Active vibration isolation system for CLIC final focus

International audienceWith pinpoint accuracy, the next generation of Linear Collider such as CLIC will collide electron and positron beams at a centre of mass energy of 3 TeV with a desired peak luminosity of 2*1034 cm-2s-1. One of the many challenging features of CLIC is its ability to collide beams at the sub-nanometer scale at the Interaction Point (IP). Such a high level of accuracy could only be achieved by integrating Active Vibration Isolation systems (AVI) upstream of the collision to prevent the main source of vibration: Ground Motion (GM). Complementary control systems downstream of the collision (Interaction Point FeedBack (IPFB), Orbit FeedBack (OFB)) allow low frequency vibration rejection. This paper focuses on a dedicated AVI table designed for the last focusing quadrupole (QD0) where the specifications are the most stringent. Combining FeedForward (FF) and FeedBack (FB) techniques, the prototype is able to reduce GM down to 0.6 nm RMS(4Hz) experimentally without any load. These performances couldn't be achieved without cutting edge-technology such as sub-nanometer piezo actuators, ultra-low noise accelerometers and seismometers and an accurate guidance system. The whole AVI system is described in details. Further developments concern the integration of the final focusing magnet above the AVI table, first as part of the simulation with its dynamical model, and finally, as a realistic prototype

Advanced Virgo: A second-generation interferometric gravitational wave detector

Advanced Virgo is the project to upgrade the Virgo interferometric detector of gravitational waves, with the aim of increasing the number of observable galaxies (and thus the detection rate) by three orders of magnitude. The project is now in an advanced construction phase and the assembly and integration will be completed by the end of 2015. Advanced Virgo will be part of a network, alongside the two Advanced LIGO detectors in the US and GEO HF in Germany, with the goal of contributing to the early detections of gravitational waves and to the opening a new window of observation on the universe. In this paper we describe the main features of the Advanced Virgo detector and outline the status of the construction

The Renin prosequence enhances constitutive secretion of Renin and optimizes Renin activity.

Renin is cleaved from its precursor prorenin into mature renin. We investigated the impact of the renin proregion on the generation and secretion of enzymatically active renin. We compared the effects of the following sequences of human prorenin with those of wild type prorenin[1-383]: prosequence [1-43], hinge sequence [1-62], Des[1-43]prorenin ("renin"), Des[1-62]prorenin and prorenin[N260]. These sequences were individually expressed in CV1 cells (constitutive pathway model) and AtT20 cells (regulated and constitutive pathways model), and Des[1-43]prorenin was also coexpressed together with the different prosequences. Renin concentration and activity were measured in cell extracts and culture media. Deletion of the prosequence reduces renin activity in both cell types, but it leaves (total) renin concentration unchanged. Coexpression of the prosequence with renin enhances renin secretion in both cell types: Constitutively secreted renin is enhanced by coexpression of renin together with any of the prosequence containing molecules [1-43], [1-62] or prorenin[N260]. Immunofluorescence in AtT20 cells shows lysosomal typical labeling of prorenin and Des[1-43]prorenin. In AtT20 cells expressing prorenin[1-383], stimulation of regulated secretion increases prorenin but not renin release. The renin prosequence [1-43] optimizes renin activity possibly through appropriate protein folding and it enhances the constitutive secretion of (pro)renin. The major part of generated renin may be targeted to lysosomes

Dibasic cleavage site is required for sorting to the regulated secretory pathway for both pro- and neuropeptide Y

To investigate the signals governing routing of biologically active peptides to the regulated secretory pathway, we have expressed mutated and non-mutated proneuropeptide Y (ProNPY) in pituitary-derived AtT20 cells. The mutations were carried out on dibasic cleavage site and or ProNPY C-terminal sequence. Targeting to the regulated secretory pathway was studied using protein kinase A (8-BrcAMP), protein kinase C (phorbol myristate acetate) specific activators and protein synthesis inhibitor cycloheximide, and by pulse chase. The analysis of expressed peptides in cells and culture media indicated that: neuropeptide Y (NPY) and ProNPY were differently secreted, whilst NPY was exclusively secreted via regulatory pathway; ProNPY was secreted via regulated and constitutive-like secretory pathways. ProNPY secretion behaviour was not Proteolytic cleavage efficiency-dependent. The dibasic cleavage was essential for ProNPY and NPY cAMP-dependent regulated secretion and may have function as a retention signal

The somatostatin-28(1-12)-NPAMAP sequence: an essential helical-promoting motif governing prosomatostatin processing at mono- and dibasic sites

Proline residues, known to have special structural properties, induce particular conformations which participate in some biological functions. Two prolines (Pro(-9), Pro(-5)) located near the processing sites (Arg(-15) and Arg(-2)Lys(-)(1)) of human prosomatostatin were previously shown to be important for cleavage of the precursor into somatostatin-28 (S-28) and somatostatin-14 (S-14) [Gomez et al. (1989) EMBO J. 8, 2911-2916]. In this study, the importance of the pentapeptide P-A-M-A-P sequence (P-(X)(3)-P pattern), located in the S-28(1-12) segment connecting the mono- and dibasic cleavage sites, was investigated by using site-directed mutagenesis. Analysis of prosomatostatin-derived peptides produced by expression of mutated cDNA species in Neuro2A cells indicated that (i) deletion of PAMAP decreased S-14 production, (ii) deletion of the two Pro residues almost abolished the cleavage at the dibasic site, and (iii) Pro displacement generating the AMAPP motif resulted in a decrease of S-28 production. Moreover, both theoretical and spectroscopic studies of synthetic peptides reproducing the S-28(1-12) sequence bearing critical mutations showed that this sequence can organize as an alpha helical structure. These observations demonstrate that NPAMAP constitutes an accurate alpha-helix nucleation motif allowing for the generation of equal amounts of S-28 and S-14 from their common precursor in Neuro2A cells. Moreover, they emphasize the importance of the S-28(1-12) segment joining Arg(-15) and Arg(-2)Lys(-1) cleavage sites whose conformational organization is essential for controlling their accessibility to the appropriate processing proteases

Renal endothelin receptor type B upregulation in rats with low or high renin hypertension.

OBJECTIVES: To evaluate the role of endothelin-1 (ET-1) in hypertension, we investigated density and distribution of ETA and ETB receptors in hearts and kidneys of deoxycorticosterone acetate (DOCA)-salt and 1 kidney -- 1 clip (1K1C) hypertensive rats. METHODS: Five groups of uninephrectomized Wistar rats were put on a low salt diet. Three groups of rats drank tap water and two groups received saline. One group of each regimen received DOCA subcutaneously and two corresponding groups without DOCA served as controls. The fifth group of rats had the renal artery clipped to induce 1K1C hypertension. At 6 weeks, mean arterial pressure (MAP) was recorded and membrane binding assays using 125I-ET-1 were carried out. RESULTS: MAP was increased from control 122 +/- 3 to 155 +/- 6 and 218 +/- 11 mmHg in DOCA-salt and 1K1C rats, respectively, and cardiac weight index was increased. ETA receptors were predominantly expressed in the heart, whereas ETB receptors were predominant in the kidney. In the kidneys, the density of the ETB receptor subtype was upregulated in DOCA-salt and 1K1C rats from 160 +/- 8 to 217 +/- 12 and 190 +/- 2 fmol/mg (P < 0.05), respectively, and ETA tended to be downregulated (P = 0.057). Plasma renin activity was decreased in DOCA-salt rats from 17 +/- 3 to 0.17 +/- 0.01 ng/ml per h and increased in 1K1C rats on low salt diet to 30 +/- 5 ng/ml per h. CONCLUSIONS: Since ETB is the predominant endothelin receptor in the kidneys, upregulation of the ETB receptor mediating vasodilation and downregulation of the ETA receptor mediating vasoconstriction would be compatible with a mainly renal counter-regulatory effect of endothelin-1 to hypertension. Both low and high renin models of hypertension may be affected

PANDORE: an environmental box for ITk integration tests

International audiencePANDORE is the environmental box that is going to be used for the quality control of loaded local supports of the ATLAS ITk Pixel Outer Barrel at LAPP (Annecy, France). First PANDORE, its interlock system, diphasic CO$_{2}$ cooling station, and data acquisition system are described. Subsequently, the results of the qualification tests are shown. Given the complexity of the ITk Pixel Outer Barrel system, several loading sites are going to be needed. By documenting the state-of-the-art of PANDORE, this note aims to help the wide ITk Pixel community in the discussion for standardizing the quality control procedure and equipment of the loaded local supports