448 research outputs found

    Study of the Validity of K. Bane's Formulae for the CLIC Accelerator Structure

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    The comprehension of short range wakefields is essential for the design of CLIC. Useful tools are the Karl Bane's formulae which provide geometrical parameterization of the short range wake for periodic rotational-symmetric structures. The comparison of 2D computations based on ABCI with predicted results and the study of the range of validity of these formulae are the subjects of this paper. An extended model for rounded iris structures is also proposed

    Technical Specification for the CLIC Two-Beam Module

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    A high-energy (0.5-3 TeV centre-of-mass), highluminosity Compact Linear Collider (CLIC) is being studied at CERN [1]. The CLIC main linacs, 21-km long each, are composed of 2-m long two beam modules. This paper presents their current layout, the main requirements for the different sub-systems (alignment, supporting, stabilization, cooling and vacuum) as well as the status of their integration

    Modulation of omv production by the lysis module of the dlp12 defective prophage of Escherichia coli k12

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    Outer membrane vesicles (OMVs) are nanostructures mostly produced by blebbing of the outer membrane in Gram negative bacteria. They contain biologically active proteins and perform a variety of processes. OMV production is also a typical response to events inducing stress in the bacterial envelope. In these cases, hypervesiculation is regarded as a strategy to avoid the dangerous accumulation of undesired products within the periplasm. Several housekeeping genes influence the biogenesis of OMVs, including those correlated with peptidoglycan and cell wall dynamics. In this work, we have investigated the relationship between OMV production and the lysis module of the E. coli DLP12 cryptic prophage. This module is an operon encoding a holin, an endolysin and two spannins, and is known to be involved in cell wall maintenance. We find that deleting the lysis module increases OMV production, suggesting that during evolution this operon has been domes-ticated to regulate vesiculation, likely through the elimination of non‐recyclable peptidoglycan frag-ments. We also show that the expression of the lysis module is negatively regulated by environmental stress stimuli as high osmolarity, low pH and low temperature. Our data further highlight how defective prophages finely contribute to bacterial host fitness

    A nanoporous surface is essential for glomerular podocyte differentiation in three-dimensional culture.

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    Although it is well recognized that cell-matrix interactions are based on both molecular and geometrical characteristics, the relationship between specific cell types and the three-dimensional morphology of the surface to which they are attached is poorly understood. This is particularly true for glomerular podocytes - the gatekeepers of glomerular filtration - which completely enwrap the glomerular basement membrane with their primary and secondary ramifications. Nanotechnologies produce biocompatible materials which offer the possibility to build substrates which differ only by topology in order to mimic the spatial organization of diverse basement membranes. With this in mind, we produced and utilized rough and porous surfaces obtained from silicon to analyze the behavior of two diverse ramified cells: glomerular podocytes and a neuronal cell line used as a control. Proper differentiation and development of ramifications of both cell types was largely influenced by topographical characteristics. Confirming previous data, the neuronal cell line acquired features of maturation on rough nanosurfaces. In contrast, podocytes developed and matured preferentially on nanoporous surfaces provided with grooves, as shown by the organization of the actin cytoskeleton stress fibers and the proper development of vinculin-positive focal adhesions. On the basis of these findings, we suggest that in vitro studies regarding podocyte attachment to the glomerular basement membrane should take into account the geometrical properties of the surface on which the tests are conducted because physiological cellular activity depends on the three-dimensional microenvironment

    Short GRBs at the dawn of the gravitational wave era

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    We derive the luminosity function and redshift distribution of short Gamma Ray Bursts (SGRBs) using (i) all the available observer-frame constraints (i.e. peak flux, fluence, peak energy and duration distributions) of the large population of Fermi SGRBs and (ii) the rest-frame properties of a complete sample of Swift SGRBs. We show that a steep ϕ(L)∝L−a\phi(L)\propto L^{-a} with a>2.0 is excluded if the full set of constraints is considered. We implement a Monte Carlo Markov Chain method to derive the ϕ(L)\phi(L) and ψ(z)\psi(z) functions assuming intrinsic Ep-Liso and Ep-Eiso correlations or independent distributions of intrinsic peak energy, luminosity and duration. To make our results independent from assumptions on the progenitor (NS-NS binary mergers or other channels) and from uncertainties on the star formation history, we assume a parametric form for the redshift distribution of SGRBs. We find that a relatively flat luminosity function with slope ~0.5 below a characteristic break luminosity ~3×1052\times10^{52} erg/s and a redshift distribution of SGRBs peaking at z~1.5-2 satisfy all our constraints. These results hold also if no Ep-Liso and Ep-Eiso correlations are assumed. We estimate that, within ~200 Mpc (i.e. the design aLIGO range for the detection of GW produced by NS-NS merger events), 0.007-0.03 SGRBs yr−1^{-1} should be detectable as gamma-ray events. Assuming current estimates of NS-NS merger rates and that all NS-NS mergers lead to a SGRB event, we derive a conservative estimate of the average opening angle of SGRBs: Ξjet\theta_{jet}~3-6 deg. Our luminosity function implies an average luminosity L~1.5×1052\times 10^{52} erg/s, nearly two orders of magnitude higher than previous findings, which greatly enhances the chance of observing SGRB "orphan" afterglows. Efforts should go in the direction of finding and identifying such orphan afterglows as counterparts of GW events.Comment: 13 pages, 5 figures, 2 tables. Accepted for publication in Astronomy & Astrophysics. Figure 5 and angle ranges corrected in revised versio

    Proteinuria in focal segmental glomerulosclerosis: role of circulating factors and therapeutic approach.

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    The clinical course of primary Focal Segmental Glomerulosclerosis (FSGS) is frequently complicated by nephrotic range proteinuria and progression to renal failure. The high recurrence rate of the disease in transplanted kidney suggests the hypothesis that such patients have a circulating factor that alters glomerular capillary permeability. In recent years some authors found that serum from patients with FSGS increases glomerular permeability to albumin and partially identified the permeability factor (PF) as a protein of 30-50 Kd m.w. The removal of this protein by means of Plasma Exchange (PE) or plasma Immunoadsorption by Protein A (IA) decreased proteinuria. In this report we provide preliminary data about the prevalence of PF and the therapeutic effect of its removal by IA, in 3 pts with recurrence in the transplanted kidney, and 4 with FSGS of the native kidneys. They were resistant to corticosteroids (CS) and immunosuppressive (IS) therapy. 10 IA sessions were performed in 4 weeks: if a remission was achieved IA was gradually tapered. The level of PF in the serum was measured by an in vitro assay to determine the glomerular permeability to albumin. The FSGS was histologically proven in all cases and the degree of evolution was evaluated. PF levels, serum creatinine, daily proteinuria and serum albumin were monitored. The 3 patients with recurrent FSGS had a normalization of the PF levels; 2 had a clinical remission. In FSGS of native kidneys PF was elevated in 3/4 cases; 1 had a clinical remission; 2 with extensive sclerohyalinosis and 1 without PF levels did not improve. Our results confirm that most patients with FSGS have high PF serum levels and suggest that its removal can be beneficial

    A role for the ELAV RNA-binding proteins in neural stem cells : stabilization of Msi1 mRNA

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    Post-transcriptional regulation exerted by neural-specific RNA-binding proteins plays a pivotal role in the development and maintenance of the nervous system. Neural ELAV proteins are key inducers of neuronal differentiation through the stabilization and/or translational enhancement of target transcripts bearing the AU-rich elements (AREs), whereas Musashi-1 maintains the stem cell proliferation state by acting as a translational repressor. Since the gene encoding Musashi-1 (Msi1) contains a conserved ARE in its 3' untranslated region, the authors focused on the possibility of a mechanistic relation between ELAV proteins and Musashi-1 in cell fate commitment. Colocalization of neural ELAV proteins with Musashi-1 clearly shows that ELAV proteins are expressed at early stages of neural commitment, whereas interaction studies demonstrate that neural ELAV proteins exert an ARE-dependent binding activity on the Msi1 mRNA. This binding activity has functional effects, since the ELAV protein family member HuD is able to stabilize the Msi1 ARE-contg. mRNA in a sequence-dependent way in a deadenylation/degrdn. assay. Furthermore activation of the neural ELAV proteins by phorbol esters in human SH-SY5Y cells is assocd. with an increase of Musashi-1 protein content in the cytoskeleton. The authors propose that ELAV RNA-binding proteins exert an important post-transcriptional control on Musashi-1 expression in the transition from proliferation to neural differentiation of stem/progenitor cells
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