Biomedical subjects

R R Freeman

Publications and source records attributed to R R Freeman.

At least 19 recordsLinked to original sources

PubMed2006

Proton radiography of a laser-driven implosion.

Protons accelerated by a picosecond laser pulse have been used to radiograph a 500 microm diameter capsule, imploded with 300 J of laser light in 6 symmetrically incident beams of wavelength 1.054 microm and pulse length 1 ns. Point projection proton backlighting was used to characterize the density gradients at discrete times through the implosion. Asymmetries were diagnosed both during the early and stagnation stages of the implosion. Comparison with analytic scattering theory and simple Monte Carlo simulations were consistent with a 3+/-1 g/cm3 core with diameter 85+/-10 microm. Scaling simulations show that protons>50 MeV are required to diagnose asymmetry in ignition scale conditions.

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PubMed2006

Fast-electron transport and heating of solid targets in high-intensity laser interactions measured by K alpha fluorescence.

We present experimental results on fast-electron energy deposition into solid targets in ultrahigh intensity laser-matter interaction. X-ray K alpha emission spectroscopy with absolute photon counting served to diagnose fast-electron propagation in multilayered targets. Target heating was measured from ionization-shifted K alpha emission. Data show a 200 microm fast-electron range in solid Al. The relative intensities of spectrally shifted Al K alpha lines imply a mean temperature of a few tens of eV up to a 100 microm depth. Experimental results suggest refluxing of the electron beam at target rear side. They were compared with the predictions of both a collisional Monte Carlo and a collisional-electromagnetic, particle-fluid transport code. The validity of the code modeling of heating in such highly transient conditions is discussed.

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PubMed2005

Ultraintense laser-produced fast-electron propagation in gas jets.

We study the propagation of fast electrons in a gas at different densities. A large relativistic electron current is produced by focusing a short-pulse ultrahigh-intensity laser on a metallic target. It then propagates in a gas jet placed behind the foil. Shadowgraphy in the gas shows an electron cloud moving at sub-relativistic average velocities. The experiment shows (i) the essential role of the density of background material for allowing propagation of fast electrons, (ii) the importance of the ionization phase which produces free electrons available for the return current, and (iii) the effect of electrostatic fields on fast-electron propagation.

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PubMed2004

Plasma devices to guide and collimate a high density of MeV electrons.

The development of ultra-intense lasers has facilitated new studies in laboratory astrophysics and high-density nuclear science, including laser fusion. Such research relies on the efficient generation of enormous numbers of high-energy charged particles. For example, laser-matter interactions at petawatt (10(15) W) power levels can create pulses of MeV electrons with current densities as large as 10(12) A cm(-2). However, the divergence of these particle beams usually reduces the current density to a few times 10(6) A cm(-2) at distances of the order of centimetres from the source. The invention of devices that can direct such intense, pulsed energetic beams will revolutionize their applications. Here we report high-conductivity devices consisting of transient plasmas that increase the energy density of MeV electrons generated in laser-matter interactions by more than one order of magnitude. A plasma fibre created on a hollow-cone target guides and collimates electrons in a manner akin to the control of light by an optical fibre and collimator. Such plasma devices hold promise for applications using high energy-density particles and should trigger growth in charged particle optics.

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PubMed2004

K(alpha) fluorescence measurement of relativistic electron transport in the context of fast ignition.

Electron transport within solid targets, irradiated by a high-intensity short-pulse laser, has been measured by imaging K(alpha) radiation from high- Z layers (Cu, Ti) buried in low- Z (CH, Al) foils. Although the laser spot is approximately 10 microm [full width at half maximum (FWHM)], the electron beam spreads to > or =70 microm FWHM within <20 microm of penetration into an Al target then, at depths >100 microm, diverges with a 40 degree spreading angle. Monte Carlo and analytic models are compared to our data. We find that a Monte Carlo model with a heuristic model for the electron injection gives a reasonable fit with our data.

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PubMed2004

Theory of the Kapitza-Dirac diffraction effect.

We treat the Kapitza-Dirac diffraction effect observed recently by Batelaan et al. using a newly developed nonperturbative quantum-field scattering theory. Our theory shows that an electron beam passing perpendicularly through a focused standing light wave can produce diffraction patterns. Our theory predicts (1) the minimum value of the ponderomotive energy is (Planck's over 2 pi omega)(2)/m(e)c(2), (2) the critical laser intensity above which the first pair of electron diffraction peaks will occur, and (3) the existence of sidebands in the electron spectra separated far from the central band by a momentum of several hundred photons. Our theory provides a unified explanation of the experimental results of Bucksbaum et al. and Batelaan et al.

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PubMed2002

Enhancement of proton acceleration by hot-electron recirculation in thin foils irradiated by ultraintense laser pulses.

MeV-proton production from solid targets irradiated by 100-fs laser pulses at intensities above 1x10(20) W cm(-2) has been studied as a function of initial target thickness. For foils 100 microm thick the proton beam was characterized by an energy spectrum of temperature 1.4 MeV with a cutoff at 6.5 MeV. When the target thickness was reduced to 3 microm the temperature was 3.2+/-0.3 MeV with a cutoff at 24 MeV. These observations are consistent with modeling showing an enhanced density of MeV electrons at the rear surface for the thinnest targets, which predicts an increased acceleration and higher proton energies.

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PubMed2001

Experimental measurements of deep directional columnar heating by laser-generated relativistic electrons at near-solid density.

In our experiments, we irradiated solid CH targets with a 400 J, 5 ps, 3 x 10(19) W/cm(2) laser, and we used x-ray imaging and spectroscopic diagnostics to monitor the keV x-ray emission from thin Al or Au tracer layers buried within the targets. The experiments were designed to quantify the spatial distribution of the thermal electron temperature and density as a function of buried layer depth; these data provide insights into the behavior of relativistic electron currents which flow within the solid target and are directly and indirectly responsible for the heating. We measured approximately 200-350 eV temperatures and near-solid densities at depths ranging from 5 to 100 microm beneath the target surface. Time-resolved x-ray spectra from Al tracers indicate that the tracers emit thermal x rays and cool slowly compared to the time scale of the laser pulse. Most intriguingly, we consistently observe annular x-ray images in all buried tracer-layer experiments, and these data show that the temperature distribution is columnar, with enhanced heating along the edges of the column. The ring diameters are much greater than the laser focal spot diameter and do not vary significantly with the depth of the tracer layer for depths greater than 30 microm. The local temperatures are 200-350 eV for all tracer depths. We discuss recent simulations of the evolution of electron currents deep within solid targets irradiated by ultra-high-intensity lasers, and we discuss how modeling and analytical results suggest that the annular patterns we observe may be related to locally strong growth of the Weibel instability. We also suggest avenues for future research in order to further illuminate the complex physics of relativistic electron transport and energy deposition inside ultra-high-intensity laser-irradiated solid targets.

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PubMed1988

Immunization against Plasmodium falciparum with recombinant polypeptides produced in Escherichia coli.

Two proteins produced in recombinant Escherichia coli and containing amino acid sequences from the Plasmodium falciparum precursor to major merozoite surface antigens (PMMSA) have been partially purified. These proteins, together with a preparation of merozoites, have been used to immunize animals. The antibody response and the degree of protection were compared. Animals immunized with merozoites produced antibodies reacting with many P. falciparum proteins, whereas a response specific for PMMSA was detected in those receiving the recombinant material. Incomplete protection was conferred to both groups and there was no apparent correlation between antibody levels and protection.

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PubMed1987

Depression of virus-specific cytotoxic T-cell responses during murine malaria.

Mice with self-limiting P. yoelii or fatal P. berghei infections exhibited a markedly impaired ability to mount specific splenic cytotoxic T-lymphocyte responses to immunization with infectious ectromelia (EV), vaccinia (VAC), or lymphocytic choriomeningitis viruses (LCMV). Lymph node responsiveness, however, was not impaired. Primary CTL responses were depressed in mice immunized 7 days after P. berghei infection, while in P. yoelii-infected mice, depressed responses were detected only during the period corresponding with maximal parasitemia (days 9-12). Secondary VAC-specific CTL responses in vitro by spleen cells of mice previously immunized during P. yoelii infection were also depressed if UV-inactivated rather than infectious VAC was used for immunization. In addition, spleen cells of mice already immune to VAC failed to yield normal secondary CTL responses in vitro during the period of maximal P. yoelii parasitaemia. Collectively, these findings indicate that, during patent malaria infections, priming for and expression of virus-specific CTL responses may be inhibited.

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PubMed1986

Structural diversity of the major surface antigen of Plasmodium falciparum merozoites.

The structures of the major merozoite surface antigen of Plasmodium falciparum and the gene encoding it were indistinguishable for the Wellcome strain and the Thai clone T9/94 but different for clones T9/96, T9/98, and T9/101. The central portion of the gene is subject to the greatest variation in structure. The protein from all five lines was found to be posttranslationally modified by covalent addition of both carbohydrate and fatty acid.

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PubMed1985

Isolation of a Plasmodium falciparum rhoptry protein.

A monoclonal antibody raised against the malaria parasite Plasmodium falciparum recognised a protein of 140000 molecular weight which was synthesized during schizogony. The protein has been purified by monoclonal antibody affinity chromatography from extracts of parasitized red cells. Antibodies against the protein have been used to determine its subcellular location. The protein is not expressed on the merozoite surface and has been located in the rhoptries, the apical organelles of the merozoite.

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PubMed1985

Vaccination with a purified blood-stage malaria antigen in mice: correlation of protection with T cell mediated immunity.

A purified 230,000 mol wt protein antigen from the lethal mouse malaria parasite Plasmodium yoelii YM which had previously been shown to be highly effective as a vaccine, was tested for its ability to stimulate specific helper T cells and T cells responsible for delayed hypersensitivity. Strong stimulation was found in both assays, but larger doses were required for delayed hypersensitivity, correlating well with the requirements for protection. It is suggested that T stimulation may be a requirement for effective protection by purified antigens in malaria.

Animals↗

PubMed1984

Protective antigens of rodent and human bloodstage malaria.

Bloodstage malaria parasites are antigenically complex, but individual antigens can be identified and analysed using monoclonal antibodies. Two monoclonal antibodies that recognize a 235 000 molecular mass Plasmodium yoelii rhoptry protein provide some protection when injected into mice against a challenge infection. The purified rhoptry protein also provides protective immunity against P. yoelii YM when used to vaccinate mice and fulminating infections are converted into self-limiting, reticulocyte-restricted infections. Another monoclonal antibody immunoprecipitates a 230 000 molecular mass protein and a series of proteolytic processing fragments. At least one of these processing fragments, probably a 90 000 molecular mass species, is located on the merozoite surface. Mice immunized with the purified protein were protected against challenge infection with P. yoelii YM. This antigen may provide protection by inducing a cell-mediated immune response. A monoclonal antibody raised against P. falciparum schizonts reacts with a 195 000 molecular mass protein which is synthesized in schizonts and subsequently cleaved. Fragments of the 195 000 molecular mass protein are expressed as major antigens on the merozoite surface. The 195 000 molecular mass P. falciparum protein and the 230 000 molecular mass P. yoelii protein belong to a class of malaria parasite antigens which probably is important in the induction of a protective immune response in the host.

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PubMed1984

The three major antigens on the surface of Plasmodium falciparum merozoites are derived from a single high molecular weight precursor.

A 195,000 mol wt Plasmodium falciparum protein and processing fragments derived from it have been purified by monoclonal antibody affinity chromatography. A polyvalent antiserum has been raised against the purified protein and used to identify the terminal processing products associated with the merozoite. Three unique fragments of 83,000, 42,000, and 19,000 mol wt are present and they represent the major surface antigens of P. falciparum merozoites.

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PubMed1984

Expression of cloned cDNA for a major surface antigen of Plasmodium falciparum merozoites.

A cDNA library of P. falciparum was constructed. Using size-selected mRNA as a probe several clones were isolated which hybridized to mRNAs larger than 5 kilobases (kb). The cDNA insert of pFC 17, which hybridizes to 5.6-kb mRNA was expressed by fusion to anthranilate synthetase I in a plasmid expression vector. The expressed fusion protein was shown to contain epitopes of a 195-kDa protein which is the precursor to 3 major surface antigens of P. falciparum merozoites.

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PubMed1984

Ultrastructural localization of protective antigens of Plasmodium yoelii merozoites by the use of monoclonal antibodies and ultrathin cryomicrotomy.

The production of two hybridoma cell lines secreting monoclonal antibodies (MAb), both of which react specifically with erythrocytic merozoites of Plasmodium yoelii in the indirect immunofluorescence assay, has been reported earlier. MAb 25.77 was reactive with a localized region within each merozoite, while MAb 25.1 appeared to be specific for the plasma membrane of schizonts and merozoites. The parasite antigens recognized by antibodies 25.77 and 25.1 are proteins of 235,000 and 230,000 molecular weight, respectively, both of which induce protective immunity against P. yoelii in mice. In order to establish the precise localization of these protective antigens within erythrocyte merozoites, ultrathin cryomicrotomy was used in conjunction with the MAb and protein A-gold. This technique showed that gold particles were exclusively concentrated over the rhoptries when erythrocytic merozoites were incubated with MAb 25.77. On the other hand, gold particles were distributed uniformly over the merozoite surface when parasites were incubated with MAb 25.1. These results demonstrate, for the first time, that a protective antigen of the erythrocytic stage of P. yoelii is localized within the rhoptries as well as on the merozoite surface.

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PubMed1984

Characterization of a high molecular weight protective antigen of Plasmodium yoelii.

A 230 000 molecular weight Plasmodium yoelii protective antigen was characterized. Two monoclonal antibodies against P. yoelii immunoprecipitated the 230 000 mol. wt protein and a number of lower molecular weight polypeptides. These polypeptides were shown by peptide mapping and specific antibody binding to be fragments of the large protein. Iodination experiments suggested that the lower molecular weight species may be present on the surface of the merozoite. The protein was found not to be glycosylated. By serology, related antigens were shown to be associated with blood-stage schizonts of P. vinckei subspp., P. chabaudi subspp. and P. falciparum.

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