Altered stress stimulation of inward rectifier potassium channels in Andersen-Tawil syndrome

Inward rectifier potassium channels of the Kir2 subfamily are important determinants of the electrical activity of brain and muscle cells. Genetic mutations in Kir2.1 associate with Andersen-Tawil syndrome (ATS), a familial disorder leading to stress-triggered periodic paralysis and ventricular arrhythmia. To identify the molecular mechanisms of this stress trigger, we analyze Kir channel function and localization electrophysiologically and by time-resolved confocal microscopy. Furthermore, we employ a mathematical model of muscular membrane potential. We identify a novel corticoid signaling pathway that, when activated by glucocorticoids, leads to enrichment of Kir2 channels in the plasma membranes of mammalian cell lines and isolated cardiac and skeletal muscle cells. We further demonstrate that activation of this pathway can either partly restore (40% of cases) or further impair (20% of cases) the function of mutant ATS channels, depending on the particular Kir2.1 mutation. This means that glucocorticoid treatment might either alleviate or deteriorate symptoms of ATS depending on the patient's individual Kir2.1 genotype. Thus, our findings provide a possible explanation for the contradictory effects of glucocorticoid treatment on symptoms in patients with ATS and may open new pathways for the design of personalized medicines in ATS therapy. © FASEB.

An all-in-one dry chemistry immunoassay for the screening of coccidiostat nicarbazin in poultry eggs and liver

An automated immunoassay for the detection of nicarbazin residues in poultry eggs and liver was developed. The assay was based on a novel all-in-one dry chemistry concept and time-resolved fluorometry. The analyte specific antibody was immobilized into a single microtiter well and covered with an insulation layer, on top of which the label was dried in a small volume. The extracted sample was added automatically to the dry microtiter well, and the result was available within 18 min. Due to the rapidity and simplicity, the quantitative immunoassay could also be used as a high throughput screening method. The analytical limit of detection for the assay was calculated as 0.1 ng mL(-1) (n = 12) and the functional limit of detection as 3.2 ng g(-1) for egg (n = 6) and 11.3 ng g(-1) for liver (n = 6) samples. The sample recovery varied from 97.3 to 115.6%. Typically, the intra-assay variations were less than 10%, and interassay variations ranged between 8.1 and 13.6%.

Recent fast electron energy transport experiments relevant to fast ignition inertial fusion

A number of experiments have been undertaken at the Rutherford Appleton Laboratory that were designed to investigate the physics of fast electron transport relevant to fast ignition inertial fusion. The laser, operating at a wavelength of 1054 nm, provided pulses of up to 350 J of energy on target in a duration that varied in the range 0.5-5 ps and a focused intensity of up to 10(21) W cm(-2). A dependence of the divergence of the fast electron beam with intensity on target has been identified for the first time. This dependence is reproduced in two-dimensional particle-in-cell simulations and has been found to be an intrinsic property of the laser-plasma interaction. A number of ideas to control the divergence of the fast electron beam are described. The fractional energy transfer to the fast electron beam has been obtained from calibrated, time-resolved, target rear-surface radiation temperature measurements. It is in the range 15-30%, increasing with incident laser energy on target. The fast electron temperature has been measured to be lower than the ponderomotive potential energy and is well described by Haines' relativistic absorption model.

OPTICAL-ABSORPTION SPECTROSCOPY STUDY OF THE ROLE OF PLASMA CHEMISTRY IN YBA2CU3O7 PULSED LASER DEPOSITION

Time-resolved optical absorption spectroscopy techniques were used to study Ba, metastable Ba+, and YO absorptions in the laser-produced plasma plume from a YBa2Cu3O7 target. Results obtained indicate an initial explosive removal of material from the target sur-face followed by a subsequent evaporation process. Some YO is ejected from the target in molecular form, particularly at laser fluence

ENHANCED VOLUME PRODUCTION OF NEGATIVE-IONS IN THE POST DISCHARGE OF A MULTICUSP HYDROGEN DISCHARGE

In this paper we demonstrate a new concept in the production of negative hydrogen ions in a low-pressure multicusp discharge. The discharge voltage is modulated to produce a non-Maxwellian, hot-electron plasma during the current pulse, followed by a cool Maxwellian electron plasma in the post discharge. This procedure, of separating in time the required hot and cold electron plasmas required for volume H- production, is called a temporal filter. The time evolution of the electron energy distribution function is measured using the time-resolved second derivative of a Langmuir probe characteristic. Time-resolved measurements of the negative ion density are made using laser photodetachment. The measurements show that the negative ion density in the center of the source, at a gas pressure of 0.07 Pa, increases by a factor of 2 when the discharge is switched off. At this low pressure the average H- beam current extracted from the source, when operated with a discharge current of 1 A in the pulse modulated mode exceeds the H- beam current from a 5 A continuously operated source. The increase in efficiency of the pulsed source is explained in terms of a two-step H- production mechanism.

WASP-52b, WASP-58b, WASP-59b, and WASP-60b: Four new transiting close-in giant planets

We present the discovery of four new transiting hot jupiters, detected mainly from SuperWASP-North and SOPHIE observations. These new planets, WASP-52b, WASP-58b, WASP-59b, and WASP-60b, have orbital periods ranging from 1.7 to 7.9 days, masses between 0.46 and 0.94 M_Jup, and radii between 0.73 and 1.49 R_Jup. Their G1 to K5 dwarf host stars have V magnitudes in the range 11.7-13.0. The depths of the transits are between 0.6 and 2.7%, depending on the target. With their large radii, WASP-52b and 58b are new cases of low-density, inflated planets, whereas WASP-59b is likely to have a large, dense core. WASP-60 shows shallow transits. In the case of WASP-52 we also detected the Rossiter-McLaughlin anomaly via time-resolved spectroscopy of a transit. We measured the sky-projected obliquity lambda = 24 (+17/-9) degrees, indicating that WASP-52b orbits in the same direction as its host star is rotating and that this prograde orbit is slightly misaligned with the stellar equator. These four new planetary systems increase our statistics on hot jupiters, and provide new targets for follow-up studies.

Dynamics of relativistic transparency and optical shuttering in expanding overdense plasmas

Overdense plasmas are usually opaque to laser light. However, when the light is of sufficient intensity to drive electrons in the plasma to near light speeds, the plasma becomes transparent. This process—known as relativistic transparency—takes just a tenth of a picosecond. Yet all studies of relativistic transparency so far have been restricted to measurements collected over timescales much longer than this, limiting our understanding of the dynamics of this process. Here we present time-resolved electric field measurements (with a temporal resolution of ~ 50 fs) of the light, initially reflected from, and subsequently transmitted through, an expanding overdense plasma. Our result provides insight into the dynamics of the transparent-overdense regime of relativistic plasmas, which should be useful in the development of laser-driven particle accelerators, X-ray sources and techniques for controlling the shape and contrast of intense laser pulses.

A J-band detection of the sub-stellar mass donor in SDSS J1433+1011

We present time-resolved J-band spectroscopy of the short-period cataclysmic variable SDSS J143317.78+101123.3. We detect absorption lines from the sub-stellar donor star in this system, which contributes 38 +/- 5 per cent to the J-band light. From the relative strengths of the absorption lines in the J band, we estimate the spectral type of the donor star to be L2 +/- 1. These data are the first spectroscopic detection of a donor with a confirmed sub-stellar mass in a cataclysmic variable, and the spectral type is consistent with that expected from semi-empirical evolutionary models.

Using skew mapping, we have been able to derive an estimate for the radial velocity of the donor of K-d = 520 +/- 60 km/s. This value is consistent with, though much less precise than, predictions from mass determinations found via photometric fitting of the eclipse light curves.

Probing chemistry and kinetics of reactions in heterogeneous catalysts

Using benzene hydrogenation over Pt/SiO2 as an industrially-relevant example, we show that state-of-the-art neutron total scattering methods spanning a wide Q-range now permit relevant time-resolved catalytic chemistry to be probed directly in situ within the pore of the catalyst. The method gives access to the reaction rates on both nanometric and atomic length scales, whilst simultaneously providing an atomistic structural viewpoint on the reaction mechanism itself.

CI Aql: a Type Ia supernova progenitor?

If recurrent novae are progenitors of Type Ia supernovae, their white dwarfs must have masses close to the Chandrasekhar limit. The most reliable means of determining white dwarf masses in recurrent novae is dynamically, via radial-velocity and rotational-broadening measurements of the companion star. Such measurements require the system to be both eclipsing and to show absorption features from the secondary star. Prior to the work reported here, the only dynamical mass estimate of a recurrent nova was for U Sco, which has a white dwarf mass of 1.55 +/- 0.24 Msolar (Thoroughgood et al. 2001). We present new time-resolved, intermediate-resolution spectroscopy of the eclipsing recurrent nova CI Aquilae (CI Aql) during quiescence. We find the mass of the white dwarf to be 1.00 +/- 0.14 Msolar and the mass of the secondary star to be 2.32 +/- 0.19 Msolar. We estimate the radius of the secondary to be 2.07 +/- 0.06 Rsolar, implying that it is a slightly-evolved early A-type star. The high mass ratio of q = 2.35 +/- 0.24 and the high secondary-star mass implies that the mass transfer occurs on a thermal timescale. We suggest that CI Aql is rapidly evolving into a supersoft X-ray source, and ultimately may explode as a Type Ia supernova within 10 Myr.

Experimental investigation of hole boring and light sail regimes of RPA by varying laser and target parameters

Temporal evolution of plasma jets from micrometre-scale thick foils following the interaction of intense (3 × 10 W cm ) laser pulses is studied systematically by time resolved optical interferometry. The fluid velocity in the plasma jets is determined by comparing the data with 2D hydrodynamic simulation, which agrees with the expected hole-boring (HB) velocity due to the laser radiation pressure. The homogeneity of the plasma density across the jets has been found to be improved substantially when irradiating the laser at circular polarization compared to linear polarization. While overdense plasma jets were formed efficiently for micrometre thick targets, decreasing the target areal density and/or increasing the irradiance on the target have provided indication of transition from the 'HB' to the 'light sail (LS)' regime of RPA, characterized by the appearance of narrow-band spectral features at several MeV/nucleon in proton and carbon spectra.

Probing charge screening dynamics and electrochemical processes at the solid–liquid interface with electrochemical force microscopy

The presence of mobile ions complicates the implementation of voltage-modulated scanning probe microscopy techniques such as Kelvin probe force microscopy (KPFM). Overcoming this technical hurdle, however, provides a unique opportunity to probe ion dynamics and electrochemical processes in liquid environments and the possibility to unravel the underlying mechanisms behind important processes at the solid–liquid interface, including adsorption, electron transfer and electrocatalysis. Here we describe the development and implementation of electrochemical force microscopy (EcFM) to probe local bias- and time-resolved ion dynamics and electrochemical processes at the solid–liquid interface. Using EcFM, we demonstrate contact potential difference measurements, consistent with the principles of open-loop KPFM operation. We also demonstrate that EcFM can be used to investigate charge screening mechanisms and electrochemical reactions in the probe–sample junction. We further establish EcFM as a force-based imaging mode, allowing visualization of the spatial variability of sample-dependent local electrochemical properties.

Direct Observation of Density-Gradient Effects in Harmonic Generation from Plasma Mirrors

High-order harmonics and attosecond pulses of light can be generated when ultraintense, ultrashort laser pulses reflect off a solid-density plasma with a sharp vacuum interface, i.e., a plasma mirror. We demonstrate experimentally the key influence of the steepness of the plasma-vacuum interface on the interaction, by measuring the spectral and spatial properties of harmonics generated on a plasma mirror whose initial density gradient scale length L is continuously varied. Time-resolved interferometry is used to separately measure this scale length. 

Specific Noncompetitive Immunoassay for HT-2 Mycotoxin Detection

Here we demonstrate a novel homogeneous one-step immunoassay, utilizing a pair of recombinant antibody antigen-binding fragments (Fab), that is specific for HT-2 toxin and has a positive readout. Advantages over the conventional competitive immunoassay formats such as enzyme-linked immunosorbent assay (ELISA) are the specificity, speed, and simplicity of the assay. Recombinant antibody HT2-10 Fab recognizing both HT-2 and T-2 toxins was developed from a phage display antibody library containing 6 × 10(7) different antibody clones. Specificity of the immunoassay was introduced by an anti-immune complex (IC) antibody binding the primary antibody-HT-2 toxin complex. When the noncompetitive immune complex assay was compared to the traditional competitive assay, an over 10-fold improvement in sensitivity was observed. Although the HT2-10 antibody has 100% cross-reactivity for HT-2 and T-2 toxins, the immune complex assay is highly specific for HT-2 alone. The assay performance with real samples was evaluated using naturally contaminated wheat reference material. The half-maximal effective concentration (EC50) value of the time-resolved fluorescence resonance energy transfer (TR-FRET) assay was 9.6 ng/mL, and the limit of detection (LOD) was 0.38 ng/mL (19 μg/kg). The labeled antibodies can be predried to the assay vials, e.g., microtiter plate wells, and readout is ready in 10 min after the sample application.

Laser Driven Neutron Sources: Characteristics, Applications and Prospects

The basics of laser driven neutron sources, properties and possible applications are discussed. We describe the laser driven nuclear processes which trigger neutron generation, namely, nuclear reactions induced by laser driven ion beam (ion n), thermonuclear fusion by implosion and photo-induced nuclear (gamma n) reactions. Based on their main properties, i.e. point source (< 100 μm) and short durations (< ns), different applications are described, such as radiography, time-resolved spectroscopy and pump-probe experiments. Prospects on the development of laser technology suggest that, as higher intensities and higher repetition rate lasers become available (for example, using DPSSL technology), laser driven methodologies may provide neutron fluxes comparable to that achieved by accelerator driven neutron sources in the near future.