Runaway electron imaging spectrometry (REIS) system.

A portable Runaway Electron Imaging and Spectrometry System (REIS) was developed in ENEA-Frascati to measure synchrotron radiation spectra from in-flight runaway electrons in tokamaks. The REIS is a wide-angle optical system collecting simultaneously visible and infrared emission spectra using an incoherent bundle of fibers, in a spectral range that spans from 500 nm to 2500 nm, and visible images using a CCD color microcamera at a rate of 25 frames/s. The REIS system is supervised and managed using a dedicated LabVIEW program to acquire data simultaneously from three spectrometers every 20 ms (configurable down to 10 ms). An overview of the REIS architecture and acquisition system and resulting experimental data obtained in FTU are presented and discussed in this paper.

Hepatic and cardiac and iron overload detected by T2* magnetic resonance (MRI) in patients with myelodisplastic syndrome: A cross-sectional study.

INTRODUCTION: Transfusion-dependent anemia and iron overload are associatedwith reduced survival in myelodysplastic syndrome (MDS). This cross-sectional study aimed to evaluate the prevalence of hepatic and cardiac overload in patients with MDS as measured by T2* magnetic resonance imaging (MRI), and its correlation with survival. METHODS: MDS or chronic myelomonocytic leukemia patients had iron overload evaluated by T2* MRI. HIO was considered when hepatic iron concentration ≥ 2 g/mg. Cardiac iron overload was considered with a T2*-value < 20 ms. RESULTS: Among 71 patients analyzed, median hepatic iron concentration was 3.9 g/mg (range 0.9-16 g/mg), and 68%of patients had hepatic iron overload. Patients with hepatic iron overload had higher mean ferritin levels (1182 ng/mL versus 185 ng/mL, p < 0.0001), transferrin saturation (76% versus 34%, p < 0.0001) and lower survival rates. Median cardiac T2*value was 42 ms (range 19.7-70.1 ms), and only one patienthad a T2* value indicative of cardiac iron overload. CONCLUSIONS: Hepatic iron overload is found in two thirds of patients, even in cases without laboratory signs of iron overload. Hepatic iron overload by T2* MRI is associated with a decreased risk of survival in patients with MDS.

Design of gamma-ray spectrometers optimized for fast particle studies at ITER.

A set of gamma ray spectrometers has been designed for ITER within the Radial Gamma Ray Spectrometer (RGRS) project. The aim of this project is designing a system, integrated with the ITER radial neutron camera, which is able to measure the gamma-rays emitted from the plasma with a good energy resolution (about 1.5% at 4.44 MeV) and at high counting rates (in excess of 1 MHz). The RGRS will be able to operate both in the D phase and in the full-power DT phase and will measure gamma rays from (i) reactions between fast ions, such as α particles, and light impurities and (ii) bremsstrahlung emission generated by runaway electron interactions with both plasma bulk and tokamak walls. The RGRS detectors are arranged in nine lines of sights (able to cover a radial region with r < a/3), each featuring a large LaBr3 scintillator crystal. Due to the high neutron flux and magnetic field, several solutions have been adopted to guarantee a good signal to background ratio and MHz counting rate capabilities. The RGRS is capable to combine space and energy distribution measurements of α particles and runaway electrons, which will help the study of the fast particle physics in a burning plasma.

The role of chemical speciation, chemical fractionation and calcium disruption in manganese-induced developmental toxicity in zebrafish (Danio rerio) embryos.

Manganese (Mn) is an essential nutrient that can be toxic in excess concentrations, especially during early development stages. The mechanisms of Mn toxicity is still unclear, and little information is available regarding the role of Mn speciation and fractionation in toxicology. We aimed to investigate the toxic effects of several chemical forms of Mn in embryos of Danio rerio exposed during different development stages, between 2 and 122h post fertilization. We found a stage-specific increase of lethality associated with hatching and removal of the chorion. Mn(II), ([Mn(H2O)6](2+)) appeared to be the most toxic species to embryos exposed for 48h, and Mn(II) citrate was most toxic to embryos exposed for 72 and/or 120h. Manganese toxicity was associated with calcium disruption, manganese speciation and metal fractionation, including bioaccumulation in tissue, granule fractions, organelles and denaturated proteins.

SERCA2a gene transfer prevents intimal proliferation in an organ culture of human internal mammary artery.

Coronary restenosis, a major complication of percutaneous balloon angioplasty, results from neointimal proliferation of vascular smooth muscle cells (VSMCs). The sarco/endoplasmic reticulum calcium ATPase 2a isoform (SERCA2a), specific to contractile VSMCs, has been reported previously to be involved in the control of the Ca(2+)-signaling pathways governing proliferation and migration. Moreover, SERCA2a gene transfer was reported to inhibit in vitro VSMC proliferation and to prevent neointimal thickening in a rat carotid injury model. The aim of this study was to evaluate the potential therapeutic interest of SERCA2a gene transfer for prevention of in-stent restenosis using a ex vivo model of human left internal mammary artery (hIMA) intimal thickening. Left hIMAs, obtained at the time of aorto-coronary bypass surgeries, were subjected to balloon dilatation followed by infection for 30 min with adenoviruses encoding either human SERCA2 and green fluorescence protein (GFP) or control gene (ß-galactosidase, ß-gal) and GFP. Proliferation of subendothelial VSMCs and neointimal thickening were observed in balloon-injured hIMA maintained 14 days in organ culture under constant pressure and perfusion. SERCA2a gene transfer prevented vascular remodeling and significantly (P<0.01, n=5) reduced neointimal thickening in injured arteries (intima/media ratio was 0.07±0.01 vs 0.40±0.03 in ß-gal-infected arteries). These findings could have potential implications for treatment of pathological in-stent restenosis.

Exploration of ion temperature profile measurements at JET using the upgraded neutron profile monitor.

The neutron profile monitor (NPM), routinely used at the Joint European Torus for neutron emissivity profile measurements, consists of two fan-shaped arrays of collimators and each line of sight (LOS) is equipped with a NE213 liquid organic scintillator for simultaneous measurements of the 2.5 MeV and 14 MeV neutrons. A digital system developed in ENEA has replaced the analog acquisition electronics and now enables the NPM to perform spatially resolved neutron spectrometry by providing neutron pulse height spectra (PHS) for each LOS. However, the NPM was not originally designed as a spectrometer and, therefore, lacks several key features, such as detailed measurements of the detector response functions and the presence of detector stability monitors. We present a proof of principle of ion temperature profile measurements derived from the NPM PHS in high plasma current discharges using simulated detector response functions.

Mechanisms of manganese-induced neurotoxicity in primary neuronal cultures: the role of manganese speciation and cell type.

Manganese (Mn) is an essential trace element required for the proper functioning of a variety of physiological processes. However, chronic exposures to Mn can cause neurotoxicity in humans, especially when it occurs during critical stages of the central nervous system development. The mechanisms mediating this phenomenon as well as the contribution of Mn speciation and the sensitivity of different types of neuronal cells in such toxicity are poorly understood. This study was aimed to investigate the mechanisms mediating the toxic effects of MnCl(2), Mn(II) citrate, Mn(III) citrate, and Mn(III) pyrophosphate in primary cultures of neocortical (CTX) and cerebellar granular (CGC) neurons. Cell viability, mitochondrial function, and glutathione levels were evaluated after Mn exposure. CGC were significantly more susceptible to Mn-induced toxicity when compared with CTX. Moreover, undifferentiated CGC were more vulnerable to Mn toxicity than mature neurons. Mitochondrial dysfunction was observed after the exposure to all the tested Mn species. Ascorbate protected CGC against Mn-induced neurotoxicity, and this event seemed to be related to the dual role of ascorbate in neurons, acting as antioxidant and metabolic energetic supplier. CTX were protected from Mn-induced toxicity by ascorbate only when coincubated with lactate. These findings reinforce and extend the notion of the hazardous effects of Mn toward neuronal cells. In addition, the present results indicate that Mn-induced neurotoxicity is influenced by brain cell types, their origins, and developmental stages as well as by the chemical speciation of Mn, thus providing important information about Mn-induced developmental neurotoxicity and its risk assessment.

Experimental observation of increased threshold electric field for runaway generation due to synchrotron radiation losses in the FTU Tokamak.

The threshold electric field for runaway generation has been investigated during runaway suppression experiments by means of electron-cyclotron-resonance heating in the flattop phase of FTU discharges. Runaway suppression has been experimentally found to occur at electric fields substantially larger than those predicted by the relativistic collisional theory of runaway generation, ER=nee3lnΛ/4πε0(2)mec2. These experimental results are consistent with an increase of the critical electric field due to the electron synchrotron radiation losses. No runaway electrons are found in FTU experiments below the radiation threshold. These results support evidence for a new threshold electric field for runaway generation that accounts for the effect of the synchrotron losses, and which should be considered when making predictions on runaway generation and mitigation in devices such as ITER.

Distribution and behavior of manganese in the Alto do Paranapanema Basin.

This paper reports manganese (Mn) fractionation in samples collected from the water column and sediments in an environmental protection area in the Alto do Paranapanema Basin (São Paulo State, Brazil). The three locations studied showed equivalent Mn levels, with moderate seasonal differences (p < 0.05). The sediment samples contained five Mn species (p < 0.05): iron and manganese (hydr)oxides > Mn bound to carbonates approximately exchangeable Mn approximately Mn bound to silicates > Mn bound to organic matter (p < 0.05). The water samples contained three species (p < 0.05): particulate Mn > labile Mn approximately non-labile Mn. The data suggest that Mn has a natural origin (Enrichment Factor EF < 2; Geoaccumulation Index I(geo) < 0) and moderate environmental risk (Risk Assessment Code RAC approximately 30%). At the same time, under certain conditions some manganese species could be present in a state of equilibrium between the water column and sediment. These results could provide a basis for Mn management in the Alto do Paranapanema Basin.

Disruption avoidance in the Frascati Tokamak Upgrade by means of magnetohydrodynamic mode stabilization using electron-cyclotron-resonance heating.

Disruption avoidance by stabilization of MHD modes through injection of ECRH at different radial locations is reported. Disruptions have been induced in the FTU (Frascati Tokamak Upgrade) deuterium plasmas by Mo injection or by exceeding the density limit (D gas puffing). ECRH is triggered when the V(loop) exceeds a preset threshold value. Coupling between MHD modes (m/n=3/2, 2/1, 3/1) occurs before disruption. Direct heating of one coupled mode is sufficient to avoid disruptions, while heating close to the mode leads to disruption delay. These results could be relevant for the International Thermonuclear Experimental Reactor tokamak operation.

Enhanced production of runaway electrons during a disruptive termination of discharges heated with lower hybrid power in the Frascati Tokamak Upgrade.

We report on the observation of a large production of runaway electrons during a disruptive termination of discharges heated with lower-hybrid waves at the Frascati Tokamak Upgrade. The runaway current plateaus, which can carry up to 80% of the predisruptive current, are observed more often than in normal Ohmic disruptions. The largest runaway currents correspond to the slowest plasma current decay rates. This trend is opposite to what is observed in most tokamaks. We attribute this anomalous behavior to the acceleration of the preexistent wave-resonant suprathermal electrons during the disruption decay phase. These results could be relevant for the operation of the ITER tokamak whenever a sizeable amount of lower-hybrid power is made available.

Changes in airborne fungi from the outdoors to indoor air; large HVAC systems in nonproblem buildings in two different climates.

Little is known about the changes in occurrence and distribution of airborne fungi as they are transported in the airstream from the outdoor air through the heating, ventilation, and air conditioning (HVAC) system to the indoor air. To better understand this, airborne fungi were analyzed in the HVAC systems of two large office buildings in different climate zones. Fungal samples were taken in each of the walk-in chambers of the HVAC systems using a six-stage Andersen Sampler with malt extract agar. Results showed that fungal species changed with different locations in the HVAC systems. The outdoor air intake produced the greatest filtration effect for both the counts and species of outdoor air fungi. The colony forming unit (CFU) counts and species diversity was further reduced in the air directly after the filters. The cooling coils also had a substantial filtration effect. However, in room air the CFU counts were double and the mixture of fungal species was different from the air leaving the HVAC system at the supply air outlet in most locations. Diffusion of outdoor air fungi to the indoors did not explain the changes in the mixture of airborne fungi from the outdoor air to the indoor air, and some of the fungi present in the indoor air did not appear to be transported indoors by the HVAC systems.

Protective role of uncoupling protein 2 in atherosclerosis.

BACKGROUND: Uncoupling protein 2 (UCP2) regulates the production of reactive oxygen species in macrophages. However, its role in atherosclerosis is unknown. METHODS AND RESULTS: Irradiated low-density lipoprotein receptor deficient mice (LDLR-/-) were transplanted with bone marrow from either UCP2 deficient mice (Ucp2-/-) or wild type mice (Ucp2+/+). Mice were fed an atherogenic diet for 7 weeks. Engraftment of bone marrow cells was confirmed by the presence of UCP2 protein expression in spleen cell mitochondria of Ucp2+/+ transplanted mice and its absence in Ucp2-/- transplanted mice. Leukocyte counts and plasma cholesterol levels were comparable in both groups. We found a marked increase in atherosclerotic lesion size in the thoracic aorta of Ucp2-/- transplanted mice compared with control Ucp2+/+ transplanted mice (8.3+/-0.9% versus 4.3+/-0.4%, respectively; P<0.005), as well as in the aortic sinus (150 066+/-12 388 microm2 versus 105 689+/-9 727 microm2, respectively; P<0.05). This was associated with increased nitrotyrosine staining, which suggests enhanced oxidative stress. Analysis of plaque composition revealed a significant increase in macrophage accumulation (P<0.05) and apoptosis (P<0.05), along with a decrease in collagen content (P<0.05), suggesting a potentially more vulnerable phenotype. CONCLUSION: These results suggest a protective role for UCP2 against atherosclerosis.

Design and applications of methods for fluorescence detection of iron in biological systems.

Fluorescence metalosensors provide a means to detect iron in biological systems that is versatile, economical, sensitive and of a high-throughput nature. They rely on relatively high-affinity iron-binding carriers conjugated to highly fluorescent probes that undergo quenching after metal complexation. Metal specificity is determined by probes containing either an iron-binding moiety of high affinity (type A) or of relatively lower affinity (type B) used in combination with a strong specific iron chelator. Due to the heterogeneous nature of biological systems, the apparent metal-binding affinity and complexation stoichiometry ought to be specifically defined. Fluoresceinated moieties coupled to metal-binding cores detect Fe at sub-micromolar concentrations and even sub-microlitre volumes (i.e. cells). Although an ideal probe should also be specific for a particular oxidation state of iron, in physiological conditions that property might be difficult to attain. Quantification of labile iron in cells has relied on the ability of permeant iron chelators to restore the fluorescence of probes quenched by intracellular Fe. Modern design of probes aims to (a) improve probe targeting to specific cell compartments and (b) create probes that respond to metal binding by signal enhancement.

Discharges in the JET tokamak where the safety factor profile is identified as the critical factor for triggering internal transport barriers.

Joint European Torus discharges which demonstrate the critical role the safety factor profile, q, can play in the formation of internal transport barriers (ITB) are examined. In these discharges, the target parameters, including the E x B flows, were kept virtually the same, except for the q profile. In a discharge with a nonmonotonic q, an ITB was triggered whereas a discharge with monotone q made no such transition. Thus, there is strong evidence that the q profile was the critical factor for the triggering of an ITB. Possible interpretations of this finding are discussed.

JET quasistationary internal-transport-barrier operation with active control of the pressure profile.

Quasistationary operation has been achieved on the Joint European Torus tokamak in internal-transport-barrier (ITB) scenarios, with the discharge time limited only by plant constraints. Full current drive was obtained over all the high performance phase by using lower hybrid current drive. For the first time feedback control on the total pressure and on the electron temperature profile was implemented by using, respectively, the neutral beams and the ion-cyclotron waves. Although impurity accumulation could be a problem in steady state ITBs, these experiments bring some elements to answer to it.

Labile iron in parenteral iron formulations and its potential for generating plasma nontransferrin-bound iron in dialysis patients.

BACKGROUND: Labile plasma iron (LPI) associated with iron supplementation has been implicated in complications found in dialysis patients. As LPI can potentially catalyse oxygen radical generation, we determined the presence of labile iron in the parenteral preparations and the frequency of occurrence of LPI in dialysis patients. DESIGN: The capacity to donate iron to apotransferrin (apo-) or to the chelator desferrioxamine (DFO) was measured with fluorescein-Tf (Fl-Tf) and Fl-DFO, respectively. Those probes undergo quenching upon binding to iron. Iron-catalysed generation of oxidant species was determined with dihydrorhodamine. Plasma nontransferrin-bound iron (NTBI), here termed LPI, was determined by mobilization of iron from low-affinity binding sites with oxalate, followed by its quantification with Fl-Tf in the presence of Ga(III). RESULTS: Normal individuals and most (80%) dialysis patients, analysed at least 1 week after iron supplementation showed no detectable (<0.2 microm) LPI. However, approximately 20% of the patients (n = 71) showed significant LPI levels (>0.2 microm), in some cases weeks after iron administration. LPI levels correlated best (r2 = 0.9) with Tf saturation. The iron preparations contained 2-6% low molecular weight and redox-active iron, most of which is chelated by Tf. CONCLUSIONS: Parenteral iron formulations contain a small but significant fraction of redox-active iron, most of which is scavenged by apo-Tf within <1 h. Therefore, oxidant stress associated with iron infusion is likely to be transient. The bulk of the polymeric iron is apparently inaccessible to apo-Tf. Although LPI might return to normal within 2 h of intravenous iron infusion, the long-term persistence of low-level LPI in up to 20% of end stage renal disease (ESRD) patients indicates that complete clearance of the intravenous iron may be more protracted than originally estimated.

Inhibition of transforming growth factor-beta signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice.

Atherosclerosis is a disease of the arterial wall that seems to be tightly modulated by the local inflammatory balance. Whereas a large body of evidence supports a role for proinflammatory mediators in disease progression, the understanding of the role of the antiinflammatory component in the modulation of plaque progression is only at its beginning. TGF-beta1, -beta2, and -beta3 are cytokines/growth factors with broad activities on cells and tissues in the cardiovascular system and have been proposed to play a role in the pathogenesis of atherosclerosis. However, no study has examined the direct role of TGF-beta in the development and composition of advanced atherosclerotic lesions. In the present study, we show that inhibition of TGF-beta signaling using a neutralizing anti-TGF-beta1, -beta2, and -beta3 antibody accelerates the development of atherosclerotic lesions in apoE-deficient mice. Moreover, inhibition of TGF-beta signaling favors the development of lesions with increased inflammatory component and decreased collagen content. These results identify a major protective role for TGF-beta in atherosclerosis.

Age and gender effects on cardiomyocyte apoptosis in the normal human heart.

BACKGROUND: Animal studies have suggested that apoptosis could play a significant role in the myocardial aging process. Although no information is available in humans, the paradigm that cardiomyocyte apoptosis is increased in the aged human heart has been widely propagated. Moreover, it is unknown whether gender differences may influence cardiomyocyte apoptosis. METHODS: Cardiomyocyte apoptosis was compared between subjects ranging in age from 21 to 93 years (22 men and 19 women), free of any cardiovascular disease, who died of either violent or natural causes. Strict inclusion and exclusion criteria were used to ensure that the selected hearts accurately represented normal aging. RESULTS: Apoptosis was detected using the TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) technique (controls for TUNEL included negative staining for splicing factor SC-35 and for Ki-67 antigen). The percentage of cardiomyocyte death ranged from 0% to 0.0437%, with no correlation with the age of the subject (p =.85). However, the percentage of apoptosis was threefold higher in men than in women (0.0133% +/- 0.0030% vs 0.0042% +/- 0.0008%, respectively; p <.01). CONCLUSIONS: Our results in humans do not support the hypothesis that aging influences the percentage of cardiomyocyte apoptosis. However, gender appears to be an important determinant of the occurrence of apoptosis.

Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability.

Interleukin (IL)-18 is the interferon-gamma-inducing factor and has other proinflammatory properties. The precise role of IL-18 in immunoinflammatory diseases remains poorly understood. In this study, we show that in vivo electrotransfer of an expression-plasmid DNA encoding for murine IL-18 binding protein (BP) (the endogenous inhibitor of IL-18) prevents fatty streak development in the thoracic aorta of apoE knockout mice and slows progression of advanced atherosclerotic plaques in the aortic sinus. More importantly, transfection with the IL-18BP plasmid induces profound changes in plaque composition (decrease in macrophage, T cell, cell death, and lipid content and increase in smooth muscle cell and collagen content) leading to a stable plaque phenotype. These results identify for the first time a critical role for IL-18/IL-18BP regulation in atherosclerosis and suggest a potential role for IL-18 inhibitors in reduction of plaque development/progression and promotion of plaque stability. The full text of this article is available at http://www.circresaha.org.