| 1. |
- Acharya, B. S., et al.
(författare)
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Introducing the CTA concept
- 2013
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Feroci, M., et al.
(författare)
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The large observatory for x-ray timing
- 2014
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
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Konferensbidrag (refereegranskat)abstract
- The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
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| 4. |
- Aleksic, J., et al.
(författare)
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DETECTION OF VERY HIGH ENERGY gamma-RAY EMISSION FROM THE PERSEUS CLUSTER HEAD-TAIL GALAXY IC 310 BY THE MAGIC TELESCOPES
- 2010
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Ingår i: The Astrophysical Journal Letters. - 2041-8205. ; 723:2, s. l207-L212
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Tidskriftsartikel (refereegranskat)abstract
- We report on the detection with the MAGIC telescopes of very high energy (VHE) gamma-rays from IC 310, a head-tail radio galaxy in the Perseus galaxy cluster, observed during the interval 2008 November to 2010 February. The Fermi satellite has also detected this galaxy. The source is detected by MAGIC at a high statistical significance of 7.6 sigma in 20.6 hr of stereo data. The observed spectral energy distribution is flat with a differential spectral index of -2.00 +/- 0.14. The mean flux above 300 GeV, between 2009 October and 2010 February, (3.1 +/- 0.5) x 10(-12) cm(-2) s(-1), corresponds to (2.5 +/- 0.4)% of Crab Nebula units. Only an upper limit, of 1.9% of Crab Nebula units above 300 GeV, was obtained with the 2008 data. This, together with strong hints (>3 sigma) of flares in the middle of 2009 October and November, implies that the emission is variable. The MAGIC results favor a scenario with the VHE emission originating from the inner jet close to the central engine. More complicated models than a simple one-zone synchrotron self-Compton (SSC) scenario, e. g., multi-zone SSC, external Compton, or hadronic, may be required to explain the very flat spectrum and its extension over more than three orders of magnitude in energy.
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| 5. |
- Beulens, J. W. J., et al.
(författare)
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Alcohol consumption and risk of type 2 diabetes in European men and women : influence of beverage type and body size The EPIC-InterAct study
- 2012
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Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 272:4, s. 358-370
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the association between alcohol consumption and type 2 diabetes, and determine whether this is modified by sex, body mass index (BMI) and beverage type. Design: Multicentre prospective casecohort study. Setting: Eight countries from the European Prospective Investigation into Cancer and Nutrition cohort. Subjects: A representative baseline sample of 16 154 participants and 12 403 incident cases of type 2 diabetes. Interventions: Alcohol consumption assessed using validated dietary questionnaires. Main outcome measures: Occurrence of type 2 diabetes based on multiple sources (mainly self-reports), verified against medical information. Results: Amongst men, moderate alcohol consumption was nonsignificantly associated with a lower incidence of diabetes with a hazard ratio (HR) of 0.90 (95% CI: 0.781.05) for 6.112.0 versus 0.16.0 g day-1, adjusted for dietary and diabetes risk factors. However, the lowest risk was observed at higher intakes of 24.196.0 g day-1 with an HR of 0.86 (95% CI: 0.750.98). Amongst women, moderate alcohol consumption was associated with a lower incidence of diabetes with a hazard ratio of 0.82 (95% CI: 0.720.92) for 6.112.0 g day-1 (P interaction gender <0.01). The inverse association between alcohol consumption and diabetes was more pronounced amongst overweight (BMI = 25 kg m-2) than normal-weight men and women (P interaction < 0.05). Adjusting for waist and hip circumference did not alter the results for men, but attenuated the association for women (HR=0.90, 95% CI: 0.791.03 for 6.112.0 g day-1). Wine consumption for men and fortified wine consumption for women were most strongly associated with a reduced risk of diabetes. Conclusions: The results of this study show that moderate alcohol consumption is associated with a lower risk of type 2 diabetes amongst women only. However, this risk reduction is in part explained by fat distribution. The relation between alcohol consumption and type 2 diabetes was stronger for overweight than normal-weight women and men.
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| 6. |
- 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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| 7. |
- Duarte-Salles, T., et al.
(författare)
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Dairy products and risk of hepatocellular carcinoma: The European Prospective Investigation into Cancer and Nutrition
- 2014
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Ingår i: International Journal of Cancer. - : Wiley-Liss Inc.. - 0020-7136 .- 1097-0215. ; 135:7, s. 1662-1672
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Tidskriftsartikel (refereegranskat)abstract
- Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (Ncases = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (Ncases = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin-like growth factor (IGF)-I levels. For cohort analyses, multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed-up for an average of 11 years (person-years follow-up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13-2.43; ptrend = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; ptrend = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; ptrend = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65-1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case-control study, similar results were observed among hepatitis-free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration. What's New? Currently, the role of dairy product intake in the development of hepatocellular carcinoma (HCC) is unclear. Using detailed data from a large multi-centric prospective cohort, this study investigated the association between consumption of total and specific dairy products with first incident HCC. The study found that higher dairy product consumption, particularly milk and cheese, was associated with increased HCC risk. Dietary calcium, vitamin D, fat and protein did not explain the observed associations. However, higher circulating IGF-I levels may play a role. © 2014 UICC.
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| 8. |
- McKay, James D., et al.
(författare)
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A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
- 2011
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
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| 9. |
- Purdue, Mark P, et al.
(författare)
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Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:1, s. 60-65
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10⁻⁸) and rs7579899 (P = 2.3 × 10⁻⁹), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 × 10⁻¹⁴). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 × 10⁻⁸). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.
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| 10. |
- Wu, Xifeng, et al.
(författare)
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A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:2, s. 456-462
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome- wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r(2) = 0.64, D' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 x 10(-10) and P = 6.07 x 10(-9), respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.
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