| 1. |
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| 2. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)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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| 3. |
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| 5. |
- Bar, N., et al.
(author)
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A reference map of potential determinants for the human serum metabolome
- 2020
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In: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Journal article (peer-reviewed)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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| 6. |
- Wilman, H. R., et al.
(author)
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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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In: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Journal article (peer-reviewed)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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| 7. |
- Akimov, D., et al.
(author)
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Physics with WASA and PROMICE
- 1994
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In: Physics with GeV-particle beams, Juelich 1994. ; , s. 519-530
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Conference paper (peer-reviewed)
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| 8. |
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| 9. |
- Thomas, B., et al.
(author)
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Global Cardiovascular and Renal Outcomes of Reduced GFR
- 2017
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In: 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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Journal article (peer-reviewed)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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| 10. |
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| 11. |
- Andres, E., et al.
(author)
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Selected recent results from AMANDA
- 2001
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In: ICHEP 2000. Proceedings of the 30th International Conference on High Energy Physics. - : World Scientific. ; , s. 965-968
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Conference paper (peer-reviewed)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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| 12. |
- Axelsson, A, et al.
(author)
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Excited superdeformed band in Eu-143
- 1999
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In: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 6:2, s. 175-183
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Journal article (peer-reviewed)abstract
- A new superdeformed band has been discovered in a EUROBALL experiment and assigned to Eu-143. It has a maximum intensity of 35% of the Eu-143 yrast superdeformed band and the transition energies of the two bands are very similar. Based on comparison with cranked shell model calculations the new band is tentatively assigned the high-N intruder configuration pi 6(2)nu 7(0) and the parity and signature quantum numbers (pi, alpha) = (-1, +1/2). In addition to the already known high-energy transition at 3361 keV another discrete line at 2715 keV was found to be in coincidence with the yrast superdeformed band. However, it was not possible to connect the decay out of either of the superdeformed bands to, known normally deformed states.
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| 13. |
- Axelsson, A, et al.
(author)
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Excited superdeformed band in Eu-143
- 1999
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In: EUROPEAN PHYSICAL JOURNAL A. - : SPRINGER VERLAG. - 1434-6001. ; 6:2, s. 175-183
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Journal article (other academic/artistic)abstract
- A new superdeformed band has been discovered in a EUROBALL experiment and assigned to Eu-143. It has a maximum intensity of 35% of the Eu-143 yrast superdeformed band and the transition energies of the two bands are very similar. Based on comparison with
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Karle, A., et al.
(author)
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Observation of high energy atmospheric neutrinos with AMANDA
- 2000
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In: AIP Conference Proceedings. - : American Institute of Physics (AIP). ; , s. 823-827
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Conference paper (peer-reviewed)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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| 20. |
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| 21. |
- Langstrom, B, et al.
(author)
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PET i klinisk verksamhet.
- 1995
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In: Läkartidningen. ; 92, s. 3202-
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Journal article (other academic/artistic)
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| 22. |
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| 23. |
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| 24. |
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| 26. |
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| 27. |
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| 28. |
- Askebjer, P., et al.
(author)
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On the age vs depth and optical clarity of deep ice at South Pole
- 1995
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In: Journal of Glaciology. - 0022-1430 .- 1727-5652. ; 41:139, s. 445-454
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Journal article (peer-reviewed)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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| 29. |
- Bak-Coleman, Joseph B., et al.
(author)
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Stewardship of global collective behavior
- 2021
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:27
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Journal article (peer-reviewed)abstract
- Collective behavior provides a framework for understanding how the actions and properties of groups emerge from the way individuals generate and share information. In humans, information flows were initially shaped by natural selection yet are increasingly structured by emerging communication technologies. Our larger, more complex social networks now transfer high-fidelity information over vast distances at low cost. The digital age and the rise of social media have accelerated changes to our social systems, with poorly understood functional consequences. This gap in our knowledge represents a principal challenge to scientific progress, democracy, and actions to address global crises. We argue that the study of collective behavior must rise to a crisis discipline just as medicine, conservation, and climate science have, with a focus on providing actionable insight to policymakers and regulators for the stewardship of social systems.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Bergstrom, L., et al.
(author)
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The AMANDA experiment : Status and prospects for indirect dark matter detection
- 1996
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In: The identification of dark matter. Proceedings, 1st International Workshop, Sheffield, UK, September 8-12, 1996. ; , s. 521-528
-
Conference paper (peer-reviewed)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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| 34. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Bracco, A, et al.
(author)
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Search for the GDR built on superdeformed nuclei
- 2000
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In: PHYSICA SCRIPTA. - : ROYAL SWEDISH ACAD SCIENCES. - 0281-1847. ; T88, s. 182-188
-
Journal article (peer-reviewed)abstract
- An experiment aiming at finding evidence for gamma-decay of the giant dipole resonance built on superdeformed nuclear states has been made using the EUROBALL gamma-detector array coupled to the large BaF2 detectors of the HECTOR system. The reaction Pd-11
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| 42. |
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| 43. |
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| 44. |
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| 45. |
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| 46. |
- Gilbert, M. R., et al.
(author)
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Perspectives on multiscale modelling and experiments to accelerate materials development for fusion
- 2021
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In: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 554
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Research review (peer-reviewed)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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| 47. |
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| 48. |
- Halzen, F., et al.
(author)
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From the first neutrino telescope, the antarctic muon and neutrino detector array AMANDA, to the IceCube observatory
- 1999
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In: 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
-
Conference paper (peer-reviewed)
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| 49. |
- Hulth, P. O., et al.
(author)
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The AMANDA experiment
- 1996
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In: Neutrino '96. Proceedings, 17th International Conference on Neutrino Physics and Astrophysics, Helsinki, Finland, June 13-19, 1996. ; , s. 518-523
-
Conference paper (peer-reviewed)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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| 50. |
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