Letter

The onset of type I edge localized modes (ELMs) is investigated on the DIII-D tokamak. A fast imaging camera is used with an integration time of 1 νs and a time between frames of about 15 νs continuously recording for a period of 1.3 s. It is observed that type I ELMs onset starts with a precursor oscillation at the mid-plane caused by a toroidally rotating localized structure with a spatial scale increasing with time. This is confirmed by the toroidal set of magnetic probes and continues until the filamentary structure(s) strongly interacts with the first wall at the outer mid-plane. This triggers a strong plasma-wall interaction that later spreads to affect the whole scrape-off layer. The properties of the observed localized structure(s) are in good agreement with the ballooning finger structure occurring in the early non-linear phase of the peeling-ballooning instability. © 2009 IAEA, Vienna.Wakatani M, 1999, NUCL FUSION, V39, P2175, DOI 10.1088-0029-5515-39-12-302; Antar GY, 2006, PHYS PLASMAS, V13, DOI 10.1063-1.2198210; Becoulet M, 2003, PLASMA PHYS CONTR F, V45, pA93, DOI 10.1088-0741-3335-45-12A-007; Coda S, 2001, NUCL FUSION, V41, P1885, DOI 10.1088-0029-5515-41-12-316; Cowley S, 1996, PHYS PLASMAS, V3, P1848, DOI 10.1063-1.871980; Cowley SC, 2003, PLASMA PHYS CONTR F, V45, pA31, DOI 10.1088-0741-3335-45-12A-003; Eich T, 2005, PLASMA PHYS CONTR F, V47, P815, DOI 10.1088-0741-3335-47-6-007; Hill DN, 1997, J NUCL MATER, V241, P182, DOI 10.1016-S0022-3115(97)80039-6; Kirk A, 2005, PLASMA PHYS CONTR F, V47, P315, DOI 10.1088-0741-3335-47-2-008; Kirk A, 2005, PLASMA PHYS CONTR F, V47, P995, DOI 10.1088-0741-3335-47-7-003; Leonard AW, 2003, PHYS PLASMAS, V10, P1765, DOI 10.1063-1.1567723; Snyder PB, 2005, PHYS PLASMAS, V12, DOI 10.1063-1.1873792; Solomon WM, 2004, REV SCI INSTRUM, V75, P3481, DOI 10.1063-1.1790042; Wade MR, 2005, PHYS REV LETT, V94, DOI 10.1103-PhysRevLett.94.225001; Zohm H, 1996, PLASMA PHYS CONTR F, V38, P1213, DOI 10.1088-0741-3335-38-8-01234

Characterising anomalous transport in accretion disks from X-ray observations

Whilst direct observations of internal transport in accretion disks are not yet possible, measurement of the energy emitted from accreting astrophysical systems can provide useful information on the physical mechanisms at work. Here we examine the unbroken multi-year time variation of the total X-ray flux from three sources: Cygnus X-1 , the microquasar GRS 1915+105 , and for comparison the nonaccreting Crab nebula. To complement previous analyses, we demonstrate that the application of advanced statistical methods to these observational time-series reveals important contrasts in the nature and scaling properties of the transport processes operating within these sources. We find the Crab signal resembles Gaussian noise; the Cygnus X-1 signal is a leptokurtic random walk whose self-similar properties persist on timescales up to three years; and the GRS 1915+105 signal is similar to that from Cygnus X-1, but with self-similarity extending possibly to only a few days. This evidence of self-similarity provides a robust quantitative characterisation of anomalous transport occuring within the systems

Epigenetic Characterization of the FMR1 Gene and Aberrant Neurodevelopment in Human Induced Pluripotent Stem Cell Models of Fragile X Syndrome

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. In addition to cognitive deficits, FXS patients exhibit hyperactivity, attention deficits, social difficulties, anxiety, and other autistic-like behaviors. FXS is caused by an expanded CGG trinucleotide repeat in the 5′ untranslated region of the Fragile X Mental Retardation (FMR1) gene leading to epigenetic silencing and loss of expression of the Fragile X Mental Retardation protein (FMRP). Despite the known relationship between FMR1 CGG repeat expansion and FMR1 silencing, the epigenetic modifications observed at the FMR1 locus, and the consequences of the loss of FMRP on human neurodevelopment and neuronal function remain poorly understood. To address these limitations, we report on the generation of induced pluripotent stem cell (iPSC) lines from multiple patients with FXS and the characterization of their differentiation into post-mitotic neurons and glia. We show that clones from reprogrammed FXS patient fibroblast lines exhibit variation with respect to the predominant CGG-repeat length in the FMR1 gene. In two cases, iPSC clones contained predominant CGG-repeat lengths shorter than measured in corresponding input population of fibroblasts. In another instance, reprogramming a mosaic patient having both normal and pre-mutation length CGG repeats resulted in genetically matched iPSC clonal lines differing in FMR1 promoter CpG methylation and FMRP expression. Using this panel of patient-specific, FXS iPSC models, we demonstrate aberrant neuronal differentiation from FXS iPSCs that is directly correlated with epigenetic modification of the FMR1 gene and a loss of FMRP expression. Overall, these findings provide evidence for a key role for FMRP early in human neurodevelopment prior to synaptogenesis and have implications for modeling of FXS using iPSC technology. By revealing disease-associated cellular phenotypes in human neurons, these iPSC models will aid in the discovery of novel therapeutics for FXS and other autism-spectrum disorders sharing common pathophysiology.FRAXA Research FoundationHarvard Stem Cell Institute (seed grant)Stanley Medical Research InstituteNational Institute of Mental Health (U.S.) (grant #R33MH087896

Modulation of 11β-hydroxysteroid dehydrogenase as a strategy to reduce vascular inflammation

Atherosclerosis is a chronic inflammatory disease in which initial vascular damage leads to extensive macrophage and lymphocyte infiltration. Although acutely glucocorticoids suppress inflammation, chronic glucocorticoid excess worsens atherosclerosis, possibly by exacerbating systemic cardiovascular risk factors. However, glucocorticoid action within the lesion may reduce neointimal proliferation and inflammation. Glucocorticoid levels within cells do not necessarily reflect circulating levels due to pre-receptor metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSDs). 11β-HSD2 converts active glucocorticoids into inert 11-keto forms. 11β-HSD1 catalyses the reverse reaction, regenerating active glucocorticoids. 11β-HSD2-deficiency/ inhibition causes hypertension, whereas deficiency/ inhibition of 11β-HSD1 generates a cardioprotective lipid profile and improves glycemic control. Importantly, 11β-HSD1-deficiency/ inhibition is atheroprotective, whereas 11β-HSD2-deficiency accelerates atherosclerosis. These effects are largely independent of systemic risk factors, reflecting modulation of glucocorticoid action and inflammation within the vasculature. Here, we consider whether evidence linking the 11β-HSDs to vascular inflammation suggests these isozymes are potential therapeutic targets in vascular injury and atherosclerosis

Gravitational Effects on the Morphology and Kinetics of Photodeposition of Polydiacetylene Thin Films From Monomer Solutions

The goal of this proposed work is to study gravitational effects on the photodeposition of polydiacetylene thin films from monomer solutions onto transparent substrates. Polydiacetylenes have been an extensively studied class of organic polymers because they exhibit many unusual and interesting properties, including electrical conductivity and optical nonlinearity. Their long polymeric chains render polydiacetylenes readily conducive to thin film formation, which is necessary for many applications. These applications require thin polydiacetylene films possessing uniform thicknesses, high purity, minimal inhomogeneities and defects (such as scattering centers), etc. Also, understanding and controlling the microstructure and morphology of the films is important for optimizing their electronic and optical properties. The lack of techniques for processing polydiacetylenes into such films has been the primary limitation to their commercial use. We have recently discovered a novel method for the formation of polydiacetylene thin films using photo-deposition from monomer solutions onto transparent substrates with UV light. This technique is very simple to carry out, and can yield films with superior quality to those produced by conventional methods. Furthermore, these films exhibit good third-order properties and are capable of waveguiding. We have been actively studying the chemistry of diacetylene polymerization in solution and the photo-deposition of polydiacetylene thin films from solution. It is well-known that gravitational factors such as buoyancy-driven convection and sedimentation can affect chemical and mass transport processes in solution. One important aspect of polydiacetylene thin film photodeposition in solution, relevant to microgravity science, is that heat generated by absorption of UV radiation induces thermal density gradients that under the influence of gravity, can cause fluid flows (buoyancy-driven convection). Additionally, changes in the chemical composition of the solution during polymerization may cause solutal convection. These fluid flows affect transport of material to and from the film surface and thereby affect the kinetics of the growth process. This manifests itself in the morphology of the resulting films; films grown under the influence of convection tend to have less uniform thicknesses, and can possess greater inhomogeneities and defects. Specifically, polydiacetylene films photodeposited from solution, when viewed under a microscope, exhibit very small particles of solid polymer which get transported by convection from the bulk solution to the surface of the growing film and become embedded. Even when carried out under conditions designed to minimize unstable density gradients (i.e., irradiating the solution from the top), some fluid flow still takes place (particles remain present in the films). It is also possible that defect nucleation may be occurring within the films or on the surface of the substrate; this, too, can be affected by convection (as is the case with crystal growth). Hence films grown in 1-g will, at best, still possess some defects. The objective of this proposal is to investigate, both in 1-g and in low-g, the effects of gravitational factors (primarily convection) on the dynamics of these processes, and on the quality, morphology, and properties of the films obtained

Chromosomal single-strand break repair and neurological disease: Implications on transcription and emerging genomic tools

Cells are constantly exposed to various sources of DNA damage that pose a threat to their genomic integrity. One of the most common types of DNA breaks are single-strand breaks (SSBs). Mutations in the repair proteins that are important for repairing SSBs have been reported in several neurological disorders. While several tools have been utilised to investigate SSBs in cells, it was only through recent advances in genomics that we are now beginning to understand the architecture of the non-random distribution of SSBs and their impact on key cellular processes such as transcription and epigenetic remodelling. Here, we discuss our current understanding of the genome-wide distribution of SSBs, their link to neurological disorders and summarise recent technologies to investigate SSBs at the genomic level

The subscale orbital fluid transfer experiment

The Subscale Orbital Fluid Transfer Experiment (SOFTE) is a planned Shuttle Orbiter fluid transfer experiment. CASP (Center for Advanced Space Propulsion) performed certain aspects of the conceptual design of this experiment. The CASP work consisted of the conceptual design of the optical system, the search for alternative experimental fluids, the determination of the flow meter specifications and the examination of materials to use for a bladder that will empty one of the tanks in the experiment

Genotoxic and Anatomical Deteriorations Associated with Potentially Toxic Elements Accumulation in Water Hyacinth Grown in Drainage Water Resources

Potentially toxic elements (PTEs)-induced genotoxicity on aquatic plants is still an open question. Herein, a single clone from a population of water hyacinth covering a large distribution area of Nile River (freshwater) was transplanted in two drainage water resources to explore the hazardous effect of PTEs on molecular, biochemical and anatomical characters of plants compared to those grown in freshwater. Inductivity Coupled Plasma (ICP) analysis indicated that PTEs concentrations in water resources were relatively low in most cases. However, the high tendency of water hyacinth to bio-accumulate and bio-magnify PTEs maximized their concentrations in plant samples (roots in particular). A Random Amplified Polymorphic DNA (RAPD) assay showed the genotoxic effects of PTEs on plants grown in drainage water. PTEs accumulation caused substantial alterations in DNA profiles including the presence or absence of certain bands and even the appearance of new bands. Plants grown in drainage water exhibited several mutations on the electrophoretic profiles and banding pattern of total protein, especially proteins isolated from roots. Several anatomical deteriorations were observed on PTEs-stressed plants including reductions in the thickness of epidermis, cortex and endodermis as well as vascular cylinder diameter. The research findings of this investigation may provide some new insights regarding molecular, biochemical and anatomical responses of water hyacinth grown in drainage water resources.</jats:p

DNA supercoiling enhances DNA condensation by ParB proteins.

The ParABS system plays a critical role in bacterial chromosome segregation. The key component of this system, ParB, loads and spreads along DNA to form a local protein-DNA condensate known as a partition complex. As bacterial chromosomes are heavily supercoiled due to the continuous action of RNA polymerases, topoisomerases and nucleoid-associated proteins, it is important to study the impact of DNA supercoiling on the ParB-DNA partition complex formation. Here, we use an in-vitro single-molecule assay to visualize ParB on supercoiled DNA. Unlike most DNA-binding proteins, individual ParB proteins are found to not pin plectonemes on supercoiled DNA, but freely diffuse along supercoiled DNA. We find that DNA supercoiling enhances ParB-DNA condensation, which initiates at lower ParB concentrations than on DNA that is torsionally relaxed. ParB proteins induce a DNA-protein condensate that strikingly absorbs all supercoiling writhe. Our findings provide mechanistic insights that have important implications for our understanding of bacterial chromosome organization and segregation