 days. The elevation of serum and hepatic triglyceride in mice fed 30% fructose was reversed by WAY treatment. Histologically, WAY significantly reduced triglyceride accumulation in liver, attenuated microphage infiltration and protected the junction integrity in intestine. Moreover, WAY remarkably decreased portal endotoxin level, and lowered serum TNFα concentration. In lipopolysaccharide (LPS)-induced NAFLD model, WAY attenuated serum TNFα level. Moreover, WAY suppressed LPS-induced expression of hepatic lipid droplet protein adipose differentiation-related protein (ADRP), down-regulation of it in mice fed 30% fructose. Furthermore, WAY repressed lipid accumulation and ADRP expression in a dose-dependent manner in palmitic acid (PA)-treated HepG2 and Huh7 cells. WAY suppressed TNFα-induced ADRP up-regulation via competing with AP-1 for ADRP promoter binding region. Together, our findings suggest that WAY, an FXR agonist, attenuates liver steatosis through multiple mechanisms critically involved in the development of hepatosteatosis, and represents a candidate for NAFLD treatment. PMID:24875360

  20. 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. PMID:26942679

  1. 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

  2. Dual Activation of the Bile Acid Nuclear Receptor FXR and G-Protein-Coupled Receptor TGR5 Protects Mice against Atherosclerosis

    PubMed Central

    Miyazaki-Anzai, Shinobu; Masuda, Masashi; Levi, Moshe; Keenan, Audrey L.; Miyazaki, Makoto

    2014-01-01

    Bile acid signaling is a critical regulator of glucose and energy metabolism, mainly through the nuclear receptor FXR and the G protein-coupled receptor TGR. The purpose of the present study was to investigate whether dual activation of FXR and TGR5 plays a significant role in the prevention of atherosclerosis progression. To evaluate the effects of bile acid signaling in atherogenesis, ApoE−/− mice and LDLR−/− mice were treated with an FXR/TGR5 dual agonist (INT-767). INT-767 treatment drastically reduced serum cholesterol levels. INT-767 treatment significantly reduced atherosclerotic plaque formation in both ApoE−/− and LDLR−/− mice. INT-767 decreased the expression of pro-inflammatory cytokines and chemokines in the aortas of ApoE−/− mice through the inactivation of NF-κB. In addition, J774 macrophages treated with INT-767 had significantly lower levels of active NF-κB, resulting in cytokine production in response to LPS through a PKA dependent mechanism. This study demonstrates that concurrent activation of FXR and TGR5 attenuates atherosclerosis by reducing both circulating lipids and inflammation. PMID:25237811

  3. Computer-aided design optimization with the use of a fast dose model for linear-accelerator-based stereotactic radiosurgery

    NASA Astrophysics Data System (ADS)

    Suh, Tae S.; Bova, Frank J.; Yoon, Sei C.; Choe, Bo Y.; Kim, Moon C.; Shinn, Kyung S.; Bahk, Yong W.; Ha, Sung W.; Park, Charn I.

    1996-04-01

    In order to efficiently plan non-spherical radiosurgical targets we have used computer-aided design optimization techniques with a fast dose model. A study of the spatial dose distribution for single or multiple non-coplanar arcs was carried out using a 18 cm diameter spherical head model. The dose distribution generated from the 3D dose computation algorithm can be represented by a simple analytic form. Two analytic dose models were developed to represent the dose for preset multiple non-coplanar arcs or a single arc: spherical and cylindrical. The spherical and cylindrical dose models compute dose quickly for each isocentre and single arc. Our approach then utilizes a computer-aided design optimization (CAD) with the use of two fast approximate dose models to determine the positions of isocentres and arcs. The implementation of CAD with fast dose models was demonstrated. While the fast dose models are only approximations of the true dose distribution, it is shown that this approximate model is sufficient to optimize isocentric position, collimator size and arc positions with CAD.

  4. Calculation for optimization of the experimental conditions for RBS analysis at the HUS 5SDH-2 tandem accelerator

    NASA Astrophysics Data System (ADS)

    Phong, Le Hong Khiem Ho, Vi; Nghia, Nguyen The

    2015-06-01

    The dependences of the depth and mass resolutions of analysis using Rutherford Backscattering Spectrometry (RBS) on some experimental conditions (such as the beam energy, the target tilting angle, etc.) have been investigated. A computer program for simulating the RBS spectra and for calculating the depth and mass resolution under different experimental conditions was developed. The results of calculation were experimentally checked by using some reference samples. The good agreements between calculated and experimental values have been found. The optimum analysis conditions over a wide range of RBS applications based on our calculation can be chosen. This investigation was conducted by using the RBS system at HUS 5SDH-2 Tandem accelerator at the Hanoi University of Science.

  5. Discovery of 6-(4-{[5-Cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl]methoxy}piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic Acid: A Novel FXR Agonist for the Treatment of Dyslipidemia.

    PubMed

    Genin, Michael J; Bueno, Ana B; Agejas Francisco, Javier; Manninen, Peter R; Bocchinfuso, Wayne P; Montrose-Rafizadeh, Chahrzad; Cannady, Ellen A; Jones, Timothy M; Stille, John R; Raddad, Eyas; Reidy, Charles; Cox, Amy; Michael, M Dodson; Michael, Laura F

    2015-12-24

    The farnesoid X receptor (FXR) is a member of the "metabolic" subfamily of nuclear receptors. Several FXR agonists have been reported in the literature to have profound effects on plasma lipids in animal models. To discover novel and effective therapies for dyslipidemia and atherosclerosis, we have developed a series of potent FXR agonists that robustly lower plasma LDL and vLDL in LDLr-/- mice. To this end the novel piperidinylisoxazole system LY2562175 was discovered. This molecule is a potent and selective FXR agonist in vitro and has robust lipid modulating properties, lowering LDL and triglycerides while raising HDL in preclinical species. The preclinical ADME properties of LY2562175 were consistent with enabling once daily dosing in humans, and it was ultimately advanced to the clinic for evaluation in humans. The synthesis and biological profile of this molecule is discussed. PMID:26568144

  6. Coordinated Actions of FXR and LXR in Metabolism: From Pathogenesis to Pharmacological Targets for Type 2 Diabetes

    PubMed Central

    Ding, Lin; Pang, Shuguang; Sun, Yongmei; Tian, Yuling; Yu, Li; Dang, Ningning

    2014-01-01

    Type 2 diabetes (T2D) is the most prevalent metabolic disease, and many people are suffering from its complications driven by hyperglycaemia and dyslipidaemia. Nuclear receptors (NRs) are ligand-inducible transcription factors that mediate changes to metabolic pathways within the body. As metabolic regulators, the farnesoid X receptor (FXR) and the liver X receptor (LXR) play key roles in the pathogenesis of T2D, which remains to be clarified in detail. Here we review the recent progress concerning the physiological and pathophysiological roles of FXRs and LXRs in the regulation of bile acid, lipid and glucose metabolism and the implications in T2D, taking into account that these two nuclear receptors are potential pharmaceutical targets for the treatment of T2D and its complications. PMID:24872814

  7. 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.

  8. Linear Accelerators

    NASA Astrophysics Data System (ADS)

    Sidorin, Anatoly

    2010-01-01

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

  9. 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.

  10. 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.

    PubMed

    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. PMID:25655198

  11. H2 S inhibits apo(a) expression and secretion through PKCα/FXR and Akt/HNF4α pathways in HepG2 cells.

    PubMed

    Qu, Kai; Liu, Ya-Mi; He, Xing-Lan; Zhang, Hai; Zhang, Kai; Peng, Juan; Tang, Ya-Ling; Yu, Xiao-Hua; Zeng, Jun-Fa; Lei, Jian-Jun; Wei, Dang-Heng; Wang, Zuo

    2016-08-01

    Lipoprotein(a) [Lp(a)] is a strong genetic risk factor for coronary heart diseases. However, the metabolism of this protein remains poorly understood. Efficient and specific drugs that can decrease high plasma levels of Lp(a) have not been developed yet. Hydrogen sulfide (H2 S), a member of the gas transmitter family, performs important biological actions, including protection against cardiovascular diseases and maintenance of the lipid metabolism equilibrium in hepatocytes and adipocytes. In this study, we investigated the possible molecular mechanism of H2 S that influences apolipoprotein(a) [apo(a)] biosynthesis. We also determined the effects of H2 S on apo(a) expression and secretion in HepG2 cells as well as the underlying mechanisms. Results showed that H2 S significantly inhibited the expression and secretion levels of apo(a). These effects were attenuated by the PKCα inhibitor and FXR siRNA. H2 S also reduced HNF4α expression and enhanced FXR expression. The Akt inhibitor partially reversed H2 S-induced inhibition of apo(a) and HNF4α expression and apo(a) secretion. This study reveals that H2 S suppressed apo(a) expression and secretion via the PKCα-FXR and PI3K/Akt-HNF4α pathways. PMID:27298021

  12. Reduction in bile acid pool causes delayed liver regeneration accompanied by down-regulated expression of FXR and c-Jun mRNA in rats.

    PubMed

    Dong, Xiushan; Zhao, Haoliang; Ma, Xiaoming; Wang, Shiming

    2010-02-01

    The present study attempted to examine the effects of bile acid pool size on liver regeneration after hepatectomy. The rats were fed on 0.2% cholic acid (CA) or 2% cholestyramine for 7 days to induce a change in the bile acid size, and then a partial hepatectomy (PH) was performed. Rats fed on the normal diet served as the controls. Measurements were made on the rate of liver regeneration, the labeling indices of PCNA, the plasma total bile acids (TBA), and the mRNA expression of cholesterol 7alpha-hydroxylase (CYP7A1), farnesoid X receptor (FXR), and transcription factor c-Jun or c-fos. As compared with the normal and CA groups, the rate of liver regeneration was decreased on the day 3, and 7 after PH; the peak of the labeling indices of PCNA was delayed and the labeling indices were significantly reduced on the day 1; the TBA were also decreased on the day 1; the expression of FXR decreased but that of CYP7A1 increased at any given time; at the 1st, and 3rd h, the expression of c-Jun was declined in the cholestyramine group. The reduction in the bile acid pool size was found to delay the liver regeneration, which may be caused by the down-regulation of FXR and c-Jun expression. PMID:20155456

  13. 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

  14. Simultaneous diastereo- and enantioseparation of farnesoid X receptor (FXR) agonists with a quinine carbamate-based chiral stationary phase.

    PubMed

    Sardella, Roccaldo; Marinozzi, Maura; Ianni, Federica; Lisanti, Antonella; Natalini, Benedetto

    2013-01-01

    In the frame of a project aimed at finding non-steroidal farnesoid X receptor (FXR) agonists, we identified 4-(2,4-dimethoxyphenyl)-3,6-dimethyl-1-(2-tolyl)-4,8-dihydro-1H-pyrazole[3,4-e][1,4]thiazepin-7-one (1) as a hit endowed with FXR activity. Most of the compounds synthesised during the hit-to-lead optimisation work were characterised by the presence of two chiral centres and were therefore obtained as mixtures of anti(±)- and syn(±)-diastereoisomers. A restricted sub-set of species harboured with a carboxylic acid group on the distal phenyl ring of the biphenyl (a(±)5 (A1) and s(±)5 (S1)) or the phenoxyphenyl (a(±)6 (A2) and s(±)6 (S2)) moiety at C-4 position of the pyrazole[3,4-e][1,4]thiazepin-7-one core, resulted in suitable diastereo- and enantioresolution with a quinine (QN) carbamate-derived chiral stationary phase (CSP). Differently from the compounds usually analysed with QN-based CSPs, the couples A1/S1 and A2/S2 were atypical selectands, in which the two chiral carbon atoms reside at a remote position with respect to the carboxylic function, the main "point of attack" to the CSP. We produced evidence that the scarcely employed normal-phase (NP) eluent systems represent the elective choice for achieving the simultaneous diastereo- and enantioseparation of this class of compounds over the usually preferred reversed-phase (RP) and polar-organic (PO) modes of elution. Indeed, after the optimisation of the eluent composition, NP conditions allowed to obtain profitable enantioselectivity profiles, along with excellent diastereoselectivity levels (α(A1) = 1.07, R (S)(A1) = 1.15; α(S1) = 1.09, R (S)(S1) = 1.47; α(A2) = 1.08, R (S)(A2) = 1.31; and α(S2) = 1.06, R (S)(S2) = 1.18). The optimised NP methods are suitable for simultaneously providing information on the diastereo- and enantiopurity of the investigated compounds. PMID:22932813

  15. 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.

  16. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  17. 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

  18. 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

  19. Breakthrough: Fermilab Accelerator Technology

    ScienceCinema

    None

    2014-08-12

    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.

  20. Breakthrough: Fermilab Accelerator Technology

    SciTech Connect

    2012-04-23

    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.

  1. CEBAF accelerator achievements

    SciTech Connect

    Y.C. Chao, M. Drury, C. Hovater, A. Hutton, G.A. Krafft, M. Poelker, C. Reece, M. Tiefenback

    2011-06-01

    In the past decade, nuclear physics users of Jefferson Lab's Continuous Electron Beam Accelerator Facility (CEBAF) have benefited from accelerator physics advances and machine improvements. As of early 2011, CEBAF operates routinely at 6 GeV, with a 12 GeV upgrade underway. This article reports highlights of CEBAF's scientific and technological evolution in the areas of cryomodule refurbishment, RF control, polarized source development, beam transport for parity experiments, magnets and hysteresis handling, beam breakup, and helium refrigerator operational optimization.

  2. Comparison of effects of VDR versus PXR, FXR and GR ligands on the regulation of CYP3A isozymes in rat and human intestine and liver.

    PubMed

    Khan, Ansar A; Chow, Edwin C Y; van Loenen-Weemaes, Anne-miek M A; Porte, Robert J; Pang, K Sandy; Groothuis, Geny M M

    2009-05-12

    In this study, we compared the regulation of CYP3A isozymes by the vitamin D receptor (VDR) ligand 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) against ligands of the pregnane X receptor (PXR), the glucocorticoid receptor (GR) and the farnesoid X receptor (FXR) in precision-cut tissue slices of the rat jejunum, ileum, colon and liver, and human ileum and liver. In the rat, 1,25(OH)(2)D(3) strongly induced CYP3A1 mRNA, quantified by qRT-PCR, along the entire length of the intestine, induced CYP3A2 only in ileum but had no effect on CYP3A9. In contrast, the PXR/GR ligand, dexamethasone (DEX), the PXR ligand, pregnenolone-16 alpha carbonitrile (PCN), and the FXR ligand, chenodeoxycholic acid (CDCA), but not the GR ligand, budesonide (BUD), induced CYP3A1 only in the ileum, none of them influenced CYP3A2 expression, and PCN, DEX and BUD but not CDCA induced CYP3A9 in jejunum, ileum and colon. In rat liver, CYP3A1, CYP3A2 and CYP3A9 mRNA expression was unaffected by 1,25(OH)(2)D(3), whereas CDCA decreased the mRNA of all CYP3A isozymes; PCN induced CYP3A1 and CYP3A9, BUD induced CYP3A9, and DEX induced all three CYP3A isozymes. In human ileum and liver, 1,25(OH)(2)D(3) and DEX induced CYP3A4 expression, whereas CDCA induced CYP3A4 expression in liver only. In conclusion, the regulation of rat CYP3A isozymes by VDR, PXR, FXR and GR ligands differed for different segments of the rat and human intestine and liver, and the changes did not parallel expression levels of the nuclear receptors. PMID:19429418

  3. Oleanolic acid attenuates obstructive cholestasis in bile duct-ligated mice, possibly via activation of NRF2-MRPs and FXR antagonism.

    PubMed

    Chen, Pan; Li, Jingjie; Fan, Xiaomei; Zeng, Hang; Deng, Rongrong; Li, Dongshun; Huang, Min; Bi, Huichang

    2015-10-15

    Obstructive cholestasis is characterized by impairment of hepatic canalicular bile efflux and there are no clinically effective drugs to cure except surgeries. Previously we revealed that oleanolic acid (OA) protected against lithocholic acid (LCA)-induced intrahepatic cholestasis in mice. Cholestasis caused by LCA is characterized by segmental bile duct obstruction, whether OA possesses the beneficial effect on completed obstructive cholestasis induced by bile duct ligation (BDL) remains unknown. In this study, we demonstrated that BDL-induced mice liver pathological change, and increase in serum levels of ALT, AST and ALP were all significantly reduced by OA (20 mg/kg, i.p.). Meanwhile, OA also lowered total bilirubin and total bile acids levels in serum, as well as total bile acids level in liver, in contrast, urinary total bile acids output was remarkably up-regulated by OA. Gene expression analysis showed that OA caused significant increased mRNA expression of MRP3 and MRP4 located at hepatic basolateral membrane, and restoration of MRP2 and BSEP located at hepatic cannalicular membrane. Furthermore, significant NRF2 protein accumulation in nucleus was also observed in OA treated mice. In mice primary cultured hepatocytes, the effects of OA on MRP2, MRP3 and MRP4 expression were directly proved to be mediated via NRF2 activation, and BSEP downregulation induced by OA was in part due to FXR antagonism. Luciferase assay performed in Hep G2 cells also illustrated that OA was a partial FXR antagonist. Taken together, we conclude that OA attenuates obstructive cholestasis in BDL mice, possibly via activation of NRF2-MRPs and FXR antagonism. PMID:26297978

  4. 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.

  5. Plasma accelerators

    SciTech Connect

    Ruth, R.D.; Chen, P.

    1986-03-01

    In this paper we discuss plasma accelerators which might provide high gradient accelerating fields suitable for TeV linear colliders. In particular we discuss two types of plasma accelerators which have been proposed, the Plasma Beat Wave Accelerator and the Plasma Wake Field Accelerator. We show that the electric fields in the plasma for both schemes are very similar, and thus the dynamics of the driven beams are very similar. The differences appear in the parameters associated with the driving beams. In particular to obtain a given accelerating gradient, the Plasma Wake Field Accelerator has a higher efficiency and a lower total energy for the driving beam. Finally, we show for the Plasma Wake Field Accelerator that one can accelerate high quality low emittance beams and, in principle, obtain efficiencies and energy spreads comparable to those obtained with conventional techniques.

  6. A comparison of ALPHAScreen, TR-FRET, and TRF as assay methods for FXR nuclear receptors.

    PubMed

    Glickman, J Fraser; Wu, Xiang; Mercuri, Robert; Illy, Chantal; Bowen, Benjamin R; He, Yang; Sills, Matthew

    2002-02-01

    New developments in detection technologies are providing a variety of biomolecular screening strategies from which to choose. Consequently, we performed a detailed analysis of both separation-based and non-separation-based formats for screening nuclear receptor ligands. In this study, time-resolved fluorescence resonance energy transfer (TR-FRET), ALPHAScreen, and time-resolved fluorescence (TRF) assays were optimized and compared with respect to sensitivity, reproducibility, and miniaturization capability. The results showed that the ALPHAScreen system had the best sensitivity and dynamic range. The TRF assay was more time consuming because of the number of wash steps necessary. The TR-FRET assay had less interwell variation, most likely because of ratiometric measurement. Both the ALPHAScreen and the TR-FRET assays were miniaturized to 8-microl volumes. Of the photomultiplier tube-based readers, the ALPHAScreen reader (ALPHAQuest) presented the advantage of faster reading times through simultaneous reading with four photomultiplier tubes. PMID:11897050

  7. Shaping of pulses in optical grating-based laser systems for optimal control of electrons in laser plasma wake-field accelerator

    SciTech Connect

    Toth, Cs.; Faure, J.; Geddes, C.G.R.; van Tilborg, J.; Leemans, W.P.

    2003-05-01

    In typical chirped pulse amplification (CPA) laser systems, scanning the grating separation in the optical compressor causes the well know generation of linear chirp of frequency vs. time in a laser pulse, as well as a modification of all the higher order phase terms. By setting the compressor angle slightly different from the optimum value to generate the shortest pulse, a typical scan around this value will produce significant changes to the pulse shape. Such pulse shape changes can lead to significant differences in the interaction with plasmas such as used in laser wake-field accelerators. Strong electron yield dependence on laser pulse shape in laser plasma wake-field electron acceleration experiments have been observed in the L'OASIS Lab of LBNL [1]. These experiments show the importance of pulse skewness parameter, S, defined here on the basis of the ratio of the ''head-width-half-max'' (HWHM) and the ''tail-width-halfmax'' (TWHM), respectively.

  8. 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

  9. Spallator - accelerator breeder

    SciTech Connect

    Steinberg, M.

    1985-01-01

    The concept involves the use of spallation neutrons produced by interaction of a high energy proton (1 to 2 GeV) from a linear accelerator (LINAC) with a heavy metal target (uranium). The principal spallator concept is based on generating fissile fuel for use in LWR nuclear power plants. The spallator functions in conjunction with a reprocessing plant to regenerate and produce the Pu-239 or U-233 for fabrication into fresh LWR reactor fuel elements. Advances in proton accelerator technology has provided a solid base for predicting performance and optimizing the design of a reliable, continuous wave, high-current LINAC required by a fissile fuel production machine.

  10. '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.

  11. Accelerated Reader.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO.

    This paper provides an overview of Accelerated Reader, a system of computerized testing and record-keeping that supplements the regular classroom reading program. Accelerated Reader's primary goal is to increase literature-based reading practice. The program offers a computer-aided reading comprehension and management program intended to motivate…

  12. 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).

  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. 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.

  16. 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.

  17. Acceleration switch

    DOEpatents

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

    1979-08-29

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

  18. 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.

  19. 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.

  20. LINEAR ACCELERATOR

    DOEpatents

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

    1959-02-17

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

  1. GPU accelerated dislocation dynamics

    NASA Astrophysics Data System (ADS)

    Ferroni, Francesco; Tarleton, Edmund; Fitzgerald, Steven

    2014-09-01

    In this paper we analyze the computational bottlenecks in discrete dislocation dynamics modeling (associated with segment-segment interactions as well as the treatment of free surfaces), discuss the parallelization and optimization strategies, and demonstrate the effectiveness of Graphical Processing Unit (GPU) computation in accelerating dislocation dynamics simulations and expanding their scope. Individual algorithmic benchmark tests as well as an example large simulation of a thin film are presented.

  2. 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.

  3. Acceleration Studies

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.

    1993-01-01

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

  4. Direct amidation of carboxylic acids catalyzed by ortho-iodo arylboronic acids: catalyst optimization, scope, and preliminary mechanistic study supporting a peculiar halogen acceleration effect.

    PubMed

    Gernigon, Nicolas; Al-Zoubi, Raed M; Hall, Dennis G

    2012-10-01

    The importance of amides as a component of biomolecules and synthetic products motivates the development of catalytic, direct amidation methods employing free carboxylic acids and amines that circumvent the need for stoichiometric activation or coupling reagents. ortho-Iodophenylboronic acid 4a has recently been shown to catalyze direct amidation reactions at room temperature in the presence of 4A molecular sieves as dehydrating agent. Herein, the arene core of ortho-iodoarylboronic acid catalysts has been optimized with regards to the electronic effects of ring substitution. Contrary to the expectation, it was found that electron-donating substituents are preferable, in particular, an alkoxy substituent positioned para to the iodide. The optimal new catalyst, 5-methoxy-2-iodophenylboronic acid (MIBA, 4f), was demonstrated to be kinetically more active than the parent des-methoxy catalyst 4a, providing higher yields of amide products in shorter reaction times under mild conditions at ambient temperature. Catalyst 4f is recyclable and promotes the formation of amides from aliphatic carboxylic acids and amines, and from heteroaromatic carboxylic acids and other functionalized substrates containing moieties like a free phenol, indole and pyridine. Mechanistic studies demonstrated the essential role of molecular sieves in this complex amidation process. The effect of substrate stoichiometry, concentration, and measurement of the catalyst order led to a possible catalytic cycle based on the presumed formation of an acylborate intermediate. The need for an electronically enriched ortho-iodo substituent in catalyst 4f supports a recent theoretical study (Marcelli, T. Angew. Chem. Int. Ed.2010, 49, 6840-6843) with a purported role for the iodide as a hydrogen-bond acceptor in the orthoaminal transition state. PMID:23013456

  5. 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.

  6. 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…

  7. 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.

  8. 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.

  9. Accelerated Profile HMM Searches

    PubMed Central

    Eddy, Sean R.

    2011-01-01

    Profile hidden Markov models (profile HMMs) and probabilistic inference methods have made important contributions to the theory of sequence database homology search. However, practical use of profile HMM methods has been hindered by the computational expense of existing software implementations. Here I describe an acceleration heuristic for profile HMMs, the “multiple segment Viterbi” (MSV) algorithm. The MSV algorithm computes an optimal sum of multiple ungapped local alignment segments using a striped vector-parallel approach previously described for fast Smith/Waterman alignment. MSV scores follow the same statistical distribution as gapped optimal local alignment scores, allowing rapid evaluation of significance of an MSV score and thus facilitating its use as a heuristic filter. I also describe a 20-fold acceleration of the standard profile HMM Forward/Backward algorithms using a method I call “sparse rescaling”. These methods are assembled in a pipeline in which high-scoring MSV hits are passed on for reanalysis with the full HMM Forward/Backward algorithm. This accelerated pipeline is implemented in the freely available HMMER3 software package. Performance benchmarks show that the use of the heuristic MSV filter sacrifices negligible sensitivity compared to unaccelerated profile HMM searches. HMMER3 is substantially more sensitive and 100- to 1000-fold faster than HMMER2. HMMER3 is now about as fast as BLAST for protein searches. PMID:22039361

  10. 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

  11. 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).

  12. 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

  13. 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].

  14. Summary report: Working Group 2 on 'Plasma Based Acceleration Concepts'

    SciTech Connect

    Leemans, W. P.; Esarey, E.

    1999-07-12

    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.

  15. 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

  16. 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)

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Intestine-specific Deletion of Sirt1 in Mice Impairs DCoH2–HNF1α–FXR Signaling and Alters Systemic Bile Acid Homeostasis

    PubMed Central

    Kazgan, Nevzat; Metukuri, Mallikarjuna R.; Purushotham, Aparna; Lu, Jing; Rao, Anuradha; Lee, Sangkyu; Pratt-Hyatt, Matthew; Lickteig, Andrew; Csanaky, Ivan; Zhao, Yingming; Dawson, Paul A.; Li, Xiaoling

    2014-01-01

    Background & Aims Sirtuin 1 (SIRT1), the most conserved mammalian NAD+-dependent protein deacetylase, is an important metabolic sensor in many tissues. However, little is known about its role in the small intestine, which absorbs and senses nutrients. We investigated the functions of intestinal Sirt1 in systemic bile acid and cholesterol metabolism in mice. Methods Sirt1 was specifically deleted from intestines of mice using the Flox-villin-Cre system (Sirt1 iKO mice). Intestinal and heptic tissues were collected, and bile acid absorption was analyzed using the everted gut sac experiment. Systemic bile acid metabolism was studied in Sirt1 iKO and Flox control mice placed on standard diets, diets containing 0.5% cholic acid or 1.25% cholesterol, or lithogenic diets. Results Sirt1 iKO mice had reduced intestinal Fxr signaling via Hnf1a compared with controls, which reduced expression of the bile acid transporter genes Asbt and Mcf2l (encodes Ost) and absorption of ileal bile acids. Sirt1 regulated Hnf1α–Fxr signaling partially through Dcoh2, which increases dimerization of Hnf1α. Sirt1 was found to deacetylate DCoH2, promoting its interaction with Hnf1α and inducing DNA binding by Hnf1α. Intestine-specific deletion of Sirt1 increased hepatic bile acid biosynthesis, reduced hepatic accumulation of bile acids, and protected animals from liver damage from high-bile acid diets. Conclusions Intestinal Sirt1, a key nutrient sensor, is required for ileal bile acid absorption and systemic bile acid homeostasis in mice. We delineated the mechanism of metabolic regulation of Hnf1α–Fxr signaling. Reagents designed to inhibit intestinal SIRT1 might be developed to treat bile acid-related diseases such as cholestasis. PMID:24389307

  3. 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.

  4. Attention's Accelerator.

    PubMed

    Reinhart, Robert M G; McClenahan, Laura J; Woodman, Geoffrey F

    2016-06-01

    How do people get attention to operate at peak efficiency in high-pressure situations? We tested the hypothesis that the general mechanism that allows this is the maintenance of multiple target representations in working and long-term memory. We recorded subjects' event-related potentials (ERPs) indexing the working memory and long-term memory representations used to control attention while performing visual search. We found that subjects used both types of memories to control attention when they performed the visual search task with a large reward at stake, or when they were cued to respond as fast as possible. However, under normal circumstances, one type of target memory was sufficient for slower task performance. The use of multiple types of memory representations appears to provide converging top-down control of attention, allowing people to step on the attentional accelerator in a variety of high-pressure situations. PMID:27056975

  5. Acceleration modules in linear induction accelerators

    NASA Astrophysics Data System (ADS)

    Wang, Shao-Heng; Deng, Jian-Jun

    2014-05-01

    The Linear Induction Accelerator (LIA) is a unique type of accelerator that is capable of accelerating kilo-Ampere charged particle current to tens of MeV energy. The present development of LIA in MHz bursting mode and the successful application into a synchrotron have broadened LIA's usage scope. Although the transformer model is widely used to explain the acceleration mechanism of LIAs, it is not appropriate to consider the induction electric field as the field which accelerates charged particles for many modern LIAs. We have examined the transition of the magnetic cores' functions during the LIA acceleration modules' evolution, distinguished transformer type and transmission line type LIA acceleration modules, and re-considered several related issues based on transmission line type LIA acceleration module. This clarified understanding should help in the further development and design of LIA acceleration modules.

  6. Plasma-based Accelerator with Magnetic Compression

    SciTech Connect

    Paul F. Schmit and Nathaniel J. Fisch

    2012-06-28

    Electron dephasing is a major gain-inhibiting effect in plasma-based accelerators. A novel method is proposed to overcome dephasing, in which the modulation of a modest (#24; O(10 kG)), axial, uniform magnetic field in the acceleration channel leads to densification of the plasma through magnetic compression, enabling direct, time-resolved control of the plasma wave properties. The methodology is broadly applicable and can be optimized to improve the leading acceleration approaches, including plasma beat-wave, plasma wakefield, and laser wakefield acceleration. The advantages of magnetic compression compared to other proposed schemes to overcome dephasing are identified.

  7. Plasma-based accelerator with magnetic compression.

    PubMed

    Schmit, P F; Fisch, N J

    2012-12-21

    Electron dephasing is a major gain-inhibiting effect in plasma-based accelerators. A novel method is proposed to overcome dephasing, in which the modulation of a modest [~O(10 kG)], axial, uniform magnetic field in the acceleration channel leads to densification of the plasma through magnetic compression, enabling direct, time-resolved control of the plasma wave properties. The methodology is broadly applicable and can be optimized to improve the leading acceleration approaches, including plasma beat wave, plasma wakefield, and laser wakefield acceleration. The advantages of magnetic compression are compared to other proposed techniques to overcome dephasing. PMID:23368475

  8. Plasma-Based Accelerator with Magnetic Compression

    NASA Astrophysics Data System (ADS)

    Schmit, P. F.; Fisch, N. J.

    2012-12-01

    Electron dephasing is a major gain-inhibiting effect in plasma-based accelerators. A novel method is proposed to overcome dephasing, in which the modulation of a modest [˜O(10kG)], axial, uniform magnetic field in the acceleration channel leads to densification of the plasma through magnetic compression, enabling direct, time-resolved control of the plasma wave properties. The methodology is broadly applicable and can be optimized to improve the leading acceleration approaches, including plasma beat wave, plasma wakefield, and laser wakefield acceleration. The advantages of magnetic compression are compared to other proposed techniques to overcome dephasing.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Progress on plasma accelerators

    SciTech Connect

    Chen, P.

    1986-05-01

    Several plasma accelerator concepts are reviewed, with emphasis on the Plasma Beat Wave Accelerator (PBWA) and the Plasma Wake Field Accelerator (PWFA). Various accelerator physics issues regarding these schemes are discussed, and numerical examples on laboratory scale experiments are given. The efficiency of plasma accelerators is then revealed with suggestions on improvements. Sources that cause emittance growth are discussed briefly.

  14. 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.

  15. 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).

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Induction linear accelerator technology for SDIO applications

    SciTech Connect

    Birx, D.; Reginato, L.; Rogers, D.; Trimble, D.

    1986-11-01

    The research effort reported concentrated primarily on three major activities. The first was aimed at improvements in the accelerator drive system of an induction linac to meet the high repetition rate requirements of SDI applications. The second activity centered on a redesign of the accelerator cells to eliminate the beam breakup instabilities, resulting in optimized beam transport. The third activity sought to improve the source of electrons to achieve a higher quality beam to satisfy the requirement of the free electron laser. (LEW)

  2. Overview of SNS accelerator shielding analyses

    SciTech Connect

    Popova, I.; Gallmeier, F. X.; Ferguson, P.; Iverson, E.; Lu, W.

    2012-07-01

    The Spallation Neutron Source is an accelerator driven neutron scattering facility for materials research. During all phases of SNS development, including design, construction, commissioning and operation, extensive neutronics work was performed in order to provide adequate shielding, to assure safe facility operation from radiation protection point of view, and to optimize performance of the accelerator and target facility. Presently, most of the shielding work is concentrated on the beam lines and instrument enclosures to prepare for commissioning, safe operation and adequate radiation background in the future. Although the accelerator is built and in operation mode, there is extensive demand for shielding and activation analyses. It includes redesigning some parts of the facility, facility upgrades, designing additional structures, storage and transport containers for accelerator structures taken out of service, and performing radiation protection analyses and studies on residual dose rates inside the accelerator. (authors)

  3. 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.

  4. 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.

  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. New Targets for New Accelerators

    NASA Astrophysics Data System (ADS)

    Frentz, Bryce; Manukyan, Khachatur; Aprahamian, Ani

    2013-10-01

    New accelerators, such as the 5 MV Sta Ana accelerator at the University of Notre Dame, will produce more powerful beams up to 100's of μAmps. These accelerators require a complete rethinking of target preparation since the high intensity of such beams would melt conventional targets. Traditionally, accelerator targets are made with a tantalum backing because of its high atomic mass. However, tantalum is brittle, a poor conductor, and, if produced commercially, often contains impurities (e.g. fluorine) that produce undesirable background and reaction products. Tungsten, despite its brittle structure and poor conductivity, has a high atomic mass and lacks impurities, making it a more desirable backing. In conjunction with tungsten's properties, copper is robust and a far superior thermal conductor. We describe a new method of reactive joining that we developed for creating targets that use the advantageous properties of both tungsten and copper. This process involved placing a reactive mixture between tungsten and copper and applying a load force. The mixture is then ignited, and while under pressure, the system produces conditions to join the materials. We present our investigation to optimize the process of reactive joining, as well as some of the final target's properties. This work was supported by the National Science Foundation under Grant PHY-1068192.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Angular Acceleration Without Torque?

    NASA Astrophysics Data System (ADS)

    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.2

  16. Sustained linear acceleration

    NASA Technical Reports Server (NTRS)

    Fraser, T. M.

    1973-01-01

    The subjective effects of sustained acceleration are discussed, including positive, negative, forward, backward, and lateral acceleration effects. Physiological effects, such as retinal and visual response, unconsciousness and cerebral function, pulmonary response, and renal output, are studied. Human tolerance and performance under sustained acceleration are ascertained.

  17. 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.

  18. 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…

  19. Feedback: Theory and Accelerator Applications

    NASA Astrophysics Data System (ADS)

    Himel, T.

    The use of feedback to stabilize the beam and improve the performance of accelerators is becoming more common. The methods used to design the feedback algorithms are introduced and some practical implementation details are described. The design of a PID loop using classical control techniques is covered as is the design of an optimal controller using modern control theory. Some adaptive control techniques are also briefly described. Examples are given of multiple-input-multiple-output loops and of how to handle systems of many interacting feedback loops.

  20. 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.

  1. 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.

  2. Fiber Accelerating Structures

    SciTech Connect

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

    2010-08-25

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

  3. 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.

  4. Acceleration-Augmented LQG Control of an Active Magnetic Bearing

    NASA Technical Reports Server (NTRS)

    Feeley, Joseph J.

    1993-01-01

    A linear-quadratic-gaussian (LQG) regulator controller design for an acceleration-augmented active magnetic bearing (AMB) is outlined. Acceleration augmentation is a key feature in providing improved dynamic performance of the controller. The optimal control formulation provides a convenient method of trading-off fast transient response and force attenuation as control objectives.

  5. Plasma inverse transition acceleration

    SciTech Connect

    Xie, Ming

    2001-06-18

    It can be proved fundamentally from the reciprocity theorem with which the electromagnetism is endowed that corresponding to each spontaneous process of radiation by a charged particle there is an inverse process which defines a unique acceleration mechanism, from Cherenkov radiation to inverse Cherenkov acceleration (ICA) [1], from Smith-Purcell radiation to inverse Smith-Purcell acceleration (ISPA) [2], and from undulator radiation to inverse undulator acceleration (IUA) [3]. There is no exception. Yet, for nearly 30 years after each of the aforementioned inverse processes has been clarified for laser acceleration, inverse transition acceleration (ITA), despite speculation [4], has remained the least understood, and above all, no practical implementation of ITA has been found, until now. Unlike all its counterparts in which phase synchronism is established one way or the other such that a particle can continuously gain energy from an acceleration wave, the ITA to be discussed here, termed plasma inverse transition acceleration (PITA), operates under fundamentally different principle. As a result, the discovery of PITA has been delayed for decades, waiting for a conceptual breakthrough in accelerator physics: the principle of alternating gradient acceleration [5, 6, 7, 8, 9, 10]. In fact, PITA was invented [7, 8] as one of several realizations of the new principle.

  6. 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.

  7. 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.

  8. 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.

  9. Laser guiding for GeV laser-plasma accelerators.

    PubMed

    Leemans, Wim; Esarey, Eric; Geddes, Cameron; Schroeder, Carl; Tóth, Csaba

    2006-03-15

    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 at Lawrence Berkeley National Laboratory (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. PMID:16483950

  10. 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)

  11. Space Acceleration Measurement System

    NASA Technical Reports Server (NTRS)

    1993-01-01

    This training video, presented by the Lewis Research Center's Space Experiments Division, gives a background and detailed instructions for preparing the space acceleration measurement system (SAMS) for use. The SAMS measures, conditions, and records forces of low gravity accelerations, and is used to determine the effect of these forces on various experiments performed in microgravity. Inertial sensors are used to measure positive and negative acceleration over a specified frequency range. The video documents the SAMS' uses in different configurations during shuttle missions.

  12. 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)

  13. Accelerating into the future

    NASA Astrophysics Data System (ADS)

    Murray, Cherry

    2009-05-01

    Accelerator science has traditionally been associated with high-energy physics and nuclear physics. But the use of accelerators in other areas of science, as well as in medicine and industry, is steadily growing. Accelerators are now, for example, used to treat cancer using proton therapy, which can deposit radiation onto a tumour while causing much less damage to surrounding healthy tissue than with other treatment techniques.

  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. 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.

  16. Miniaturization Techniques for Accelerators

    SciTech Connect

    Spencer, James E.

    2003-05-27

    The possibility of laser driven accelerators [1] suggests the need for new structures based on micromachining and integrated circuit technology because of the comparable scales. Thus, we are exploring fully integrated structures including sources, optics (for both light and particle) and acceleration in a common format--an accelerator-on-chip (AOC). Tests suggest a number of preferred materials and techniques but no technical or fundamental roadblocks at scales of order 1 {micro}m or larger.

  17. 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.

  18. 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.

  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. PMID:24365468

  20. 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.

  1. Scaling FFAG accelerator for muon acceleration

    SciTech Connect

    Lagrange, JB.; Planche, T.; Mori, Y.

    2011-10-06

    Recent developments in scaling fixed field alternating gradient (FFAG) accelerators have opened new ways for lattice design, with straight sections, and insertions like dispersion suppressors. Such principles and matching issues are detailed in this paper. An application of these new concepts is presented to overcome problems in the PRISM project.

  2. 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.

  3. 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.

  4. Synchronized Ion Acceleration by Ultraintense Slow Light.

    PubMed

    Brantov, A V; Govras, E A; Kovalev, V F; Bychenkov, V Yu

    2016-02-26

    An effective scheme of synchronized laser-triggered ion acceleration and the corresponding theoretical model are proposed for a slow light pulse of relativistic intensity, which penetrates into a near-critical-density plasma, strongly slows, and then increases its group velocity during propagation within a target. The 3D particle-in-cell simulations confirm this concept for proton acceleration by a femtosecond petawatt-class laser pulse experiencing relativistic self-focusing, quantify the characteristics of the generated protons, and demonstrate a significant increase of their energy compared with the proton energy generated from optimized ultrathin solid dense foils. PMID:26967421

  5. Synchronized Ion Acceleration by Ultraintense Slow Light

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    An effective scheme of synchronized laser-triggered ion acceleration and the corresponding theoretical model are proposed for a slow light pulse of relativistic intensity, which penetrates into a near-critical-density plasma, strongly slows, and then increases its group velocity during propagation within a target. The 3D particle-in-cell simulations confirm this concept for proton acceleration by a femtosecond petawatt-class laser pulse experiencing relativistic self-focusing, quantify the characteristics of the generated protons, and demonstrate a significant increase of their energy compared with the proton energy generated from optimized ultrathin solid dense foils.

  6. Accelerators (4/5)

    ScienceCinema

    None

    2011-10-06

    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.

  7. J-PARC Accelerator

    SciTech Connect

    Yamazaki, Yoshishige

    2008-02-21

    The Japan Proton Accelerator Research Complex (J-PARC) is under construction in Tokai site. The linac beam commissioning started last fall, while the beam commissioning of the 3-GeV Rapid-Cycling Synchrotron (RCS) will start this fall. The status of the J-PARC accelerator is reported with emphasis on the technical development accomplished for the J-PARC.

  8. 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.

  9. 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.

  10. Accelerators Beyond The Tevatron?

    SciTech Connect

    Lach, Joseph

    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?

  11. 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.

  12. 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.

  13. Accelerators (5/5)

    ScienceCinema

    None

    2011-10-06

    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. Accelerating global forest mortality

    NASA Astrophysics Data System (ADS)

    McDowell, N. G.

    2014-12-01

    Forest mortality is apparently accelerating globally. The evidence supporting this contention is now substantial, as is the evidence suggesting the acceleration has just begun and will become progressively worse in upcoming decades. I will review the data and models used to make these contentions.

  15. Accelerators (3/5)

    ScienceCinema

    None

    2011-10-06

    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.

  16. 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.

  17. 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.

  18. Graphics Processing Unit Acceleration of Gyrokinetic Turbulence Simulations

    NASA Astrophysics Data System (ADS)

    Hause, Benjamin; Parker, Scott

    2012-10-01

    We find a substantial increase in on-node performance using Graphics Processing Unit (GPU) acceleration in gyrokinetic delta-f particle-in-cell simulation. Optimization is performed on a two-dimensional slab gyrokinetic particle simulation using the Portland Group Fortran compiler with the GPU accelerator compiler directives. We have implemented the GPU acceleration on a Core I7 gaming PC with a NVIDIA GTX 580 GPU. We find comparable, or better, acceleration relative to the NERSC DIRAC cluster with the NVIDIA Tesla C2050 computing processor. The Tesla C 2050 is about 2.6 times more expensive than the GTX 580 gaming GPU. Optimization strategies and comparisons between DIRAC and the gaming PC will be presented. We will also discuss progress on optimizing the comprehensive three dimensional general geometry GEM code.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. The MESA accelerator

    SciTech Connect

    Aulenbacher, Kurt

    2013-11-07

    The MESA accelerator will operate for particle and nuclear physics experiments in two different modes. A first option is conventional c.w. acceleration yielding 150-200MeV spin-polarized external beam. Second, MESA will be operated as a superconducting multi-turn energy recovery linac (ERL), opening the opportunity to perform experiments with a windowless target with beam current of up to 10 mA. The perspectives for innovative experiments with such a machine are discussed together with a sketch of the accelerator physics issues that have to be solved.

  4. 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 .

  5. Accelerator Toolbox for MATLAB

    SciTech Connect

    Terebilo, Andrei

    2001-05-29

    This paper introduces Accelerator Toolbox (AT)--a collection of tools to model particle accelerators and beam transport lines in the MATLAB environment. At SSRL, it has become the modeling code of choice for the ongoing design and future operation of the SPEAR 3 synchrotron light source. AT was designed to take advantage of power and simplicity of MATLAB--commercially developed environment for technical computing and visualization. Many examples in this paper illustrate the advantages of the AT approach and contrast it with existing accelerator code frameworks.

  6. 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.

  7. 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.

  8. 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.

  9. 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)

  10. 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.

  11. 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.

  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. Principles of Induction Accelerators

    NASA Astrophysics Data System (ADS)

    Briggs*, Richard J.

    The basic concepts involved in induction accelerators are introduced in this chapter. The objective is to provide a foundation for the more detailed coverage of key technology elements and specific applications in the following chapters. A wide variety of induction accelerators are discussed in the following chapters, from the high current linear electron accelerator configurations that have been the main focus of the original developments, to circular configurations like the ion synchrotrons that are the subject of more recent research. The main focus in the present chapter is on the induction module containing the magnetic core that plays the role of a transformer in coupling the pulsed power from the modulator to the charged particle beam. This is the essential common element in all these induction accelerators, and an understanding of the basic processes involved in its operation is the main objective of this chapter. (See [1] for a useful and complementary presentation of the basic principles in induction linacs.)

  14. Accelerator on a Chip

    ScienceCinema

    England, Joel

    2014-07-16

    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)

  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. 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.

  17. 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.

  18. Accelerator vibration issues

    SciTech Connect

    Tennant, R.A.

    1985-01-01

    Vibrations induced in accelerator structures can cause particle-beam jitter and alignment difficulties. Sources of these vibrations may include pump oscillations, cooling-water turbulence, and vibrations transmitted through the floor to the accelerator structure. Drift tubes (DT) in a drift tube linac (DTL) are components likely to affect beam jitter and alignment because they normally have a heavy magnet structure on the end of a long and relatively small support stem. The natural vibrational frequencies of a drift tube have been compared with theoretical predictions. In principle, by knowing natural frequencies of accelerator components and system vibrational frequncies, an accelerator can be designed that does not have these frequencies coinciding. 2 refs., 2 figs., 2 tabs.

  19. 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.

  20. 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 .

  1. 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.

  2. Gait analysis using gravitational acceleration measured by wearable sensors.

    PubMed

    Takeda, Ryo; Tadano, Shigeru; Todoh, Masahiro; Morikawa, Manabu; Nakayasu, Minoru; Yoshinari, Satoshi

    2009-02-01

    A novel method for measuring human gait posture using wearable sensor units is proposed. The sensor units consist of a tri-axial acceleration sensor and three gyro sensors aligned on three axes. The acceleration and angular velocity during walking were measured with seven sensor units worn on the abdomen and the lower limb segments (both thighs, shanks and feet). The three-dimensional positions of each joint are calculated from each segment length and joint angle. Joint angle can be estimated mechanically from the gravitational acceleration along the anterior axis of the segment. However, the acceleration data during walking includes three major components; translational acceleration, gravitational acceleration and external noise. Therefore, an optimization analysis was represented to separate only the gravitational acceleration from the acceleration data. Because the cyclic patterns of acceleration data can be found during constant walking, a FFT analysis was applied to obtain some characteristic frequencies in it. A pattern of gravitational acceleration was assumed using some parts of these characteristic frequencies. Every joint position was calculated from the pattern under the condition of physiological motion range of each joint. An optimized pattern of the gravitational acceleration was selected as a solution of an inverse problem. Gaits of three healthy volunteers were measured by walking for 20s on a flat floor. As a result, the acceleration data of every segment was measured simultaneously. The characteristic three-dimensional walking could be shown by the expression using a stick figure model. In addition, the trajectories of the knee joint in the horizontal plane could be checked by visual imaging on a PC. Therefore, this method provides important quantitive information for gait diagnosis. PMID:19121522

  3. 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.

  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. 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.

  6. Microwave inverse Cerenkov accelerator

    SciTech Connect

    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 TM{sub 01} 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 5{pi}mm-mrad. Experiments on sample alumina tubes have been conducted that verify the theoretical dispersion relation for the TM{sub 01} 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. {copyright} {ital 1997 American Institute of Physics.}

  7. 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.

  8. LHCb GPU acceleration project

    NASA Astrophysics Data System (ADS)

    Badalov, A.; Cámpora, D.; Neufeld, N.; Vilasís-Cardona, X.

    2016-01-01

    The LHCb detector is due to be upgraded for processing high-luminosity collisions, which will increase data bandwidth to the event filter farm from 100 GB/s to 4 TB/s, encouraging us to look for new ways of accelerating Online reconstruction. The Coprocessor Manager is a new framework for integrating LHCb's existing computation pipelines with massively parallel algorithms running on GPUs and other accelerators. This paper describes the system and analyzes its performance.

  9. 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.

  10. 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.

  11. Multimegawatt cyclotron autoresonance accelerator

    SciTech Connect

    Hirshfield, J.L.; LaPointe, M.A.; Ganguly, A.K.; Yoder, R.B.; Wang, C.

    1996-05-01

    Means are discussed for generation of high-quality multimegawatt gyrating electron beams using rf gyroresonant acceleration. TE{sub 111}-mode cylindrical cavities in a uniform axial magnetic field have been employed for beam acceleration since 1968; such beams have more recently been employed for generation of radiation at harmonics of the gyration frequency. Use of a TE{sub 11}-mode waveguide for acceleration, rather than a cavity, is discussed. It is shown that the applied magnetic field and group velocity axial tapers allow resonance to be maintained along a waveguide, but that this is impractical in a cavity. In consequence, a waveguide cyclotron autoresonance accelerator (CARA) can operate with near-100{percent} efficiency in power transfer from rf source to beam, while cavity accelerators will, in practice, have efficiency values limited to about 40{percent}. CARA experiments are described in which an injected beam of up to 25 A, 95 kV has had up to 7.2 MW of rf power added, with efficiencies of up to 96{percent}. Such levels of efficiency are higher than observed previously in any fast-wave interaction, and are competitive with efficiency values in industrial linear accelerators. Scaling arguments suggest that good quality gyrating megavolt beams with peak and average powers of 100 MW and 100 kW can be produced using an advanced CARA, with applications in the generation of high-power microwaves and for possible remediation of flue gas pollutants. {copyright} {ital 1996 American Institute of Physics.}

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Computation applied to particle accelerator simulations

    SciTech Connect

    Herrmannsfeldt, W.B. ); Yan, Y.T. )

    1991-07-01

    The rapid growth in the power of large-scale computers has had a revolutionary effect on the study of charged-particle accelerators that is similar to the impact of smaller computers on everyday life. Before an accelerator is built, it is now the absolute rule to simulate every component and subsystem by computer to establish modes of operation and tolerances. We will bypass the important and fruitful areas of control and operation and consider only application to design and diagnostic interpretation. Applications of computers can be divided into separate categories including: component design, system design, stability studies, cost optimization, and operating condition simulation. For the purposes of this report, we will choose a few examples taken from the above categories to illustrate the methods and we will discuss the significance of the work to the project, and also briefly discuss the accelerator project itself. The examples that will be discussed are: (1) the tracking analysis done for the main ring of the Superconducting Supercollider, which contributed to the analysis which ultimately resulted in changing the dipole coil diameter to 5 cm from the earlier design for a 4-cm coil-diameter dipole magnet; (2) the design of accelerator structures for electron-positron linear colliders and circular colliding beam systems (B-factories); (3) simulation of the wake fields from multibunch electron beams for linear colliders; and (4) particle-in-cell simulation of space-charge dominated beams for an experimental liner induction accelerator for Heavy Ion Fusion. 8 refs., 9 figs.

  19. The APT Accelerator.*

    NASA Astrophysics Data System (ADS)

    Lawrence, George P.

    1996-05-01

    The accelerator for the Accelerator Production of Tritium (APT) project is a high-power RF linac designed to produce a 100-mA CW proton beam at an energy of 1300 MeV. A heavy-metal target produces large quantities of spallation neutrons, which are slowed to thermal energies and captured in a feed material to make tritium. The baseline accelerator design consists of a 75-keV proton injector, a 7-MeV radio-frequency quadrupole (RFQ), a 100-MeV coupled-cavity drift-tube linac (CCDTL), and a 1300-MeV side-coupled linac (SCL). The RFQ operates at a frequency of 350 MHz, while the CCDTL and SCL operate at 700-MHz. A quadrupole-magnet transport system conveys the 1300-MeV beam to production target/blanket assemblies where beam expanders using non-linear magnetic elements transform the linac output distribution into large-area rectangular distributions having a nearly uniform density. All the linac accelerating structures use conventional water-cooled copper technology. The SCL section is based on the well-proven 800-MeV LANSCE high-duty-factor linac at Los Alamos. The CCDTL is a new hybrid accelerating structure that combines the best features of the conventional drift-tube linac and the coupled-cavity linac to provide efficient and stable acceleration in the intermediate velocity range. Approximately 263 1-MW CW klystrons are needed to drive the 130-MW proton beam. The total ac-power requirement for the APT plant is about 438 MW, most of which is needed for the accelerator. An advanced-technology option is being considered that would replace the conventional SCL with a superconducting RF linac composed of sequences of 4-cell elliptical-type cavities. This option would reduce the electric power consumption significantly and would provide increased operational flexibility. * Work supported by the US Department of Energy.

  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. High energy plasma accelerators

    SciTech Connect

    Tajima, T.

    1985-05-01

    Colinear intense laser beams ..omega../sub 0/, kappa/sub 0/ and ..omega../sub 1/, kappa/sub 1/ shone on a plasma with frequency separation equal to the electron plasma frequency ..omega../sub pe/ are capable of creating a coherent large longitudinal electric field E/sub L/ = mc ..omega../sub pe//e of the order of 1GeV/cm for a plasma density of 10/sup 18/ cm/sup -3/ through the laser beat excitation of plasma oscillations. Accompanying favorable and deleterious physical effects using this process for a high energy beat-wave accelerator are discussed: the longitudinal dephasing, pump depletion, the transverse laser diffraction, plasma turbulence effects, self-steepening, self-focusing, etc. The basic equation, the driven nonlinear Schroedinger equation, is derived to describe this system. Advanced accelerator concepts to overcome some of these problems are proposed, including the plasma fiber accelerator of various variations. An advanced laser architecture suitable for the beat-wave accelerator is suggested. Accelerator physics issues such as the luminosity are discussed. Applications of the present process to the current drive in a plasma and to the excitation of collective oscillations within nuclei are also discussed.

  2. Acoustic particle acceleration sensors

    SciTech Connect

    Franklin, J.B.; Barry, P.J.

    1996-04-01

    A crossed dipole array provides a directional receiving capability in a relatively small sensor package and is therefore very attractive for many applications in acoustics. Particle velocity measurements on two axes perpendicular to each other are required to provide the dipole signals. These can be obtained directly using particle velocity sensors or via simple transfer functions using acceleration and displacement sensors. Also, the derivative of the acoustic pressure with respect to space provides a signal proportional to the particle acceleration and gives rise to the pressure gradient sensor. Each of these sensors has strengths and drawbacks depending on the frequency regime of interest, the noise background, and whether a point or a line configuration of dipole sensors is desired. In this paper, the performance of acceleration sensors is addressed using a sensor concept developed at DREA. These sensors exploit bending stresses in a cantilever beam of piezoelectric material to obtain wide bandwidth and high sensitivity. Models which predict the acceleration sensitivity, pressure sensitivity, and natural frequency for this type of sensor are described. Experimental results obtained using several different versions of these sensors are presented and compared with theory. The predicted performance of acceleration sensors are compared with that of pressure gradient arrays and particle velocity sensors. {copyright} {ital 1996 American Institute of Physics.}

  3. Dielectric laser accelerators

    NASA Astrophysics Data System (ADS)

    England, R. Joel; Noble, Robert J.; Bane, Karl; Dowell, David H.; Ng, Cho-Kuen; Spencer, James E.; Tantawi, Sami; Wu, Ziran; Byer, Robert L.; Peralta, Edgar; Soong, Ken; Chang, Chia-Ming; Montazeri, Behnam; Wolf, Stephen J.; Cowan, Benjamin; Dawson, Jay; Gai, Wei; Hommelhoff, Peter; Huang, Yen-Chieh; Jing, Chunguang; McGuinness, Christopher; Palmer, Robert B.; Naranjo, Brian; Rosenzweig, James; Travish, Gil; Mizrahi, Amit; Schachter, Levi; Sears, Christopher; Werner, Gregory R.; Yoder, Rodney B.

    2014-10-01

    The use of infrared lasers to power optical-scale lithographically fabricated particle accelerators is a developing area of research that has garnered increasing interest in recent years. The physics and technology of this approach is reviewed, which is referred to as dielectric laser acceleration (DLA). In the DLA scheme operating at typical laser pulse lengths of 0.1 to 1 ps, the laser damage fluences for robust dielectric materials correspond to peak surface electric fields in the GV /m regime. The corresponding accelerating field enhancement represents a potential reduction in active length of the accelerator between 1 and 2 orders of magnitude. Power sources for DLA-based accelerators (lasers) are less costly than microwave sources (klystrons) for equivalent average power levels due to wider availability and private sector investment. Because of the high laser-to-particle coupling efficiency, required pulse energies are consistent with tabletop microJoule class lasers. Combined with the very high (MHz) repetition rates these lasers can provide, the DLA approach appears promising for a variety of applications, including future high-energy physics colliders, compact light sources, and portable medical scanners and radiative therapy machines.

  4. 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.

  5. Plasma-based accelerator structures

    SciTech Connect

    Schroeder, Carl B.

    1999-12-01

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

  6. Issues regarding acceleration in crystals

    SciTech Connect

    Chen, P.; Cline, D.B.; Gabella, W.E.

    1992-12-01

    Both self-acceleration and laser-acoustic acceleration in crystals are considered. The conduction electrons in the crystal are treated as a plasma and are the medium through which the acceleration takes place. Self-acceleration is the possible acceleration of part of a bunch due to plasma oscillations driven by the leading part. Laser- acoustic acceleration uses a laser in quasi-resonance with an acoustic wave to pump up the plasma oscillation to accelerate a beam. Self-driven schemes though experimentally simple seem problematic because single bunch densities must be large.

  7. 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.

  8. 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.

  9. Accelerating the culture change!

    PubMed

    Klunk, S W; Panetta, J; Wooten, J

    1996-11-01

    Exide Electronics, a major supplier of uninterruptible power system equipment, embarked on a journey of changing a culture to improve quality, enhance customer responsiveness, and reduce costs. This case study examines the evolution of change over a period of seven years, with particular emphasis on the most recent years, 1992 through 1995. The article focuses on the Raleigh plant operations and describes how each succeeding year built on the successes and fixed the shortcomings of the prior years to accelerate the culture change, including corrective action and continuous improvement processes, organizational structures, expectations, goals, achievements, and pitfalls. The real challenge to changing the culture was structuring a dynamic approach to accelerate change! The presentation also examines how the evolutionary process itself can be created and accelerated through ongoing communication, regular feedback of progress and goals, constant evaluation and direction of the process, and measuring and paying for performance. PMID:10162360

  10. 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.

  11. Cosmic Plasma Wakefield Acceleration

    NASA Astrophysics Data System (ADS)

    Chen, Pisin; Tajima, Toshiki; Takahashi, Yoshiyuki

    2002-10-01

    A cosmic acceleration mechanism is introduced which is based on the wakefields excited by the Alfven shocks in a relativistically flowing plasma. We show that there exists a threshold condition for transparency below which the accelerating particle is collision-free and suffers little energy loss in the plasma medium. The stochastic encounters of the random accelerating-decelerating phases results in a power-law energy spectrum: f([epsilon]) [is proportional to] 1/[epsilon]2. As an example, we discuss the possible production of super-GZK ultra high energy cosmic rays (UHECR) in the atmosphere of gamma ray bursts. The estimated event rate in our model agrees with that from UHECR observations. [copyright] 2002 American Institute of Physics

  12. 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.

  13. Studies of accelerated compact toruses

    SciTech Connect

    Hartman, C.W.; Eddleman, J.; Hammer, J.H.

    1983-01-04

    In an earlier publication we considered acceleration of plasma rings (Compact Torus). Several possible accelerator configurations were suggested and the possibility of focusing the accelerated rings was discussed. In this paper we consider one scheme, acceleration of a ring between coaxial electrodes by a B/sub theta/ field as in a coaxial rail-gun. If the electrodes are conical, a ring accelerated towards the apex of the cone undergoes self-similar compression (focusing) during acceleration. Because the allowable acceleration force, F/sub a/ = kappaU/sub m//R where (kappa < 1), increases as R/sup -2/, the accelerating distance for conical electrodes is considerably shortened over that required for coaxial electrodes. In either case, however, since the accelerating flux can expand as the ring moves, most of the accelerating field energy can be converted into kinetic energy of the ring leading to high efficiency.

  14. 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.

  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. Influence of Reverse Expansion of Laser Plasma on Ions Acceleration

    NASA Astrophysics Data System (ADS)

    Sysoev, Alexander A.; Gracheva, O. I.; Karpov, A. V.

    Effect of laser plasma reverse extension is described in this paper. Influence of the effect on ion acceleration in a laser ion source is researched. This effect leads to sedimentation of ions on metal target, which significantly impacts acceleration time of other ions. In this case, the ions also tend to travel major part of their path with constant velocity. This allows one to consider movement of the ions in plasma drift space, when optimizing time focusing ability of the TOF analyzer.

  17. 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.

  18. 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.

  19. 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.

  20. High intensity hadron accelerators

    SciTech Connect

    Teng, L.C.

    1989-05-01

    This rapporteur report consists mainly of two parts. Part I is an abridged review of the status of all High Intensity Hadron Accelerator projects in the world in semi-tabulated form for quick reference and comparison. Part II is a brief discussion of the salient features of the different technologies involved. The discussion is based mainly on my personal experiences and opinions, tempered, I hope, by the discussions I participated in in the various parallel sessions of the workshop. In addition, appended at the end is my evaluation and expression of the merits of high intensity hadron accelerators as research facilities for nuclear and particle physics.

  1. 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.

  2. 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

  3. 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

  4. Hot spots and dark current in advanced plasma wakefield accelerators

    NASA Astrophysics Data System (ADS)

    Manahan, G. G.; Deng, A.; Karger, O.; Xi, Y.; Knetsch, A.; Litos, M.; Wittig, G.; Heinemann, T.; Smith, J.; Sheng, Z. M.; Jaroszynski, D. A.; Andonian, G.; Bruhwiler, D. L.; Rosenzweig, J. B.; Hidding, B.

    2016-01-01

    Dark current can spoil witness bunch beam quality and acceleration efficiency in particle beam-driven plasma wakefield accelerators. In advanced schemes, hot spots generated by the drive beam or the wakefield can release electrons from higher ionization threshold levels in the plasma media. These electrons may be trapped inside the plasma wake and will then accumulate dark current, which is generally detrimental for a clear and unspoiled plasma acceleration process. Strategies for generating clean and robust, dark current free plasma wake cavities are devised and analyzed, and crucial aspects for experimental realization of such optimized scenarios are discussed.

  5. Efficient Optical Energy Harvesting in Self-Accelerating Beams

    NASA Astrophysics Data System (ADS)

    Bongiovanni, Domenico; Hu, Yi; Wetzel, Benjamin; Robles, Raul A.; Mendoza González, Gregorio; Marti-Panameño, Erwin A.; Chen, Zhigang; Morandotti, Roberto

    2015-08-01

    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.

  6. 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.

  7. 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.

  8. 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)

  9. Two-beam accelerator

    SciTech Connect

    Selph, F.B.

    1984-09-01

    In the two-beam accelerator (TBA) concept, an electron linear accelerator structure is established in which two beams propagate. One is an intense low energy beam that is made to undergo free electron lasing to produce microwaves. These microwaves are then coupled to another part of the structure where they act to produce a high longitudinal electric gradient that is used to accelerate a second relatively low intensity electron beam to very high energies. The TBA was originally suggested by Sessler as a possible means for economically achieving linear collider energies of 100 GeV and above. Although still in a conceptual stage, the TBA is an inherently plausible concept that combines the free electron laser (FEL) with several well-known technologies - high current induction linacs, microwave waveguides, and traveling-wave linac structures - in a novel and interesting way. Two characteristics of the TBA that make it a particularly suitable candidate for achieving high energies are its ability to operate at higher frequencies than typical present-day linacs (say 30 GHz as compared with 3 GHz), and to be an efficient means for delivering power to a hitherto unattainable high-gradient structure (say 250 MV/m) that the higher frequency makes possible. These high accelerating gradients will permit much shorter linac structures for a given energy.

  10. 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.

  11. 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.

  12. Calculating Beam Breakup in Superconducting Linear Accelerators

    SciTech Connect

    Geoffrey Krafft; Joseph Bisognano; Sharon Laubach

    1990-02-09

    As the intensity of a particle beam passing through a linear accelerator is raised, interactions between particles play an increasingly prominent role in determining the overall dynamics of the beam. These many body effects, known collectively as beam breakup, tend to degrade the quality of the transported beam, and hence they must be calculated to accurately predict the evolution of the beam as it traverses the accelerator. Several codes which compute various collective effects have been developed and used to simulate the dynamics of beams passing through superconducting accelerator structures. All the codes use the same basic algorithm: the beam is tracked through elements giving the focusing forces on the particles, and at the appropriate locations in the linac, localized forces are impressed on the particles which model the electromagnetic interactions. Here, a difficulty is that the usual ''Coulomb'' interaction between particles is changed by the electromagnetic environment of the accelerator. By such calculations it has been shown that recirculating linear accelerators such as the one being built at the Continuous Electron Beam Accelerator Facility (CEBAF) should remain stable against multipass beam breakup instability as long as the average current does not exceed about 20 mA, that the beam quality at CEBAF will be degraded when the single bunch charge approaches 10{sup 9} electrons, and that the beam quality of superconducting linacs that are optimized for high current transport begins to decrease at around 10{sup 10} electrons per bunch. The latter result is of interest to individuals who would use superconducting linacs as beam sources for free electron lasers or for superconducting colliders for high energy physics research.

  13. 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.

  14. 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.

  15. Plasma wakefield acceleration in self-ionized gas or plasmas.

    PubMed

    Deng, S; Barnes, C D; Clayton, C E; O'Connell, C; Decker, F J; Erdem, O; Fonseca, R A; Huang, C; Hogan, M J; Iverson, R; Johnson, D K; Joshi, C; Katsouleas, T; Krejcik, P; Lu, W; Marsh, K A; Mori, W B; Muggli, P; Tsung, F

    2003-10-01

    Tunnel ionizing neutral gas with the self-field of a charged particle beam is explored as a possible way of creating plasma sources for a plasma wakefield accelerator [Bruhwiler et al., Phys. Plasmas (to be published)]. The optimal gas density for maximizing the plasma wakefield without preionized plasma is studied using the PIC simulation code OSIRIS [R. Hemker et al., in Proceeding of the Fifth IEEE Particle Accelerator Conference (IEEE, 1999), pp. 3672-3674]. To obtain wakefields comparable to the optimal preionized case, the gas density needs to be seven times higher than the plasma density in a typical preionized case. A physical explanation is given. PMID:14683089

  16. 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

  17. 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.

  18. Accelerators and Neutron Capture Therapy

    NASA Astrophysics Data System (ADS)

    Burlon, A. A.; Kreiner, A. J.; Valda, A.

    2002-08-01

    Within the frame of Accelerator Based Boron Neutron Capture Therapy (AB-BNCT), the 7Li (p,n) 7Be reaction, relatively near its energy threshold is one of the most promising, due to its high yield and low neutron energy. In this work a thick LiF target irradiated with a proton beam was studied as a neutron source. The 1.88-2.0 MeV proton beam was produced by the tandem accelerator TANDAR at CNEA's facilities in Buenos Aires. A water-filled phantom, containing a boron sample was irradiated with the resulting neutron flux. The 10B(n,αγ)7Li boron neutron capture reaction produces a 0.478 MeV gamma ray in 94% of the cases. The neutron yield was measured through the detection of this gamma ray using a hyperpure germanium detector with an anti-Compton shield. In addition, the thermal neutron flux was evaluated at different depths inside the phantom using bare and Cd-covered gold foils. A maximum neutron thermal flux of 1.4×108 cm-2s-1mA-1 was obtained at 4.2 cm from the phantom surface. In order to optimize the design of the neutron production target and the beam shaping assembly extensive Monte Carlo Neutron and Photon (MCNP) simulations have been performed. Neutron fields from a thick LiF and a Li metal target (with both a D2O-graphite and a Al/AlF3-graphite moderator/reflector assembly) were evaluated along the centerline of a head and a whole body phantom. Simulations were carried out for 1.89, 2.0 and 2.3 MeV proton beams. The results show that it is more advantageous to irradiate the target with 2.3 MeV near-resonance protons, instead of very near threshold, because of the higher neutron yield at this energy. On the other hand, the Al/AlF3-graphite exhibits a more efficient performance than D2O in terms of tumor to maximum healthy tissue dose ratio. Treatment times of less than 15 min and tumor control probabilities larger than 98% are obtained for a 50 mA, 2.3 MeV proton beam. The alternative neutron-producing reaction 13C(d,n) is also briefly reviewed. A

  19. Stacked insulator induction accelerator gaps

    SciTech Connect

    Houck, T.I.; Westenskow, G.A.; Kim, J.S.; Eylon, S.; Henestroza, E.; Yu, S.S.; Vanecek, D.

    1997-05-01

    Stacked insulators, with alternating layers of insulating material and conducting film, have been shown to support high surface electrical field stresses. We have investigated the application of the stacked insulator technology to the design of induction accelerator modules for the Relativistic-Klystron Two-Beam Accelerator program. The rf properties of the accelerating gaps using stacked insulators, particularly the impedance at frequencies above the beam pipe cutoff frequency, are investigated. Low impedance is critical for Relativistic-Klystron Two-Beam Accelerator applications where a high current, bunched beam is trsnsported through many accelerating gaps. An induction accelerator module designs using a stacked insulator is presented.

  20. Superconducting Cavities for the APT Accelerator

    NASA Astrophysics Data System (ADS)

    Krawczyk, Frank L.; Gentzlinger, Robert C.; Montoya, Debbie I.; Rusnak, Brian; Shapiro, Alan H.

    1997-05-01

    One type of design for an Accelerator Production of Tritium (APT) facility being investigated at LANL consists mainly of a linear accelerator using superconducting rf cavities for the acceleration of a high current cw proton beam. For electron accelerators with particles moving at almost the speed of light (β=1.0), resonators with a rounded shape, consisting of elliptical, circular and straight sections, are well established. They are referred to as ``elliptical'' cavities. For the APT-design, this shape has been adapted for much slower proton beams from a β of less than 0.64 to slightly above 0.82. This is a new energy range, in which resonators of an elliptical type have never been used before. Simulations with the well-proven electromagnetic modeling tools MAFIA and SUPERFISH were performed. The structures have been optimized for their rf properties as well as for beam dynamics requirements. Single cell test cavities are under construction and will be tested in our structures laboratory. Their performance in terms of obtainable gradients, Q and multipacting behavior, as well as a comparison of the major rf parameters with the results of the cavity simulations, will be reported.

  1. 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.

  2. High-field dipoles for future accelerators

    SciTech Connect

    Wipf, S.L.

    1984-09-01

    This report presents the concept for building superconducting accelerator dipoles with record high fields. Economic considerations favor the highest possible current density in the windings. Further discussion indicates that there is an optimal range of pinning strength for a superconducting material and that it is not likely for multifilamentary conductors to ever equal the potential performance of tape conductors. A dipole design with a tape-wound, inner high-field winding is suggested. Methods are detailed to avoid degradation caused by flux jumps and to overcome problems with the dipole ends. Concerns for force support structure and field precision are also addressed. An R and D program leading to a prototype 11-T dipole is outlined. Past and future importance of superconductivity to high-energy physics is evident from a short historical survey. Successful dipoles in the 10- to 20-T range will allow interesting options for upgrading present largest accelerators.

  3. GPU accelerated particle visualization with Splotch

    NASA Astrophysics Data System (ADS)

    Rivi, M.; Gheller, C.; Dykes, T.; Krokos, M.; Dolag, K.

    2014-07-01

    Splotch is a rendering algorithm for exploration and visual discovery in particle-based datasets coming from astronomical observations or numerical simulations. The strengths of the approach are production of high quality imagery and support for very large-scale datasets through an effective mix of the OpenMP and MPI parallel programming paradigms. This article reports our experiences in re-designing Splotch for exploiting emerging HPC architectures nowadays increasingly populated with GPUs. A performance model is introduced to guide our re-factoring of Splotch. A number of parallelization issues are discussed, in particular relating to race conditions and workload balancing, towards achieving optimal performances. Our implementation was accomplished by using the CUDA programming paradigm. Our strategy is founded on novel schemes achieving optimized data organization and classification of particles. We deploy a reference cosmological simulation to present performance results on acceleration gains and scalability. We finally outline our vision for future work developments including possibilities for further optimizations and exploitation of hybrid systems and emerging accelerators.

  4. NEW ACCELERATION METHODS

    SciTech Connect

    Sessler, A.M.

    1984-07-01

    But a glance at the Livingston chart, Fig. 1, of accelerator particle energy as a function of time shows that the energy has steadily, exponentially, increased. Equally significant is the fact that this increase is the envelope of diverse technologies. If one is to stay on, or even near, the Livingston curve in future years then new acceleration techniques need to be developed. What are the new acceleration methods? In these two lectures I would like to sketch some of these new ideas. I am well aware that they will probably not result in high energy accelerators within this or the next decade, but conversely, it is likely that these ideas will form the basis for the accelerators of the next century. Anyway, the ideas are stimulating and suffice to show that accelerator physicists are not just 'engineers', but genuine scientists deserving to be welcomed into the company of high energy physicists. I believe that outsiders will find this field surprisingly fertile and, certainly fun. To put it more personally, I very much enjoy working in this field and lecturing on it. There are a number of review articles which should be consulted for references to the original literature. In addition there are three books on the subject. Given this material, I feel free to not completely reference the material in the remainder of this article; consultation of the review articles and books will be adequate as an introduction to the literature for references abound (hundreds are given). At last, by way of introduction, I should like to quote from the end of Ref. 2 for I think the remarks made there are most germane. Remember that the talk was addressed to accelerator physicists: 'Finally, it is often said, I think by physicists who are not well-informed, that accelerator builders have used up their capital and now are bereft of ideas, and as a result, high energy physics will eventually--rather soon, in fact--come to a halt. After all, one can't build too many machines greater than

  5. 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.

  6. 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.

  7. Review of ion accelerators

    SciTech Connect

    Alonso, J.

    1990-06-01

    The field of ion acceleration to higher energies has grown rapidly in the last years. Many new facilities as well as substantial upgrades of existing facilities have extended the mass and energy range of available beams. Perhaps more significant for the long-term development of the field has been the expansion in the applications of these beams, and the building of facilities dedicated to areas outside of nuclear physics. This review will cover many of these new developments. Emphasis will be placed on accelerators with final energies above 50 MeV/amu. Facilities such as superconducting cyclotrons and storage rings are adequately covered in other review papers, and so will not be covered here.

  8. 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.

  9. 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.

  10. 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. (Gr

    1992-01-01

    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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Accelerator research studies

    SciTech Connect

    Not Available

    1993-01-01

    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 second 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,'' (P.I., M. Reiser); TASK B, Study of Collective Ion Acceleration by Intense Electron Beams and Pseudospark Produced High Brightness Electron Beams,'' (Co-P.I.'s, W.W. Destler, M. Reiser, M.J. Rhee, and C.D. Striffler); TASK C, Study of a Gyroklystron High-Power Microwave Source for Linear Colliders,'' (Co-P.I.'s, V.L. Granatstein, W. Lawson, M. Reiser, and C.D. Striffler). In this report we document the progress that has been made during the past year for each of the three tasks.

  16. 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

  17. ATLAS accelerator laboratory report

    SciTech Connect

    Den Hartog, P.

    1986-01-01

    The operation of the ATLAS Accelerator is reported. Modifications are reported, including the installation of conductive tires for the Pelletron chain pulleys, installation of a new high frequency sweeper system at the entrance to the linac, and improvements to the rf drive ports of eight resonators to correct failures in the thermally conductive ceramic insulators. Progress is reported on the positive-ion injector upgrade for ATLAS. Also reported are building modifications and possible new uses for the tandem injector. (LEW)

  18. 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.

  19. Accelerator simulation using computers

    SciTech Connect

    Lee, M.; Zambre, Y.; Corbett, W.

    1992-01-01

    Every accelerator or storage ring system consists of a charged particle beam propagating through a beam line. Although a number of computer programs exits that simulate the propagation of a beam in a given beam line, only a few provide the capabilities for designing, commissioning and operating the beam line. This paper shows how a multi-track'' simulation and analysis code can be used for these applications.

  20. Accelerator simulation using computers

    SciTech Connect

    Lee, M.; Zambre, Y.; Corbett, W.

    1992-01-01

    Every accelerator or storage ring system consists of a charged particle beam propagating through a beam line. Although a number of computer programs exits that simulate the propagation of a beam in a given beam line, only a few provide the capabilities for designing, commissioning and operating the beam line. This paper shows how a ``multi-track`` simulation and analysis code can be used for these applications.

  1. 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.

  2. 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. PMID:17799689

  3. 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.

  4. Applications of electrostatic accelerators

    SciTech Connect

    Norton, G.A.; Klody, G.M.

    1995-10-01

    Most applications of electrostatic accelerators fit into two main groups, materials analysis and materials modification. Materials analysis includes routine use of Rutherford Backscattering for quality control applications in the semiconductor field. Particle induced x-ray emission (PDCE) is used in fields from art history through environmental sciences. X-ray imaging using 5 MeV DC electron beams and fast pulsed neutron analysis (PFNA) for plastic explosive and drug detection provide promise in the area of security. Accelerator based mass spectrometry (AMS) is having a profound effect in a wide variety of fields which rely on counting extremely rare isotopes in small samples. Materials modification provides a very significant economic impact in the field of semiconductors. Virtually all semiconductor devices now rely on ion implantation with ion beam energies ranging from a few kilovolts to several MeV. With some mention of electron beams, this talk will concentrate primarily on the applications of MeV ion beams from electrostatic accelerators.

  5. 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.

  6. Tandem betatron accelerator

    NASA Astrophysics Data System (ADS)

    Keinigs, Rhon K.

    1991-04-01

    1407_50The tandem betatron is a compact, high-current induction accelerator that has the capability to accelerate electrons to an energy of order one gigavolt. Based upon the operating principle of a conventional betatron, the tandem betatron employs two synchronized induction cores operating 180 degrees out of phase. Embedded within the cores are the vacuum chambers, and these are connected by linear transport sections to allow for moving the beam back and forth between the two betatrons. The 180 degree phase shift between the core fluxes permits the circumvention of the flux swing constraint that limits the maximum energy gain of a conventional betatron. By transporting the beam between the synchronized cores, an electron can access more than one acceleration cycle, and thereby continue to gain energy. This added degree of freedom also permits a significant decrease in the size of the magnet system. Biasing coils provide independent control of the confining magnetic field. Provided that efficient beam switching can be performed, it appears feasible that a one gigavolt electron beam can be generated and confined. At this energy, a high current electron beam circulating in a one meter radius orbit could provide a very intense source of short wavelength ((lambda) < 10 nm) synchrotron radiation. This has direct application to the emerging field of x-ray lithography. At more modest energies (10 MeV-30 MeV) a compact tandem betatron could be employed in the fields of medical radiation therapy, industrial radiography, and materials processing.

  7. 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)

  8. 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.

  9. 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.

  10. 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.

  11. Summary report: Working Group 2 on {open_quotes}Plasma Based Acceleration Concepts{close_quotes}

    SciTech Connect

    Leemans, W.P.; Esarey, E.; Esarey, E.

    1999-07-01

    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. {copyright} {ital 1999 American Institute of Physics.}

  12. Progress on laser plasma accelerators

    SciTech Connect

    Chen, P.

    1986-04-01

    Several laser plasma accelerator schemes are reviewed, with emphasis on the Plasma Beat Wave Accelerator (PBWA). Theory indicates that a very high acceleration gradient, of order 1 GeV/m, can exist in the plasma wave driven by the beating lasers. Experimental results obtained on the PBWA experiment at UCLA confirms this. Parameters related to the PBWA as an accelerator system are derived, among them issues concerning the efficiency and the laser power and energy requirements are discussed.

  13. 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.

  14. KEKB accelerator control system

    NASA Astrophysics Data System (ADS)

    Akasaka, Nobumasa; Akiyama, Atsuyoshi; Araki, Sakae; Furukawa, Kazuro; Katoh, Tadahiko; Kawamoto, Takashi; Komada, Ichitaka; Kudo, Kikuo; Naito, Takashi; Nakamura, Tatsuro; Odagiri, Jun-ichi; Ohnishi, Yukiyoshi; Sato, Masayuki; Suetake, Masaaki; Takeda, Shigeru; Takeuchi, Yasunori; Yamamoto, Noboru; Yoshioka, Masakazu; Kikutani, Eji

    2003-02-01

    The KEKB accelerator control system including a control computer system, a timing distribution system, and a safety control system are described. KEKB accelerators were installed in the same tunnel where the TRISTAN accelerator was. There were some constraints due to the reused equipment. The control system is based on Experimental Physics and Industrial Control System (EPICS). In order to reduce the cost and labor for constructing the KEKB control system, as many CAMAC modules as possible are used again. The guiding principles of the KEKB control computer system are as follows: use EPICS as the controls environment, provide a two-language system for developing application programs, use VMEbus as frontend computers as a consequence of EPICS, use standard buses, such as CAMAC, GPIB, VXIbus, ARCNET, RS-232 as field buses and use ergonomic equipment for operators and scientists. On the software side, interpretive Python and SAD languages are used for coding application programs. The purpose of the radiation safety system is to protect personnel from radiation hazards. It consists of an access control system and a beam interlock system. The access control system protects people from strong radiation inside the accelerator tunnel due to an intense beam, by controlling access to the beamline area. On the other hand, the beam interlock system prevents people from radiation exposure by interlocking the beam operation. For the convenience of accelerator operation and access control, the region covered by the safety system is divided into three major access control areas: the KEKB area, the PF-AR area, and the beam-transport (BT) area. The KEKB control system required a new timing system to match a low longitudinal acceptance due to a low-alpha machine. This timing system is based on a frequency divider/multiply technique and a digital delay technique. The RF frequency of the KEKB rings and that of the injector Linac are locked with a common divisor frequency. The common

  15. Direct Particle Acceleration in Astroplasmas

    NASA Astrophysics Data System (ADS)

    Hoshino, M.

    2002-10-01

    The high energy particle acceleration mechanisms are discussed by focusing on the direct acceleration in the astrophysical context. We specifically argue that the relativistic magnetic reconnection and the shock surfing/surfatron processes can efficiently accelerate charged particles to a relativistic energy, and that those mechanisms may produce a non-thermal, power-law energy spectrum. [copyright] 2002 American Institute of Physics

  16. Laser Wakefield acceleration with high relativistic pumps

    NASA Astrophysics Data System (ADS)

    Katsouleas, T.; Mori, W. B.; Darrow, C. B.

    1989-10-01

    Preliminary scaling laws are found for the laser wakefield accelerator in the very non-linear regime where the normalized laser pump strengh Voscc=eE0/mω0c≳1. Two important non-linear effects are an increase in the wake phase velocity (and hence the particle dephasing length) and an increase in the laser pulse length for optimal wake excitation. Application of the results to the proposed Livermore High-Brightness Lasers (HBL) is discussed here and in the accompanying paper by C. B. Darrow, et al. A preliminary 1-D PIC simulation is presented.

  17. 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.

  18. Dispositional Optimism

    PubMed Central

    Carver, Charles S.; Scheier, Michael F.

    2014-01-01

    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. PMID:24630971

  19. 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.

  20. 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.

  1. 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.

  2. 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…

  3. 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.

  4. Recent Advances in Plasma Acceleration

    SciTech Connect

    Hogan, Mark

    2007-03-19

    The costs and the time scales of colliders intended to reach the energy frontier are such that it is important to explore new methods of accelerating particles to high energies. Plasma-based accelerators are particularly attractive because they are capable of producing accelerating fields that are orders of magnitude larger than those used in conventional colliders. In these accelerators a drive beam, either laser or particle, produces a plasma wave (wakefield) that accelerates charged particles. The ultimate utility of plasma accelerators will depend on sustaining ultra-high accelerating fields over a substantial length to achieve a significant energy gain. More than 42 GeV energy gain was achieved in an 85 cm long plasma wakefield accelerator driven by a 42 GeV electron drive beam in the Final Focus Test Beam (FFTB) Facility at SLAC. Most of the beam electrons lose energy to the plasma wave, but some electrons in the back of the same beam pulse are accelerated with a field of {approx}52 GV/m. This effectively doubles their energy, producing the energy gain of the 3 km long SLAC accelerator in less than a meter for a small fraction of the electrons in the injected bunch. Prospects for a drive-witness bunch configuration and high-gradient positron acceleration experiments planned for the SABER facility will be discussed.

  5. 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.

  6. 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.

  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. 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.

  9. 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.

  10. Adaptation and generalization in acceleration dependent force fields

    PubMed Central

    Hwang, Eun Jung; Smith, Maurice A.; Shadmehr, Reza

    2005-01-01

    Any passive rigid inertial object that we hold in our hand, e.g., a tennis racquet, imposes a field of forces on the arm that depends on limb position, velocity, and acceleration. A fundamental characteristic of this field is that the forces due to acceleration and velocity are linearly separable in the intrinsic coordinates of the limb. In order to learn such dynamics with a collection of basis elements, a control system would generalize correctly and therefore perform optimally if the basis elements that were sensitive to limb velocity were not sensitive to acceleration, and vice versa. However, in the mammalian nervous system proprioceptive sensors like muscle spindles encode a nonlinear combination of all components of limb state, with sensitivity to velocity dominating sensitivity to acceleration. Therefore, limb state in the space of proprioception is not linearly separable despite the fact that this separation is a desirable property of control systems that form models of inertial objects. In building internal models of limb dynamics, does the brain use a representation that is optimal for control of inertial objects, or a representation that is closely tied to how peripheral sensors measure limb state? Here we show that in humans, patterns of generalization of reaching movements in acceleration dependent fields are strongly inconsistent with basis elements that are optimized for control of inertial objects. Unlike a robot controller that models the dynamics of the natural world and represents velocity and acceleration independently, internal models of dynamics that people learn appear to be rooted in the properties of proprioception, nonlinearly responding to the pattern of muscle activation and representing velocity more strongly than acceleration. PMID:16292640

  11. 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.

  12. Colliding Laser Pulses for Laser-Plasma Accelerator Injection Control

    SciTech Connect

    Plateau, G. R.; Geddes, C. G. R.; Matlis, N. H.; Mittelberger, D. E.; Nakamura, K.; Schroeder, C. B.; Esarey, E.; Leemans, W. P.; Cormier-Michel, E.

    2010-11-04

    Decoupling injection from acceleration is a key challenge to achieve compact, reliable, tunable laser-plasma accelerators (LPA). In colliding pulse injection the beat between multiple laser pulses can be used to control energy, energy spread, and emittance of the electron beam by injecting electrons in momentum and phase into the accelerating phase of the wake trailing the driver laser pulse. At LBNL, using automated control of spatiotemporal overlap of laser pulses, two-pulse experiments showed stable operation and reproducibility over hours of operation. Arrival time of the colliding beam was scanned, and the measured timing window and density of optimal operation agree with simulations. The accelerator length was mapped by scanning the collision point.

  13. Colliding Laser Pulses for Laser-Plasma Accelerator Injection Control

    NASA Astrophysics Data System (ADS)

    Plateau, G. R.; Geddes, C. G. R.; Matlis, N. H.; Cormier-Michel, E.; Mittelberger, D. E.; Nakamura, K.; Schroeder, C. B.; Esarey, E.; Leemans, W. P.

    2010-11-01

    Decoupling injection from acceleration is a key challenge to achieve compact, reliable, tunable laser-plasma accelerators (LPA) [1, 2]. In colliding pulse injection the beat between multiple laser pulses can be used to control energy, energy spread, and emittance of the electron beam by injecting electrons in momentum and phase into the accelerating phase of the wake trailing the driver laser pulse [3, 4, 5, 6, 7]. At LBNL, using automated control of spatiotemporal overlap of laser pulses, two-pulse experiments showed stable operation and reproducibility over hours of operation. Arrival time of the colliding beam was scanned, and the measured timing window and density of optimal operation agree with simulations [8]. The accelerator length was mapped by scanning the collision point.

  14. 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. __________________________________________________

  15. 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.

  16. 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)

  17. Accelerations in Flight

    NASA Technical Reports Server (NTRS)

    Norton, F H; Allen, E T

    1921-01-01

    This report deals with the accelerations obtained in flight on various airplanes at Langley Field for the purpose of obtaining the magnitude of the load factors in flight and to procure information on the behavior of an airplane in various maneuvers. The instrument used in these tests was a recording accelerometer of a new type designed by the technical staff of the National Advisory Committee for Aeronautics. The instrument consists of a flat steel spring supported rigidly at one end so that the free end may be deflected by its own weight from its neutral position by any acceleration acting at right angles to the plane of the spring. This deflection is measured by a very light tilting mirror caused to rotate by the deflection of the spring, which reflected the beam of light onto a moving film. The motion of the spring is damped by a thin aluminum vane which rotates with the spring between the poles of an electric magnet. Records were taken on landings and takeoffs, in loops, spins, spirals, and rolls.

  18. Optical Bragg accelerators.

    PubMed

    Mizrahi, Amit; Schächter, Levi

    2004-01-01

    It is demonstrated that a Bragg waveguide consisting of a series of dielectric layers may form an excellent optical acceleration structure. Confinement of the accelerating fields is achieved, for both planar and cylindrical configurations by adjusting the first dielectric layer width. A typical structure made of silica and zirconia may support gradients of the order of 1 GV/m with an interaction impedance of a few hundreds of ohms and with an energy velocity of less than 0.5c. An interaction impedance of about 1000 Omega may be obtained by replacing the Zirconia with a (fictitious) material of epsilon=25. Special attention is paid to the wake field developing in such a structure. In the case of a relatively small number of layers, it is shown that the total electromagnetic power emitted is proportional to the square of the number of electrons in the macrobunch and inversely proportional to the number of microbunches; this power is also inversely proportional to the square of the internal radius of the structure for a cylindrical structure, and to the width of the vacuum core in a planar structure. Quantitative results are given for a higher number of dielectric layers, showing that in comparison to a structure bounded by metallic walls, the emitted power is significantly smaller due to propagation bands allowing electromagnetic energy to escape. PMID:15324182

  19. 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.

  20. Broadband accelerator control network

    SciTech Connect

    Skelly, J.; Clifford, T.; Frankel, R.

    1983-01-01

    A broadband data communications network has been implemented at BNL for control of the Alternating Gradient Synchrotron (AG) proton accelerator, using commercial CATV hardware, dual coaxial cables as the communications medium, and spanning 2.0 km. A 4 MHz bandwidth Digital Control channel using CSMA-CA protocol is provided for digital data transmission, with 8 access nodes available over the length of the RELWAY. Each node consists of an rf modem and a microprocessor-based store-and-forward message handler which interfaces the RELWAY to a branch line implemented in GPIB. A gateway to the RELWAY control channel for the (preexisting) AGS Computerized Accelerator Operating system has been constructed using an LSI-11/23 microprocessor as a device in a GPIB branch line. A multilayer communications protocol has been defined for the Digital Control Channel, based on the ISO Open Systems Interconnect layered model, and a RELWAY Device Language defined as the required universal language for device control on this channel.