The information system for LHC parameters and layouts

The construction of the Large Hadron Collider, LHC, at CERN implies both the handling of a huge amount of information and the control of the coherence of this information. The LHC machine parameters have to be maintained coherent as the design evolves from the conceptual stage to the actual, installed, machine and have to be made available to all concerned. Design data is provided in many different formats from the machine builders, drawings, technical documents, meeting notes, lattice simulation input files, etc. The World Wide Web is being used to make the information accessible both at CERN and at the external collaborating laboratories. In this paper we describe the implementation of an Oracle database as the central common repository for machine parameters and of information for the automatic generation of CAD layout drawings and WWW pages. This system is integrated in a larger context, the EDMS system for the LHC project, which encompasses both the accelerator and the experiments

Structure liming reduces draught requirement on clay soil

Liming with ‘structure lime’, comprising approximately 80–85% ground limestone and 15–20% slaked lime, has been promoted in subsidised environmental schemes in Sweden since 2010 to increase clay aggregate stability and mitigate particulate phosphorus losses to surface waters. To date, approximately 65,000 ha have been structure-limed. Apart from stabilising aggregates, liming may also improve other physical properties, such as soil strength. This study examined the effect of increasing application rate (0–16 t ha-1) of structure lime on soil strength, approximated by horizontal (draught requirement) and vertical (penetrometer resistance) measurements, in eight field soils (clay content 26–38%) to which structure lime had been applied two, three, four or six years previously. Draught requirement when cultivating with a multipurpose cultivator significantly decreased (by 11%) with the highest application rate of structure lime (16 t ha-1) compared with an unlimed control. This reduced the wheel power requirement by 7.1 kW and diesel consumption by 1.2–1.4 L ha-1, and lowered CO2 emissions by 3–4 kg ha-1. To clarify the general effect of structure liming, the mean value of all limed treatments was compared with that of the unlimed control. This showed that structure liming in general significantly reduced the draught requirement (by 7%). However, penetrometer resistance measurements revealed no significant effects of structure liming and no relation between draught requirement and penetrometer resistance measurements. Overall, the results indicate that structure liming can reduce fuel consumption, due to easier soil tillage, and thus lower CO2 emissions

The CEDAR Project

The LHC project at CERN requires both the handling of a huge amount of engineering information and the control of the coherence of this information as the design work evolves on the machine and the experiments. A commercial Engineering Data Management System, (EDMS), is being implemented to manage data for the design, construction, installation and maintenance of both the accelerator and the experiments. This CERN-wide project is called CEDAR The World Wide Web is used to make the information accessible at CERN and in the external collaborating laboratories around the world. In this paper we describe the objectives of the CEDAR project, the different subprojects in the machine and the experiments as well as the first results of the implementation work

De-Novo Identification of PPARγ/RXR Binding Sites and Direct Targets during Adipogenesis

BACKGROUND: The pathophysiology of obesity and type 2 diabetes mellitus is associated with abnormalities in endocrine signaling in adipose tissue and one of the key signaling affectors operative in these disorders is the nuclear hormone transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma). PPARgamma has pleiotropic functions affecting a wide range of fundamental biological processes including the regulation of genes that modulate insulin sensitivity, adipocyte differentiation, inflammation and atherosclerosis. To date, only a limited number of direct targets for PPARgamma have been identified through research using the well established pre-adipogenic cell line, 3T3-L1. In order to obtain a genome-wide view of PPARgamma binding sites, we applied the pair end-tagging technology (ChIP-PET) to map PPARgamma binding sites in 3T3-L1 preadipocyte cells. METHODOLOGY/PRINCIPAL FINDINGS: Coupling gene expression profile analysis with ChIP-PET, we identified in a genome-wide manner over 7700 DNA binding sites of the transcription factor PPARgamma and its heterodimeric partner RXR during the course of adipocyte differentiation. Our validation studies prove that the identified sites are bona fide binding sites for both PPARgamma and RXR and that they are functionally capable of driving PPARgamma specific transcription. Our results strongly indicate that PPARgamma is the predominant heterodimerization partner for RXR during late stages of adipocyte differentiation. Additionally, we find that PPARgamma/RXR association is enriched within the proximity of the 5' region of the transcription start site and this association is significantly associated with transcriptional up-regulation of genes involved in fatty acid and lipid metabolism confirming the role of PPARgamma as the master transcriptional regulator of adipogenesis. Evolutionary conservation analysis of these binding sites is greater when adjacent to up-regulated genes than down-regulated genes, suggesting the primordial function of PPARgamma/RXR is in the induction of genes. Our functional validations resulted in identifying novel PPARgamma direct targets that have not been previously reported to promote adipogenic differentiation. CONCLUSIONS/SIGNIFICANCE: We have identified in a genome-wide manner the binding sites of PPARgamma and RXR during the course of adipogenic differentiation in 3T3L1 cells, and provide an important resource for the study of PPARgamma function in the context of adipocyte differentiation

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity