Recent progress towards a physics-based understanding of the H-mode transition

Results from recent experiment and numerical simulation point towards a picture of the L-H transition in which edge shear flows interacting with edge turbulence create the conditions needed to produce a non-zero turbulent Reynolds stress at and just inside the LCFS during L-mode discharges. This stress acts to reinforce the shear flow at this location and the flow drive gets stronger as heating is increased. The L-H transition ensues when the rate of work done by this stress is strong enough to drive the shear flow to large values, which then grows at the expense of the turbulence intensity. The drop in turbulence intensity momentarily reduces the heat flux across the magnetic flux surface, which then allows the edge plasma pressure gradient to build. A sufficiently strong ion pressure gradient then locks in the H-mode state. These results are in general agreement with previously published reduced 0D and 1D predator prey models. An extended predator-prey model including separate ion and electron heat channels yields a non-monotonic power threshold dependence on plasma density provided that the fraction of heat deposited on the ions increases with plasma density. Possible mechanisms to explain other macroscopic transition threshold criteria are identified. A number of open questions and unexplained observations are identified, and must be addressed and resolved in order to build a physics-based model that can yield predictions of the macroscopic conditions needed for accessing H-mode

Driving calmodulin protein towards conformational shift by changing ionization states of select residues

Proteins are complex systems made up of many conformational sub-states which are mainly determined by the folded structure. External factors such as solvent type, temperature, pH and ionic strength play a very important role in the conformations sampled by proteins. Here we study the conformational multiplicity of calmodulin (CaM) which is a protein that plays an important role in calcium signaling pathways in the eukaryotic cells. CaM can bind to a variety of other proteins or small organic compounds, and mediates different physiological processes by activating various enzymes. Binding of calcium ions and proteins or small organic molecules to CaM induces large conformational changes that are distinct to each interacting partner. In particular, we discuss the effect of pH variation on the conformations of CaM. By using the pKa values of the charged residues as a basis to assign protonation states, the conformational changes induced in CaM by reducing the pH are studied by molecular dynamics simulations. Our current view suggests that at high pH, barrier crossing to the compact form is prevented by repulsive electrostatic interactions between the two lobes. At reduced pH, not only is barrier crossing facilitated by protonation of residues, but also conformations which are on average more compact are attained. The latter are in accordance with the fluorescence resonance energy transfer experiment results of other workers. The key events leading to the conformational change from the open to the compact conformation are (i) formation of a salt bridge between the N-lobe and the linker, stabilizing their relative motions, (ii) bending of the C-lobe towards the N-lobe, leading to a lowering of the interaction energy between the two-lobes, (iii) formation of a hydrophobic patch between the two lobes, further stabilizing the bent conformation by reducing the entropic cost of the compact form, (iv) sharing of a Ca+2 ion between the two lobes

EGFR oligomerization organizes kinase-active dimers into competent signalling platforms

Epidermal growth factor receptor (EGFR) signalling is activated by ligand-induced receptor dimerization. Notably, ligand binding also induces EGFR oligomerization, but the structures and functions of the oligomers are poorly understood. Here, we use fluorophore localization imaging with photobleaching to probe the structure of EGFR oligomers. We find that at physiological epidermal growth factor (EGF) concentrations, EGFR assembles into oligomers, as indicated by pairwise distances of receptor-bound fluorophore-conjugated EGF ligands. The pairwise ligand distances correspond well with the predictions of our structural model of the oligomers constructed from molecular dynamics simulations. The model suggests that oligomerization is mediated extracellularly by unoccupied ligand-binding sites and that oligomerization organizes kinase-active dimers in ways optimal for auto-phosphorylation in trans between neighbouring dimers. We argue that ligand-induced oligomerization is essential to the regulation of EGFR signalling

Hermes : global plasma edge fluid turbulence simulations

The transport of heat and particles in the relatively collisional edge regions of magnetically confined plasmas is a scientifically challenging and technologically important problem. Understanding and predicting this transport requires the self-consistent evolution of plasma fluctuations, global profiles and flows, but the numerical tools capable of doing this in realistic (diverted) geometry are only now being developed. Here a 5-field reduced 2-fluid plasma model for the study of instabilities and turbulence in magnetised plasmas is presented, built on the BOUT++ framework. This cold ion model allows the evolution of global profiles, electric fields and flows on transport timescales, with flux-driven cross-field transport determined self-consistently by electromagnetic turbulence. Developments in the model formulation and numerical implementation are described, and simulations are performed in poloidally limited and diverted tokamak configurations

Feasibility study for a correlation electron cyclotron emission turbulence diagnostic based on nonlinear gyrokinetic simulations

This paper describes the use of nonlinear gyrokinetic simulations to assess the feasibility of a new correlation electron cyclotron emission (CECE) diagnostic that has been proposed for the Alcator C-Mod tokamak (Marmar et al 2009 Nucl. Fusion 49 104014). This work is based on a series of simulations performed with the GYRO code (Candy and Waltz 2003 J. Comput. Phys. 186 545). The simulations are used to predict ranges of fluctuation level, peak poloidal wavenumber and radial correlation length of electron temperature fluctuations in the core of the plasma. The impact of antenna pattern and poloidal viewing location on measurable turbulence characteristics is addressed using synthetic diagnostics. An upper limit on the CECE sample volume size is determined. The modeling results show that a CECE diagnostic capable of measuring transport-relevant, long-wavelength (k[subscript θ]ρ[subscript s] < 0.5) electron temperature fluctuations is feasible at Alcator C-Mod.United States. Dept. of Energy (DE-FC02-C99ER54512-CMOD

A global compilation of coccolithophore calcification rates

The biological production of calcium carbonate (CaCO3), a process termed calcification, is a key term in the marine carbon cycle. A major planktonic group responsible for such pelagic CaCO3 production (CP) is the coccolithophores, single-celled haptophytes that inhabit the euphotic zone of the ocean. Satellite-based estimates of areal CP are limited to surface waters and open-ocean areas, with current algorithms utilising the unique optical properties of the cosmopolitan bloom-forming species Emiliania huxleyi, whereas little understanding of deep-water ecology, optical properties or environmental responses by species other than E. huxleyi is currently available to parameterise algorithms or models. To aid future areal estimations and validate future modelling efforts we have constructed a database of 2765CP measurements, the majority of which were measured using 12 to 24h incorporation of radioactive carbon (14C) into acid-labile inorganic carbon (CaCO3). We present data collated from over 30 studies covering the period from 1991 to 2015, sampling the Atlantic, Pacific, Indian, Arctic and Southern oceans. Globally, CP in surface waters ( < 20m) ranged from 0.01 to 8398µmolCm−3d−1 (with a geometric mean of 16.1µmolCm−3d−1). An integral value for the upper euphotic zone (herein surface to the depth of 1% surface irradiance) ranged from  < 0.1 to 6mmolCm−2d−1 (geometric mean 1.19mmolCm−2d−1). The full database is available for download from PANGAEA at https://doi.org/10.1594/PANGAEA.888182

Multi-exon deletions of the FBN1 gene in Marfan syndrome

BACKGROUND: Mutations in the fibrillin -1 gene (FBN1) cause Marfan syndrome (MFS), an autosomal dominant multi-system connective tissue disorder. The 200 different mutations reported in the 235 kb, 65 exon-containing gene include only one family with a genomic multi-exon deletion. METHODS: We used long-range RT-PCR for mutation detection and long-range genomic PCR and DNA sequencing for identification of deletion breakpoints, allele-specific transcript analyses to determine stability of the mutant RNA, and pulse-chase studies to quantitate fibrillin synthesis and extracellular matrix deposition in cultured fibroblasts. Southern blots of genomic DNA were probed with three overlapping fragments covering the FBN1 coding exons RESULTS: Two novel multi-exon FBN1 deletions were discovered. Identical nucleotide pentamers were found at or near the intronic breakpoints. In a Case with classic MFS, an in-frame deletion of exons 42 and 43 removed the C-terminal 24 amino acids of the 5(th) LTBP (8-cysteine) domain and the adjacent 25(th) calcium-binding EGF-like (6-cysteine) domain. The mutant mRNA was stable, but fibrillin synthesis and matrix deposition were significantly reduced. A Case with severe childhood-onset MFS has a de novo deletion of exons 44–46 that removed three EGF-like domains. Fibrillin protein synthesis was normal, but matrix deposition was strikingly reduced. No genomic rearrangements were detected by Southern analysis of 18 unrelated MFS samples negative for FBN1 mutation screening. CONCLUSIONS: Two novel deletion cases expand knowledge of mutational mechanisms and genotype/phenotype correlations of fibrillinopathies. Deletions or mutations affecting an LTBP domain may result in unstable mutant protein cleavage products that interfere with microfibril assembly

Informed design of educational technology for teaching and learning? Towards an evidence-informed model of good practice

The aim of this paper is to model evidence-informed design based on a selective critical analysis of research articles. We draw upon findings from an investigation into practitioners’ use of educational technologies to synthesise and model what informs their designs. We found that practitioners’ designs were often driven by implicit assumptions about learning. These shaped both the design of interventions and the methods sought to derive evaluations and interpret the findings. We argue that interventions need to be grounded in better and explicit conceptualisations of what constitutes learning in order to have well-informed designs that focus on improving the quality of student learning

Atrioventricular block of intraoperative device closure perimembranous ventricular septal defects; a serious complication

<p>Abstract</p> <p>Background</p> <p>Atrioventricular block (AVB) is a well-reported complication after closure of perimembranous ventricular septal defects (VSDs). To report the occurrence of AVB either during or following closure of perimembranous VSDs using a novel "hybrid" method involving a minimal inferior median incision and of intraoperative device closure of the perimembranous VSDs.</p> <p>Methods</p> <p>Between January 2009 and January 2011, patients diagnosed with perimembranous VSDs eligible for intraoperative device closure with a domestic occluder were identified. All patients were assessed by real-time transesophageal echocardiography (TEE) and electrocardiography.</p> <p>Results</p> <p>Of the 97 included patients, 94 were successfully occluded using this approach. Complete AVB occurred in only one case and one case of Mobitz type II AVB was diagnosed intraoperatively. In both patients, the procedure was aborted and the AVBs quickly resolved. Glucocorticosteroids were administered to another two patients who developed Mobitz type II AVB intraoperatively. Those two patients converted to Mobitz type I AVB 3 days and 5 days postsurgically. During the follow-up period (range, 6-24 months), one patient developed complete AVB 1 week following device insertion. Surgical device removal was followed by a rapid and complete recovery of atrioventricular conduction.</p> <p>Conclusions</p> <p>Intraoperative device closure of perimembranous VSDs with a domestic occluder resulted in excellent closure rates; however, AVB is a serious complication that can occur either during or any time after device closure of perimembranous VSDs. The technique described herein may reduce the incidence of perioperative AVB complications. Surgeons are encouraged to closely monitor all patients postsurgically to ensure AVB does not occur in their patients. Additional long-term data to better identify the prevalence and risk factors for AVB in treated patients are needed.</p