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Initial damage in human interphase chromosomes from alpha particles with linear energy transfers relevant to radon exposure.

To determine the efficiency at which alpha particles at LETs chosen to simulate exposure to radon progeny break chromosomes, the premature chromosome condensation technique was used to measure breaks soon after irradiation. Noncycling human fibroblasts were irradiated with graded doses of monoenergetic alpha particles accelerated to produce LETs of 90, 120, 150, 180 and 200 keV/microns at the midpoint of the cell nuclei. Premature chromosome condensation was initiated immediately after irradiation and cells were scored for the total number of prematurely condensed chromosomes and fragments per cell. Similar experiments were conducted with 250 kVp X rays for comparison. Irradiation with alpha particles produced 8.6 to 13.1 excess fragments per gray, while X rays produced 5.8 excess fragments, resulting in RBEs around 2. Calculations of the number of breaks produced on average by a single particle traversal of a cell nucleus indicated that at the LETs tested more than one break (1.5-2.8) was produced by each traversal, the maximum being that produced by 180 keV/microns alpha particles. When chromosome aberrations are scored at metaphase after high-LET irradiation, RBEs considerably greater than those recorded here (approximately 2) have been reported. These results showing relatively small differences in initial break levels for alpha particles in the LET range of the radon progeny relative to X rays indicate that the greater aberration frequencies are not due principally to an increase in breakage efficiency, but interactions between breaks along the same particle track are important.

Alpha Particles↗

Developments in radiotherapy.

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) in 2001. The assessment included a review of future developments in radiotherapy and an estimate of the potential benefits of improved radiotherapy in Sweden. The conclusions reached from this review can be summarized as: Successively better knowledge is available on dose-response relationships for tumours and normal tissues at different fractionation schedules and treated volumes. Optimization of dose levels and fractionation schedules should improve the treatment outcome. Improved treatment results may be expected with even more optimized fractionation schedules. The radiosensitivity of the tumour is dependent on the availability of free oxygen in the cells. The oxygen effect has been studied for a long time and new knowledge has emerged, but there is still no consensus on the best way to minimize its negative effect in the treatment of hypoxic tumours. Development in imaging techniques is rapid, improving accuracy in outlining targets and organs at risk. This is a prerequisite for advanced treatment planning. More accurate treatment can be obtained using all the computer techniques that are successively made available for calculating dose distributions, controlling the accelerator and multileaf collimator (MLC) and checking patient set-up. Optimized treatment plans can be achieved using inverse dose planning and intensity modulation radiation therapy (IMRT). Optimization algorithms based on biological data from clinical trials could be a part of future dose planning. New genetic markers might be developed that give a measure of the radiation responsiveness of tumours and normal tissue. This could lead to more individualized treatments. New types of radiation sources may be expected: protons, light ions, and improved beams (and compounds) for boron neutron capture therapy (BNCT). Proton accelerators with scanned-beam systems and energy modulation give good dose distribution. The results reported with carbon ions from Japan and Germany are promising. An interesting development is to verify the dose and position for the irradiated volume with PET on line. Safer margins are obtained and the treatment volume can thus be limited. Very large accelerators are needed to accelerate the carbon ions. Still, it should be possible to keep the costs per patient at the same level as those for other types of advanced radiotherapy, since far fewer treatments per patient are needed. It might also be possible to treat new groups of patients. Increased resources are needed to introduce all the currently available techniques. New types of particle accelerators require large investments and a new structure of radiotherapy in Sweden.

Brachytherapy↗

Sand filter clogging by septic tank effluent.

The aim of this study was to characterise conditions and factors affecting fine sand clogging by septic tank effluent on the basis of physical modelling. The physical model consisted of 12 sand columns dosed with sewage from one household (5 persons), preliminary treated in a septic tank. Hydraulic loadings of the sand filters were equal to 82 mm/d. The mean discharge from sand columns, measured as the effluent volume collected during 10 minutes, decreased significantly over the experiment period from 34 cm3/min in August 2000 to 20 cm3/min in August 2001 at the same temperature of about 20 degrees C. First the columns clogged almost completely after 480 days in December 2001, however six columns had remained unclogged till the end of the experiment (March 2002). The temperature had a significant impact on hydraulic conductivity. A vertical distribution of accumulated mass and biomass was investigated in partly clogged sand. Microscopic survey of the clogging layer showed a presence of live micro-organisms, residuals of dead micro-organisms, particularly pieces of small animal armour and many fibres. These particles accelerated the accumulation of solids in the upper clogging layer. The study indicated that temperature impact on the filter hydraulic conductivity was more significant for biological activity, than for sewage viscosity.

Biomass↗

Systemic inflammatory response induced by particulate matter air pollution: the importance of bone-marrow stimulation.

The relationship between the level of particulate air pollution (PM(10)) and the mortality and morbidity rates from respiratory and cardiovascular diseases is well established, but the biological mechanisms responsible for these associations are still unclear. The injurious effects of particulate air pollution may be either local (in the lung) or systemic. Bone-marrow release of leukocytes and platelets is an important component of the systemic inflammatory response. We have developed methods to quantify bone-marrow stimulation and showed in animals that acute exposure to ambient particles accelerates the transit of polymorphonuclear leukocytes (PMN) through the marrow whereas chronic exposure expands the size of the bone marrow pool of PMN. Human studies showed that an episode of severe air pollution stimulates the bone marrow in a manner similar to that observed in animals. In vitro and in vivo studies suggest that alveolar macrophage produce the mediators implicated in the bone marrow response to ambient particles. Cytokines produced in the lung due to deposition of ambient particles also appear in the circulation. In vitro and in vivo studies have shown that PMN recently released from the bone marrow preferentially sequester in pulmonary capillaries, are less chemotactic, and contain more damaging granular enzymes, all factors that potentate their ability to damage alveolar tissue. In animals that naturally develop atherosclerosis, deposition of ambient particles in the lung causes progression of atherosclerotic plaques with phenotypic changes in atherosclerotic plaques characteristic of lesions vulnerable to rupture. We conclude that exposure to ambient particulate matter air pollution induces a systemic inflammatory response that includes the release of inflammatory mediators into the circulation that stimulate the bone marrow to release leukocytes and platelets. We postulate that this systemic response to particulate air pollution augments lung inflammation and changes the phenotype of atherosclerotic plaques to make them more vulnerable to rupture.

Air Pollutants↗

Quasimonoenergetic deuteron bursts produced by ultraintense laser pulses.

We report on the generation and laser acceleration of bunches of energetic deuterons with a small energy spread at about 2 MeV. This quasimonoenergetic peak within the ion energy spectrum was observed when heavy-water microdroplets were irradiated with ultrashort laser pulses of about 40 fs duration and high (10(-8)) temporal contrast, at an intensity of 10(19) W/cm(2). The results can be explained by a simple physical model related to spatial separation of two ion species within a finite-volume target. The production of quasimonoenergetic ions is a long-standing goal in laser-particle acceleration; it could have diverse applications such as in medicine or in the development of future compact ion accelerators.

Journal Article↗

Broad energy spectrum of laser-accelerated protons for spallation-related physics.

A beam of MeV protons, accelerated by ultraintense laser-pulse interactions with a thin target foil, is used to investigate nuclear reactions of interest for spallation physics. The laser-generated proton beam is shown (protons were measured) to have a broad energy distribution, which closely resembles the expected energy spectrum of evaporative protons (below 50 MeV) produced in GeV-proton-induced spallation reactions. The protons are used to quantify the distribution of residual radioisotopes produced in a representative spallation target (Pb), and the results are compared with calculated predictions based on spectra modeled with nuclear Monte Carlo codes. Laser-plasma particle accelerators are shown to provide data relevant to the design and development of accelerator driven systems.

Journal Article↗

Polymer size and concentration effects on the size of gold nanoparticles capped by polymeric thiols.

Gold nanoparticles stabilized by thiol-terminated poly(ethylene glycol) monomethyl ethers with molecular weights ranging from 350 to 2000 have been prepared at thiol-to-gold molar ratios ranging from 3:1 to 1:8. Particle size distributions have been constructed for these particles from transmission electron microscopy images of hundreds of particles for each variation in synthetic conditions. The mean diameters of these particles range from 1.5 to 3.2 nm, with a slight increase in particle size with decreasing thiol content; these particles are smaller than those prepared using alkanethiols at similar thiol-to-gold ratios. Particles prepared under thiol-poor conditions exhibit much greater polydispersity than those prepared under thiol-rich conditions and include numerically rare large-particle outliers that contain much of the gold in the sample. The mean diameters of the gold nanoparticles decrease slightly with increasing polymer weight, especially under thiol-rich conditions. A simple model is developed to predict the trends in nanoparticle diameter that would result were the polymer's steric bulk protecting the nanoparticles from additional growth the principal factor controlling nanoparticle size in this system. This model predicts a much stronger dependence on thiol concentration than has been experimentally observed and a dependence on polymer molecular weight opposite to that experimentally observed. This suggests that the polymers' steric bulk is not the principal reason that these polymers yield smaller nanoparticles than alkanethiols at similar thiol-to-gold ratios. It is instead proposed that polar polymers may yield small nanoparticles by accelerating particle nucleation via coordination between functional groups in the polymer and atomic gold.

Gold↗

Flow cytometric method for enumeration and characterization of newly released polymorphonuclear leukocytes from the bone marrow using 5'-bromo-2'-deoxyuridine.

Inflammation accelerates polymorphonuclear leukocyte (PMN) release from the bone marrow, and these PMNs are implicated in inappropriate tissue injury. We have previously developed a method using 5'-bromo-2'-deoxyuridine (BrdU) to study PMN kinetics using an immunocytochemical grading system of PMN on cytospin slides. The aim of this study was to develop a flow cytometric method to quantify the number of positively stained PMN and grade the intensity of staining for the transit time calculation of PMN through the marrow. Dividing myeloid progenitors in the marrow of rabbits were labeled with a pulse dosage of intravenous BrdU. BrdU-labeled PMN (PMN(BrdU)) were detected in the circulation using a FITC-conjugated anti-BrdU monoclonal antibody. The PMN(BrdU) were assigned to five groups according to their FITC intensity, and the transit times of PMN at different stages of development in the marrow were calculated. Results were compared using parallel immunocytochemical analysis of the same samples. In control animals, PMN(BrdU) in the circulation peaked at 72 h after BrdU labeling with 36.0% of PMN labeled. In normal rabbits, the transit times of PMN through the mitotic pool (49.5 +/- 4.2 h) and maturation pool (65.5 +/- 3.1 h) correlated well with immunocytochemical analysis and previously published values. Using this method, we demonstrated that exposure to air pollution particles accelerates the release of PMN(BrdU) from the marrow. We conclude that a flow cytometric approach for identifying BrdU-labeled leukocytes provides an objective and accurate method for studying leukocyte kinetics and behavior.

Animals↗

Diversity in frequency response properties of saccular afferents of the toadfish, Opsanus tau.

The frequency response of primary saccular afferents of toadfish (Opsanus tau) was studied in the time and frequency domains using the reverse correlation (revcor) method. Stimuli were noise bands with flat acceleration spectra delivered as whole-body motion. The recorded acceleration waveform was averaged over epochs preceding and following each spike. This average, termed the revcor, is an estimate of the response of an equivalent linear filter intervening between body motion and spike initiation. The spectrum of the revcor estimates the shape of the equivalent linear filter. Revcor responses were brief, damped oscillations indicative of relatively broadly tuned filters. Filter shapes were generally band-pass and differed in bandwidth, band edge slope, and characteristic frequency (74 Hz to 140 Hz). Filter shapes tend to be independent of stimulus level. Afferents can be placed into two groups with respect to characteristic frequency (74-88 Hz and 140 Hz). Some high-frequency afferents share a secondary peak at the characteristic frequency of low-frequency afferents, suggesting that an afferent may receive differently tuned peripheral inputs. For some afferents having similar filter shapes, revcor responses often differ only in polarity, probably reflecting inputs from hair cells oriented in opposite directions. The origin of frequency selectivity and its diversity among saccular afferents may arise from a combination of hair cell resonance and micromechanical processes. The resulting frequency analysis is the simplest yet observed among vertebrate animals. During courtship, male toadfish produce the 'boatwhistle' call, a periodic vocalization having several harmonics of a 130 Hz fundamental frequency. The saccule encodes the waveform of acoustic particle acceleration between < 50 and about 250 Hz. Thus, the fundamental frequency component of the boatwhistle is well encoded, but the successive higher harmonics are filtered out. The boatwhistle is thus encoded as a time-domain representation of its fundamental frequency or pulse repetition rate.

Acoustic Stimulation↗

Expression of inducible angiosperm promoters in a gymnosperm, Picea glauca (white spruce).

Electrical discharge particle acceleration was used to test the transient expression of numerous inducible angiosperm promoters in a gymnosperm Picea glauca (white spruce). Promoter expression was assayed in three different tissues capable of in vitro regeneration, zygotic embryos, seedlings and embryogenic callus. The promoters tested include the light-inducible Arabidopsis and soybean ribulose-1,5-bisphosphate small subunit promoters and a maize phosphoenolpyruvate carboxylase promoter; a soybean heat-shock-inducible promoter, a soybean auxin inducible promoter and a maize alcohol dehydrogenase promoter. Promoters were cloned into a promoter-less expression vector to form a promoter-beta-glucuronidase-nopaline synthase 3' fusion. A similar construct was made using the cauliflower mosaic virus 35S (CaMV 35S) promoter as a control. All promoters were expressed in white spruce embryos, yet at levels lower than CaMV 35S. In addition, in the embryos the heat-shock and the alcohol dehydrogenase promoters showed inducible expression when given the proper induction stimulus. In seedlings, expression of all promoters was lower than in the embryos and expression was only inducible with the heat-shock promoter in the cotyledons. Of the tissues tested, the expression level of all promoters was lowest in embryogenic callus. Interestingly, the expression of the beta-glucuronidase gene in embryogenic callus was restricted to the proembryonal head cells regardless of the promoter used. These results clearly demonstrate the use of particle bombardment to test the transient expression of heterologous promoters in organized tissue and the expression of angiosperm promoters in a gymnosperm.

Cloning, Molecular↗

Type H superconductors and the vortex lattice.

Superconducting material is used, for example, in magnetic resonance imaging for medical examinations and particle accelerators in physics. Knowledge about superfluid liquids can give us deeper insight into the ways in which matter behaves in its lowest and most ordered state. Work by the author on superconduction in liquid helium established the existence of type II superconductors and proved that vortex lattices exist in superfluid helium, in the presence of magnetic fields. He showed that the Ginzburg-Landau theory could be extended to include this "new" type of superconductors, which today are in common use. His work on phase transitions of these superconductors under the influence of magnetic fields was groundbreaking, although he has worked in many other areas since then. He was awarded the Nobel prize in 2003 "for pioneering contributions to the theory of superconductors and superfluids" with V L. Ginzburg and A. J. Leggett.

Journal Article↗

Transgene copy number can be positively or negatively associated with transgene expression.

Two different types of T-DNA insert were found in tobacco plants transformed with Agrobacterium tumefaciens. High-expressing (H) types had one copy of the T-DNA at a locus and produced high expression of the transgene uidA, as measured by uidA RNA levels and beta-glucuronidase activity; low-expressing (L) types had inverted repeats of the T-DNA at a locus and produced low uidA expression. H-types from different transformants acted additively, and cross-fertilization between two different homozygous transformants with H-type inserts produced F1 plants with GUS activity that equalled the parents and individual F2 plants with 50%, 100%, 150% and 200% of parental values. However, the L-type inserts worked in trans to suppress uidA expression from H-type inserts when both were present in the same genome. Hence when a transformant homozygous for the L-type insert was crossed to one homozygous for the H-type, all plants in the F1 and F2 generations with both types of insert had low GUS activity while F2 segregants that only had the H-type inserts had high GUS activity again. Suppression of the H-type gene was associated with increased methylation of the insert. Particle acceleration was used to introduce further copies of uidA into tissues of the transformants. Regardless of the promoter used, those plants with endogenous L-type inserts showed none of the distinct loci of GUS activity readily visible in material with no inserts, showing that L-type inserts could suppress not only the uidA expression of genomic homologues, but also of copies added in vitro.

Agrobacterium tumefaciens↗

Transformation of four pathogenic Phytophthora spp by microprojectile bombardment on intact mycelia.

Phytophthora capsici, P. citricola, P. cinnamomi and P. citrophthora were transformed without the removal of cell walls by particle acceleration with plasmids containing the beta-glucuronidase gene and hygromycin B resistance. Transformants were detected by histochemical and fluorometric beta-glucuronidase assays and confirmed by Southern-blot hybridization. It was found that the promoter of a plant virus is functional in Phytophthora. In addition, a method was designed to visually identify homogeneous transformed colonies, derived from zoospores of transformed multinucleated Phytophthora mycelia, based on blue color development on plates containing X-Gluc.

Blotting, Southern↗

Iodination-deiodination. A radiochemical method for detection of structure and changes in structure in RNA.

Bound iodine is released from radioiodinated nucleotides in polymers exposed to sodium bisulfite. The rate of bisulfite-catalyzed deiodination of pyrimidines can be controlled both by change of temperature of pH and is also dependent on the molecular association of the nucleotide. The rate of release of iodine from iodocytidine in polycytidylate is greater than the rate of elimination from RNA. Experiments testing the influence of base-pairing of the iodopyrimidines in synthetic polynucleotides showed that pairing of the substituted nucleotide protected the iodine bond. The rates of bisulfite-catalyzed deiodination of several radioiodinated RNAs were measured. The action of bisulfite on all single stranded RNAs tested was multiphasic consisting of a rapid early deiodination reaction supplanted by a slower phase which was followed by reacceleration of release. The release of iodine from double stranded RNA and DNA-RNA duplexes was retarded in comparison with the release from ribosomal and messenger RNA fractions. The deiodination profiles of single and double stranded RNA suggested that the intermediate stage iodine release is governed by melting of paired zones of low stability. Late release may result from destablization of the molecule through the addition of bisulfite to the pyrimidine ring or deamination. The effect of several substances expected to complex with polynucleotides was tested. Acridine orange and ethidium bromide increased loss of iodine from ribosomal RNA but slightly decreased elimination from double stranded viral RNA. A basic protein fraction isolated from ribosomal particles accelerated the deiodination of ribosomal RNA. While the destabilization caused by this protein fraction was greater than that caused by an equal amount of albumin, as tested the effect was non-specific. The results show that a change in sensitivity to chemical deiodination may folow the interaction of small amounts of protein with polynucleotides.

Animals↗

Radiation measurements aboard NASA ER-2 high altitude aircraft with the Liulin-4J portable spectrometer.

The risks to aircrew health posed by prolonged exposure to low levels of ionizing radiation at aircraft altitudes have recently received renewed attention. Civil and military aircraft currently on the drawing board are expected to operate at higher altitudes (>12 km) and fly longer ranges than do existing aircraft, thereby exposing their crews to higher levels of ionizing radiation, for longer periods of time. We are currently carrying out dosimetric measurements of the ionizing radiation environment at approximately 20 km altitude using portable Si detectors aboard NASA's two ER-2 high altitude research aircraft. The instruments, Liulin-4J, have been extensively calibrated at several particle accelerators. With these instruments, we can measure not only absorbed dose, but also variation of the absorbed dose as a function of time. We report radiation dose measurements as function of time, altitude, and latitude for several ER-2 missions.

Aircraft↗

Particle size analysis of radioactive aerosols formed by irradiation of argon using 65 MeV quasi-monoenergetic neutrons.

The size distributions of 38Cl and 39Cl aerosols formed from the irradiation of argon gas containing di-octyl phthalate (DOP) aerosols by 65 MeV quasi-monoenergetic neutrons were measured to study the formation mechanism of radioactive aerosols in high-energy radiation fields. Both the number size distribution and the activity-weighted size distribution were measured using an electrical low-pressure impactor. It was found that the 35Cl and 39Cl aerosols are formed by attachment of the radioactive atoms generated by the neutron-induced reaction to the DOP aerosol particles.

Aerosols↗

Synthesis and properties of 18F-labeled potential myocardial blood flow tracers.

PET centers without particle accelerators make clinical PET widely available at reduced cost. For myocardial perfusion tracers, these satellite PET centers are limited to generator- produced 82Rb(+) and 62Cu[PTSM]. Their limitations motivate a search for transportable alternatives. In search of new tracers we have synthesized several 18F-labeled amines and quaternary ammonium salts. Among them, 4-[18F]fluorotri-N-methylanilinium ([18F]FTMA) has flow-tracing properties. The compound is functional, but has properties that justify a continued search.

Animals↗

Development of the fiber neutron monitor for the energy range 15-100 MeV on the International Space Station (ISS).

In order to investigate the space environment, a new neutron monitor has been prepared. The sensor consists of scintillation fibers (FIB) and will be on board the exposed facility of the Japanese Experimental module (Kibo) of the International Space Station (ISS). The sensor is one of the instruments which measures the particle and plasma environment around the ISS. The sensor will be used by the cosmonauts who work on the ISS, to help them avoid a strong particle radiation which may arrive soon. We believe that such an alert is necessary for the cosmonauts to prevent unnecessary radiation from the sun. Furthermore, the sensor will be very useful in understanding the particle acceleration mechanism at the solar surface. The design of the Engineering Model (EM) was finished and its properties were investigated. This report discusses these results.

Equipment Design↗