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

Inner versus outer E×B shear layer: an attempt to radially localize the L-H transition

EUROfusion Consortium 63305

SANS (USH1G) regulates pre-mRNA splicing by mediating the intra-nuclear transfer of tri-snRNP complexes

Splicing is catalyzed by the spliceosome, a compositionally dynamic complex assembled stepwise on pre-mRNA. We reveal links between splicing machinery components and the intrinsically disordered ciliopathy protein SANS. Pathogenic mutations in SANS/USH1G lead to Usher syndrome—the most common cause of deaf-blindness. Previously, SANS was shown to function only in the cytosol and primary cilia. Here, we have uncovered molecular links between SANS and pre-mRNA splicing catalyzed by the spliceosome in the nucleus. We show that SANS is found in Cajal bodies and nuclear speckles, where it interacts with components of spliceosomal sub-complexes such as SF3B1 and the large splicing cofactor SON but also with PRPFs and snRNAs related to the tri-snRNP complex. SANS is required for the transfer of tri-snRNPs between Cajal bodies and nuclear speckles for spliceosome assembly and may also participate in snRNP recycling back to Cajal bodies. SANS depletion alters the kinetics of spliceosome assembly, leading to accumulation of complex A. SANS deficiency and USH1G pathogenic mutations affects splicing of genes related to cell proliferation and human Usher syndrome. Thus, we provide the first evidence that splicing dysregulation may participate in the pathophysiology of Usher syndrome

Two-Dimensional Laser Diagnostics and Modeling of Counterflow Diffusion Flames

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86756/1/Sick51.pd

Macropinocytotic uptake and infection of human epithelial cells with species B2 adenovirus type 35

The human adenovirus serotype 35 (HAdV-35, short Ad35) causes kidney and urinary tract infections, and infects respiratory organs of immunocompromised individuals. Unlike other adenoviruses, Ad35 has a low seroprevalence which makes Ad35-based vectors promising candidates for gene therapy. Ad35 utilizes CD46 and integrins as receptors for infection of epithelial and hematopoietic cells. Here, we show that infectious entry of Ad35 into HeLa, human kidney HK-2 cells and normal human lung fibroblasts strongly depended on CD46 and integrins but not heparan sulfate, and variably required the large GTPase dynamin. Ad35 infections were independent of expression of the carboxy-terminal domain of AP180 which effectively blocks clathrin-mediated uptake. Ad35 infections were inhibited by small chemicals against the serine/threonine kinase Pak1 (p21-activated kinase), protein kinase C (PKC), sodium-proton exchangers, actin and acidic organelles. Remarkably, the F-actin inhibitor jasplakinolide, the Pak1 inhibitor IPA-3 or the sodium-proton exchange inhibitor EIPA blocked the endocytic uptake of Ad35. Dominant-negative proteins or small interfering RNAs against factors driving macropinocytosis, including the small GTPase Rac1, Pak1 or the Pak1 effector C-terminal binding protein 1 (CtBP1) potently inhibited Ad35 infection. Confocal laser scanning microscopy, electron microscopy and live cell imaging showed that Ad35 colocalized with fluid phase markers in large endocytic structures that were positive for CD46, alpha v integrins and also CtBP1. Our results extend earlier observations with HAdV-3 (Ad3), and establish macropinocytosis as an infectious pathway for species B human adenoviruses in epithelial and hematopoietic cells