| 1. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Thomas, B., et al.
(författare)
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Global Cardiovascular and Renal Outcomes of Reduced GFR
- 2017
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Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 28:7, s. 2167-2179
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Tidskriftsartikel (refereegranskat)abstract
- The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.
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| 6. |
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| 7. |
- Andres, E., et al.
(författare)
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Selected recent results from AMANDA
- 2001
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Ingår i: ICHEP 2000. Proceedings of the 30th International Conference on High Energy Physics. - : World Scientific. ; , s. 965-968
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Konferensbidrag (refereegranskat)abstract
- We present a selection of results based on data taken in 1997 with the 302-PMT Antarctic Muon and Neutrino Detector Array-B10 ("AMANDA-B10") array. Atmospheric neutrinos created in the northern hemisphere are observed indirectly through their charged current interactions which produce relativistic, Cherenkov-light-emitting upgoing muons in the South Pole ice cap. The reconstructed angular distribution of these events is in good agreement with expectation and demonstrates the viability of this ice-based device as a neutrino telescope. Studies of nearly vertical upgoing muons limit the available parameter space for WIMP dark matter under the assumption that WIMPS are trapped in the earth's gravitational potential well and annihilate with one another near the earth's center.
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| 8. |
- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
-
Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
-
Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 9. |
- Wilman, H. R., et al.
(författare)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 10. |
- Adriani, O., et al.
(författare)
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The gamma-400 space observatory : Status and perspectives
- 2014
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Ingår i: Proceedings of Science. - : Sissa Medialab Srl.
-
Konferensbidrag (refereegranskat)abstract
- The present design of the new space observatory GAMMA-400 is presented in this paper. The instrument has been designed for the optimal detection of gamma rays in a broad energy range (from ∼100 MeV up to 3 TeV), with excellent angular and energy resolution. The observatory will also allow precise and high statistic studies of the electron component in the cosmic rays up to the multi TeV region, as well as protons and nuclei spectra up to the knee region. The GAMMA-400 observatory will allow to address a broad range of science topics, like search for signatures of dark matter, studies of Galactic and extragalactic gamma-ray sources, Galactic and extragalactic diffuse emission, gamma-ray bursts and charged cosmic rays acceleration and diffusion mechanism up to the knee.
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| 11. |
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| 12. |
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| 13. |
- Karle, A., et al.
(författare)
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Observation of high energy atmospheric neutrinos with AMANDA
- 2000
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Ingår i: AIP Conference Proceedings. - : American Institute of Physics (AIP). ; , s. 823-827
-
Konferensbidrag (refereegranskat)abstract
- In 1997 the Antarctic Muon and Neutrino Detector Array (AMANDA) started operating with 10 strings. In an analysis of data taken during the first year of operation 188 atmospheric neutrino candidates were found. Their zenith angle distribution agrees with expectations based on Monte Carlo simulations. A preliminary upper limit is given on a diffuse flux of high energy neutrinos of astrophysical origin.
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| 14. |
- Leonov, A. A., et al.
(författare)
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The GAMMA-400 gamma-ray telescope characteristics. Angular resolution and electrons/protons separation
- 2014
-
Ingår i: Proceedings of Science. - : Sissa Medialab Srl.
-
Konferensbidrag (refereegranskat)abstract
- The measurements of gamma-ray fluxes and cosmic-ray electrons and positrons in the energy range from 100 MeV to several TeV, which will be realized by the specially designed GAMMA-400 gamma-ray telescope, concern with the following broad range of scientific topics. Search for signatures of dark matter, surveying the celestial sphere in order to study point and extended sources of gamma-rays, measuring the energy spectra of Galactic and extragalactic diffuse gamma-ray emission, study of gamma-ray bursts and gamma-ray emission from the Sun, as well as high precision measurements of spectra of high-energy electrons and positrons, protons and nuclei up to the knee. To clarify these scientific problems with the new experimental data the GAMMA-400 gamma-ray telescope possesses unique physical characteristics comparing with previous and present experiments. For gamma-ray energies more than 100 GeV GAMMA-400 provides the energy resolution ~1% and angular resolution better than 0.02 deg. The methods, developed to reconstruct the direction of incident gamma photon, are presented in this paper, as well as, the capability of the GAMMA-400 gamma-ray telescope to distinguish electrons and positrons from protons in cosmic rays is investigated. The first point concerns with the space topology of high-energy gamma photon interaction in the matter of GAMMA-400. Multiple secondary particles, generated inside gamma-ray telescope, produce significant problems to restore the direction of initial gamma photon. Also back-splash particles, i.e., charged particles and gamma photons generated in calorimeter and moved upward, mask the initial tracks of electron/positron pair from conversion of incident gamma photon. The processed methods allow us to reconstruct the direction of electromagnetic shower axis and extract the electron/positron trace. As a result, the direction of incident gamma photon with the energy of 100 GeV is calculated with an accuracy of better than 0.02 deg. The main components of cosmic rays are protons and helium nuclei, whereas the part of lepton component in the total flux is ~10 -3 for high energies. The separate contribution in proton rejection is studied for each detector system of the GAMMA-400 gamma-ray telescope. Using combined information from all detector systems allow us to provide the rejection from protons with a factor of ~4 10 5 for vertical incident particles and ~3 10 5 for particle with initial inclination of 30 deg. Science with the New Generation of High Energy Gamma-ray experiments, 10th Workshop (Scineghe2014) 04-06 June 2014 Lisbon - Portugal.
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| 15. |
- Topchiev, N. P., et al.
(författare)
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The GAMMA-400 experiment : Status and prospects
- 2015
-
Ingår i: Bulletin of the Russian Academy of Sciences: Physics. - 1062-8738. ; 79:3, s. 417-420
-
Tidskriftsartikel (refereegranskat)abstract
- The development of the GAMMA-400 γ-ray telescope continues. The GAMMA-400 is designed to measure fluxes of γ-rays and the electron-positron cosmic-ray component possibly associated with annihilation or decay of dark matter particles; and to search for and study in detail discrete γ-ray sources, to measure the energy spectra of Galactic and extragalactic diffuse γ-rays, and to study γ-ray bursts and γ-rays from the active Sun. The energy range for measuring γ-rays and electrons (positrons) is from 100 MeV to 3000 GeV. For 100-GeV γ-rays, the γ-ray telescope has an angular resolution of ∼0.01°, an energy resolution of ∼1%, and a proton rejection factor of ∼5 × 105. The GAMMA-400 will be installed onboard the Russian Space Observatory.
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| 16. |
- Raghavan, Maanasa, et al.
(författare)
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Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
-
Tidskriftsartikel (refereegranskat)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
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| 17. |
- Topchiev, N. P., et al.
(författare)
-
GAMMA-400 gamma-ray observatory
- 2015
-
Ingår i: Proceedings of Science. - : Proceedings of Science (PoS).
-
Konferensbidrag (refereegranskat)abstract
- The GAMMA-400 gamma-ray telescope with excellent angular and energy resolutions is designed to search for signatures of dark matter in the fluxes of gamma-ray emission and electrons+ positrons.Precision investigations of gamma-ray emission fromGalactic Center, Crab, Vela, Cygnus, Geminga, and other regions will be performed, as well asdiffuse gamma-rayemission,along with measurements of high-energy electron + positron and nuclei fluxes. Furthermore, it will studygamma-ray bursts and gamma-ray emission from the Sun during periods of solar activity. The energy range of GAMMA-400 is expected to be from ∼20 MeV up to TeV energies for gamma rays, up to 10 TeV for electrons + positrons, and up to 1015eV for cosmic-ray nuclei. For high-energy gamma rays with energy from 10 to 100 GeV, the GAMMA-400 angular resolution improves from 0.1° to ∼0.01° and energy resolution from 3% to ∼1%; the proton rejection factor is ∼5x105. GAMMA-400 will be installed onboardthe Russian space observatory.
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| 18. |
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| 19. |
- Barwick, S. W., et al.
(författare)
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Initial results from the AMANDA high-energy neutrino detector
- 1998
-
Ingår i: High-energy physics. Proceedings, 29th International Conference, ICHEP'98, Vancouver, Canada, July 23-29, 1998. Vol. 1, 2. ; , s. 1447-1452
-
Konferensbidrag (refereegranskat)
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| 20. |
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| 21. |
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| 22. |
- Halzen, F., et al.
(författare)
-
From the first neutrino telescope, the antarctic muon and neutrino detector array AMANDA, to the IceCube observatory
- 1999
-
Ingår i: Proceedings of the 26th International Cosmic Ray Conference, August 17-25, 1999, Salt Lake City : Invited, Rapporteur, and Highlight Papers. - : American Institute of Physics (AIP). ; , s. 428-431
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Konferensbidrag (refereegranskat)
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| 23. |
- Miller, T. C., et al.
(författare)
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Particle astrophysics in antarctica
- 1996
-
Ingår i: International School of Cosmic Ray Astrophysics: 10th Course: Toward the Millennium in Astrophysics: Problems and Prospects 16-26 Jun 1996. Erice, Italy. ; , s. 157-166
-
Konferensbidrag (refereegranskat)
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| 24. |
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| 25. |
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| 26. |
- Akimov, D., et al.
(författare)
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Physics with WASA and PROMICE
- 1994
-
Ingår i: Physics with GeV-particle beams, Juelich 1994. ; , s. 519-530
-
Konferensbidrag (refereegranskat)
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| 27. |
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| 28. |
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| 29. |
- Gilbert, M. R., et al.
(författare)
-
Perspectives on multiscale modelling and experiments to accelerate materials development for fusion
- 2021
-
Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 554
-
Forskningsöversikt (refereegranskat)abstract
- Prediction of material performance in fusion reactor environments relies on computational modelling, and will continue to do so until the first generation of fusion power plants come on line and allow long-term behaviour to be observed. In the meantime, the modelling is supported by experiments that attempt to replicate some aspects of the eventual operational conditions. In 2019, a group of leading experts met under the umbrella of the IEA to discuss the current position and ongoing challenges in modelling of fusion materials and how advanced experimental characterisation is aiding model improvement. This review draws from the discussions held during that workshop. Topics covering modelling of irradiation-induced defect production and fundamental properties, gas behaviour, clustering and segregation, defect evolution and interactions are discussed, as well as new and novel multiscale simulation approaches, and the latest effort s to link modelling to experiments through advanced observation and characterisation techniques.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Askebjer, P., et al.
(författare)
-
On the age vs depth and optical clarity of deep ice at South Pole
- 1995
-
Ingår i: Journal of Glaciology. - 0022-1430 .- 1727-5652. ; 41:139, s. 445-454
-
Tidskriftsartikel (refereegranskat)abstract
- The first four strings of phototubes for the AMANDA high-energy neutrino observatory are now frozen in place at a depth of 800 to 1000 m in ice at the South Pole. During the 1995-96 season an additional six strings will be deployed at greater depths. Provided absorption, scattering, and refraction of visible light are sufficiently small, the trajectory of a muon into which a neutrino converts can be determined by using the array of phototubes to measure the arrival times of \v{C}erenkov light emitted by the muon. To help in deciding on the depth for implantation of the six new strings, we discuss models of age vs depth for South Pole ice, we estimate mean free paths for scattering from bubbles and dust as a function of depth, and we assess distortion of light paths due to refraction at crystal boundaries and interfaces between air-hydrate inclusions and normal ice. We conclude that the depth interval 1600 to 1800 m will be suitably transparent for the next six AMANDA strings and, moreover, that the interval 1600 to 2100 m will be suitably transparent for a future 1-km 3 observatory except possibly in a region a few tens of meters thick at a depth corresponding to a peak in the dust concentration at 60 kyr BP.
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| 35. |
- ASKEBJER, P, et al.
(författare)
-
ON THE AGE VS DEPTH AND OPTICAL CLARITY OF DEEP ICE AT THE SOUTH-POLE
- 1995
-
Ingår i: JOURNAL OF GLACIOLOGY. - : INT GLACIOL SOC. - 0022-1430. ; 41:139, s. 445-454
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The first four strings of phototubes for the AMANDA high-energy neutrino observatory are now frozen in place at a depth of 800-1000 m in ice at the South Pole. During the 1995-96 season, as many as six more strings will be deployed at greater depths. Prov
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| 36. |
- Bark, R A, et al.
(författare)
-
Coexistence of triaxial and prolate shapes in Ir-171
- 1999
-
Ingår i: Nuclear Physics A. - 0375-9474 .- 1873-1554. ; 657:2, s. 113-133
-
Tidskriftsartikel (refereegranskat)abstract
- Excited states in Ir-171 have been observed for the first time. Gamma-rays were assigned to the nucleus by the recoil-decay tagging method, The ground-state band has a structure consistent with an h(11/2) proton coupled to a core of large triaxial deformation. At high spins, a bandcrossing occurs which is interpreted as a change in shape to a prolate deformation, Band-mixing calculations are performed for Ir171-175. These show that shape-coexistence between triaxial and prolate states in these nuclei follows the same systematics found in their Pt and Os neighbours. The systematics are also compared with deformations calculated for Ir171-179 using the code "Ultimate Cranker". Dipole bands were also observed, but tilted axis cranking calculations suggest that they are associated with a collective rotation.
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| 37. |
- Bergstrom, L., et al.
(författare)
-
The AMANDA experiment : Status and prospects for indirect dark matter detection
- 1996
-
Ingår i: The identification of dark matter. Proceedings, 1st International Workshop, Sheffield, UK, September 8-12, 1996. ; , s. 521-528
-
Konferensbidrag (refereegranskat)abstract
- At the AMANDA South Pole site, four new holes were drilled to depths 2050m to 2180 m and instrumented with 86 photomultipliers (PMTs) at depths1520-2000 m. Of these PMTs 79 are working, with 4-ns timing resolutionand noise rates 300 to 600 Hz. Various diagnostic devices were deployedand are working. An observed factor 60 increase in scattering length anda sharpening of the distribution of arrival times of laser pulses relative tomeasurements at 800-1000 m showed that bubbles are absent below 1500 m.Absorption lengths are 100 to 150 m at wavelengths in the blue and UV to337 nm. Muon coincidences are seen between the SPASE air shower arrayand the AMANDA PMTs at 800-1000 m and 1500-1900 m. The muon trackrate is 30 Hz for 8-fold triggers and 10 Hz for 10-fold triggers. The presentarray is the nucleus for a future expanded array. The potential of AMANDAfor SUSY dark matter search through the detection of high-energy neutrinosfrom the centre of the Sun or Earth is discussed.
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| 38. |
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| 39. |
- Contreras, ZA, et al.
(författare)
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Does early onset asthma increase childhood obesity risk? A pooled analysis of 16 European cohorts
- 2018
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 52:3
-
Tidskriftsartikel (refereegranskat)abstract
- The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3–4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3–4 years of age.Children with physician-diagnosed asthma had a higher risk for incident obesity than those without asthma (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18–2.33). Children with active asthma (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher risk for obesity (aHR 1.98, 95% CI 1.31–3.00) than those without wheeze and asthma. Persistent wheezing was associated with increased risk for incident obesity compared to never wheezers (aHR 1.51, 95% CI 1.08–2.09).Early-onset asthma and wheezing may contribute to an increased risk of developing obesity in later childhood.
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| 40. |
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| 41. |
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| 42. |
- Hallqvist, Andreas, 1973, et al.
(författare)
-
Dose escalation to 84 Gy with concurrent chemotherapy in stage III NSCLC appears excessively toxic: Results from a prematurely terminated randomized phase II trial
- 2018
-
Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 122, s. 180-186
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group launched this randomized phase II trial. Materials and Methods: NSCLC patients with stage III disease, good performance status (0-1) and adequate lung function (FEV1 > 1.0 L and CO diffusion capacity > 40%) received three cycles of cisplatin (75 mg/m(2) day 1) and vinorelbine (25 mg/m(2) day 1 and 8) every third week. Radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to 68 Gy (A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week. Results: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in arm B compared to the encouraging results of 28 and 45 months in the standard arm. The 1- and 3-year survival rates were 56% and 33% (B) and 72% and 56% (A), respectively. There were seven toxicity-related deaths due to esophageal perforations and pneumonitis: five in the escalated group and two with standard treatment. Conclusion: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 3-year survival of 56% (NCT01664663).
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| 43. |
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| 44. |
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| 45. |
- Hulth, P. O., et al.
(författare)
-
The AMANDA experiment
- 1996
-
Ingår i: Neutrino '96. Proceedings, 17th International Conference on Neutrino Physics and Astrophysics, Helsinki, Finland, June 13-19, 1996. ; , s. 518-523
-
Konferensbidrag (refereegranskat)abstract
- At the AMANDA South Pole site, four new holes were drilled to depths 2050 m to 2180 m and instrumented with 86 photomultipliers (PMTs) at depths 1520-2000 m. Of these PMTs 79 are working, with 4-ns timing resolution and noise rates 300 to 600 Hz. Various diagnostic devices were deployed and are working. An observed factor 60 increase in scattering length and a sharpening of the distribution of arrival times of laser pulses relative to measurements at 800-1000 m showed that bubbles are absent below 1500 m. Absorption lengths are 100 to 150 m at wavelengths in the blue and UV to 337 nm. Muon coincidences are seen between the SPASE air shower array and the AMANDA PMTs at 800-1000 m and 1500-1900 m. The muon track rate is 30 Hz for 8-fold triggers and 10 Hz for 10-fold triggers. The present array is the nucleus for a future expanded array.
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| 46. |
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| 47. |
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| 48. |
- Kupers, LK, et al.
(författare)
-
Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1893-
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Tidskriftsartikel (refereegranskat)abstract
- Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
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