| 41. |
- Ledoux, X., et al.
(författare)
-
The neutrons for science facility at SPIRAL-2
- 2017
-
Ingår i: ND 2016. - Les Ulis : EDP Sciences.
-
Konferensbidrag (refereegranskat)abstract
- Numerous domains, in fundamental research as well as in applications, require the study of reactions induced by neutrons with energies from few MeV up to few tens of MeV. Reliable measurements also are necessary to improve the evaluated databases used by nuclear transport codes. This energy range covers a large number of topics like transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors. A new facility called Neutrons For Science (NFS) is being built for this purpose on the GANIL site at Caen (France). NFS is composed of a pulsed neutron beam for time-of-flight facility as well as irradiation stations for cross-section measurements. Neutrons will be produced by the interaction of deuteron and proton beams, delivered by the SPIRAL-2 linear accelerator, with thick or thin converters made of beryllium or lithium. Continuous and quasi-mono-energetic spectra will be available at NFS up to 40 MeV. In this fast energy region, the neutron flux is expected to be up to 2 orders of magnitude higher than at other existing time-of-flight facilities. In addition, irradiation stations for neutron-, proton- and deuteron-induced reactions will allow performing cross-section measurements by the activation technique. After a description of the facility and its characteristics, the experiments to be performed in the short and medium term will be presented.
|
|
| 42. |
- Scott, Robert A., et al.
(författare)
-
A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
-
Tidskriftsartikel (refereegranskat)abstract
- Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
|
|
| 43. |
- Burgess, S., et al.
(författare)
-
Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables
- 2010
-
Ingår i: Statistics in medicine. - : Wiley. - 1097-0258 .- 0277-6715. ; 29:12, s. 1298-311
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes.
|
|
| 44. |
|
|
| 45. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
-
Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
-
Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
-
Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
|
|
| 46. |
- Ledoux, X., et al.
(författare)
-
The Neutrons for Science Facility at SPIRAL-2
- 2014
-
Ingår i: Nuclear Data Sheets. - : Elsevier BV. - 0090-3752 .- 1095-9904. ; 119, s. 353-356
-
Tidskriftsartikel (refereegranskat)abstract
- The Neutrons For Science (NFS) facility is a component of SPIRAL-2 laboratory under construction at Caen (France). SPIRAL-2 is dedicated to the production of high intensity Radioactive Ions Beams (RIB). It is based on a high-power linear accelerator (LINAG) to accelerate deuterons beams in order to produce neutrons by breakup reactions on a C converter. These neutrons will induce fission in U-238 for production of radioactive isotopes. Additionally to the RIB production, the proton and deuteron beams delivered by the accelerator will be used in the NFS facility. NFS is composed of a pulsed neutron beam and irradiation stations for cross-section measurements and material studies. The beams delivered by the LINAG will allow producing intense neutron beams in the 100 keV-40 MeV energy range with either a continuous or quasi-mono-energetic spectrum. At NFS available average fluxes will be up to 2 orders of magnitude higher than those of other existing time-of-flight facilities in the 1 MeV - 40 MeV range. NFS will be a very powerful tool for fundamental physics and application related research in support of the transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors. The facility and its characteristics are described, and several examples of the first potential experiments are presented.
|
|
| 47. |
- Maksimovic, M., et al.
(författare)
-
First observations and performance of the RPW instrument on board the Solar Orbiter mission
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
-
Tidskriftsartikel (refereegranskat)abstract
- The Radio and Plasma Waves (RPW) instrument on the ESA Solar Orbiter mission is designed to measure in situ magnetic and electric fields and waves from the continuum up to several hundred kHz. The RPW also observes solar and heliospheric radio emissions up to 16 MHz. It was switched on and its antennae were successfully deployed two days after the launch of Solar Orbiter on February 10, 2020. Since then, the instrument has acquired enough data to make it possible to assess its performance and the electromagnetic disturbances it experiences. In this article, we assess its scientific performance and present the first RPW observations. In particular, we focus on a statistical analysis of the first observations of interplanetary dust by the instrument's Thermal Noise Receiver. We also review the electro-magnetic disturbances that RPW suffers, especially those which potential users of the instrument data should be aware of before starting their research work.
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
- Tuskan, G A, et al.
(författare)
-
The genome of black cottonwood, Populus trichocarpa (Torr. & Gray).
- 2006
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 313:5793, s. 1596-604
-
Tidskriftsartikel (refereegranskat)abstract
- We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.
|
|
