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Biomedical subjects

C E Clayton

Publications and source records attributed to C E Clayton.

At least 19 recordsLinked to original sources

Positron production by x rays emitted by betatron motion in a plasma wiggler.

Positrons in the energy range of 3-30 MeV, produced by x rays emitted by betatron motion in a plasma wiggler of 28.5 GeV electrons from the SLAC accelerator, have been measured. The extremely high-strength plasma wiggler is an ion column induced by the electron beam as it propagates through and ionizes dense lithium vapor. X rays in the range of 1-50 MeV in a forward cone angle of 0.1 mrad collide with a 1.7 mm thick tungsten target to produce electron-positron pairs. The positron spectra are found to be strongly influenced by the plasma density and length as well as the electron bunch length. By characterizing the beam propagation in the ion column these influences are quantified and result in excellent agreement between the measured and calculated positron spectra.

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Hose instability and wake generation by an intense electron beam in a self-ionized gas.

The propagation of an intense relativistic electron beam through a gas that is self-ionized by the beam's space charge and wakefields is examined analytically and with 3D particle-in-cell simulations. Instability arises from the coupling between a beam and the offset plasma channel it creates when it is perturbed. The traditional electron hose instability in a preformed plasma is replaced with this slower growth instability depending on the radius of the ionization channel compared to the electron blowout radius. A new regime for hose stable plasma wakefield acceleration is suggested.

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Multi-GeV energy gain in a plasma-wakefield accelerator.

A plasma-wakefield accelerator has accelerated particles by over 2.7 GeV in a 10 cm long plasma module. A 28.5 GeV electron beam with 1.8 x 10(10) electrons is compressed to 20 microm longitudinally and focused to a transverse spot size of 10 microm at the entrance of a 10 cm long column of lithium vapor with density 2.8 x 10(17) atoms/cm3. The electron bunch fully ionizes the lithium vapor to create a plasma and then expels the plasma electrons. These electrons return one-half plasma period later driving a large amplitude plasma wake that in turn accelerates particles in the back of the bunch by more than 2.7 GeV.

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High energy gain of trapped electrons in a tapered, diffraction-dominated inverse-free-electron laser.

Energy gain of trapped electrons in excess of 20 MeV has been demonstrated in an inverse-free-electron-laser (IFEL) accelerator experiment. A 14.5 MeV electron beam is copropagated with a 400 GW CO2 laser beam in a 50 cm long undulator strongly tapered in period and field amplitude. The Rayleigh range of the laser, approximately 1.8 cm, is much shorter than the undulator length yielding a diffraction-dominated interaction. Experimental results on the dependence of the acceleration on injection energy, laser focus position, and laser power are discussed. Simulations, in good agreement with the experimental data, show that most of the energy gain occurs in the first half of the undulator at a gradient of 70 MeV/m and that the structure in the measured energy spectrum arises because of higher harmonic IFEL interaction in the second half of the undulator.

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Enhanced acceleration of injected electrons in a laser-beat-wave-induced plasma channel.

Enhanced energy gain of externally injected electrons by a approximately 3 cm long, high-gradient relativistic plasma wave (RPW) is demonstrated. Using a CO2 laser beat wave of duration longer than the ion motion time across the laser spot size, a laser self-guiding process is initiated in a plasma channel. Guiding compensates for ionization-induced defocusing (IID) creating a longer plasma, which extends the interaction length between electrons and the RPW. In contrast to a maximum energy gain of 10 MeV when IID is dominant, the electrons gain up to 38 MeV energy in a laser-beat-wave-induced plasma channel.

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Nonresonant beat-wave excitation of relativistic plasma waves with constant phase velocity for charged-particle acceleration.

The nonresonant beat-wave excitation of relativistic plasma waves is studied in two-dimensional simulations and experiments. It is shown through simulations that, as opposed to the resonant case, the accelerating electric fields associated with the nonresonant plasmons are always in phase with the beat-pattern of the laser pulse. The excitation of such nonresonant relativistic plasma waves is shown to be possible for plasma densities as high as 14 times the resonant density. The density fluctuations and the fields associated with these waves have significant magnitudes, facts confirmed experimentally using collinear Thomson scattering and electron injection, respectively. The applicability of these results towards eventual phase-locked acceleration of prebunched and externally injected electrons is discussed.

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Plasma wakefield acceleration in self-ionized gas or plasmas.

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.

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Plasma-wakefield acceleration of an intense positron beam.

Plasma wakefields are both excited and probed by propagating an intense 28.5 GeV positron beam through a 1.4 m long lithium plasma. The main body of the beam loses energy in exciting this wakefield while positrons in the back of the same beam can be accelerated by the same wakefield as it changes sign. The scaling of energy loss with plasma density as well as the energy gain seen at the highest plasma density is in excellent agreement with simulations.

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Ultrarelativistic-positron-beam transport through meter-scale plasmas.

We report on the first study of the dynamic transverse forces imparted to an ultrarelativistic positron beam by a long plasma in the underdense regime. Focusing of the 28.5 GeV beam is observed from time-resolved beam profiles after the 1.4 m plasma. The strength of the imparted force varies along the approximately 12 ps full length of the bunch as well as with plasma density. Computer simulations substantiate the longitudinal aberration seen in the data and reveal mechanisms for emittance degradation.

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Transverse envelope dynamics of a 28.5-GeV electron beam in a long plasma.

The transverse dynamics of a 28.5-GeV electron beam propagating in a 1.4 m long, (0-2)x10(14) cm(-3) plasma are studied experimentally in the underdense or blowout regime. The transverse component of the wake field excited by the short electron bunch focuses the bunch, which experiences multiple betatron oscillations as the plasma density is increased. The spot-size variations are observed using optical transition radiation and Cherenkov radiation. In this regime, the behavior of the spot size as a function of the plasma density is well described by a simple beam-envelope model. Dynamic changes of the beam envelope are observed by time resolving the Cherenkov light.

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X-ray emission from betatron motion in a plasma wiggler.

The successful utilization of an ion channel in a plasma to wiggle a 28.5-GeV electron beam to obtain broadband x-ray radiation is reported. The ion channel is induced by the electron bunch as it propagates through an underdense 1.4-meter-long lithium plasma. The quadratic density dependence of the spontaneously emitted betatron x-ray radiation and the divergence angle of approximately (1-3)x10(-4) radian of the forward-emitted x-rays as a consequence of betatron motion in the ion channel are in good agreement with theory. The absolute photon yield and the peak spectral brightness at 14.2-keV photon energy are estimated.

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Characterisation of the growth and differentiation in vivo and in vitro-of bloodstream-form Trypanosoma brucei strain TREU 927.

Trypanosoma brucei TREU 927/4 has been chosen as the reference strain targeted for complete sequencing of the genome of the African trypanosome. This line is pleomorphic in mammalian hosts and is fly transmissible; however it is relatively unstable with respect to variable surface glycoprotein (VSG) expression. Therefore, we subjected TREU 927/4 to 27 rapid syringe passages through mice, and derived a cloned line which expressed Glasgow University Trypanozoon antigen type (GUTat) 10.1 with relative stability. This line also retained pleomorphism in the bloodstream, being able to generate homogeneous populations of stumpy forms in mice. Furthermore, these parasites remain able to transform to procyclic forms synchronously in vitro and can complete their life cycle in tsetse flies. The passaged cell line was also adapted to in vitro bloodstream-form culture and transfected with a construct encoding the tetracycline repressor (TETR) protein. The resulting TETR subline no longer expressed the GUTat 10.1 VSG but remained able to generate uniform populations of stumpy form cells in mice immunocompromised with cyclophosphamide. They could also differentiate to procyclic forms synchronously in vitro. The generated lines and analyses of their growth and differentiation will provide a basic resource for the analysis and interpretation of gene function in the T. brucei genome reference strain.

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Inhaled carbon monoxide and hyperoxic lung injury in rats.

Because carbon monoxide (CO) has been proposed to have anti-inflammatory properties, we sought protective effects of CO in pulmonary O(2) toxicity, which leads rapidly to lung inflammation and respiratory failure. Based on published studies, we hypothesized that CO protects the lung against O(2) by selectively increasing expression of antioxidant enzymes, thereby decreasing oxidative injury and inflammation. Rats exposed to O(2) with or without CO [50-500 parts/million (ppm)] for 60 h were compared for lung wet-to-dry weight ratio (W/D), pleural fluid volume, myeloperoxidase (MPO) activity, histology, expression of heme oxygenase-1 (HO-1), and manganese superoxide dismutase (Mn SOD) proteins. The brains were evaluated for histological evidence of damage from CO. In O(2)-exposed animals, lung W/D increased from 4.8 in normal rats to 6.3; however, only CO at 200 and 500 ppm decreased W/D significantly (to 5.9) during O(2) exposure. Large volumes of pleural fluid accumulated in all rats, with no significant CO treatment effect. Lung MPO values increased after O(2) and were not attenuated by CO treatment. CO did not enhance lung expression of oxidant-responsive proteins Mn SOD and HO-1. Animals receiving O(2) and CO at 200 or 500 ppm showed significant apoptotic cell death in the cortex and hippocampus by immunochemical staining. Thus significant protection by CO against O(2)-induced lung injury could not be confirmed in rats, even at CO concentrations associated with apoptosis in the brain.

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Genetic manipulation of kinetoplastida.

During the 1980s, many kinetoplastid genes were cloned and their function inferred from homology with genes from other organisms, location of the corresponding proteins or expression in heterologous systems. Up until 1990, before the availability of DNA transfection methodology, we could not analyze the function of kinetoplastid genes within the organisms themselves. Since then, it has become possible to create and complement mutants, to overexpress foreign proteins in the parasites, to knock out genes and even to switch off essential functions. However, these methods are not equally applicable in all parasites. Here, Christine Clayton highlights the differences and similarities between the most commonly used model organisms, and assesses the relative advantages of different approaches and parasites for different types of investigation.

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Metabolic compartmentation in African trypanosomes.

Differences between host and parasite energy metabolism are eagerly sought after as potential targets for antiparasite chemotherapy. In Kinetoplastia, the first seven steps of glycolysis are compartmented inside glycosomes, organelles that are related to the peroxisomes of higher eukaryotes. This arrangement is unique in the living world. In this review, Christine Clayton and Paul Michels discuss the implications of this unusual metabolic compartmentation for the regulation of trypanosome energy metabolism, and describe how an adequate supply of energy is maintained in different species and life cycle stages.

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The 3'-untranslated regions from the Trypanosoma brucei phosphoglycerate kinase-encoding genes mediate developmental regulation.

The phosphoglycerate kinase (PGK)-encoding genes of Trypanosoma brucei are transcribed in a polycistronic fashion, but the mRNAs encoding the three PGK isozymes show differing developmental regulation. We demonstrate here that the 3'-untranslated regions of the major cytoplasmic and glycosomal PGK isozymes are capable of conferring the anticipated types of regulation on a transfected reporter gene.

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