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Biomedical subjects

K A Marsh

Publications and source records attributed to K A Marsh.

At least 19 recordsLinked to original sources
PubMed2006

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.

Journal Article↗
PubMed2005

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.

Journal Article↗
PubMed2004

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.

Journal Article↗
PubMed2004

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.

Journal Article↗
PubMed2003

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.

Journal Article↗
PubMed2003

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.

Journal Article↗
PubMed2003

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.

Journal Article↗
PubMed2002

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.

Journal Article↗
PubMed2002

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.

Journal Article↗
PubMed2001

Measurements of radiation near an atomic spectral line from the interaction of a 30 GeV electron beam and a long plasma.

Emissions produced or initiated by a 30-GeV electron beam propagating through a approximately 1-m long heat pipe oven containing neutral and partially ionized vapor have been measured near atomic spectral lines in a beam-plasma wakefield experiment. The Cerenkov spatial profile has been studied as a function of oven temperature and pressure, observation wavelength, and ionizing laser intensity and delay. The Cerenkov peak angle is affected by the creation of plasma, and estimates of neutral and plasma density have been extracted. Increases in visible background radiation, consistent with increased plasma recombination emissions due to dissipation of wakefields, were simultaneously measured.

Journal Article↗
PubMed1997

Receptor-stimulated phospholipase C activity in human umbilical artery cultured endothelial cells grown in a low oxygen environment.

Endothelial cells of the human umbilical blood vessels are widely cultured in an oxygen tension (21%) far above that in which they exist in vivo (3%). This study investigates the effect of the long term culture (ca. 1 month) of human umbilical artery endothelial cells in a reduced oxygen environment (3%: HUAEC3) in comparison to cells grown in a 'normoxic' environment (21%: HUAEC21). Despite reports of altered metabolic pathways and reduced membrane integrity in other cell types, the characteristics of HUAEC3 were found to be similar to those of HUAEC21 with respect to morphology, immunocytochemical profile and in vitro growth rates. Cellular glutathione was maintained in these cells although ATP levels in HUAEC3 were found to be significantly lower than those observed in HUAEC21. The phosphoinositide responses of the HUAEC3 to a variety of agonists were also found to be of similar magnitude to those observed in HUAEC21. In addition, the pharmacological characteristics of the phospholipase C-linked histamine H1 and P2y2 (P2U) receptors were not changed by culture of cells in a low oxygen environment.

Adenosine Triphosphate↗
PubMed1996

Desensitization of muscarinic receptor-coupled inositol phospholipid hydrolysis in human detrusor cultured smooth cells.

PURPOSE: The aim of this study was to investigate the desensitization characteristics of muscarinic M3 receptors in primary cultures of human detrusor smooth muscle cells. MATERIALS AND METHODS: Cell cultures were prepared from cold cup pinch biopsies of the human detrusor muscles by explant culture methods. Accumulation of (3)H-inositol phosphates was measured on confluent monolayers as described previously in detail. Desensitization was achieved by preincubating the cells with carbachol or histamine for 5 to 60 minutes. RESULTS: Carbachol induced a concentration-dependent increase in phosphoinositide turnover in naive cells, the response being rapid and evident after only a 30-second exposure to the agonist. Preincubation of the cells with carbachol produced a concentration-dependent decrease in the inositol phosphate response to a second challenge with carbachol. Preexposure to carbachol for only 5 minutes prior to a rechallenge reduced the mean size of response of the second stimulation to 49% of that observed in naive cells. Preexposure of the cells to histamine did not alter the response of the cells to a subsequent challenge with carbachol and vice versa. CONCLUSIONS: The muscarinic receptors retained by human detrusor smooth muscle cells in culture are susceptible to a desensitization of the carbachol-induced increase phosphoinositide turnover observed in these cells. This desensitization is rapid, and the results indicate that it is homologous and does not occur via a postreceptor mechanism but at the level of the receptor itself.

Carbachol↗
PubMed1995

Expression of muscarinic M3-receptors coupled to inositol phospholipid hydrolysis in human detrusor cultured smooth muscle cells.

PURPOSE: To investigate the effect of muscarinic receptor agonists and antagonists on the accumulation of inositol phosphates in cultures of human detrusor smooth muscle cells. MATERIALS AND METHODS: Primary explant culture was used to derive smooth muscle cell lines from small bladder biopsies. The cells were loaded with [3H]-myoinositol, stimulated with muscarinic agonists, and the accumulation of [3H]-inositol phosphates was measured by liquid scintillation counting. RESULTS: Carbachol (EC50 8.3 microM.), methacholine (EC50 7.5 microM.), oxotremorine (EC50 2.5 microM.) and pilocarpine (EC50 8.3 microM.) produced concentration-dependent rises in the accumulation of total [3H]-inositol phosphates. M1 (pirenzepine), M2 (methoctramine) and M3 (4-DAMP and pf-HHSiD) muscarinic receptor antagonists significantly antagonized the response induced by a submaximal concentration of carbachol (100 microM.). The apparent pA2 values were atropine (9.4), 4-DAMP (9.2), pfHHSid (7.4), pirenzepine (6.9) and methoctramine (6.3). CONCLUSIONS: These results indicate that human detrusor smooth muscle cells in culture express M3 muscarinic receptors which are linked to phosphoinositide hydrolysis.

Carbachol↗
PubMed1994

Des-Arg9-bradykinin-induced increases in intracellular calcium ion concentration in single bovine tracheal smooth muscle cells.

1. Dynamic video imaging was used to measure the des-Arg9-bradykinin-induced changes in the intracellular free calcium ion concentration ([Ca2+]i) of single bovine tracheal smooth muscle (BTSM) cells. 2. In the presence of extracellular calcium ions, des-Arg9-bradykinin (1 nM-10 microM) produced a concentration-dependent increase in the [Ca2+]i over basal levels yielding an EC50 value of 316 nM. The percentage of cells responding to each concentration of des-Arg9-bradykinin also increased in a concentration-dependent manner (from 9% to 100%). 3. The bradykinin B2 receptor antagonist, D-Arg[Hyp3,Thi5,8,D-Phe7]-bradykinin (10 microM), was without effect on the calcium response of the cells when added 2 min prior to des-Arg9-bradykinin (100 nM). However, the B1 receptor antagonist, des-Arg9Leu8-bradykinin (10 microM), completely abolished the des-Arg9-bradykinin-induced response. 4. Under calcium-free conditions, des-Arg9-bradykinin induced an increase in [Ca2+]i at concentrations of 1 microM and 10 microM. The response to 10 microM des-Arg9-bradykinin was reduced by preincubation of either D-Arg[Hyp3, Thi5,8,D-Phe7]-bradykinin (10 microM) or des-Arg9Leu8-bradykinin (10 microM). 5. We conclude that bradykinin B1 receptors are expressed by cultured BTSM cells and mediate the des-Arg9-bradykinin-induced influx of calcium ions at low agonist concentrations (< 1 microM). At higher concentrations, des-Arg9-bradykinin (1 microM and 10 microM) can stimulate both B1 and B2 receptors to effect intracellular calcium release under calcium-free conditions.

Animals↗
PubMed1993

Isolation and characterization of multiple cell types from a single human colonic carcinoma: tumourigenicity of these cell types in a xenograft system.

The HCA-7 cell line was established from a moderately well differentiated mucinous adenocarcinoma of the colon, which showed histological heterogeneity. This was reflected in the morphological heterogeneity in early passages of the HCA-7 cell line but diminished as the cells were passaged in vitro. Nine subpopulations were isolated from early passage cultures of the HCA-7 line and maintained as cell lines. Each subpopulation demonstrated a unique set of stable biological characteristics in vitro. When established in vivo, there was a wide variation in xenograft generation time. The parent cell line gave rise to six distinct xenograft patterns, two of which had been observed in the primary carcinoma. Individual subpopulations yielded characteristic tumours which were composed of between one and four organizational patterns. Xenografts differed in both the organization of cells and the cell differentiation within the different patterns. Mucous cells were absent from some tumours while abundant in others. The subpopulations isolated from the HCA-7 cell line provide a new and extensive model system for studying the generation and maintenance of phenotypic heterogeneity in colorectal carcinoma.

Adenocarcinoma, Mucinous↗
PubMed1993

Characteristics of the bradykinin-induced changes in intracellular calcium ion concentration of single bovine tracheal smooth muscle cells.

1. Single bovine tracheal smooth muscle (BTSM) cells were cultured and used to measure bradykinin-induced changes in [Ca2+]i by dynamic video imaging. 2. Bradykinin (10 pM-10 microM)-induced an increase in [Ca2+]i over basal levels (69 +/- 2 nM; n = 353) which was concentration-dependent (log EC50 = -8.7 M) in the presence of extracellular calcium ions (2 mM). The bradykinin B2 receptor antagonist, D-Arg[Hyp3,Thi5,8,D-Phe7]- bradykinin, produced a parallel shift to the right of the bradykinin concentration-response curve (log EC50 = -7.1 M and -5.8 M in the presence of 1 microM and 10 microM antagonist respectively) yielding an apparent KD of 26 nM. 3. In the absence of extracellular calcium ions (with 0.1 mM EGTA), bradykinin (10 pM-10 microM) produced a uniform increase in [Ca2+]i from a basal level of 33 +/- 2 nM (n = 140) to approximately 180 nM in BTSM cells indicating an 'all-or-nothing' release of intracellular calcium ions. In the presence of 10 microM D-Arg[Hyp3,Thi5,8,D-Phe7]-bradykinin no responses could be induced by bradykinin at concentrations below 100 nM. However, at 100 nM and 1 microM bradykinin there was no change in the uniform increase in [Ca2+]i in these cells previously observed. 4. In both the absence or presence of D-Arg[Hyp3,Thi5,8,D-Phe7]-bradykinin, there was a concentration-dependent increase in the percentage of cells responding to bradykinin (frequency) under calcium-rich or calcium-free conditions. Individual cells also demonstrated a difference in the sensitivity to any particular concentration of bradykinin. 5. A latency in the response of cells to bradykinin was observed both in calcium-containing and calcium-free conditions.6. We conclude that bradykinin B2 receptors are expressed by BTSM cells and are involved in the bradykinin-induced increase in [Ca2+]i. It appears that the increase in [Ca2+], can be mediated via a graded influx of calcium ions from the extracellular space or an 'all-or-nothing' release from intracellular stores.

Adamantane↗