| 1. |
- Abdallah, J., et al.
(författare)
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Mechanical construction and installation of the ATLAS tile calorimeter
- 2013
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 8, s. T11001-
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Tidskriftsartikel (refereegranskat)abstract
- This paper summarises the mechanical construction and installation of the Tile Calorimeter for the ATLAS experiment at the Large Hadron Collider in CERN, Switzerland. The Tile Calorimeter is a sampling calorimeter using scintillator as the sensitive detector and steel as the absorber and covers the central region of the ATLAS experiment up to pseudorapidities +/- 1.7. The mechanical construction of the Tile Calorimeter occurred over a period of about 10 years beginning in 1995 with the completion of the Technical Design Report and ending in 2006 with the installation of the final module in the ATLAS cavern. During this period approximately 2600 metric tons of steel were transformed into a laminated structure to form the absorber of the sampling calorimeter. Following instrumentation and testing, which is described elsewhere, the modules were installed in the ATLAS cavern with a remarkable accuracy for a structure of this size and weight.
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| 2. |
- Abdallah, J., et al.
(författare)
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The optical instrumentation of the ATLAS Tile Calorimeter
- 2013
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 8, s. P01005-
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Tidskriftsartikel (refereegranskat)abstract
- The Tile Calorimeter, covering the central region of the ATLAS experiment up to pseudorapidities of +/-1.7, is a sampling device built with scintillating tiles that alternate with iron plates. The light is collected in wave-length shifting (WLS) fibers and is read out with photomultipliers. In the characteristic geometry of this calorimeter the tiles lie in planes perpendicular to the beams, resulting in a very simple and modular mechanical and optical layout. This paper focuses on the procedures applied in the optical instrumentation of the calorimeter, which involved the assembly of about 460,000 scintillator tiles and 550,000 WLS fibers. The outcome is a hadronic calorimeter that meets the ATLAS performance requirements, as shown in this paper.
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| 3. |
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| 4. |
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| 5. |
- Bruggmann, P., et al.
(författare)
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Historical epidemiology of hepatitis C virus (HCV) in selected countries
- 2014
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Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 5-33
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Tidskriftsartikel (refereegranskat)abstract
- Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6358000 cases in 2008 and Brazil with 2106000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
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| 6. |
- Razavi, H., et al.
(författare)
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The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm
- 2014
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Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21:Suppl. 1, s. 34-59
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Tidskriftsartikel (refereegranskat)abstract
- The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
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| 7. |
- Sutton, M. A., et al.
(författare)
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Towards a climate-dependent paradigm of ammonia emission and deposition
- 2013
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Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 1471-2970 .- 0962-8436. ; 368:1621
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Tidskriftsartikel (refereegranskat)abstract
- Existing descriptions of bi-directional ammonia (NH3) land-atmosphere exchange incorporate temperature and moisture controls, and are beginning to be used in regional chemical transport models. However, such models have typically applied simpler emission factors to upscale the main NH3 emission terms. While this approach has successfully simulated the main spatial patterns on local to global scales, it fails to address the environment-and climate-dependence of emissions. To handle these issues, we outline the basis for a new modelling paradigm where both NH3 emissions and deposition are calculated online according to diurnal, seasonal and spatial differences in meteorology. We show how measurements reveal a strong, but complex pattern of climatic dependence, which is increasingly being characterized using ground-based NH3 monitoring and satellite observations, while advances in process-based modelling are illustrated for agricultural and natural sources, including a global application for seabird colonies. A future architecture for NH3 emission-deposition modelling is proposed that integrates the spatio-temporal interactions, and provides the necessary foundation to assess the consequences of climate change. Based on available measurements, a first empirical estimate suggests that 5 degrees C warming would increase emissions by 42 per cent (28-67%). Together with increased anthropogenic activity, global NH3 emissions may increase from 65 (45-85) Tg N in 2008 to reach 132 (89-179) Tg by 2100.
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| 8. |
- Wedemeyer, H., et al.
(författare)
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Strategies to manage hepatitis C virus (HCV) disease burden
- 2014
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Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 60-89
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Tidskriftsartikel (refereegranskat)abstract
- The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
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| 9. |
- Hudson, Lawrence N., et al.
(författare)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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| 10. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 11. |
- Cryan, James P., et al.
(författare)
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Auger Electron Angular Distribution of Double Core-Hole States in the Molecular Reference Frame
- 2010
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 105:8, s. 083004-
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Tidskriftsartikel (refereegranskat)abstract
- The Linac Coherent Light Source free electron laser is a source of high brightness x rays, 2×1011 photons in a ∼5 fs pulse, that can be focused to produce double core vacancies through rapid sequential ionization. This enables double core vacancy Auger electron spectroscopy, an entirely new way to study femtosecond chemical dynamics with Auger electrons that probe the local valence structure of molecules near a specific atomic core. Using 1.1 keV photons for sequential x-ray ionization of impulsively aligned molecular nitrogen, we observed a rich single-site double core vacancy Auger electron spectrum near 413 eV, in good agreement with ab initio calculations, and we measured the corresponding Auger electron angle dependence in the molecular frame.
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| 12. |
- Glownia, James M., et al.
(författare)
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Time-resolved pump-probe experiments at the LCLS
- 2010
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Ingår i: Optics Express. - 1094-4087. ; 18:17, s. 17620-17630
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Tidskriftsartikel (refereegranskat)abstract
- The first time-resolved x-ray/optical pump-probe experiments at the SLAC Linac Coherent Light Source (LCLS) used a combination of feedback methods and post-analysis binning techniques to synchronize an ultrafast optical laser to the linac-based x-ray laser. Transient molecular nitrogen alignment revival features were resolved in time-dependent x-ray-induced fragmentation spectra. These alignment features were used to find the temporal overlap of the pump and probe pulses. The strong-field dissociation of x-ray generated quasi-bound molecular dications was used to establish the residual timing jitter. This analysis shows that the relative arrival time of the Ti:Sapphire laser and the x-ray pulses had a distribution with a standard deviation of approximately 120 fs. The largest contribution to the jitter noise spectrum was the locking of the laser oscillator to the reference RF of the accelerator, which suggests that simple technical improvements could reduce the jitter to better than 50 fs.
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| 13. |
- Cryan, J P, et al.
(författare)
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Molecular frame Auger electron energy spectrum from N2
- 2012
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Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 45:5, s. 055601-
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Tidskriftsartikel (refereegranskat)abstract
- Here we present the first angle-resolved, non-resonant (normal) Auger spectra for impulsively aligned nitrogen molecules. We have measured the angular pattern of Auger electron emission following K -shell photoionization by 1.1 keV photons from the Linac Coherent Light Source (LCLS). Using strong-field-induced molecular alignment to make molecular frame measurements is equally effective for both repulsive and quasi-bound final states. The capability to resolve Auger emission angular distributions in the molecular frame of reference provides a new tool for spectral assignments in congested Auger electron spectra that takes advantage of the symmetries of the final diction states. Based on our experimental results and theoretical predictions, we propose the assignment of the spectral features in the Auger electron spectrum.
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| 14. |
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| 15. |
- Souza, P. P. C., et al.
(författare)
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IL-4 and IL-13 inhibit IL-1 beta and TNF-alpha induced kinin B-1 and B-2 receptors through a STAT6-dependent mechanism
- 2013
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 169:2, s. 400-412
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose Bone resorption induced by interleukin-1 (IL-1) and tumour necrosis factor (TNF-) is synergistically potentiated by kinins, partially due to enhanced kinin receptor expression. Inflammation-induced bone resorption can be impaired by IL-4 and IL-13. The aim was to investigate if expression of B1 and B2 kinin receptors can be affected by IL-4 and IL-13. Experimental Approach We examined effects in a human osteoblastic cell line (MG-63), primary human gingival fibroblasts and mouse bones by IL-4 and IL-13 on mRNA and protein expression of the B1 and B2 kinin receptors. We also examined the role of STAT6 by RNA interference and using Stat6-/- mice. Key Results IL-4 and IL-13 decreased the mRNA expression of B1 and B2 kinin receptors induced by either IL-1 or TNF- in MG-63 cells, intact mouse calvarial bones or primary human gingival fibroblasts. The burst of intracellular calcium induced by either bradykinin (B2 agonist) or des-Arg10-Lys-bradykinin (B1 agonist) in gingival fibroblasts pretreated with IL-1 was impaired by IL-4. Similarly, the increased binding of B1 and B2 ligands induced by IL-1 was decreased by IL-4. In calvarial bones from Stat6-deficient mice, and in fibroblasts in which STAT6 was knocked down by siRNA, the effect of IL-4 was decreased. Conclusions and Implications These data show, for the first time, that IL-4 and IL-13 decrease kinin receptors in a STAT6-dependent mechanism, which can be one important mechanism by which these cytokines exert their anti-inflammatory effects and impair bone resorption.
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| 16. |
- Wetterskog, Daniel, 1978, et al.
(författare)
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Mutation profiling of adenoid cystic carcinomas from multiple anatomical sites identifies mutations in the RAS pathway, but no KIT mutations
- 2013
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Ingår i: Histopathology. - : Wiley. - 0309-0167. ; 62:4, s. 543-550
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Tidskriftsartikel (refereegranskat)abstract
- Aims The majority of adenoid cystic carcinomas (AdCCs), regardless of anatomical site, harbour the MYB–NFIB fusion gene. The aim of this study was to characterize the repertoire of somatic genetic events affecting known cancer genes in AdCCs. Methods and results DNA was extracted from 13 microdissected breast AdCCs, and subjected to a mutation survey using the Sequenom OncoCarta Panel v1.0. Genes found to be mutated in any of the breast AdCCs and genes related to the same canonical molecular pathways, as well as KIT, a proto-oncogene whose protein product is expressed in AdCCs, were sequenced in an additional 68 AdCCs from various anatomical sites by Sanger sequencing. Using the Sequenom MassARRAY platform and Sanger sequencing, mutations in BRAF and HRAS were identified in three and one cases, respectively (breast, and head and neck). KIT, which has previously been reported to be mutated in AdCCs, was also investigated, but no mutations were identified. Conclusions Our results demonstrate that mutations in genes pertaining to the canonical RAS pathway are found in a minority of AdCCs, and that activating KIT mutations are either absent or remarkably rare in these cancers, and unlikely to constitute a driver and therapeutic target for patients with AdCC.
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| 17. |
- dos Reis, Fabio Bueno, Jr., et al.
(författare)
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Nodulation and nitrogen fixation by Mimosa spp. in the Cerrado and Caatinga biomes of Brazil
- 2010
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 186:4, s. 934-946
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Tidskriftsartikel (refereegranskat)abstract
- P>An extensive survey of nodulation in the legume genus Mimosa was undertaken in two major biomes in Brazil, the Cerrado and the Caatinga, in both of which there are high degrees of endemicity of the genus. Nodules were collected from 67 of the 70 Mimosa spp. found. Thirteen of the species were newly reported as nodulating. Nodules were examined by light and electron microscopy, and all except for M. gatesiae had a structure typical of effective Mimosa nodules. The endosymbiotic bacteria in nodules from all of the Mimosa spp. were identified as Burkholderia via immunolabelling with an antibody against Burkholderia phymatum STM815. Twenty of the 23 Mimosa nodules tested were shown to contain nitrogenase by immunolabelling with an antibody to the nitrogenase Fe- (nifH) protein, and using the delta 15N (15N natural abundance) technique, contributions by biological N-2 fixation of up to 60% of total plant N were calculated for Caatinga Mimosa spp. It is concluded that nodulation in Mimosa is a generic character, and that the preferred symbionts of Brazilian species are Burkholderia. This is the first study to demonstrate N-2 fixation by beta-rhizobial symbioses in the field.
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| 18. |
- Lopes, P. C., et al.
(författare)
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Cyclosporine A enhances gluconeogenesis while sirolimus impairs insulin signaling in peripheral tissues after 3 weeks of treatment
- 2014
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Ingår i: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952 .- 1356-1839. ; 91:1, s. 61-73
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Tidskriftsartikel (refereegranskat)abstract
- Cyclosporine A (CsA) and sirolimus (SRL) are immunosuppressive agents (IA) associated with new-onset diabetes after transplantation (NODAT). This study aims to evaluate the effects of 3-weeks of treatment with either CsA (5 mg/kg BW/day) or SRL (1 mg/kg BW/day) on insulin signaling and expression of markers involved in glucose metabolism in insulin-sensitive tissues, in Wistar rats. Although no differences were observed in fasting glucose, insulin or C-peptide levels, both treated groups displayed an impaired glucose excursion during both glucose and insulin tolerance tests. These results suggest glucose intolerance and insulin resistance. An increase in glucose-6-phosphatase protein levels (68%, p<0.05) and in protein-tyrosine phosphatase 1B (163%,p<0.05), a negative regulator of insulin was observed in the CsA-treated group in the liver, indicating enhanced gluconeogenesis and increased insulin resistance. On the other hand, glucokinase protein levels were decreased in the SRL group (35%, p < 0.05) compared to vehicle, suggesting a decrease in glucose disposal. SRI treatment also reduced peroxisome proliferator-activated receptor gamma coactivator 1 alpha protein expression in muscle (similar to 50%, p<0.05), while no further protein alterations were observed in muscle and perirenal adipose tissue nor with the CsA treatment. Moreover, the phosphorylation of key proteins of the insulin signaling cascade was suppressed in the SRL group, but was unchanged by the CsA treatment. Taken together, these data suggest that CsA treatment enhances gluconeogenic factors in liver, while SRL treatment impairs insulin signaling in peripheral tissues, which can contribute to the development of insulin resistance and NODAT associated with immunosuppressive therapy.
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