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1.
  • Abat, E., et al. (författare)
  • Study of the response of the ATLAS central calorimeter to pions of energies from 3 to 9 GeV
  • 2009
  • Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002 .- 1872-9576. ; 607:2, s. 372-386
  • Tidskriftsartikel (refereegranskat)abstract
    • A fully instrumented slice of the ATLAS central detector was exposed to test beams from the SPS (Super Proton Synchrotron) at CERN in 2004. in this paper, the response of the central calorimeters to pions with energies in the range between 3 and 9 GeV is presented. The linearity and the resolution of the combined calorimetry (electromagnetic and hadronic calorimeters) was measured and compared to the prediction of a detector simulation program using the toolkit Geant 4. (C) 2009 Elsevier B.V. All rights reserved.
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2.
  • Beral, V, et al. (författare)
  • Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58515 women with breast cancer and 95067 women without the disease
  • 2002
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 87, s. 1234-45
  • Tidskriftsartikel (refereegranskat)abstract
    • Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1 % per 10 g per day, P < 0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers= 1.03, 95% CI 0.98 - 1.07, and for current smokers=0.99, 0.92 - 1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. (C) 2002 Cancer Research UK.
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4.
  • Casolino, M., et al. (författare)
  • Cosmic-ray observations of the heliosphere with the PAMELA experiment
  • 2006
  • Ingår i: Astrophysics. - : Elsevier BV. ; , s. 1848-1852
  • Konferensbidrag (refereegranskat)abstract
    • The PAMELA experiment is a multi-purpose apparatus built around a permanent magnet spectrometer, with the main goal of studying in detail the antiparticle component of cosmic rays. The apparatus will be carried in space by means of a Russian satellite, due to launch in 2005, for a three year-long mission. The characteristics of the detectors composing the instrument, alongside the long lifetime of the mission and the orbital characteristics of the satellite, will allow to address several items of cosmic-ray physics. In this paper, we will focus on the solar and heliospheric observation capabilities of PAMELA.
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5.
  • Casolino, M., et al. (författare)
  • Launch of the space experiment PAMELA
  • 2008
  • Ingår i: Advances in Space Research. - : Elsevier. - 0273-1177 .- 1879-1948. ; 42:3, s. 455-466
  • Tidskriftsartikel (refereegranskat)abstract
    • PAMELA is a satellite borne experiment designed to study with great accuracy cosmic rays of galactic, solar, and trapped nature in a wide energy range (protons 80 MeV-700 GeV, electrons 50 MeV-400 GeV). Main objective is the study of the antimatter component: antiprotons (80 MeV-190 GeV), positrons (50 MeV-270 GeV) and search for antimatter with a precision of the order of 10-8. The experiment, housed on board the Russian Resurs-DK I satellite, was launched on June 15th, 2006 in a 350 x 600 km orbit with all inclination of 70'. The detector is composed of a series of scintillator counters arranged at the extremities of a permanent magnet spectrometer to provide charge, time-of-flight, and rigidity information. Lepton/hadron identification is performed by a silicon-tungsten calorimeter and a neutron detector placed at the bottom of the device. An anticounter system is used offline to reject false triggers coming from the satellite. In self-trigger mode the calorimeter, the neutron detector, and a shower tail catcher are capable of an independent measure of the lepton component up to 2 TeV. In this work we describe the experiment, its scientific objectives, and the performance in the first months after launch.
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7.
  • Papini, P., et al. (författare)
  • In-flight performances of the PAMELA satellite experiment
  • 2008
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 588:1-2, s. 259-266
  • Tidskriftsartikel (refereegranskat)abstract
    • PAMELA is a satcllite-borne experiment designed to study with great accuracy charged particles in the cosmic radiation with a particular focus on antiparticles. The experiment, housed on board the Russian Resurs-DK1 satellite, was launched on June 15, 2006 in a 350 x 600 km orbit with an inclination of 70 degrees. The apparatus comprises a time-of-flight system, a silicon-microstrip magnetic spectrometer, a silicon-tungsten electromagnetic calorimeter, an anticoincidence system, a shower tail catcher scintillator and a neutron detector. The combination of these devices allows charged particle identification over a wide energy range. In this work, the detector design is reviewed and the in-orbit performances in the first months after the launch are presented.
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8.
  • Stozhkov, Y. I., et al. (författare)
  • About Separation of Hadron and Electromagnetic Cascades in the Pamela Calorimeter
  • 2005
  • Ingår i: International Journal of Modern Physics A. - 0217-751X .- 1793-656X. ; 20:29, s. 6745-6748
  • Tidskriftsartikel (refereegranskat)abstract
    • Results of calibration of the PAMELA instrument at the CERN facilities are discussed. In September, 2003, the calibration of the Neutron Detector together with the Calorimeter was performed with the CERN beams of electrons and protons with energies of 20-180 GeV. The implementation of the Neutron Detector increases a rejection factor of hadrons from electrons about ten times. The results of calibration are in agreement with calculations.
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9.
  • Aad, G., et al. (författare)
  • The ATLAS Experiment at the CERN Large Hadron Collider
  • 2008
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08003
  • Forskningsöversikt (refereegranskat)abstract
    • The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
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10.
  • Adriani, O., et al. (författare)
  • The Pamela experiment ready for flight
  • 2007
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 572:1, s. 471-473
  • Tidskriftsartikel (refereegranskat)abstract
    • The Pamela apparatus will allow precise measurements of cosmic rays in Low Earth Orbit, mainly focusing on the antiparticles component. The apparatus is now ready for flight, and the launch is foreseen during June 2006. The paper briefly reports the status of the experiment, and the performances of the various components as measured before the launch.
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  • Bongi, M, et al. (författare)
  • PAMELA : A satellite experiment for antiparticles measurement in cosmic rays
  • 2004
  • Ingår i: IEEE Transactions on Nuclear Science. - 0018-9499 .- 1558-1578. ; 51:3, s. 854-859
  • Tidskriftsartikel (refereegranskat)abstract
    • PAMELA is a satellite-borne experiment that will study the antiproton and positron fluxes in cosmic rays in a wide range of energy (from 80 MeV up to 190 GeV for antiprotons and from 50 MeV up to 270 GeV for positrons) and with high statistics, and that will measure the antihelium/helium ratio with a sensitivity of the order of 10(-8). The detector will fly on-board a polar orbiting Resurs DK1 satellite, which will be launched into space by a Soyuz rocket in 2004 from Baikonur cosmodrome in Kazakhstan, for a 3-year-long mission. Particle identification and energy measurements are performed in the PAMELA apparatus using the following subdetectors: a magnetic spectrometer made up of a permanent magnet equipped with double-sided microstrip silicon detectors, an electromagnetic imaging calorimeter composed of layers of tungsten absorber and silicon detectors planes, a transition radiation detector made of straw tubes interleaved with carbon fiber radiators, a plastic scintillator time-of-flight and trigger system, a set of anticounter plastic scintillator detectors, and a neutron detector. The features of the detectors and the main results obtained in beam test sessions are presented.
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13.
  • Canzian, Federico, et al. (författare)
  • Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3).
  • 2009
  • Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 9, s. 257-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). METHODS: We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. RESULTS: Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. CONCLUSION: Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.
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14.
  • Charlton, D. G., et al. (författare)
  • System tests of radiation hard optical links for the ATLAS semiconductor tracker
  • 2000
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 443:03-feb, s. 430-446
  • Tidskriftsartikel (refereegranskat)abstract
    • A prototype optical data and Timing Trigger and Control transmission system based on LEDs and PIN-diodes has been constructed. The system would be suitable in terms of radiation hardness and radiation length for use in the ATLAS SemiConductor Tracker. Bit error rate measurements were performed for the data links and for the links distributing the Timing, Trigger and Control data from the counting room to the front-end modules. The effects of cross-talk between the emitters and receivers were investigated. The advantages of using Vertical Cavity Surface Emitting Lasers (VCSELs) instead of LEDs are discussed.
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15.
  • Colas, J., et al. (författare)
  • Position resolution and particle identification with the ATLAS EM calorimeter
  • 2005
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 550:02-jan, s. 96-115
  • Tidskriftsartikel (refereegranskat)abstract
    • In the years between 2000 and 2002 several pre-series and series modules of the ATLAS EM barrel and end-cap calorimeter were exposed to electron, photon and pion beams. The performance of the calorimeter with respect to its finely segmented first sampling has been studied. The polar angle resolution has been found to be in the range 50-60 (mrad)/root E(GeV). The pi(0) rejection has been measured to be about 3.5 for 90% photon selection efficiency at PT = 50GeV/c. e-pi separation studies have indicated that a pion fake rate of (0.07-0.5)% can be achieved while maintaining 90% electron identification efficiency for energies up to 40 GeV.
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16.
  • Cox, David G., et al. (författare)
  • A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)
  • 2006
  • Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 8:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Androgens have been hypothesised to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol or their binding to the oestrogen receptor and/ or androgen receptor ( AR) in the breast. Here, we report on the results of a large and comprehensive study of the association between genetic variation in the AR gene and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium ( BPC3). Methods The underlying genetic variation was determined by first sequencing the coding regions of the AR gene in a panel of 95 advanced breast cancer cases. Second, a dense set of markers from the public database was genotyped in a panel of 349 healthy women. The linkage disequilibrium relationships ( blocks) across the gene were then identified, and haplotypetagging single nucleotide polymorphisms ( htSNPs) were selected to capture the common genetic variation across the locus. The htSNPs were then genotyped in the nested breast cancer cases and controls from the Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study, and Women's Health Study cohorts ( 5,603 breast cancer cases and 7,480 controls). Results We found no association between any genetic variation ( SNP, haplotype, or the exon 1 CAG repeat) in the AR gene and risk of breast cancer, nor were any statistical interactions with known breast cancer risk factors observed. Conclusion Among postmenopausal Caucasian women, common variants of the AR gene are not associated with risk of breast cancer.
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17.
  • Cox, David G, et al. (författare)
  • Haplotypes of the estrogen receptor beta gene and breast cancer risk
  • 2008
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 122:2, s. 387-392
  • Tidskriftsartikel (refereegranskat)abstract
    • Exposure to exogenous (oral contraceptives, postmenopausal hormone therapy) and endogenous (number of ovulatory cycles, adiposity) steroid hormones is associated with breast cancer risk. Breast cancer risk associated with these exposures could hypothetically be modified by genes in the steroid hormone synthesis, metabolism and signaling pathways. Estrogen receptors are the first step along the path of signaling cell growth and development upon stimulation with estrogens. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium has systematically selected haplotype tagging SNPs in genes along the steroid hormone synthesis, metabolism and binding pathways, including the estrogen receptor beta (ESR2) gene. Four htSNPs tag the 6 major (>5% frequency) haplotypes of the ESR2 gene. These polymorphisms have been genotyped in 5,789 breast cancer cases and 7,761 controls nested within the American Cancer Society Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study and Women's Health Study cohorts. None of the SNPs were independently associated with breast cancer risk. One haplotype of the ESR2 gene was associated with breast cancer risk before correction for multiple testing (OR 1.17, 95% CI 1.07-1.28, p = 0.0007). This haplotype remained associated with breast cancer risk after adjustment for multiple testing using a permutation procedure. There was no statistically significant heterogeneity in SNP or haplotype odds ratios across cohorts. These data suggest that inherited variants in ESR2 (while possibly conferring a small increased risk of breast cancer) are not associated with appreciable (OR > 1.2) changes in breast cancer risk among Caucasian women.
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18.
  • Eid, O.I., et al. (författare)
  • Allyl type radical formation in X-irradiated glutarimide crystals studied by ENDOR and ENDOR-induced EPR
  • 2004
  • Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 6:13, s. 3604-3610
  • Tidskriftsartikel (refereegranskat)abstract
    • Glutarimide single crystals X-irradiated at room temperature were reinvestigated at 150 K with the purpose to obtain information about possible ring opening and other fragmentation processes involving free radicals in this compound, previously only observed to take place in aqueous solutions. In previous work, using EPR,ENDOR and EIE spectroscopy, two H-abstraction radicals present in a 3:1 relative ratio in the irradiated crystals were identified. In the present work the detection of a third radical species, III, is reported. The g- and hyperfine coupling tensors for all three radicals at 150 K were obtained. Based on simulations of the EPR spectra the relative abundance of the three radicals was estimated to be 60, 25 and 15% for radicals I, II and III, respectively. Radical III is proposed to be of the allyl radical type -CH=CH-1CH- formed formally by a concerted H2 elimination from C2 and C3 of radical I and/or from C3 and C4 of radical II. This proposal and structure is at variance with observations from aqueous solution studies of succinimide, where the CO-CH2 bond was susceptible for rupture. However, the assignment is consistent with density functional theory (DFT) calculations, predicting equivalent hyperfine interactions to the two a-type protons at C2 and C4 in excellent. agreement with the experimentally determined hyperfine coupling tensors. EIE results confirmed that both couplings originate from the same radical species. Possible mechanisms for the formation of radical III are discussed.
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  • Gonzalez, CA, et al. (författare)
  • Smoking and the risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2003
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 107:4, s. 629-634
  • Tidskriftsartikel (refereegranskat)abstract
    • Smoking has recently been recognised as causally associated with the development of gastric cancer (GC). However, evidence on the effect by sex, duration and intensity of smoking, anatomic subsite and cessation of smoking is limited. Our objective was to assess the relation between tobacco use and GC incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC). We studied data from 521,468 individuals recruited from 10 European countries taking part in the EPIC study. Participants completed lifestyle questionnaires that included questions on lifetime consumption of tobacco and diet in 1991-1998. Participants were followed until September 2002, and during that period 305 cases of stomach cancer were identified. After exclusions, 274 were eligible for the analysis, using the Cox proportional hazard model. After adjustment for educational level, consumption of fresh fruit, vegetables and preserved meat, alcohol intake and body mass index (BMI), there was a significant association between cigarette smoking and gastric cancer risk: the hazard ratio (HR) for ever smokers was 1.45 (95% confidence interval [CI] = 1.08-1.94). The HR of current cigarette smoking was 1.73 (95% CI = 1.06-2.83) in males and 1.87 (95% CI = 1.12-3.12) in females. Hazard ratios increased with intensity and duration of cigarette smoked. A significant decrease of risk was observed after 10 years of quitting smoking. A preliminary analysis of 121 cases with identified anatomic site showed that current cigarette smokers had a higher HR of GC in the cardia (HR = 4.10) than in the distal part of the stomach (HR = 1.94). In this cohort, 17.6 % (95% CI = 10.5-29.5 %) of GC cases may be attributable to smoking. Findings from this large study support the causal relation between smoking and gastric cancer in this European population. Stomach cancer should be added to the burden of diseases caused by smoking. (C) 2003 Wiley-Liss, Inc.
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23.
  • Johansson, M., et al. (författare)
  • Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line
  • 2002
  • Ingår i: Toxicology in Vitro. - 0887-2333 .- 1879-3177. ; 16:2, s. 113-121
  • Tidskriftsartikel (refereegranskat)abstract
    • The formation of steroids in the H295R human adrenocortical carcinoma cell line was analysed by HPLC or RIA, and based on these data the apparent catalytic activities of CYP11A, CYP17, CYP21 and CYP11B1 in this cell line were calculated. The environmental pollutant 3-methylsulfonyl-DDE (3-MeSO2-DDE) and the cytochrome P450 (CYP) inhibitors ketoconazole, metyrapone and aminoglutethimide were studied for their effects on the steroid formation. Metyrapone (IC50) of 1 microM) and 3-MeSO2-DDE (10 microM: 66 +/- 10% of control) were found to inhibit the apparent CYP11B1 activity. Ketoconazole inhibited all enzymes examined with the greatest effects on CYP11B1 (IC50) of 2.5 microM). Aminoglutethimide was examined only for effects on CYP11A activity and was shown to inhibit pregnenolone formation (20 microM: 61 +/- 4% of control). The possibility of studying all CYP enzymes in the corticosteroidogenesis makes this cell line a valuable test system to examine effects of chemicals, such as suspected endocrine disruptors, on the human glucocorticoid hormone synthesis. The inhibition of cortisol formation by 3-MeSO2-DDE supports an interaction with the active site of CYP11B1, as previously reported in mouse adrenocortical Y1 cells. In mice, this interaction led to metabolic activation and a high adrenotoxicity of 3-MeSO2-DDE. Therefore studies on the adrenotoxicity of 3-MeSO2-DDE in humans are needed.
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24.
  • Koski, Timo, et al. (författare)
  • Clustering by Adaptive Local Search with multiple search operators
  • 2000
  • Ingår i: Pattern Analysis and Applications. - : Springer Science and Business Media LLC. - 1433-7541 .- 1433-755X. ; 3:4, s. 348-357
  • Tidskriftsartikel (refereegranskat)abstract
    • Local Search (LS) has proven to be an efficient optimisation technique in clustering applications and in the minimisation of stochastic complexity of a data set. In the present paper, we propose two ways of organising LS in these contexts, the Multi-operator Local Search (MOLS) and the Adaptive Multi-Operator Local Search (AMOLS), and compare their performance to single operator (random swap) LS method and repeated GLA (Generalised Lloyd Algorithm). Both of the proposed methods use several different LS operators to solve the problem. MOLS applies the operators cyclically in the same order, whereas AMOLS adapts itself to favour the operators which manage to improve the result more frequently. We use a large database of binary vectors representing strains of bacteria belonging to the family Enterobacteriaceae and a binary image as our test materials. The new techniques turn out to be very promising in these tests.
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25.
  • Lund, S. S., et al. (författare)
  • Targeting hyperglycaemia with either metformin or repaglinide in non-obese patients with type 2 diabetes: results from a randomized crossover trial
  • 2007
  • Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 9:3, s. 394-407
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Metformin is the 'drug-of-first-choice' in obese patients with type 2 diabetes mellitus (T2DM) due to its antihyperglycaemic and cardiovascular protective potentials. In non-obese patients with T2DM, insulin secretagogues are empirically used as first choice. In this investigator-initiated trial, we evaluated the effect of metformin vs. an insulin secretagogue, repaglinide on glycaemic regulation and markers of inflammation and insulin sensitivity in non-obese patients with T2DM. Methods: A single-centre, double-masked, double-dummy, crossover study during 2 x 4 months involved 96 non-obese (body mass index <= 27 kg/m(2)) insulin-naive patients with T2DM. At enrolment, previous oral hypoglycaemic agents (OHA) were stopped and patients entered a 1-month run-in on diet-only treatment. Hereafter, patients were randomized to either repaglinide 2 mg thrice daily followed by metformin 1 g twice daily or vice versa each during 4 months with 1-month washout between interventions. Results: End-of-treatment levels of haemoglobin A(1c) (HbA(1c)), fasting plasma glucose, mean of seven-point home-monitored plasma glucose and fasting levels of high-sensitivity C-reactive protein and adiponectin were not significantly different between treatments. However, body weight, waist circumference, fasting serum levels of insulin and C-peptide were lower and less number of patients experienced hypoglycaemia during treatment with metformin vs. repaglinide. Both drugs were well tolerated. Conclusions: In non-obese patients with T2DM, overall glycaemic regulation was equivalent with less hypoglycaemia during metformin vs. repaglinide treatment for 2 x 4 months. Metformin was more effective targeting non-glycaemic cardiovascular risk markers related to total and abdominal body fat stores as well as fasting insulinaemia. These findings may suggest the use of metformin as the preferred OHA also in non-obese patients with T2DM.
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26.
  • Lund, Ulla, et al. (författare)
  • Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys
  • 2003
  • Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 284:6, s. 1226-1234
  • Tidskriftsartikel (refereegranskat)abstract
    • The size and charge-selective properties of the glomerular barrier are partly controversial. Glomerular sieving coefficients (theta) for proteins have rarely been determined noninvasively before in vivo. Therefore, theta was assessed vs. glomerular filtration rate (GFR; Cr-51-EDTA clearance) in intact rats for radiolabeled myoglobin, kappa-dimer, neutral horseradish peroxidase (nHRP), neutral human serum albumin (nHSA), and native albumin (HSA). To obtain theta, glomerular tracer clearance, assessed from the 7- to 8-min kidney uptake of protein, was divided by the GFR. The data were fitted with a two-pore model of glomerular permeability, where the small-pore radius was 37.35 +/- 1.11(SE) Angstrom, and the "unrestricted pore area over diffusion path length" (A(0)/DeltaX) 1.84 +/- 0.43 . 10(6) cm. Although seemingly horizontal for nHRP and nHSA, the log theta vs. GFR curves showed slightly negative slopes for the proteins investigated in the GFR interval of 2-4.5 ml/min. Strong negative ( linear) correlations between ( log) theta and GFR were obtained for myoglobin (P = 0.002) and HSA (P = 0.006), whereas they were relatively weak for nHRP and nHSA and nonsignificant for kappa-dimer. theta for nHSA was markedly higher than that for HSA. In conclusion, there were no indications of increases in theta vs. GFR, as indicative of concentration polarization, for the proteins investigated at high GFRs. Furthermore, the glomerular small-pore radius assessed from endogenous (neutral) protein sieving data was found to be smaller than previously determined using dextran or Ficoll as test molecules.
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27.
  • Manuguerra, M., et al. (författare)
  • Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions
  • 2007
  • Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 28:2, s. 414-422
  • Tidskriftsartikel (refereegranskat)abstract
    • It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n = 124), lung cancer (n = 116) and myeloid leukemia (n = 169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P < 0.001, mean CVC of 6.60, P = 0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C > T (mean prediction error of 22%, P < 0.001, mean CVC consistency of 7.40, P < 0.037). For leukemia, a 3-loci model including RAD52-2259C > T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P < 0.001) and a maximum CVC of 4.40 (P = 0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.
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28.
  • Menvielle, Gwenn, et al. (författare)
  • The role of smoking and diet in explaining educational inequalities in lung cancer incidence.
  • 2009
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 101:5, s. 321-330
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Studies in many countries have reported higher lung cancer incidence and mortality in individuals with lower socioeconomic status. METHODS: To investigate the role of smoking in these inequalities, we used data from 391,251 participants in the European Prospective Investigation into Cancer and Nutrition study, a cohort of individuals in 10 European countries. We collected information on smoking (history and quantity), fruit and vegetable consumption, and education through questionnaires at study entry and gathered data on lung cancer incidence for a mean of 8.4 years. Socioeconomic status was defined as the highest attained level of education, and participants were grouped by sex and region of residence (Northern Europe, Germany, or Southern Europe). Relative indices of inequality (RIIs) of lung cancer risk unadjusted and adjusted for smoking were estimated using Cox regression models. Additional analyses were performed by histological type. RESULTS: During the study period, 939 men and 692 women developed lung cancer. Inequalities in lung cancer risk (RII(men) = 3.62, 95% confidence interval [CI] = 2.77 to 4.73, 117 vs 52 per 100,000 person-years for lowest vs highest education level; RII(women) = 2.39, 95% CI = 1.77 to 3.21, 46 vs 25 per 100,000 person-years) decreased after adjustment for smoking but remained statistically significant (RII(men) = 2.29, 95% CI = 1.75 to 3.01; RII(women) = 1.59, 95% CI = 1.18 to 2.13). Large RIIs were observed among men and women in Northern European countries and among men in Germany, but inequalities in lung cancer risk were reverse (RIIs < 1) among women in Southern European countries. Inequalities differed by histological type. Adjustment for smoking reduced inequalities similarly for all histological types and among men and women in all regions. In all analysis, further adjustment for fruit and vegetable consumption did not change the estimates. CONCLUSION: Self-reported smoking consistently explains approximately 50% of the inequalities in lung cancer risk due to differences in education.
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29.
  • Nielsen, Peter, et al. (författare)
  • Multi-level Theoretical Framework – Meadow Background document no1
  • 2009
  • Ingår i: Meadow reports. ; 1, s. 1-59
  • Forskningsöversikt (refereegranskat)abstract
    • This report is one outcome of workpackage 2 in the EU funded MEADOW project. Its aim has been to establish an overview of theoretical literature in surveys on organisational change, innovation and work conditions. An international team of scholars have cooperated on this task. Scholars from Aalborg University (Denmark) have coordinated the workpackage and accepted responsibility for establishing a comprehensive multilevel framework regarding theories on organisational change, innovation and work conditions.
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30.
  • Olsson, Sara, 1970-, et al. (författare)
  • Radiation dose measurements with alanine/agarose gel and thin alanine films around a 192Ir brachytherapy source, using ESR spectroscopy
  • 2002
  • Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 47:8, s. 1333-1356
  • Tidskriftsartikel (refereegranskat)abstract
    • Alanine/agarose gel and alanine films in stacks have been used for measurements of absorbed dose around an HDR 192Ir source in a vaginal cylinder-applicator, with and without a 180° tungsten shield. The gel and the films were analysed by means of ESR spectroscopy and calibrated against an ion chamber in a 4 MV photon beam to obtain absolute dose values. The gel serves as both dosimeter and phantom material, and the thin (130 μm) films are used to achieve an improved spatial resolution in the dose estimations.Experimental values were compared with Monte Carlo simulations using two different codes. Results from the measurements generally agree with the simulations to within 5%, for both the alanine/agarose gel and the alanine films.
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31.
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32.
  • Ryder, JW, et al. (författare)
  • Use of a novel impermeable biotinylated photolabeling reagent to assess insulin- and hypoxia-stimulated cell surface GLUT4 content in skeletal muscle from type 2 diabetic patients
  • 2000
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 49:4, s. 647-654
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell surface GLUT4 levels in skeletal muscle from nine type 2 diabetic subjects and nine healthy control subjects have been assessed by a new technique that involves the use of a biotinylated photo-affinity label. A profound impairment in GLUT4 translocation to the skeletal muscle cell surface in response to insulin was observed in type 2 diabetic patients. Levels of insulin-stimulated cell surface GLUT4 above basal in type 2 diabetic patients were only approximately 10% of those observed in healthy subjects. The magnitude of the defect in GLUT4 translocation in type 2 diabetic patients was greater than that observed for glucose transport activity, which was approximately 50% of that in healthy subjects. Reduced GLUT4 translocation is therefore a major contributor to the impaired glucose transport activity in skeletal muscle from type 2 diabetic subjects. When a marked impairment in GLUT4 translocation occurs, the contribution of other transporters to transport activity becomes apparent. In response to hypoxia, marked reductions in skeletal muscle cell surface GLUT4 levels were also observed in type 2 diabetic patients. Therefore, a defect in a common late stage in signal transduction and/or a direct impairment in the GLUT4 translocation process accounts for reduced glucose transport in type 2 diabetic patients.
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33.
  • Setiawan, Veronica Wendy, et al. (författare)
  • CYP17 genetic variation and risk of breast and prostate cancer from the national Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)
  • 2007
  • Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 16:11, s. 2237-2246
  • Tidskriftsartikel (refereegranskat)abstract
    • CYP17 encodes cytochrome p450c17 alpha, which mediates activities essential for the production of sex steroids. Common germ line variation in the CYP17 gene has been related to inconsistent results in breast and prostate cancer, with most studies focusing on the nonsynonymous single nucleotide polymorphism (SNP) T27C (rs743572). We comprehensively characterized variation in CYP17 by direct sequencing of exons followed by dense genotyping across the 58 kb region around CYP17 in five racial/ethnic populations. Two blocks of strong linkage disequilibrium were identified and nine haplotype-tagging SNPs, including T27C, were chosen to predict common haplotypes (R-h(2) >= 0.85). These haplotype-tagging SNPs were genotyped in 8,138 prostate cancer cases and 9,033 controls, and 5,333 breast cancer cases and 7,069 controls from the Breast and Prostate Cancer Cohort Consortium. We observed borderline significant associations with prostate cancer for rs2486758 [TC versus TT, odds ratios (OR), 1.07; 95% confidence intervals (95% Cl), 1.00-1.14; CC versus TT, OR, 1.09; 95% CI, 0.95-1.26; P trend = 0.04] and rs6892 (AG versus AA, OR, 1.08; 95% CI, 1.00-1.15; GG versus AA, OR, 1.11; 95% CI, 0.95-1.30; P trend = 0.03). We also observed marginally significant associations with breast cancer for rs4919687 (GA versus GG, OR, 1.04; 95% CI, 0.97-1.12, AA versus GG, OR, 1.17; 95% CI, 1.03-1.34; P trend = 0.03) and rs4919682 (CT versus CC, OR, 1.04; 95% CI, 0.97-1.12; TT versus CC, OR, 1.16; 95% CI, 1.01-1.33; P trend = 0.04). Common variation at CYP17 was not associated with circulating sex steroid hormones in men or postmenopausal women. Our findings do not support the hypothesis that common germ line variation in CYP17 makes a substantial contribution to postmenopausal breast or prostate cancer susceptibility.
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34.
  • Spokes, L., et al. (författare)
  • MEAD: An interdisciplinary study of the marine effects of atmospheric deposition in the Kattegat
  • 2006
  • Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 140:3, s. 453-462
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper summarises the results of the EU funded MEAD project, an interdisciplinary study of the effects of atmospheric nitrogen deposition on the Kattegat Sea between Denmark and Sweden. The study considers emissions of reactive nitrogen gases, their transport, transformations, deposition and effects on algal growth together with management options to reduce these effects. We conclude that atmospheric deposition is an important source of fixed nitrogen to the region particularly in summer, when nitrogen is the limiting nutrient for phytoplankton growth, and contributes to the overall eutrophication pressures in this region. However, we also conclude that it is unlikely that atmospheric deposition can, on its own, induce algal blooms in this region. A reduction of atmospheric nitrogen loads to this region will require strategies to reduce emissions of ammonia from local agriculture and Europe wide reductions in nitrous oxide emissions. (c) 2005 Elsevier Ltd. All rights reserved.
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35.
  • Tengberg, Anders, 1962, et al. (författare)
  • Intercalibration of benthic flux chambers II. Hydrodynamic characterization and flux comparisons of 14 different designs
  • 2005
  • Ingår i: Marine Chemistry. - : Elsevier BV. - 0304-4203. ; 94:1-4, s. 147-173
  • Tidskriftsartikel (refereegranskat)abstract
    • We have compared 14 different sediment incubation chambers, most of them were used on bottom landers. Measurements of mixing time, pressure gradients at the bottom and Diffusive Boundary Layer thickness (DBL) were used to describe the hydrodynamic properties of the chambers and sediment-water solute fluxes of silicate (34 replicates) and oxygen (23 replicates) during three subsequently repeated incubation experiments on a homogenized, macrofauna-free sediment. The silicate fluxes ranged from 0.24 to 1.01 mmol m(-2) day(-1) and the oxygen fluxes from 9.3 to 22.6 mmol m(-2) day(-1). There was no statistically significant correlation between measured fluxes and the chamber design or between measured fluxes and hydrodynamic settings suggesting that type of chamber was not important in these flux measurements. For verification of sediment homogeneity, 61 samples of meiofauna were taken and identified to major taxa. In addition. 13 sediment cores were collected. sectioned into 5-10-mm slices and separated into pore water and solid phase. The pore water profiles of disolved silicale were used to calculate diffusive fluxes of silicate. These fluxes ranged from 0.63 to 0.87 mmol m(-2) day(-1). All of the collected sediment parameters indicated that the sediment homogenization process had been satisfactorily accomplished, hydrodynamic variations inside and between chambers are a reflection of the chamber design and the stirring device, In general. pump stirrers with diffusers give a more even distribution of bottom currents and DBL thicknesses than paddle wheel-type stirrers, Most chambers display no or low static differential pressures when the water is mixed at rates of normal Use, Consequently. there is a low risk of creating stirrer induced pressure effects on the measured fluxes. Centrally placed stirrers are preferable to off-center placed stirrers which are more difficult to map and do not seem to give any hydrodynamic advantages, A vertically rotating stirrer gives about five times lower static differential pressures at the same stirring, speed as the same stirrer mounted horizontally If the aim is to simulate or mimic resuspension at high flow velocities, it cannot be satisfactorily done in a chamber using it horizontal (standing) rotating impeller (as is the case for most chambers in use) due to the creation of unnatural conditions. i,e. large static differential pressures and pre-mature resuspension at certain locations in the chamber. (c) 2004 Elsevier B.V. All rights reserved.
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36.
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37.
  • Vestad, T.A., et al. (författare)
  • EPR dosimetric properties of formates
  • 2003
  • Ingår i: Applied Radiation and Isotopes. - 0969-8043 .- 1872-9800. ; 59:2-3, s. 181-188
  • Tidskriftsartikel (refereegranskat)abstract
    • As a part of a program to develop an electron paramagnetic resonance (EPR) dosimeter suited for clinical use (doses in the cGy range), polycrystalline samples of lithium formate monohydrate (HCO2Li·H 2O), magnesium formate dihydrate (C2H2O 4Mg·2H2O), and calcium formate (C2H 2O4Ca) have been examined. L-Alanine was included for comparison and reference. Samples were irradiated with 60Co ?-rays and 60-220kV X-rays. The dosimeter response was assessed using the peak-to-peak amplitude of the first-derivative EPR spectrum. Dose-response curves for the 60Co ?-irradiated samples were constructed, and the dependences of the response on the photon energy, microwave power, and modulation amplitude were studied. Stability of the irradiation products upon storage (signal fading) was also investigated. Lithium formate monohydrate is by far the best candidate of the tested formates, suitable for measuring doses down to approximately 0.1Gy. Lithium formate monohydrate is more sensitive than alanine by a factor of 5.6-6.8 in the tested photon energy range, it exhibits no zero-dose signal and shows a linear dose response in the dose range from 0.2 to 1000Gy. Its EPR signal was found unchanged in shape and intensity 1 week after irradiation to 10Gy. Various less favorable properties rendered the other formates generally unsuitable, although calcium formate exhibits some interesting EPR dosimetric properties. © 2003 Elsevier Ltd. All rights reserved.
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38.
  • Vineis, P., et al. (författare)
  • Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers
  • 2007
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 18:7, s. 1230-1242
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia). Patients and methods: The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase 11 metabolizing genes and methylenetetrahydrofolate reductase (MTHFR). Results: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55.
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