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H2DCF-DA (dihydrodichlorofluorescein diacetate) is widely used to evaluate ‘cellular oxidative stress’. After passing through the plasma membrane, this lipophilic and non-fluorescent compound is de-esterified to a hydrophilic alcohol [H2DCF (dihydrodichlorofluorescein)] that may be oxidized to fluorescent DCF (2′,7′-dichlorofluorescein) by a process usually considered to involve ROS (reactive oxygen species). It is, however, not always recognized that, being a hydrophilic molecule, H2DCF does not cross membranes, except for the outer fenestrated mitochondrial ones. It is also not generally realized that oxidation of H2DCF is dependent either on Fenton-type reactions or on unspecific enzymatic oxidation by cytochrome c, for neither superoxide, nor H2O2, directly oxidizes H2DCF. Consequently, oxidation of H2DCF requires the presence of either cytochrome c or of both redox-active transition metals and H2O2. Redox-active metals exist mainly within lysosomes, whereas cytochrome c resides bound to the outer side of the inner mitochondrial membrane. Following exposure to H2DCF-DA, weak mitochondrial fluorescence was found in both the oxidation-resistant ARPE-19 cells and the much more sensitive J774 cells. This fluorescence was only marginally enhanced following short exposure to H2O2, showing that by itself it is unable to oxidize H2DCF. Cells that were either exposed to the lysosomotropic detergent MSDH (O-methylserine dodecylamide hydrochloride), exposed to prolonged oxidative stress, or spontaneously apoptotic showed lysosomal permeabilization and strong DCF-induced fluorescence. The results suggest that DCF-dependent fluorescence largely reflects relocation to the cytosol of lysosomal iron and/or mitochondrial cytochrome c. [ABSTRACT FROM AUTHOR]

The fastest swimming fishes in relation to size are found among coral reef fish larvae on their way to settle on reefs. By testing two damselfishes, Chromis atripectoralis and Pomacentrus amboinensis, we show that the high swimming speeds of the pre-settlement larvae are accompanied by the highest rates of oxygen uptake ever recorded in ectothermic vertebrates. As expected, these high rates of oxygen uptake occur at the cost of poor hypoxia tolerance. However, hypoxia tolerance is needed when coral reef fishes seek nocturnal shelter from predators within coral colonies, which can become severely hypoxic microhabitats at night. When the larvae settle on the reef, we found that they go through a striking respiratory transformation, i.e. the capacity for rapid oxygen uptake falls, while the ability for high-affinity oxygen uptake at low oxygen levels is increased. This transition to hypoxia tolerance is needed when they settle on the reef; this was strengthened by our finding that small resident larvae of Acanthochromis polyacanthus, a damselfish lacking a planktonic larval stage, do not display such a transition, being well adapted to hypoxia and showing relatively low maximum rates of oxygen uptake that change little with age. [ABSTRACT FROM AUTHOR]

Objectives: To apply the normalized resistance interpretation (NRI) method to Etest MIC results which have higher precision than conventional log2 dilution MIC tests due to the inclusion of intermediate values. If successful, NRI might provide an objective tool for the definition of epidemiological MIC cut-off values.Methods: MICs of tigecycline and other antimicrobial agents were determined for 4771 clinical isolates comprising five Gram-positive and 13 Gram-negative species or species groups using the Etest. Histograms of MIC values were constructed for each species and NRI calculations were applied to them. An upper MIC limit of 2.5 SD above the theoretical mean of the normalized distribution was used for setting the epidemiological cut-off values.Results: Calculated cut-off values for wild-type strains were between 0.11 and 0.96 mg/L for Gram-positive species, and between 0.44 and 8.3 mg/L for Gram-negative species, except for Pseudomonas aeruginosa, which had a cut-off value of 450 mg/L, consistent with earlier reports on the lack of activity of tigecycline against this species.Conclusions: NRI offers an objective method for the analysis of MICs produced using Etests and the determination of epidemiological MIC cut-off values. [ABSTRACT FROM AUTHOR]

Mouthbrooding occurs among several groups of fishes. Although a mouth full of eggs can be expected to pose a considerable respiratory problem, to our knowledge no study has examined respiratory consequences of mouthbrooding in fishes, or how hypoxia or strenuous swimming may affect the success of this reproductive strategy. In two species of cardinalfish (Apogon fragilis and Apogon leptacanthus), from the reef at Lizard Island (Great Barrier Reef), we found that mouthbrooding significantly reduced the ability to take up oxygen at low ambient oxygen levels. While the direct energetic cost of mouthbrooding appeared insignificant at rest in well-oxygenated water, mouthbrooding significantly reduced the respiratory scope of the fishes and their capacity for sustained aerobic swimming. The males spat out their eggs in hypoxia. Interestingly, the species with the larger brood, A. fragilis, spat out the brood at a higher water [O2] than did A. leptacanthus, which had a smaller mean brood mass. Moreover, in contrast to mouthbrooding A. leptacanthus, mouthbrooding A. fragilis was unable to increase its ventilatory frequency in response to hypoxia. This suggests a trade-off situation between hypoxia tolerance and brood size. Apparently, A. fragilis has sacrificed hypoxia tolerance in favour of a large brood size to a greater extent than has A. leptacanthus. [ABSTRACT FROM AUTHOR]

SUMMARY:: While medical science has struggled to find ways to counteract anoxic brain damage with limited success, evolution has repeatedly solved this problem. The best-studied examples of anoxia-tolerant vertebrates are the crucian carp and some North American Freshwater turtles. These can survive anoxia for days to months, depending of temperature. Both animals successfully fight any major fall in brain ATP levels, but the strategies they use to accomplish this are quite divergent. The anoxic turtle suppresses brain activity to such a degree that it becomes virtually comatose. The underlying mechanisms involve closing down ion conductances and releasing GABA and adenosine. By contrast, the crucian carp remains active in anoxia, although it suppresses selected brain functions, and avoids lactate self-poisoning by producing an exotic anaerobic end-product. These animals provide unique models for studying anoxic survival mechanisms both on a molecular and physiological level. [ABSTRACT FROM AUTHOR]

While the family-based analysis of genetic and environmental contributions to continuous or Gaussian traits is now straightforward using the linear mixed models approach, the corresponding analysis of complex binary traits is still rather limited. In the latter we usually rely on twin studies or pairs of relatives, but these studies often have limited sample size or have difficulties in dealing with the dependence between the pairs. Direct analysis of extended family data can potentially overcome these limitations. In this paper, we will describe various genetic models that can be analysed using an extended family structure. We use the generalized linear mixed model to deal with the family structure and likelihood-based methodology for parameter inference. The method is completely general, accommodating arbitrary family structures and incomplete data. We illustrate the methodology in great detail using the Swedish birth registry data on pre-eclampsia, a hypertensive condition induced by pregnancy. The statistical challenges include the specification of sensible models that contain a relatively large number of variance components compared to standard mixed models. In our illustration the models will account for maternal or foetal genetic effects, environmental effects, or a combination of these and we show how these effects can be readily estimated using family data. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Using respirometry, we examined the hypoxia tolerance of 31 teleost fish species (seven families) inhabiting coral reefs at a 2–5 m depth in the lagoon at Lizard Island (Great Barrier Reef, Australia). All fishes studied maintained their rate of oxygen consumption down to relatively severe hypoxia (20–30% air saturation). Indeed, most fishes appeared unaffected by hypoxia until the oxygen level fell below 10% of air saturation. This, hitherto unrecognized, hypoxia tolerance among coral reef fishes could reflect adaptations to nocturnal hypoxia in tide pools. It may also be needed to enable fishes to reside deep within branching coral at night to avoid predation. Widespread hypoxia tolerance in a habitat with such an extreme biodiversity as coral reefs indicate that there is a wealth of hypoxia related adaptations to be discovered in reef fishes. [ABSTRACT FROM AUTHOR]

For the Large Hadron Collider luminosity upgrade, two of the NbTi 8.3 T main bending dipoles will be replaced by two shorter Nb3Sn 11.2 T dipoles to create space for the installation of collimators in the dispersion suppression region. With the aim to verify the design features, several 2 m long 11 T models have been constructed and tested at CERN. During the fabrication and assembly of, so far, seven single and two double aperture short model magnets, several challenges were identified and tackled. These include reproducibility in coil fabrication and assembly procedure, as well as control of mechanical stresses in the conductor and surrounding structure. In order to limit coil over-compression and improve reproducibility, the cable insulation was re-optimized. In addition, a review of the collaring procedure of the 11 T magnet was launched with the goal of reducing the risk of conductor degradation due to excessive stress. In this paper, the main fabrication and assembly steps are described, including the description of the actions taken to resolve the identified weakness. [ABSTRACT FROM AUTHOR]

First principle modeling of the lower hybrid (LH) current drive in tokamak plasmas is a longstanding activity, which is gradually gaining in accuracy thanks to quantitative comparisons with experimental observations. The ability to reproduce simulatenously the plasma current and the non-thermal bremsstrahlung radial profiles in the hard x-ray (HXR) photon energy range represents in this context a significant achievement. Though subject to limitations, ray tracing calculations are commonly used for describing wave propagation in conjunction with Fokker–Planck codes, as it can capture prominent features of the LH wave dynamics in a tokamak plasma-like toroidal refraction. This tool has been validated on several machines when the full absorption of the LH wave requires the transfer of a small fraction of power from the main lobes of the launched power spectrum to a tail at a higher parallel refractive index. Conversely, standard modeling based on toroidal refraction only becomes more challenging when the spectral gap is large, except if other physical mechanisms may dominate to bridge it, like parametric instabilities, as suggested for JET LH discharges (Cesario et al 2004 Phys. Rev. Lett. 92 175002), or fast fluctuations of the launched power spectrum or ‘tail’ LH model, as shown for Tore Supra (Decker et al 2014 Phys. Plasma21 092504). The applicability of the heuristic ‘tail’ LH model is investigated for a broader range of plasma parameters as compared to the Tore Supra study and with different LH wave characteristics. Discrepancies and agreements between simulations and experiments depending upon the different models used are discussed. The existence of a ‘tail’ in the launched power spectrum significantly improves the agreement between modeling and experiments in plasma conditions for which the spectral gap is large in EAST and Alcator C-Mod tokamaks. For the Alcator C-Mod tokamak, the experimental evolution of the HXR profiles with density suggests that this model is valid up to a line-averaged density of m−3, a statement that is confirmed by simulations of the HXR scaling law with density. While simulations with GENRAY/CQL3D codes have ascribed the fast decrease of the HXR emission with density to parasitic absorption in the scrape-off layer by collisional damping, an alternative interpretetation based on an enhanced refraction as the LH wave propagates in the vicinity of the X-point is provided by C3PO/LUKE codes. The consequences for the predictions of LH current in ITER are discussed. [ABSTRACT FROM AUTHOR]

Runaway electrons can be generated in tokamak plasmas if the accelerating force from the toroidal electric field exceeds the collisional drag force owing to Coulomb collisions with the background plasma. In ITER, disruptions are expected to generate runaway electrons mainly through knock-on collisions (Hender et al 2007 Nucl. Fusion47 S128–202), where enough momentum can be transferred from existing runaways to slow electrons to transport the latter beyond a critical momentum, setting off an avalanche of runaway electrons. Since knock-on runaways are usually scattered off with a significant perpendicular component of the momentum with respect to the local magnetic field direction, these particles are highly magnetized. Consequently, the momentum dynamics require a full 3D kinetic description, since these electrons are highly sensitive to the magnetic non-uniformity of a toroidal configuration. For this purpose, a bounce-averaged knock-on source term is derived. The generation of runaway electrons from the combined effect of Dreicer mechanism and knock-on collision process is studied with the code LUKE, a solver of the 3D linearized bounce-averaged relativistic electron Fokker–Planck equation (Decker and Peysson 2004 DKE: a fast numerical solver for the 3D drift kinetic equation Report EUR-CEA-FC-1736, Euratom-CEA), through the calculation of the response of the electron distribution function to a constant parallel electric field. The model, which has been successfully benchmarked against the standard Dreicer runaway theory now describes the runaway generation by knock-on collisions as proposed by Rosenbluth (Rosenbluth and Putvinski 1997 Nucl. Fusion37 1355–62). This paper shows that the avalanche effect can be important even in non-disruptive scenarios. Runaway formation through knock-on collisions is found to be strongly reduced when taking place off the magnetic axis, since trapped electrons can not contribute to the runaway electron population. Finally, the relative importance of the avalanche mechanism is investigated as a function of the key parameters for runaway electron formation, namely the plasma temperature and the electric field strength. In agreement with theoretical predictions, the LUKE simulations show that in low temperature and electric field the knock-on collisions becomes the dominant source of runaway electrons and can play a significant role for runaway electron generation, including in non-disruptive tokamak scenarios. [ABSTRACT FROM AUTHOR]

In the infrared wavelength region, thermopiles are an important type of detector. A major advantage of thermopiles is their non-cooling requirement. Depending on the applied absorption layer, their responsivity is often rather flat within a large wavelength region. This work presents the fabrication and characterization of a sensitivity and design optimized thermopile detector with a 4 um self-supported SiO2/SU-8 membrane. The structure consists of 240 series interconnected thermocouple junctions obtained by metal evaporation and lift-off. Two metal combinations have been evaluated, namely, nickel/titanium and aluminium/bismuth. Series resistances of 76 kO and 283 kO were measured for the Ni/Ti thermopile and the Al/Bi thermopile respectively. For the Al/Bi thermopile a responsivity of 60 V W[?]1 was achieved using a 1.56 um fibre coupled diode laser with a power of 3.5 mW. Using a white light source with a radiation flux of 0.45 W mm[?]2 a voltage response of 68 V mm2 W[?]1 was measured for the Al/Bi thermopile. The time constant of the characterized detectors was calculated to be 70 ms, using the pulsed IR laser. [ABSTRACT FROM AUTHOR]