| 1. |
- Schael, S, et al.
(author)
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Precision electroweak measurements on the Z resonance
- 2006
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Research review (peer-reviewed)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 2. |
- Willer, Cristen J., et al.
(author)
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Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 25-34
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Journal article (peer-reviewed)abstract
- Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
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| 3. |
- Chioza, B., et al.
(author)
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Evaluation of CACNA1H in European patients with childhood absence epilepsy
- 2006
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In: Epilepsy Res. - : Elsevier BV. - 0920-1211. ; 69:2, s. 177-81
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Journal article (peer-reviewed)abstract
- CACNA1H was evaluated in a resource of Caucasian European patients with childhood absence epilepsy by linkage analysis and typing of sequence variants previously identified in Chinese patients. Linkage analysis of 44 pedigrees provided no evidence for a locus in the CACNA1H region and none of the Chinese variants were found in 220 unrelated patients.
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| 4. |
- Everett, K. V., et al.
(author)
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Linkage and association analysis of CACNG3 in childhood absence epilepsy
- 2007
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In: Eur J Hum Genet. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 15:4, s. 463-72
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Journal article (peer-reviewed)abstract
- Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy characterised by absence seizures manifested by transitory loss of awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to aetiology is established but the mechanism of inheritance and the genes involved are not fully defined. Available evidence suggests that genes encoding brain expressed voltage-gated calcium channels, including CACNG3 on chromosome 16p12-p13.1, may represent susceptibility loci for CAE. The aim of this work was to further evaluate CACNG3 as a susceptibility locus by linkage and association analysis. Assuming locus heterogeneity, a significant HLOD score (HLOD = 3.54, alpha = 0.62) was obtained for markers encompassing CACNG3 in 65 nuclear families with a proband with CAE. The maximum non-parametric linkage score was 2.87 (P < 0.002). Re-sequencing of the coding exons in 59 patients did not identify any putative causal variants. A linkage disequilibrium (LD) map of CACNG3 was constructed using 23 single nucleotide polymorphisms (SNPs). Transmission disequilibrium was sought using individual SNPs and SNP-based haplotypes with the pedigree disequilibrium test in 217 CAE trios and the 65 nuclear pedigrees. Evidence for transmission disequilibrium (P < or = 0.01) was found for SNPs within a approximately 35 kb region of high LD encompassing the 5'UTR, exon 1 and part of intron 1 of CACNG3. Re-sequencing of this interval was undertaken in 24 affected individuals. Seventy-two variants were identified: 45 upstream; two 5'UTR; and 25 intronic SNPs. No coding sequence variants were identified, although four variants are predicted to affect exonic splicing. This evidence supports CACNG3 as a susceptibility locus in a subset of CAE patients.
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| 5. |
- Zeggini, Eleftheria, et al.
(author)
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
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Journal article (peer-reviewed)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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| 8. |
- Mattsson, Lars-Åke, 1945, et al.
(author)
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Efficacy and tolerability of continuous combined hormone replacement therapy in early postmenopausal women
- 2007
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In: Menopause Int. ; 13:3, s. 124-131
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Continuous combined hormone replacement therapy (ccHRT) based on estradiol valerate (E(2)V) and medroxyprogesterone acetate (MPA) is effective for relief of menopausal symptoms three years or more after the menopause. This study was undertaken to examine the efficacy and tolerability of ccHRT in early postmenopausal women (last menstrual period 1.3 years before study entry). STUDY DESIGN: This was a 52-week, randomized, double-blind, multinational study of ccHRT comprising three different dose combinations of E(2)V/MPA in 459 early postmenopausal non-hysterectomized women experiencing 30 or more moderate to severe hot flushes a week and/or vasomotor symptoms requiring treatment. MAIN OUTCOMES MEASURES: The primary endpoint was change in frequency and severity of moderate to severe hot flushes at 12 weeks. Secondary outcome measures included number of bleeding days and evaluation of tolerability. RESULTS: The frequency of hot flushes was reduced by >/=70% after one month (P<0.001 for all doses at week 2 onwards), with little evidence of statistically different dose effects. Severity of flushing was also attenuated by ccHRT. Mean number of bleeding days fell to <1 per 28-day cycle at 52 weeks. Rates of amenorrhoea approached 80-90% at the end of the study, but were significantly lower at several time points with the highest-dose regimen (2 mg E(2)V + 5 mg MPA) than with the lower-dose options (1 mg E(2)V + 2.5 mg MPA and 1 mg E(2)V + 5 mg MPA; P<0.05). Adverse events declined in frequency over time with all regimens but throughout the study were more numerous with the highest-dose regimen than with lower doses (P= 0.0002). CONCLUSIONS: Continuous combined HRT was effective for the relief of climacteric symptoms in early postmenopausal women and was well tolerated.
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| 13. |
- Kenny, John G, et al.
(author)
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The Staphylococcus aureus response to unsaturated long chain free fatty acids: survival mechanisms and virulence implications.
- 2009
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In: PLoS ONE. ; 4:2
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Journal article (peer-reviewed)abstract
- Staphylococcus aureus is an important human commensal and opportunistic pathogen responsible for a wide range of infections. Long chain unsaturated free fatty acids represent a barrier to colonisation and infection by S. aureus and act as an antimicrobial component of the innate immune system where they are found on epithelial surfaces and in abscesses. Despite many contradictory reports, the precise anti-staphylococcal mode of action of free fatty acids remains undetermined. In this study, transcriptional (microarrays and qRT-PCR) and translational (proteomics) analyses were applied to ascertain the response of S. aureus to a range of free fatty acids. An increase in expression of the sigma(B) and CtsR stress response regulons was observed. This included increased expression of genes associated with staphyloxanthin synthesis, which has been linked to membrane stabilisation. Similarly, up-regulation of genes involved in capsule formation was recorded as were significant changes in the expression of genes associated with peptidoglycan synthesis and regulation. Overall, alterations were recorded predominantly in pathways involved in cellular energetics. In addition, sensitivity to linoleic acid of a range of defined (sigB, arcA, sasF, sarA, agr, crtM) and transposon-derived mutants (vraE, SAR2632) was determined. Taken together, these data indicate a common mode of action for long chain unsaturated fatty acids that involves disruption of the cell membrane, leading to interference with energy production within the bacterial cell. Contrary to data reported for other strains, the clinically important EMRSA-16 strain MRSA252 used in this study showed an increase in expression of the important virulence regulator RNAIII following all of the treatment conditions tested. An adaptive response by S. aureus of reducing cell surface hydrophobicity was also observed. Two fatty acid sensitive mutants created during this study were also shown to diplay altered pathogenesis as assessed by a murine arthritis model. Differences in the prevalence and clinical importance of S. aureus strains might partly be explained by their responses to antimicrobial fatty acids.
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| 14. |
- Naumann, E, et al.
(author)
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beta-Glucan incorporated into a fruit drink effectively lowers serum LDL-cholesterol concentrations
- 2006
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In: American Journal of Clinical Nutrition. - 1938-3207. ; 83:3, s. 601-605
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Journal article (peer-reviewed)abstract
- Background: beta-Glucan can reduce serum concentrations of total and LDL cholesterol. The mechanism of this action is not clear, however, and it is difficult to predict the cholesterol-lowering effect of a food product enriched with beta-glucan. Objectives: We examined the effects of a beta-glucan-enriched fruit juice on serum lipids and lipoproteins and on markers of cholesterol absorption (serum concentrations of plant sterols) and synthesis (serum concentrations of lathosierol). In addition, we measured effects on lipid-soluble antioxidants. Design: After a 3-wk run-in period, healthy subjects consumed daily a fruit drink providing 5 g rice starch [placebo (control) group; n = 22] or beta-glucan from oats (n = 25) for 5 wk (parallel design). At the end of the run-in period and at the end of the intervention, blood samples were taken for analysis of lipids and lipoproteins, noncholesterol sterols, and fat-soluble antioxidants. Changes between the end of the run-in period and the end of the intervention were calculated for each subject. Differences in changes between the groups were analyzed statistically. Results: The differences between the control and beta-glucan groups in the chance in serum concentrations of total and LDL cholesterol, respectively, were -4.8% (P = 0.012) and -7.7% (P = 0.005). The differences between the groups in the change in serum concentrations of lathosterol and sitosterol were -13% (P = 0.023) and -11 % (P = 0.030), respectively. No significant effects were found on fat-soluble antioxidants. Conclusions: beta-Glucan lowers serum concentrations of total and LDL cholesterol when incorporated into a fruit drink. A reduced cholesterol absorption contributes to the cholesterol-lowering effect of beta-glucan without affecting plasma concentrations of lipid-soluble antioxidants.
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| 15. |
- Pe'er, Asaf, et al.
(author)
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A new method of determining the initial size and Lorentz factor of gamma-ray burst fireballs using a thermal emission component
- 2007
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 664:1, s. L1-L4
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Journal article (peer-reviewed)abstract
- In recent years, increasing evidence has emerged for a thermal component in the gamma- and X- ray spectrum of the prompt emission phase in gamma- ray bursts. The temperature and flux of the thermal component show a characteristic break in the temporal behavior after a few seconds. We show here that measurements of the temperature and flux of the thermal component at early times ( before the break) allow the determination of the values of two of the least restricted fireball model parameters: the size at the base of the flow and the outflow bulk Lorentz factor. Relying on the thermal emission component only, this measurement is insensitive to the inherent uncertainties of previous estimates of the bulk motion Lorentz factor. We give specific examples of the use of this method: for GRB 970828 at redshift z = 0.9578, we show that the physical size at the base of the flow is r(0) = (2.9 +/- 1.8) x 10(8) Y-0(-3/2) cm and the Lorentz factor of the flow is Gamma = (305 +/- 28) Y-0(1/4), and for GRB 990510 at z= 1.619, r(0) = (1.7 +/- 1.7) x 10(8)Y(0)(-3/2) cm and Gamma = (384 +/- 71)y(0)(1/4), where Y= 1Y(0) is the between the total fireball energy and the energy emitted in g- rays.
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