Multi-GeV Electron Acceleration in Wakefields Strongly Driven by Oversized Laser Spots.

Experiments were performed on laser wakefield acceleration in the highly nonlinear regime. With laser powers P<250 TW and using an initial spot size larger than the matched spot size for guiding, we were able to accelerate electrons to energies E_{max}>2.5 GeV, in fields exceeding 500 GV m^{-1}, with more than 80 pC of charge at energies E>1 GeV. Three-dimensional particle-in-cell simulations show that using an oversized spot delays injection, avoiding beam loss as the wakefield undergoes length oscillation. This enables injected electrons to remain in the regions of highest accelerating fields and leads to a doubling of energy gain as compared to results from using half the focal length with the same laser.

In Situ Measurement of Electron Energy Evolution in a Laser-Plasma Accelerator.

We report on a novel, noninvasive method applying Thomson scattering to measure the evolution of the electron beam energy inside a laser-plasma accelerator with high spatial resolution. The determination of the local electron energy enabled the in-situ detection of the acting acceleration fields without altering the final beam state. In this Letter we demonstrate that the accelerating fields evolve from (265±119) GV/m to (9±4) GV/m in a plasma density ramp. The presented data show excellent agreement with particle-in-cell simulations. This method provides new possibilities for detecting the dynamics of plasma-based accelerators and their optimization.

A laser driven pulsed X-ray backscatter technique for enhanced penetrative imaging.

X-ray backscatter imaging can be used for a wide range of imaging applications, in particular for industrial inspection and portal security. Currently, the application of this imaging technique to the detection of landmines is limited due to the surrounding sand or soil strongly attenuating the 10s to 100s of keV X-rays required for backscatter imaging. Here, we introduce a new approach involving a 140 MeV short-pulse (< 100 fs) electron beam generated by laser wakefield acceleration to probe the sample, which produces Bremsstrahlung X-rays within the sample enabling greater depths to be imaged. A variety of detector and scintillator configurations are examined, with the best time response seen from an absorptive coated BaF2 scintillator with a bandpass filter to remove the slow scintillation emission components. An X-ray backscatter image of an array of different density and atomic number items is demonstrated. The use of a compact laser wakefield accelerator to generate the electron source, combined with the rapid development of more compact, efficient and higher repetition rate high power laser systems will make this system feasible for applications in the field. Content includes material subject to Dstl (c) Crown copyright (2014). Licensed under the terms of the Open Government Licence except where otherwise stated. To view this licence, visit http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@ nationalarchives.gsi.gov.uk.

Quantitative analysis and modelling of hepatic iron stores using stereology and spatial statistics.

Hepatic iron overload is a common clinical problem resulting from hyperabsorption syndromes and from chronic transfusion therapy. Not only does iron loading vary between reticuloendothelial stores and hepatocytes, but iron is heterogeneously distributed within hepatocytes as well. Since the accessibility of iron particles to chelation may depend, in part, on their distribution, we sought to characterize the shape and scale of iron deposition in humans with transfusional iron overload. Toward this end, we performed a histological analysis of iron stores in liver biopsy specimens of 20 patients (1.3-57.8 mg iron/g dry tissue weight) with aid of electron and light microscopy. We estimated distributions related to variability in siderosomal size, proximity of iron centres and inter-cellular iron loading. These distributions could be well modelled by Gamma distribution functions over most of the pathologic range of iron concentrations. Thus, for a given liver iron burden, a virtual iron-overloaded liver could be created that served as a model for the true histologic appearance. Such a model may be helpful for understanding the mechanics of iron loading or in predicting response to iron removal therapy.

Author Correction: Laser-wakefield accelerators for high-resolution X-ray imaging of complex microstructures.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Laser-wakefield accelerators for high-resolution X-ray imaging of complex microstructures.

Laser-wakefield accelerators (LWFAs) are high acceleration-gradient plasma-based particle accelerators capable of producing ultra-relativistic electron beams. Within the strong focusing fields of the wakefield, accelerated electrons undergo betatron oscillations, emitting a bright pulse of X-rays with a micrometer-scale source size that may be used for imaging applications. Non-destructive X-ray phase contrast imaging and tomography of heterogeneous materials can provide insight into their processing, structure, and performance. To demonstrate the imaging capability of X-rays from an LWFA we have examined an irregular eutectic in the aluminum-silicon (Al-Si) system. The lamellar spacing of the Al-Si eutectic microstructure is on the order of a few micrometers, thus requiring high spatial resolution. We present comparisons between the sharpness and spatial resolution in phase contrast images of this eutectic alloy obtained via X-ray phase contrast imaging at the Swiss Light Source (SLS) synchrotron and X-ray projection microscopy via an LWFA source. An upper bound on the resolving power of 2.7 ± 0.3 µm of the LWFA source in this experiment was measured. These results indicate that betatron X-rays from laser wakefield acceleration can provide an alternative to conventional synchrotron sources for high resolution imaging of eutectics and, more broadly, complex microstructures.

A spectrometer for ultrashort gamma-ray pulses with photon energies greater than 10 MeV.

We present a design for a pixelated scintillator based gamma-ray spectrometer for non-linear inverse Compton scattering experiments. By colliding a laser wakefield accelerated electron beam with a tightly focused, intense laser pulse, gamma-ray photons up to 100 MeV energies and with few femtosecond duration may be produced. To measure the energy spectrum and angular distribution, a 33 × 47 array of cesium-iodide crystals was oriented such that the 47 crystal length axis was parallel to the gamma-ray beam and the 33 crystal length axis was oriented in the vertical direction. Using an iterative deconvolution method similar to the YOGI code, modeling of the scintillator response using GEANT4 and fitting to a quantum Monte Carlo calculated photon spectrum, we are able to extract the gamma ray spectra generated by the inverse Compton interaction.

Ultrafast Imaging of Laser Driven Shock Waves using Betatron X-rays from a Laser Wakefield Accelerator.

Betatron radiation from laser wakefield accelerators is an ultrashort pulsed source of hard, synchrotron-like x-ray radiation. It emanates from a centimetre scale plasma accelerator producing GeV level electron beams. In recent years betatron radiation has been developed as a unique source capable of producing high resolution x-ray images in compact geometries. However, until now, the short pulse nature of this radiation has not been exploited. This report details the first experiment to utilize betatron radiation to image a rapidly evolving phenomenon by using it to radiograph a laser driven shock wave in a silicon target. The spatial resolution of the image is comparable to what has been achieved in similar experiments at conventional synchrotron light sources. The intrinsic temporal resolution of betatron radiation is below 100 fs, indicating that significantly faster processes could be probed in future without compromising spatial resolution. Quantitative measurements of the shock velocity and material density were made from the radiographs recorded during shock compression and were consistent with the established shock response of silicon, as determined with traditional velocimetry approaches. This suggests that future compact betatron imaging beamlines could be useful in the imaging and diagnosis of high-energy-density physics experiments.

Highly efficient angularly resolving x-ray spectrometer optimized for absorption measurements with collimated sources.

Highly collimated betatron radiation from a laser wakefield accelerator is a promising tool for spectroscopic measurements. Therefore, there is a requirement to create spectrometers suited to the unique properties of such a source. We demonstrate a spectrometer which achieves an energy resolution of <5 eV at 9 keV (E∕ΔE>1800) and is angularly resolving the x-ray emission allowing the reference and spectrum to be recorded at the same time. The single photon analysis is used to significantly reduce the background noise. Theoretical performance of various configurations of the spectrometer is calculated by a ray-tracing algorithm. The properties and performance of the spectrometer including the angular and spectral resolution are demonstrated experimentally on absorption above the K-edge of a Cu foil backlit by a laser-produced betatron radiation x-ray beam.

Analysis of multivariate extreme intakes of food chemicals.

A recently published multivariate Extreme Value Theory (EVT) model is applied to the estimation of population risks associated with dietary intake of pesticides. The objective is to quantify the acute risk of pesticide intake above a threshold and relate it to the consumption of specific primary food products. As an example daily intakes of a pesticide from three foods are considered. The method models and extrapolates simultaneous intakes of pesticide, and estimates probability of exceeding unobserved large intakes. Multivariate analysis was helpful in identifying whether the avoidance of certain food combinations would reduce the likelihood of exceeding a threshold. We argue that the presented method can be an important contribution to exposure assessment studies.

Assessing the efficacy of within-animal control strategies against E. coli O157: a simulation study.

A stochastic simulation model was used to assess the efficacy of potential measures to control the levels of Escherichia coli O157 within the bovine host. The model described E. coli O157 population sizes at several sites along the bovine gut and therefore only interventions that operate at an individual animal level could be evaluated. In order to use the model to evaluate the control strategies, it was necessary to make assumptions about how each strategy affected E. coli O157 populations in vivo. The within-animal conditions under these control strategies were modelled by adjusting the growth rates of E. coli O157 at specific sites of interest in the gut, based on these assumptions. The model simulated the population dynamics of an initial dose of E. coli O157 inoculated into an animal in the presence of inhibitory probiotics or antibiotics, bactericidal antibiotics or probiotics, and following fasting. Of the control strategies considered, the use of inhibitory probiotics appeared most promising and continued development of a suitable product is to be encouraged.

A simulation model for the study of the within-animal infection dynamics of E. coli O157.

Escherichia coli 0157 can cause serious illness, even death, in humans. There is some consensus that the main reservoirs of this harmful bacterium are the rumens and intestines of cattle. Hence, a stochastic model of the bovine gut was developed to investigate the in vivo population dynamics of E. coli O157. Because bacterial numbers can reach minimal levels, a stochastic system was considered, with a birth-death process being used to represent bacterial growth and decay dynamics throughout the gastrointestinal tract. Reinfection through ingestion of bacteria present in the environment was allowed to occur and the required clustered distribution of inter-event times was implemented through the use of a random hazard doubly stochastic Poisson process. Due to the inclusion of multiple compartments, a feedback mechanism and an interest in the non-equilibrium dynamics of the process, it was not possible to obtain an analytical representation of the process and therefore, a simulation study was used to obtain results. The within-animal model can be used to explore the efficacy of control measures which act at an individual animal level.

In Vivo T1 of Blood Measurements in Children with Sickle Cell Disease Improve Cerebral Blood Flow Quantification from Arterial Spin-Labeling MRI.

BACKGROUND AND PURPOSE: Children with sickle cell disease have low hematocrit and elevated CBF, the latter of which can be assessed with arterial spin-labeling MR imaging. Quantitative CBF values are obtained by using an estimation of the longitudinal relaxation time of blood (T1blood). Because T1blood depends on hematocrit in healthy individuals, we investigated the importance of measuring T1blood in vivo with MR imaging versus calculating it from hematocrit or assuming an adult fixed value recommended by the literature, hypothesizing that measured T1blood would be the most suited for CBF quantification in children with sickle cell disease. MATERIALS AND METHODS: Four approaches for T1blood estimation were investigated in 39 patients with sickle cell disease and subsequently used in the CBF quantification from arterial spin-labeling MR imaging. First, we used 1650 ms as recommended by the literature (T1blood-fixed); second, T1blood calculated from hematocrit measured in patients (T1blood-hematocrit); third, T1blood measured in vivo with a Look-Locker MR imaging sequence (T1blood-measured); and finally, a mean value from T1blood measured in this study in children with sickle cell disease (T1blood-sickle cell disease). Quantitative flow measurements acquired with phase-contrast MR imaging served as reference values for CBF. RESULTS: T1blood-measured (1818 ± 107 ms) was higher than the literature recommended value of 1650 ms, was significantly lower than T1blood-hematocrit (2058 ± 123 ms, P < .001), and, most interesting, did not correlate with hematocrit measurements. Use of either T1blood-measured or T1blood-sickle cell disease provided the best agreement on CBF between arterial-spin labeling and phase-contrast MR imaging reference values. CONCLUSIONS: This work advocates the use of patient-specific measured T1blood or a standardized value (1818 ms) in the quantification of CBF from arterial spin-labeling in children with SCD.

Laser-wakefield accelerators as hard x-ray sources for 3D medical imaging of human bone.

A bright µm-sized source of hard synchrotron x-rays (critical energy Ecrit > 30 keV) based on the betatron oscillations of laser wakefield accelerated electrons has been developed. The potential of this source for medical imaging was demonstrated by performing micro-computed tomography of a human femoral trabecular bone sample, allowing full 3D reconstruction to a resolution below 50 µm. The use of a 1 cm long wakefield accelerator means that the length of the beamline (excluding the laser) is dominated by the x-ray imaging distances rather than the electron acceleration distances. The source possesses high peak brightness, which allows each image to be recorded with a single exposure and reduces the time required for a full tomographic scan. These properties make this an interesting laboratory source for many tomographic imaging applications.

Use of a DNA probe to analyse the dynamics of infection with rodent malaria parasites confirms that parasite clearance during crisis is predominantly strain- and species-specific.

A DNA probe, PCsv4.1, isolated from Plasmodium chabaudi chabaudi AS, generates in Southern blotting experiments restriction fragment length polymorphisms specific to a particular rodent malaria parasite line. It was used to develop an assay which allows identification and semi-quantitative compositional analysis of sample parasite populations in which one or more strains, subspecies or species were present. In experiments where mechanisms effecting parasite clearance during crisis were studied, the assay was used to determine the composition of parasite populations present in P. c. chabaudi AS infected mice challenged during crisis with homologous or heterologous parasites. It was thus confirmed that clearance mechanisms during crisis operate in a predominantly specific manner.

Laparoscopic living donor nephrectomy: advantages of the hand-assisted method.

INTRODUCTION: The laparoscopic technique for living donor nephrectomy is a technically difficult procedure that has not yet gained widespread acceptance in the transplant community. The procedure may be more acceptable if alterations to the technique made it easier to perform and decreased operative times. METHODS: In August 1998, we altered the laparoscopic procedure to include the use of a device allowing hand assistance. Subsequently, all living donor nephrectomies have been done using the hand-assisted method. In this article, the results of 10 cases performed using the original laparoscopic technique are compared with the results of 12 cases using the hand-assisted technique, and a brief description of modifications to the original technique is given. RESULTS: No patients where turned down as living donors, and no contraindications to the pure or hand-assisted laparoscopic techniques where found. The hand-assisted technique significantly reduced the operative time (2.02+/-0.44 vs. 3.12+/-0.36 hr, P<0.05) and the warm ischemic time (1.23+/-0.54 vs. 3.91+/-0.53 min, P<0.05). The length of stay and recovery time to normal activities were not different between the pure laparoscopic and hand-assisted groups. CONCLUSION: The advantages of the hand-assisted technique include the ability to use tactile sense to facilitate dissection, retraction, and exposure. In addition, the final stages of vascular stapling and kidney removal are more sure and rapid. The modifications of the laparoscopic technique presented here provide measurable and subjective improvements to laparoscopic living donor nephrectomy. The hand-assisted method of laparoscopic nephrectomy may make the operation available to more transplant centers.

Laser flow cytometric light scatter and fluorescence pulse width and pulse rise-time sizing of mammalian cells.

In laser flow cytometry, an increasingly popular technique of analytical cytology, quantitative measurements of interest include cell and nuclear diameters. Electronic circuitry for a new cell sizing technique has been developed which measured the time that signal pulses from either fluorescence or light scatter sensors exceed a preset constant fraction of the peak signal amplitude (pulse width) or the time that it takes a signal to rise between constant fractions of the peak signal amplitude on the rising side of the pulse (pulse rise-time). These pulse width or pulse rise-time measurements were related to cell or nuclear diameters and were used in combination to determine nuclear size to cell size ratios. This method of sizing was found to be independent of fluorescent or light-absorbing stain intensity, linearly related to cell or nuclear diameter, and capable of resolving small diameter differences.

Design of novel antiestrogens.

The physicochemical principle of "die and coin" complementarity proffered by Pauling and Delbruck and exemplified in Watson and Crick DNA was used to design new antineoplastic compounds. In search of an explanation for why certain molecules and not others are present in nature, biologically active small molecules were discovered to exhibit complementarity when inserted into cavities between base pairs in DNA. Ligands in the steroid/thyroid hormone/vitamin D family fit particularly well into the site 5'-dTdG-3'.5'-dCdA-3'. Degree of fit of various candidate compounds in the manner of a given hormone correlated with degree of hormonal activity. Hormone antagonists fit into the same site but in a different manner than the agonists. Computer graphics and energy calculations confirmed salient observations including the remarkable complementarity of estradiol and DNA. Using the above criteria, a new candidate antiestrogen, para-hydroxyphenyl-acetylamino-2,6-piperidinedione was successfully designed. Taken as a whole, these results coupled with recent independent findings raise the possibility that the mode of action of certain hormones and hormone antagonists may involve direct insertion into DNA mediated by classical protein receptors and other transcription factors.

Inhibition of estrogen stimulated mitogenesis by 3-phenylacetylamino-2,6-piperidinedione and its para-hydroxy analog.

3-Phenylactetylamino-2,6-piperidinedione (A10) inhibited estradiol stimulated cell growth in the MCF-7 (E3) human breast tumor cell line in vivo and in vitro. While high concentrations of A10 were needed to inhibit cell proliferation (IC50 = 3 x 10(-3) M in vitro), the compound demonstrated little toxicity. The effect appeared specific since a hydrolysis product of A10, phenylacetylglutamine, demonstrated no growth inhibitory activity at similar concentrations in MCF-7 (E3) cells in vitro. A computer designed analog, p-hydroxy A10, was more potent than A10 in inhibiting activity in MCF-7 (E3) cells in vitro. The IC50 for p-hydroxy A10 was 7 x 10(-6) M which was comparable to that of the antiestrogen, tamoxifen (IC50 1 x 10(-7) M). All three compounds caused a decline in estrogen receptor levels in a dose-dependent fashion. A10 also inhibited estradiol induction of progesterone receptors. Examination of protein kinase activity following an acute exposure to a 10(-11) M growth stimulatory dose of estradiol revealed a 168% increase in protein kinase activity over that of untreated control cells. A10 in a dose-responsive fashion inhibited the estradiol stimulated increase in protein kinase activity. The protein kinase activity was also inhibited by p-hydroxy A10. These activities of A10 and p-hydroxy A10 coupled with the low toxicity and novelty of the basic A10 structure provide an exciting possibility of developing a new class of clinically useful antineoplastic drugs with minimal side effects.

Regional effects of myocardial ischemia on epicardially recorded canine first heart sounds.

To determine whether focal changes in myocardial material properties are important in determining the response of first heart sound acceleration amplitude and frequency to myocardial ischemia, cardiac vibrations were simultaneously recorded from ischemic and nonischemic regions of canine epicardium by use of ultralight acceleration transducers. Cardiac acceleration and hemodynamics were recorded before and 5 min, 15 min, 1 h, and 2 h after left circumflex coronary artery occlusion. Peak-to-peak amplitude declined transiently in the nonischemic zone during early occlusion (P < 0.05) but was not decreased at any time in the ischemic myocardium. The median frequency of first heart sound vibrations in the ischemic region increased 31% within 5 min after occlusion (P < 0.01) and remained elevated for 2 h (P < 0.05). Nonischemic zone frequency was not statistically different from baseline at any time point. The disparate regional response of first heart sound vibrational frequency to myocardial ischemia suggests that propagating mechanical transients and myocardial contractile acceleration, rather than resonant vibrations, produce the first heart sound.