Manufacturing and Installation of the Compound Cryogenic Distribution Line for the Large Hadron Collider

The Large Hadron Collider (LHC) [1] currently under construction at CERN will make use of superconducting magnets operating in superfluid helium below 2 K. A compound cryogenic distribution line (QRL) will feed with helium at different temperatures and pressures the local elementary cooling loops in the cryomagnet strings. Low heat inleak to all temperature levels is essential for the overall LHC cryogenic performance. Following a competitive tendering, CERN adjudicated in 2001 the contract for the series line to Air Liquide (France). This paper recalls the main features of the technical specification and shows the project status. The basic choices and achievements for the industrialization phase of the series production are also presented, as well as the installation issues and status

PIONIER: a visitor instrument for the VLTI

PIONIER is a 4-telescope visitor instrument for the VLTI, planned to see its first fringes in 2010. It combines four ATs or four UTs using a pairwise ABCD integrated optics combiner that can also be used in scanning mode. It provides low spectral resolution in H and K band. PIONIER is designed for imaging with a specific emphasis on fast fringe recording to allow closure-phases and visibilities to be precisely measured. In this work we provide the detailed description of the instrument and present its updated status.Comment: Proceedings of SPIE conference Optical and Infrared Interferometry II (Conference 7734) San Diego 201

Increasing the imaging capabilities of the VLTI using integrated optics

Several scientific topics linked to the observation of extended structures around astrophysical sources (dust torus around AGN, disks around young stars, envelopes around AGBs) require imaging capability with milli-arcsecond spatial resolution. The current VLTI instruments, AMBER and MIDI, will provide in the coming months the required high angular resolution, yet without actual imaging. As a rule of thumb, the image quality accessible with an optical interferometer is directly related to the number of telescopes used simultaneously: the more the apertures, the better and the faster the reconstruction of the image. We propose an instrument concept to achieve interferometric combination of N telescopes (4 ≤ N ≤ 8) thanks to planar optics technology: 4 x 8-m telescopes in the short term and/or 8 x 1.8-m telescopes in the long term. The foreseen image reconstruction quality in the visible and/or in the near infrared will be equivalent to the one achieved with millimeter radio interferometers. Achievable spatial resolution will be better than the one foreseen with ALMA. This instrument would be able to acquire routinely 1 mas resolution images. A 13 to 20 magnitude sensitivity in spectral ranges from 0.6 to 2.5 μm is expected depending on the choice of the phase referencing guide source. High dynamic range, even on faint objects, is achievable thanks to the high accuracy provided by integrated optics for visibility amplitude and phase measurements. Based on recent validations of integrated optics presented here an imaging instrument concept can be proposed. The results obtained using the VLTI facilities give a demonstration of the potential of the proposed technique

A roadmap for the Human Developmental Cell Atlas

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development

Long-term retention on treatment with lumiracoxib 100 mg once or twice daily compared with celecoxib 200 mg once daily: A randomised controlled trial in patients with osteoarthritis

BACKGROUND: The efficacy, safety and tolerability of lumiracoxib, a novel selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated in previous studies of patients with osteoarthritis (OA). As it is important to establish the long-term safety and efficacy of treatments for a chronic disease such as OA, the present study compared the effects of lumiracoxib at doses of 100 mg once daily (o.d.) and 100 mg twice daily (b.i.d.) with those of celecoxib 200 mg o.d. on retention on treatment over 1 year. METHODS: In this 52-week, multicentre, randomised, double-blind, parallel-group study, male and female patients (aged at least 40 years) with symptomatic primary OA of the hip, knee, hand or spine were randomised (1:2:1) to lumiracoxib 100 mg o.d. (n = 755), lumiracoxib 100 mg b.i.d. (n = 1,519) or celecoxib 200 mg o.d. (n = 758). The primary objective of the study was to demonstrate non-inferiority of lumiracoxib at either dose compared with celecoxib 200 mg o.d. with respect to the 1-year retention on treatment rate. Secondary outcome variables included OA pain in the target joint, patient's and physician's global assessments of disease activity, Short Arthritis assessment Scale (SAS) total score, rescue medication use, and safety and tolerability. RESULTS: Retention rates at 1 year were similar for the lumiracoxib 100 mg o.d., lumiracoxib 100 mg b.i.d. and celecoxib 200 mg o.d. groups (46.9% vs 47.5% vs 45.3%, respectively). It was demonstrated that retention on treatment with lumiracoxib at either dose was non-inferior to celecoxib 200 mg o.d. Similarly, Kaplan-Meier curves for the probability of premature discontinuation from the study for any reason were similar across the treatment groups. All three treatments generally yielded comparable results for the secondary efficacy variables and all treatments were well tolerated. CONCLUSION: Long-term treatment with lumiracoxib 100 mg o.d., the recommended dose for OA, was as effective and well tolerated as celecoxib 200 mg o.d. in patients with OA. TRIAL REGISTRATION: clinicaltrials.gov NCT00145301

Increasing the imaging capabilities of the VLTI using integrated optics

Several scientific topics linked to the observation of extended structures around astrophysical sources (dust torus around AGN, disks around young stars, envelopes around AGBs) require imaging capability with milli-arcsecond spatial resolution. The current VLTI instruments, AMBER and MIDI, will provide in the coming months the required high angular resolution, yet without actual imaging. As a rule of thumb, the image quality accessible with an optical interferometer is directly related to the number of telescopes used simultaneously: the more the apertures, the better and the faster the reconstruction of the image. We propose an instrument concept to achieve interferometric combination of N telescopes (4 ≤ N ≤ 8) thanks to planar optics technology: 4 x 8-m telescopes in the short term and/or 8 x 1.8-m telescopes in the long term. The foreseen image reconstruction quality in the visible and/or in the near infrared will be equivalent to the one achieved with millimeter radio interferometers. Achievable spatial resolution will be better than the one foreseen with ALMA. This instrument would be able to acquire routinely 1 mas resolution images. A 13 to 20 magnitude sensitivity in spectral ranges from 0.6 to 2.5 μm is expected depending on the choice of the phase referencing guide source. High dynamic range, even on faint objects, is achievable thanks to the high accuracy provided by integrated optics for visibility amplitude and phase measurements. Based on recent validations of integrated optics presented here an imaging instrument concept can be proposed. The results obtained using the VLTI facilities give a demonstration of the potential of the proposed technique

The Response of Lactococcus lactis to Membrane Protein Production

Background: The biogenesis of membrane proteins is more complex than that of water-soluble proteins, and recombinant expression of membrane proteins in functional form and in amounts high enough for structural and functional studies is often problematic. To better engineer cells towards efficient protein production, we set out to understand and compare the cellular consequences of the overproduction of both classes of proteins in Lactococcus lactis, employing a combined proteomics and transcriptomics approach. Methodology and Findings: Highly overproduced and poorly expressed membrane proteins both resulted in severe growth defects, whereas amplified levels of a soluble substrate receptor had no effect. In addition, membrane protein overproduction evoked a general stress response (upregulation of various chaperones and proteases), which is probably due to accumulation of misfolded protein. Notably, upon the expression of membrane proteins a cell envelope stress response, controlled by the two-component regulatory CesSR system, was observed. Conclusions: The physiological response of L. lactis to the overproduction of several membrane proteins was determined and compared to that of a soluble protein, thus offering better understanding of the bottlenecks related to membrane protein production and valuable knowledge for subsequent strain engineering.

Meta-analysis of heterogeneous Down Syndrome data reveals consistent genome-wide dosage effects related to neurological processes

<p>Abstract</p> <p>Background</p> <p>Down syndrome (DS; trisomy 21) is the most common genetic cause of mental retardation in the human population and key molecular networks dysregulated in DS are still unknown. Many different experimental techniques have been applied to analyse the effects of dosage imbalance at the molecular and phenotypical level, however, currently no integrative approach exists that attempts to extract the common information.</p> <p>Results</p> <p>We have performed a statistical meta-analysis from 45 heterogeneous publicly available DS data sets in order to identify consistent dosage effects from these studies. We identified 324 genes with significant genome-wide dosage effects, including well investigated genes like <it>SOD1</it>, <it>APP</it>, <it>RUNX1 </it>and <it>DYRK1A </it>as well as a large proportion of novel genes (N = 62). Furthermore, we characterized these genes using gene ontology, molecular interactions and promoter sequence analysis. In order to judge relevance of the 324 genes for more general cerebral pathologies we used independent publicly available microarry data from brain studies not related with DS and identified a subset of 79 genes with potential impact for neurocognitive processes. All results have been made available through a web server under <url>http://ds-geneminer.molgen.mpg.de/</url>.</p> <p>Conclusions</p> <p>Our study represents a comprehensive integrative analysis of heterogeneous data including genome-wide transcript levels in the domain of trisomy 21. The detected dosage effects build a resource for further studies of DS pathology and the development of new therapies.</p

A Novel Role for Dbx1-Derived Cajal-Retzius Cells in Early Regionalization of the Cerebral Cortical Neuroepithelium

Patterning of the cerebral cortex during embryogenesis depends not only on passive diffusion of morphogens but also on signal delivery by Cajal-Retzius neurons that migrate over long distances