Pedestal and Er profile evolution during an edge localized mode cycle at ASDEX Upgrade

The upgrade of the edge charge exchange recombination spectroscopy diagnostic at ASDEX Upgrade has enabled highly spatially resolved me asurements of the impurity ion dynamics during an edge-localized mode cycle ( ELM ) with unprecedented temp oral resolution, i.e. 65 μ s. The increase of transport during an ELM induces a relaxation of the ion, electron edge gradients in impurity density and fl ows. Detailed characterization of the recovery of the edge temperature gradients reveals a difference in the ion and electron channe l: the maximum ion temperature gradient T i is re-established on similar timescales as n e , which is faster than the recovery of T e .Afterthe clamping of the maximum gradient, T i and T e at the pedestal top continue to rise up to the next ELM while n e stays constant which means that the temperatur e pedestal and the resu lting pedestal pressure widen until the next ELM. The edge radial electric fi eld E r at the ELM crash is found to reduce to typical L-mode values and its ma ximum recovers to its pre-ELM conditions on a similar time scale as for n e and T i . Within the uncertainties, the measurements of E r align with their neoclassical predictions E r,neo for most of the ELM cycle, thus indicating that E r is dominated by collisional processes. However, between 2 and 4 ms af ter the ELM crash, other contributions to E B ́ fl ow, e.g. zonal fl ows or ion orbit effects, could not be excluded within the uncertainties.European Commission (EUROfusion 633053

Investigation of inter-ELM ion heat transport in the H-mode pedestal of ASDEX Upgrade plasmas

The ion heat transport in the pedestal of H-mode plasmas is investigated in various H-mode discharges with different pedestal ion collisionalities. Interpretive modelling suggests that in all analyzed discharges the ion heat diffusivity coefficient, χ i , in the pedestal is close to the neoclassical prediction within the experimental uncertainties. The impact of changing the deposition location of the electron cyclotron resonance heating on the ion heat transport has been studied. The effect on the background profiles is small. The pre-ELM (edge localized modes) edge profiles as well as the behaviour of the electron temperature and density, ion temperature and impurity toroidal rotation during the ELM cycle are very similar in discharges with on- and off-axis ECRH heating. No significant deviation of χ i from neoclassics is observed when changing the ECRH deposition location to the plasma edge.European Commission (EUROfusion 633053)European Union (EUROfusion Grant WP14-FRF-IPP

Mitigation of plasma-wall interactions with low-Z powders in DIII-D high confinement plasmas

Experiments with low-Z powder injection in DIII-D high confinement discharges demonstrated increased divertor dissipation and detachment while maintaining good core energy confinement. Lithium (Li), boron (B), and boron nitride (BN) powders were injected in high-confinement mode plasmas ($I_p=$1 MA, $B_t=$2 T, $P_{NB}=$6 MW, $\langle n_e\rangle=3.6-5.0\cdot10^{19}$ m$^{-3}$) into the upper small-angle slot (SAS) divertor for 2-s intervals at constant rates of 3-204 mg/s. The multi-species BN powders at a rate of 54 mg/s showed the most substantial increase in divertor neutral compression by more than an order of magnitude and lasting detachment with minor degradation of the stored magnetic energy $W_{mhd}$ by 5%. Rates of 204 mg/s of boron nitride powder further reduce ELM-fluxes on the divertor but also cause a drop in confinement performance by 24% due to the onset of an $n=2$ tearing mode. The application of powders also showed a substantial improvement of wall conditions manifesting in reduced wall fueling source and intrinsic carbon and oxygen content in response to the cumulative injection of non-recycling materials. The results suggest that low-Z powder injection, including mixed element compounds, is a promising new core-edge compatible technique that simultaneously enables divertor detachment and improves wall conditions during high confinement operation

Screening a Peptide Library by DSC and SAXD: Comparison with the Biological Function of the Parent Proteins

We have recently identified the membranotropic regions of the hepatitis C virus proteins E1, E2, core and p7 proteins by observing the effect of protein-derived peptide libraries on model membrane integrity. We have studied in this work the ability of selected sequences of these proteins to modulate the Lβ-Lα and Lα-HII phospholipid phase transitions as well as check the viability of using both DSC and SAXD to screen a protein-derived peptide library. We demonstrate that it is feasible to screen a library of peptides corresponding to one or several proteins by both SAXD and DSC. This methodological combination should allow the identification of essential regions of membrane-interacting proteins which might be implicated in the molecular mechanism of membrane fusion and/or budding

Which treatment for low back pain? A factorial randomised controlled trial comparing intravenous analgesics with oral analgesics in the emergency department and a centrally acting muscle relaxant with placebo over three days [ISRCTN09719705]

BACKGROUND: About two thirds of adults suffer from backpain at some time during their life. In the emergency room many patients with acute back pain are treated with intravenous non-steroidal analgesics. Whether this treatment is superior to oral administration of non-steroidal analgesics is unknown. Intravenous administration, however, requires considerable amounts of resources and accounts for high workload in busy clinics. In the further course centrally acting muscle relaxants are prescribed but the effectiveness remains unclear. The objective of this study is on the one hand to compare the effectiveness of intravenous with oral non-steroidal analgesics for acute treatment and on the other hand to compare the effectiveness of a centrally active muscle relaxant with placebo given for three days after presentation to the ED (emergency department). METHODS/DESIGN: This study is intended as a randomised controlled factorial trial mainly for two reasons: (1) the sequence of treatments resembles the actual proceedings in every-day clinical practice, which is important for the generalisability of the results and (2) this design allows to take interactions between the two sequential treatment strategies into account. There is a patient preference arm included because patients preference is an important issue providing valuable information: (1) it allows to assess the interaction between desired treatment and outcome, (2) results can be extrapolated to a wider group while (3) conserving the advantages of a fully randomised controlled trial. CONCLUSION: We hope to shed more light on the effectiveness of treatment modalities available for acute low back pain

Calcium Triggered Lα-H2 Phase Transition Monitored by Combined Rapid Mixing and Time-Resolved Synchrotron SAXS

BACKGROUND: Awad et al. reported on the Ca(2+)-induced transitions of dioleoyl-phosphatidylglycerol (DOPG)/monoolein (MO) vesicles to bicontinuous cubic phases at equilibrium conditions. In the present study, the combination of rapid mixing and time-resolved synchrotron small-angle X-ray scattering (SAXS) was applied for the in-situ investigations of fast structural transitions of diluted DOPG/MO vesicles into well-ordered nanostructures by the addition of low concentrated Ca(2+) solutions. METHODOLOGY/PRINCIPAL FINDINGS: Under static conditions and the in absence of the divalent cations, the DOPG/MO system forms large vesicles composed of weakly correlated bilayers with a d-spacing of approximately 140 A (L(alpha)-phase). The utilization of a stopped-flow apparatus allowed mixing these DOPG/MO vesicles with a solution of Ca(2+) ions within 10 milliseconds (ms). In such a way the dynamics of negatively charged PG to divalent cation interactions, and the kinetics of the induced structural transitions were studied. Ca(2+) ions have a very strong impact on the lipidic nanostructures. Intriguingly, already at low salt concentrations (DOPG/Ca(2+)>2), Ca(2+) ions trigger the transformation from bilayers to monolayer nanotubes (inverted hexagonal phase, H(2)). Our results reveal that a binding ratio of 1 Ca(2+) per 8 DOPG is sufficient for the formation of the H(2) phase. At 50 degrees C a direct transition from the vesicles to the H(2) phase was observed, whereas at ambient temperature (20 degrees C) a short lived intermediate phase (possibly the cubic Pn3m phase) coexisting with the H(2) phase was detected. CONCLUSIONS/SIGNIFICANCE: The strong binding of the divalent cations to the negatively charged DOPG molecules enhances the negative spontaneous curvature of the monolayers and causes a rapid collapsing of the vesicles. The rapid loss of the bilayer stability and the reorganization of the lipid molecules within ms support the argument that the transition mechanism is based on a leaky fusion of the vesicles

In Silico Molecular Comparisons of C. elegans and Mammalian Pharmacology Identify Distinct Targets That Regulate Feeding

Phenotypic screens can identify molecules that are at once penetrant and active on the integrated circuitry of a whole cell or organism. These advantages are offset by the need to identify the targets underlying the phenotypes. Additionally, logistical considerations limit screening for certain physiological and behavioral phenotypes to organisms such as zebrafish and C. elegans. This further raises the challenge of elucidating whether compound-target relationships found in model organisms are preserved in humans. To address these challenges we searched for compounds that affect feeding behavior in C. elegans and sought to identify their molecular mechanisms of action. Here, we applied predictive chemoinformatics to small molecules previously identified in a C. elegans phenotypic screen likely to be enriched for feeding regulatory compounds. Based on the predictions, 16 of these compounds were tested in vitro against 20 mammalian targets. Of these, nine were active, with affinities ranging from 9 nM to 10 µM. Four of these nine compounds were found to alter feeding. We then verified the in vitro findings in vivo through genetic knockdowns, the use of previously characterized compounds with high affinity for the four targets, and chemical genetic epistasis, which is the effect of combined chemical and genetic perturbations on a phenotype relative to that of each perturbation in isolation. Our findings reveal four previously unrecognized pathways that regulate feeding in C. elegans with strong parallels in mammals. Together, our study addresses three inherent challenges in phenotypic screening: the identification of the molecular targets from a phenotypic screen, the confirmation of the in vivo relevance of these targets, and the evolutionary conservation and relevance of these targets to their human orthologs