| 1. |
- Ahrens, J., et al.
(author)
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Calibration and survey of AMANDA with the SPASE detectors
- 2004
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 522:3, s. 347-359
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Journal article (peer-reviewed)abstract
- We report on the analysis of air showers observed in coincidence by the Antarctic Muon and Neutrino detector array (AMANDA-B10) and the South Pole Air Shower Experiment (SPASE-1 and SPASE-2). We discuss the use of coincident events for calibration and survey of the deep AMANDA detector as well as the response of AMANDA to muon bundles. This analysis uses data taken during 1997 when both SPASE-1 and SPASE-2 were in operation to provide a stereo view of AMANDA. © 2003 Elsevier B.V. All rights reserved.
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| 2. |
- Ahrens, J., et al.
(author)
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Measurement of the cosmic ray composition at the knee with the SPASE-2/AMANDA-B10 detectors
- 2004
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In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 21:6, s. 565-581
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Journal article (peer-reviewed)abstract
- The mass composition of high-energy cosmic rays at energies above 1015 eV can provide crucial information for the understanding of their origin. Air showers were measured simultaneously with the SPASE-2 air shower array and the AMANDA-B10 Cherenkov telescope at the South Pole. This combination has the advantage to sample almost all high-energy shower muons and is thus a new approach to the determination of the cosmic ray composition. The change in the cosmic ray mass composition was measured versus existing data from direct measurements at low energies. Our data show an increase of the mean log atomic mass 〈lnA〉 by about 0.8 between 500 TeV and 5 PeV. This trend of an increasing mass through the "knee" region is robust against a variety of systematic effects. © 2004 Elsevier B.V. All rights reserved.
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| 3. |
- Bruder, CEG, et al.
(author)
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High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH
- 2001
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In: Human Molecular Genetics. - Oxford, United Kingdom : Oxford University Press. - 0964-6906 .- 1460-2083. ; 1, s. 271-
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Journal article (peer-reviewed)abstract
- Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CON methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.
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| 7. |
- Narod, SA, et al.
(author)
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Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers
- 2002
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105. ; 94:23, s. 1773-1779
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Journal article (peer-reviewed)abstract
- Background: Oral contraceptive use has been associated with an increase in the risk of breast cancer in young women. We examined whether this association is seen in women at high risk of breast cancer because they carry a mutation in one of two breast cancer susceptibility genes, BRCA1 and BRCA2. Methods: We performed a matched case-control study on 1311 pairs of women with known deleterious BRCA1 and/or BRCA2 mutations recruited from 52 centers in 11 countries. Women who had been diagnosed with breast cancer were matched to control subjects by year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of ovarian cancer. All study subjects completed a questionnaire about oral contraceptive use. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. All statistical tests were two-sided. Results: Among BRCA2 mutation carriers, ever use of oral contraceptives was not associated with an increased risk of breast cancer (OR = 0.94, 95% CI = 0.72 to 1.24). For BRCAI mutation carriers, ever use of oral contraceptives was associated With a modestly increased risk of breast cancer (OR = 1.20, 95 % CI = 1.02 to 1.40). However, compared with BRCA1 mutation carriers who never used oral contraceptives, those who used oral contraceptives for at least 5 years had an increased risk of breast cancer (OR = 1.33, 95% CI = 1.11 to 1.60), as did those who used oral contraceptives before age 30 (OR = 1.29, 95% CI = 1.09 to 1.52), those who were diagnosed with breast cancer before age 40 (OR = 1.38, 95% CI = 1.11 to 1.72), and those who first used oral contraceptives before 1975 (OR = 1.42, 95 % CI = 1.17 to 1.75). Conclusions: Among BRCA1 mutation carriers, women who first used oral contraceptives before 1975, who used them before age 30, or who used them for 5 or more years may have an increased risk of early-onset breast cancer. Oral contraceptives do not appear to be associated with risk of breast cancer in BRCA2 carriers, but data for BRCA2 carriers are limited.
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| 8. |
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| 9. |
- Andrieux, M. L., et al.
(author)
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Single-event upset studies of a high-speed digital optical data link
- 2001
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In: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 456:3, s. 342-351
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Journal article (peer-reviewed)abstract
- The results from a series of neutron and photon irradiation tests of a high-speed digital optical data link based on a commercial serialiser and a vertical cavity surface emitting laser are described. The link was developed as a candidate for the front-end readout of the ATLAS electromagnetic calorimeter. The components at the emitting end of the link were unaffected by neutron and photon irradiation levels exceeding those expected during 10 years of LHC running. However, the link suffered from Single-Event Upsets (SEUs) when irradiated with energetic neutrons. A very general method based on the Burst Generation Rate (BGR) model has been developed and is used to extrapolate the error rate observed during tests to that expected at the LHC. A model-independent extrapolation was used to check the BGR approach and the results were consistent once systematic errors were taken into account.
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| 10. |
- Bergström, Göran, 1964, et al.
(author)
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Mechanisms underlying the antihypertensive functions of the renal medulla
- 2004
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In: Acta Physiol Scand. - 0001-6772. ; 181:4, s. 475-86
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Journal article (peer-reviewed)abstract
- There is good evidence that the renal medulla plays a pivotal role in long-term regulation of blood pressure. 'Renal medullary' blood pressure regulating systems have been postulated to involve both exocrine (pressure natriuresis/diuresis) and endocrine [renal medullary depressor hormone (RMDH)] functions. However, recent studies indicate that pressure diuresis/natriuresis dominates the antihypertensive renal response to increased renal perfusion pressure, suggesting little physiological role for a putative RMDH in compensatory responses to acutely increased blood pressure. The medullary circulation appears to play a key role in mediating pressure diuresis, although the precise mechanisms involved remain controversial. Counter-regulatory vasodilator mechanisms (e.g. nitric oxide), at least partly mediated through cross-talk between the vasculature and the tubular epithelium, protect the medullary circulation from the vasoconstrictor effects of hormonal factors such as angiotensin II. These mechanisms also appear to contribute to compensatory responses to increased salt intake in salt-resistant individuals. Failure of these mechanisms predisposes the organism towards the development of hypertension, appears to underlie the development of some forms of experimental hypertension, and may even contribute to the pathogenesis of essential hypertension.
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| 18. |
- Moller, P, et al.
(author)
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Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy
- 2002
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In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 101:6, s. 555-559
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Journal article (peer-reviewed)abstract
- Dedicated clinics have been established for the early diagnosis and treatment of women at risk for inherited breast cancer, but the effects of such interventions are currently unproven. This second report on prospectively diagnosed inherited breast cancer from the European collaborating centres supports the previous conclusions and adds information on genetic heterogeneity and the effect of oophorectomy. Of 249 patients, 20% had carcinoma in situ (CIS), 54% had infiltrating cancer without spread (CaNO) and 26% had cancer with spread (CaN+). Five-year survival was 100% for CIS, 94% for CaNO and 72% for CaN+ (p = 0.007). Thirty-six patients had BRCA1 mutations, and 8 had BRCA2 mutations. Presence of BRCA1 mutation was associated with infiltrating cancer, high grade and lack of oestrogen receptor (p < 0.05 for all 3 characteristics). For BRCA1 mutation carriers, 5-year survival was 63% vs. 91% for noncarriers (p = 0.04). For CaNO patients, mutation carriers had 75% S-year disease-free survival vs. 96% for noncarriers (p = 0.01). Twenty-one of the mutation carriers had undergone prophylactic oophorectomy, prior to or within 6 months of diagnosis in 13 cases. All but I relapse occurred in the I S who had kept their ovaries, (p < 0.01); no relapse occurred in those who had removed the ovaries within 6 months (p = 0.04) Contralateral cancer was more frequently observed in mutation noncarriers, but this finding did not reach statistical significance. Our findings support the concept that BRCA1 cancer is biologically different from other inherited breast cancers. While current screening protocols appear satisfactory for the majority of women at risk of familial breast cancer, this may not be the case for BRCA1 mutation carriers. The observed effect of oophorectomy was striking.
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| 19. |
- Nair, G., et al.
(author)
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Minimum data rates for stabilising linear systems with unknown parameters
- 2002
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In: Preprints MTNS.
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Conference paper (peer-reviewed)abstract
- One of the most fundamental questions in the field of joint communication and control is the following: if a plant and controller communicate at a limited data rate and no restrictions but causality are placed on the coding and control policy, what is the smallest rate at which stabilisation is possible? In this paper, the problem of stabilising a deterministic, partially observed, discrete-time, linear time-invariant system using a finite data rate is investigated, with the additional complication that the system parameters are unknown constants.
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| 20. |
- Sundström, Johan, et al.
(author)
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Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures : the Framingham Heart Study.
- 2004
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In: Circulation. - 1524-4539. ; 109:23, s. 2850-6
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Journal article (peer-reviewed)abstract
- BACKGROUND: Plasma levels of matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, are increased in heart failure and in acute coronary syndromes. We investigated cross-sectional relations of plasma MMP-9 to vascular risk factors and echocardiographic left ventricular (LV) measurements. METHODS AND RESULTS: We studied 699 Framingham Study participants (mean age, 57 years; 58% women), free of heart failure and previous myocardial infarction, who underwent routine echocardiography. We examined sex-specific distributions of LV internal dimensions (LVEDD) and wall thickness (LVWT) and sampled persons with both LVEDD and LVWT below the sex-specific median (referent, n=299), with increased LVEDD (LVEDD > or =90th percentile, n=204) and increased LVWT (LVWT > or =90th percentile, n=221) in a 3:2:2 ratio. Plasma MMP-9 was detectable in 138 persons (20%). In multivariable models, increasing heart rate (OR per SD, 1.41; 95% CI, 1.17 to 1.71) and antihypertensive treatment (OR, 1.63; 95% CI, 1.06 to 2.50) were key clinical correlates of detectable plasma MMP-9. In multivariable-adjusted models, detectable plasma MMP-9 was associated with increased LVEDD (OR, 2.84; 95% CI, 1.13 to 7.11), increased LVWT (OR, 2.54; 95% CI, 1.00 to 6.46), and higher LV mass (P=0.06) in men but not in women (OR for increased LVEDD, 1.37; 95% CI, 0.54 to 3.46; for increased LVWT, 0.99; 95% CI, 0.39 to 2.52; P=0.59 for LV mass). CONCLUSIONS: In our community-based sample, detectable plasma MMP-9 levels were associated with increased LV diastolic dimensions and increased wall thickness in men. These observations indicate that plasma MMP-9 level may be a marker for cardiac extracellular matrix degradation, a process involved in LV remodeling.
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| 21. |
- Sundström, Johan, et al.
(author)
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Relations of plasma total TIMP-1 levels to cardiovascular risk factors and echocardiographic measures : the Framingham heart study.
- 2004
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In: Eur Heart J. - 0195-668X. ; 25:17, s. 1509-16
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Journal article (peer-reviewed)abstract
- AIMS: Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key regulator of extracellular matrix degradation. We examined relations of plasma total TIMP-1 to cardiovascular risk factors and echocardiographic left ventricular (LV) structure and function in a community-based sample. METHODS AND RESULTS: We studied 1069 Framingham Heart Study participants (mean age 56 years, 58% women) free of heart failure and previous myocardial infarction. Plasma TIMP-1 was higher in men compared with women, and increased with age, body mass index and total/HDL-cholesterol ratio, but decreased with alcohol intake. Plasma TIMP-1 was also directly related to smoking, diabetes and use of anti-hypertensive treatment. Adjusting for age, sex and height, plasma TIMP-1 was positively associated with LV mass, wall thickness, relative wall thickness, end-systolic diameter, and left atrial diameter and the risk of having increased LV end-diastolic diameter or increased wall thickness, and negatively correlated with fractional shortening. Additional adjustment for clinical covariates attenuated the relations of plasma TIMP-1 to most echocardiographic measures. CONCLUSIONS: In our cross-sectional investigation, plasma total TIMP-1 was related to major cardiovascular risk factors and to indices of LV hypertrophy and systolic dysfunction. This raises the possibility that cardiovascular risk factors may influence cardiovascular remodelling via extracellular matrix degradation, which may be reflected in plasma TIMP-1 levels.
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| 22. |
- Vasan, Ramachandran S, et al.
(author)
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Relations of serum aldosterone to cardiac structure : gender-related differences in the Framingham Heart Study.
- 2004
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In: Hypertension. - 1524-4563. ; 43:5, s. 957-62
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Journal article (peer-reviewed)abstract
- Aldosterone is associated with myocardial fibrosis in experimental studies and with left ventricular remodeling in heart failure patients. We hypothesized that aldosterone influences ventricular remodeling in people without congestive heart failure in the community. We examined the relations between serum aldosterone and echocardiographic left ventricular measurements in 2820 Framingham Study subjects (mean age 57 years, 58% women, 88% white) free of myocardial infarction and overt heart failure. Serum aldosterone levels were higher in women compared with men. In linear regression models (adjusted for age, systolic blood pressure, weight, height, diabetes, heart rate, hypertension treatment, and ethnicity), left ventricular wall thickness and relative wall thickness were positively related, and left ventricular diastolic dimensions were inversely related to serum aldosterone in women (P<0.05 for all), but not in men (P>0.20 for all). There was no effect modification of the relations observed in women by menopausal status. The gender-related differences in relations of serum aldosterone to relative wall thickness were consistent across subgroups defined on the basis of sex-specific median values of systolic blood pressure and body mass index. Fractional shortening, left ventricular mass, and left atrial dimensions were not related to serum aldosterone in either sex. In conclusion, in our community-based sample of individuals free of myocardial infarction and heart failure, serum aldosterone was positively associated with a left ventricular geometric pattern suggestive of concentric remodeling (increased left ventricular wall thickness and relative wall thickness but decreased internal dimensions) in women but not in men. Additional investigations are warranted to confirm these findings.
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