Converting existing optical detectors into fast x-ray detectors.

The very short burn time and small size of burning plasmas created at advanced laser-fusion facilities will require high-spatial-resolution imaging diagnostics with fast time resolution. These instruments will need to function in an environment of extremely large neutron fluxes that will cause conventional diagnostics to fail because of radiation damage and induced background levels. One solution to this challenge is to perform an ultrafast conversion of the x-ray signals into the optical regime before the neutrons are able to reach the detector and then to relay image the signal out of the chamber and into a shielded bunker, protected from the effects of these neutrons. With this goal in mind, the OMEGA laser was used to demonstrate high-temporal-resolution x-ray imaging by using an x-ray snout to image an imploding backlighter capsule onto a semiconductor. The semiconductor was simultaneously probed with the existing velocity interferometry system for any surface reflector (VISAR) diagnostic, which uses an optical streak camera and provided a one-dimensional image of the phase in the semiconductor as a function of time. The phase induced in the semiconductor was linearly proportional to the x-ray emission from the backlighter capsule. This approach would then allow a sacrificial semiconductor to be attached at the end of an optical train with the VISAR and optical streak camera placed in a shielded bunker to operate in a high neutron environment and obtain time-dependent one-dimensional x-ray images or time-dependent x-ray spectra from a burning plasma.

WEARCON: wearable home monitoring in children with asthma reveals a strong association with hospital based assessment of asthma control.

BACKGROUND: Asthma is one of the most common chronic diseases in childhood. Regular follow-up of physiological parameters in the home setting, in relation to asthma symptoms, can provide complementary quantitative insights into the dynamics of the asthma status. Despite considerable interest in asthma home-monitoring in children, there is a paucity of scientific evidence, especially on multi-parameter monitoring approaches. Therefore, the aim of this study is to investigate whether asthma control can be accurately assessed in the home situation by combining parameters from respiratory physiology sensors. METHODS: Sixty asthmatic and thirty non-asthmatic children were enrolled in the observational WEARCON-study. Asthma control was assessed according to GINA guidelines by the paediatrician. All children were also evaluated during a 2-week home-monitoring period with wearable devices; a physical activity tracker, a handheld spirometer, smart inhalers, and an ambulatory electrocardiography device to monitor heart and respiratory rate. Multiple logistic regression analysis was used to determine which diagnostic measures were associated with asthma control. RESULTS: 24 of the 27 uncontrolled asthmatic children and 29 of the 32 controlled asthmatic children could be accurately identified with this model. The final model showed that a larger variation in pre-exercise lung function (OR = 1.34 95%-CI 1.07-1.68), an earlier wake-up-time (OR = 1.05 95%-CI 1.01-1.10), more reliever use (OR = 1.11 95%-CI 1.03-1.19) and a longer respiratory rate recovery time (OR = 1.12 95%-CI 1.05-1.20) were significant contributors to the probability of having uncontrolled asthma. CONCLUSIONS: Home-monitoring of physiological parameters correlates with paediatrician assessed asthma control. The constructed multivariate model identifies 88.9% of all uncontrolled asthmatic children, indicating a high potential for monitoring of asthma control. This may allow healthcare professionals to assess asthma control at home. TRIAL REGISTRATION: Netherlands Trail Register, NL6087 . Registered 14 February 2017.

Hybrid target design for imprint mitigation in direct-drive inertial confinement fusion.

A target design for mitigating the Rayleigh-Taylor instability is proposed for use in high energy density and direct-drive inertial confinement fusion experiments. In this scheme, a thin gold membrane is offset from the main target by several-hundred microns. A strong picket on the drive beams is incident upon this membrane to produce x rays which generate the initial shock through the target. The main drive follows shortly thereafter, passing through the ablated shell and directly driving the main target. The efficacy of this scheme is demonstrated through experiments performed at the OMEGA EP facility, showing a reduction of the Rayleigh-Taylor instability growth which scales exponentially with frequency, suppressing development by at least a factor of 5 for all wavelengths below 100 µm. This results in a delay in the time of target perforation by ∼40%.

Does exercise-induced bronchoconstriction affect physical activity patterns in asthmatic children?

Exercise-induced bronchoconstriction (EIB) is a sign of uncontrolled childhood asthma and classically occurs after exercise. Recent research shows that EIB frequently starts during exercise, called breakthrough-EIB (BT-EIB). It is unknown whether this more severe type of EIB forces children to adapt their physical activity (PA) pattern in daily life. Therefore, this pilot study aims to investigate daily life PA (amount, intensity, duration, and distribution) in children with BT-EIB, 'classic' EIB, and without EIB. A Fitbit Zip activity tracker was used for one week to objectively measure daily life PA at one-minute intervals. Thirty asthmatic children participated. Children with BT-EIB were less physically active compared to children without EIB (respectively 7994 and 11,444 steps/day, p = .02). Children with BT-EIB showed less moderate-to-vigorous PA compared to the children without (respectively 117 and 170 minutes/day, p = .02). Children with EIB (both BT and classic) had significant shorter bouts of activity and a less stretched distribution of bout lengths compared to the non-EIB group (all p < .05). These results emphasize a marked association between EIB severity and PA patterns in daily life, stressing the need for a thorough clinical evaluation of exercise-induced symptoms in childhood asthma.

The Mozart study: a relation between dynamic hyperinflation and physical activity in patients with chronic obstructive pulmonary disease?

BACKGROUND: Many patients with chronic obstructive pulmonary disease (COPD) experience dyspnoea during exercise, resulting in a reduction of physical activity (PA). Dynamic hyperinflation (DH) is seen as a major cause of dyspnoea in COPD. OBJECTIVE: The objective of the current study was to investigate the relationship between DH, in terms of the amount of DH and the development and recovery rate of DH in patients with COPD, and PA. METHODS: Thirty-five patients with stable COPD were included from an outpatient clinic (14 GOLD II and 21 GOLD III, median age 65). PA was assessed using an accelerometer. Subjects underwent metronome-paced tachypnoea (MPT) to induce DH. To quantify the amount of DH during MPT, a decrease in inspiratory capacity (IC) or a change in IC as percentage of total lung capacity was used. RESULTS: No significant correlations were found between the parameters describing DH and PA. Secondary correlation analyses showed a negative correlation between static hyperinflation (SH) and PA (r = -0·39; P = 0·02). The pattern of breathing during MPT and the test itself showed high interpatient variability. CONCLUSIONS: The absence of a significant correlation between DH and PA is contrary to previous studies. SH did show a correlation with PA. The variety in results and the technical difficulties in execution of the measurements ask for a new, more reliable, method to detect DH and investigate its relation with PA in patients with COPD.

Personalized Coaching Systems to support healthy behavior in people with chronic conditions.

Chronic conditions cannot be cured but daily behavior has a major effect on the severity of secondary problems and quality of life. Changing behavior however requires intensive support in daily life, which is not feasible with a human coach. A new coaching approach - so-called Personal Coaching Systems (PCSs) - use on-body sensing, combined with smart reasoning and context-aware feedback to support users in developing and maintaining a healthier behavior. Three different PCSs will be used to illustrate the different aspects of this approach: (1) Treatment of neck/shoulder pain. EMG patterns of the Trapezius muscles are used to estimate their level of relaxation. Personal vibrotactile feedback is given, to create awareness and enable learning when muscles are insufficiently relaxed. (2) Promoting a healthy activity pattern. Using a 3D accelerometer to measure activity and a smartphone to provide feedback. Timing and content of the feedback are adapted real-time, using machine-learning techniques, to optimize adherence. (3) Management of stress during daily living. The level of stress is quantified using a personal model involving a combination of different sensor signals (EMG, ECG, skin conductance, respiration). Results show that Personal Coaching Systems are feasible and a promising and challenging way forward to coach people with chronic conditions.

Focusing of relativistic electrons in dense plasma using a resistivity-gradient-generated magnetic switchyard.

A method for producing a self-generated magnetic focussing structure for a beam of laser-generated relativistic electrons using a complex array of resistivity gradients is proposed and demonstrated using numerical simulations. The array of resistivity gradients is created by using a target consisting of alternating layers of different Z material. This new scheme is capable of effectively focussing the fast electrons even when the source is highly divergent. The application of this technique to cone-guided fast ignition inertial confinement fusion is considered, and it is shown that it may be possible to deposit over 25% of the fast electron energy into a hot spot even when the fast electron divergence angle is very large (e.g., 70° half-angle).

Crystallization and preliminary structural analysis of the giant haemoglobin from Glossoscolex paulistus at 3.2 Å.

Glossoscolex paulistus is a free-living earthworm encountered in south-east Brazil. Its oxygen transport requirements are undertaken by a giant extracellular haemoglobin, or erythrocruorin (HbGp), which has an approximate molecular mass of 3.6 MDa and, by analogy with its homologue from Lumbricus terrestris (HbLt), is believed to be composed of a total of 180 polypeptide chains. In the present work the full 3.6 MDa particle in its cyanomet state was purified and crystallized using sodium citrate or PEG8000 as precipitant. The crystals contain one-quarter of the full particle in the asymmetric unit of the I222 cell and have parameters of a = 270.8 Å, b = 320.3 Å and c = 332.4 Å. Diffraction data were collected to 3.15 Å using synchrotron radiation on beamline X29A at the Brookhaven National Laboratory and represent the highest resolution data described to date for similar erythrocruorins. The structure was solved by molecular replacement using a search model corresponding to one-twelfth of its homologue from HbLt. This revealed that HbGp belongs to the type I class of erythrocruorins and provided an interpretable initial electron density map in which many features including the haem groups and disulfide bonds could be identified.

Relativistic quasimonoenergetic positron jets from intense laser-solid interactions.

Detailed angle and energy resolved measurements of positrons ejected from the back of a gold target that was irradiated with an intense picosecond duration laser pulse reveal that the positrons are ejected in a collimated relativistic jet. The laser-positron energy conversion efficiency is ∼2×10{-4}. The jets have ∼20 degree angular divergence and the energy distributions are quasimonoenergetic with energy of 4 to 20 MeV and a beam temperature of ∼1 MeV. The sheath electric field on the surface of the target is shown to determine the positron energy. The positron angular and energy distribution is controlled by varying the sheath field, through the laser conditions and target geometry.

Limitation on prepulse level for cone-guided fast-ignition inertial confinement fusion.

The viability of fast-ignition (FI) inertial confinement fusion hinges on the efficient transfer of laser energy to the compressed fuel via multi-MeV electrons. Preformed plasma due to the laser prepulse strongly influences ultraintense laser plasma interactions and hot electron generation in the hollow cone of an FI target. We induced a prepulse and consequent preplasma in copper cone targets and measured the energy deposition zone of the main pulse by imaging the emitted K_{alpha} radiation. Simulation of the radiation hydrodynamics of the preplasma and particle in cell modeling of the main pulse interaction agree well with the measured deposition zones and provide an insight into the energy deposition mechanism and electron distribution. It was demonstrated that a under these conditions a 100 mJ prepulse eliminates the forward going component of approximately 2-4 MeV electrons.

Hot-electron energy coupling in ultraintense laser-matter interaction.

We investigate the hydrodynamic response of plasma gradients during the interaction with ultraintense energetic laser pulses using kinetic particle simulations. Energetic laser pulses are capable of compressing preformed plasma gradients over short times, while accelerating low-density plasma backward. As light is absorbed on a steepened interface, hot-electron temperature and coupling efficiency drop below the ponderomotive scaling and we are left with an absorption mechanism that strongly relies on the electrostatic potential caused by low-density preformed plasma. We describe this process, discuss properties of the resulting electron spectra and identify the parameter regime where strong compression occurs. Finally, we discuss implications for fast ignition and other applications.

Hot-electron energy coupling in ultraintense laser-matter interaction.

We investigate the hydrodynamic response of plasma gradients during the interaction with ultraintense energetic laser pulses, using kinetic particle simulations. Energetic laser pulses are capable of compressing preformed plasma gradients over short times while accelerating low-density plasma backwards. As light is absorbed on a steepened interface, hot-electron temperature and coupling efficiency drop below the ponderomotive scaling, and we are left with a new absorption mechanism that strongly relies on the electrostatic potential caused by low-density preformed plasma. We describe this process, explain electron spectra, and identify the parameter regime where strong compression occurs. Finally, we discuss the implications for fast ignition and other applications.

Absorption of short laser pulses on solid targets in the ultrarelativistic regime.

We report the first direct measurements of total absorption of short laser pulses on solid targets in the ultrarelativistic regime. The data show an enhanced absorption at intensities above 10(20) W/cm(2), reaching 60% for near-normal incidence and 80%-90% for 45 degrees incidence. Two-dimensional particle-in-cell simulations demonstrate that such high absorption is consistent with both interaction with preplasma and hole boring by the intense laser pulse. A large redshift in the second harmonic indicates a surface recession velocity of 0.035c.

Observation of the decay dynamics and instabilities of megagauss field structures in laser-produced plasmas.

Monoenergetic proton radiography was used to make the first measurements of the long-time-scale dynamics and evolution of megagauss laser-plasma-generated magnetic field structures. While a 1-ns 10(14) W/cm2 laser beam is on, the field structure expands in tandem with a hemispherical plasma bubble, maintaining a rigorous 2D cylindrical symmetry. With the laser off, the bubble continues to expand as the field decays; however, the outer field structure becomes distinctly asymmetric, indicating instability. Similarly, localized asymmetry growth in the bubble interior indicates another kind of instability. 2D LASNEX hydrosimulations qualitatively match the cylindrically averaged post-laser plasma evolution but even then it underpredicts the field dissipation rate and of course completely misses the 3D asymmetry growth.

Thermodynamic and infrared analyses of the interaction of chlorpromazine with phospholipid monolayers.

An investigation has been made of the interaction between chlorpromazine (CPZ) and monolayers of 1,2-dipalmitoyl-sn-3-glycerophosphatidylcholine (DPPC) and 1,2-dipalmitoyl-sn-3-glycero[phospho-rac-(1-glycerol)] (DPPG), both at the air/water interface and in transferred Langmuir-Blodgett films. The Gibbs free energy, DeltaG, and the compressibility modulus (C(S)(-1)), obtained from the surface pressure isotherms, indicated changes in the in-plane interactions of CPZ/DPPG mixed monolayers, with positive values of DeltaG. The arrangement of CPZ in the zwitterionic DPPC monolayers causes a weaker interaction in CPZ/DPPC mixed monolayers, with the DeltaG fluctuating around zero. IR measurements in transferred monolayers showed that CPZ did not affect the conformational order of the acyl chains, its effects being limited to the bands corresponding to the headgroups. Furthermore, since no shift was observed for the acyl chain bands, the phase transition induced by CPZ is not a liquid expanded (LE) to liquid condensed (LC) transition, as the latter is associated with chain ordering. Taken together, the IR and compressibility results demonstrate that the effect from CPZ cannot be correlated with temperature changes in the subphase for pure monolayers, in contrast to models proposed by other authors.

The interaction of meso-tetraphenylporphyrin with phospholipid monolayers.

In this article, we investigate the interaction of meso-tetraphenylporphyrin (TPP) with phospholipid monolayers. Pure TPP molecules form films at the air-water interface with large extension of aggregation, which is confirmed by UV-vis spectra of transferred monolayers. For mixed films of TPP with dipalmitoyl phosphatidyl choline (DPPC) or dipalmitoyl phosphatidyl glycerol (DPPG), on the other hand, aggregation is only significant at high surface pressures or high concentrations of TPP (above 0.1 molar ratio). This was observed via Brewster angle microscopy (BAM) for the Langmuir films and UV-vis spectroscopy for transferred layers onto solid substrates. TPP indeed causes the DPPC and DPPG monolayers to expand, especially at the liquid-expanded to liquid-condensed phase transition for DPPC. The effects from TPP cannot be explained using purely geometrical considerations, as the area per TPP molecule obtained from the isotherms is at least twice the expected value from the literature. Therefore, interaction between TPP and DPPC or DPPG should be cooperative, so that more phospholipid molecules are affected than just the first neighbors to a TPP molecule.

Interaction of two phenothiazine derivatives with phospholipid monolayers.

This paper addresses the cooperative interaction of two phenothiazine drugs, viz. trifluoperazine (TFP) and chlorpromazine (CPZ), with phospholipid monolayers as the model membrane system. Surface pressure and surface potential isotherms were obtained for mixed Langmuir monolayers of either dipalmitoyl-phosphatidyl-choline (DPPC) or dipalmitoyl-phosphatidyl-glycerol (DPPG) co-spread with TFP or CPZ. The changes in monolayer behavior caused by incorporation of a few molar ratio of drug molecules were practically within the experimental dispersion for the zwitterionic DPPC, and therefore a more refined analysis will be required to probe the interactions in an unequivocal way. For the charged DPPG, on the other hand, the surface pressure and the dipole moment were significantly affected even for TFP or CPZ concentrations as low as 0.002 molar ratio. Overall, the effects from CPZ and TFP are similar, but small differences exist which are probably due to the different protonation properties of the two drugs. For both drugs, changes are more prominent at the liftoff of the surface pressure, i.e. at the gas-condensed phase transition, with the surface pressure and surface potential isotherms becoming more expanded with the drug incorporation. With DPPG/CPZ monolayers, in particular, an additional phase transition appears at higher CPZ concentrations, which resembles the effects from increasing the subphase temperature for a pure DPPG monolayer. The dipole moment for DPPG/CPZ and DPPG/TFP monolayers decreases with the drug concentration, which means that the effects from the charged drugs are not associated with changes in the double-layer potential. Otherwise, the effective dipole moment should increase with the drug concentration. The changes caused in surface pressure and dipole moment by small concentrations of TFP or CPZ can only be explained by some cooperative effect through which the contribution from DPPG molecules changes considerably, i.e. even DPPG molecules that are not neighbor to a CPZ or TFP molecule are also affected. Such changes may occur either through a significant reorientation of the DPPG molecules or to a change in their hydration state. We discuss the cooperativity semi-quantitatively by estimating the number of lipid molecules affected by the drug interaction. CPZ and TFP also affect the morphology of DPPG monolayers, which was confirmed with Brewster angle microscopy. The biological implications from the cooperative, non-specific interaction of CPZ and TFP with membranes are also commented upon.

Diverse effects of ascorbic acid and palmitoyl ascorbate on Helicobacter pylori survival and growth.

Among many antioxidants used in the food, pharmaceutical and cosmetic industries, ascorbic acid (AA) is one of the most important. AA has been suggested to decrease the risk of gastric disease (gastritis, duodenal ulcer, and carcinoma) by direct action on Helicobacter pylori. However, there are limited studies on the possible role of AA and its derivatives such as palmitoyl ascorbate (PA) on the growth and survival of H. pylori. In the present study it was demonstrated in vitro that AA in the concentration range 10-20 mg x ml(-1) (50-100 mM) inhibited H. pylori growth in liquid medium under microaerophilic conditions. In contrast, under aerobic conditions AA in the concentration range 2-20 mg x ml(-1) (10-100 mM) significantly increased the survival of H. pylori presumably eliminating the toxic effect of reactive oxygen species on bacterial cells. The hydrophobic derivative of AA, PA (a food antioxidant), demonstrated a strong antibacterial effect, under both aerobic and microaerophilic conditions in the concentration range 0.04-0.4 mg x ml(-1) (0.1-1.0 mM). This effect was also tested on other bacterial strains: Escherichia coli, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa, Enterococcus faecalis, Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Clostridium sporogenes and Campylobacter jejuni. Among these bacterial strains, PA showed a similar inhibitory effect on B. cereus and B. subtilis as observed with H. pylori. The results suggest that PA may be considered an important AA derivative in eradication of H. pylori in vitro and in vivo and to decrease the risk for gastric diseases.

Small angle X-ray scattering study of meso-tetrakis (4-sulfonatophenyl) porphyrin in aqueous solution: a self-aggregation model.

The aggregate morphology of meso-tetrakis(4-sulfonatophenyl) porphyrin (TPPS(4)) in aqueous solution is investigated by using small angle x-ray scattering (SAXS) technique. Measurements were performed at pH 4.0 and 9.0 to monitor the pH influence on the structural parameters of the aggregates. Radii of gyration were obtained from distance distribution functions p(r) analysis. The experimental data of TPPS(4) at pH 4.0 showed well-defined oscillations characteristic of large aggregates in contrast to the SAXS curve of 5 mM TPPS(4) at pH 9.0, where both a significant decrease in the intensity and the disappearance of the oscillation peaks suggest the dissociation of the aggregate. A 340-A long "hollow" cylinder with shell thickness of 20 A, compatible to the porphyrin molecule dimension, represents well the scattering curve of the aggregates at pH 4.0. According to the fitting parameters, 26 porphyrin molecules self-associate into a ringlike configuration in the plane of the cylinder cross-section. The total number of porphyrin molecules in the whole aggregate was also estimated as approximately 3000. The model compatible to SAXS data of a hollow cylinder with J-aggregation in the cross-section and H-aggregation (columnar stacking) between the cylinder layers is consistent with optical absorption spectroscopic data both in the literature and obtained in this work.

Interaction of bovine (BSA) and human (HSA) serum albumins with ionic surfactants: spectroscopy and modelling.

The binding of several different categories of small molecules to bovine (BSA) and human (HSA) serum albumins has been studied for many years through different spectroscopic techniques to elucidate details of the protein structure and binding mechanism. In this work we present the results of the study of the interactions of BSA and HSA with the anionic sodium dodecyl sulfate (SDS), cationic cethyltrimethylammonium chloride (CTAC) and zwitterionic N-hexadecyl-N,N-dimethyl-3-ammonium-1-propanesulfonate (HPS) monitored by fluorescence spectroscopy of the intrinsic tryptophans at pH 5.0. Similarly to pH 7.0 and 9.0, at low concentrations, the interaction of BSA with these surfactants shows a quenching of fluorescence with Stern-Volmer quenching constants of (1.1+/-0.1)x10(4) M(-1), (3.2+/-0.1)x10(3) M(-1) and (2.1+/-0.1)x10(3) M(-1) for SDS, HPS and CTAC, respectively, which are associated to the 'effective' association constants to the protein. On the interaction of these surfactants with HSA, an opposite effect was observed as compared to BSA, i.e., an enhancement of fluorescence takes place. For both proteins, at low surfactant concentrations, a positive cooperativity was observed and the Hill plot model was used to estimate the number of surfactant binding sites, as well as the association constants of the surfactants to the proteins. It is worthy of notice that the binding constants for the surfactants at pH 5.0 are lower as compared to pH 7.0 and 9.0. This is probably due to fact that the protein at this acid pH is quite compact reducing the accessibility of the surfactants to the hydrophobic cavities in the binding sites. The interaction of myristic acid with both proteins shows a similar fluorescence behaviour, suggesting that the mechanism of the interaction is the same. Recently published crystallographic studies of HSA-myristate complex were used to perform a modelling study with the aim to explain the fluorescence results. The crystallographic structure reveals that a total of five myristic acid molecules are asymmetrically bound in the macromolecule. Three of these sites correspond to higher affinity ones and correlate with high association constants described in the literature. Our models for BSA and HSA with bound SDS suggest that the surfactant could be bound at the same sites as those reported in the crystal structure for the fatty acid. The differences in tryptophan vicinity upon surfactant binding are explored in the models in order to explain the observed spectroscopic changes. For BSA the quenching is due to a direct contact of a surfactant molecule with the indole of W131 residue. It is clear that the binding site in BSA which is very close, in contact with tryptophan W131, corresponds to a lower affinity site, explaining the lower binding constants obtained from fluorescence studies. In the case of HSA the enhancement of fluorescence is due to the removal of static quenching of W214 residue in the intact protein caused by nearby residues in the vicinity of this tryptophan.