| 1. |
- Schael, S, et al.
(författare)
-
Precision electroweak measurements on the Z resonance
- 2006
-
Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
-
Forskningsöversikt (refereegranskat)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.
|
|
| 2. |
- Aaron, F. D., et al.
(författare)
-
Multi-leptons with high transverse momentum at HERA
- 2009
-
Ingår i: Journal of High Energy Physics. - : Springer Science and Business Media LLC. - 1029-8479. ; :10
-
Tidskriftsartikel (refereegranskat)abstract
- Events with at least two high transverse momentum leptons (electrons or muons) are studied using the H1 and ZEUS detectors at HERA with an integrated luminosity of 0.94 fb(-1). The observed numbers of events are in general agreement with the Standard Model predictions. Seven di- and tri-lepton events are observed in e(+)p collision data with a scalar sum of the lepton transverse momenta above 100 GeV while 1.94 +/- 0.17 events are expected. Such events are not observed in e(-)p collisions for which 1.19 +/- 0.12 are predicted. Total visible and differential di-electron and di-muon photoproduction cross sections are extracted in a restricted phase space dominated by photon-photon collisions.
|
|
| 3. |
- Adolph, C, et al.
(författare)
-
Measurement of the eta -> 3 pi(0) Dalitz plot distribution with the WASA detector at COSY
- 2009
-
Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 677:1-2, s. 24-29
-
Tidskriftsartikel (refereegranskat)abstract
- In the first production run of the WASA experiment at COSY, the eta decay into three neutral pions was measured in proton-proton interactions at a proton beam kinetic energy of 1.4 GeV. The Dalitz plot of the three pious was Studied using 1.2 x 10(5) fully reconstructed events. and the quadratic slope parameter alpha was determined to be -0.027 +/- 0.008(stat) +/- 0.005(syst). The result is consistent with previous measurements and further corroborates the importance of pion-pion final state interactions. (C) 2009 Elsevier B.V. All rights reserved.
|
|
| 4. |
- Abbasi, R, et al.
(författare)
-
Extending the Search for Neutrino Point Sources with IceCube above the Horizon
- 2009
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 103:22, s. 221102-
-
Tidskriftsartikel (refereegranskat)abstract
- Point source searches with the IceCube neutrino telescope have been restricted to one hemisphere, due to the exclusive selection of upward going events as a way of rejecting the atmospheric muon background. We show that the region above the horizon can be included by suppressing the background through energy-sensitive cuts. This improves the sensitivity above PeV energies, previously not accessible for declinations of more than a few degrees below the horizon due to the absorption of neutrinos in Earth. We present results based on data collected with 22 strings of IceCube, extending its field of view and energy reach for point source searches. No significant excess above the atmospheric background is observed in a sky scan and in tests of source candidates. Upper limits are reported, which for the first time cover point sources in the southern sky up to EeV energies.
|
|
| 5. |
- Hillier, Ladeana W, et al.
(författare)
-
Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
-
Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
|
|
| 6. |
- Birney, Ewan, et al.
(författare)
-
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
-
Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
|
|
| 7. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
-
Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
-
Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
|
|
| 8. |
- Birney, Ewan, et al.
(författare)
-
Prepublication data sharing
- 2009
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7261, s. 168-170
-
Tidskriftsartikel (refereegranskat)abstract
- Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.
|
|
| 9. |
|
|
| 10. |
- Elsik, Christine G., et al.
(författare)
-
The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
-
Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
|
|
| 11. |
- Lindgren, Cecilia M, et al.
(författare)
-
Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
- 2009
-
Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000508-
-
Tidskriftsartikel (refereegranskat)abstract
- To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
|
|
| 12. |
- Adewumi, Oluseun, et al.
(författare)
-
Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
- 2007
-
Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816
-
Tidskriftsartikel (refereegranskat)abstract
- The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
|
|
| 13. |
- Aulchenko, Yurii S, et al.
(författare)
-
Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
- 2009
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:1, s. 47-55
-
Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
|
|
| 14. |
- Cubillas, Pablo, et al.
(författare)
-
Spiral Growth on Nanoporous Silicoaluminophosphate STA-7 as Observed by Atomic Force Microscopy
- 2009
-
Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 9:9, s. 4041-4050
-
Tidskriftsartikel (refereegranskat)abstract
- Atomic force microscopy was used to study the surface of STA-7 crystals. STA-7 is a silicoaluminophosphate, nanoporous solid formed by interlinked double six ring units (D6R). Observations showed the formation of three distinct types of spirals at tow supersaturation conditions. The {001} face shows spirals with isotropic shapes and a Burgers vector of 0.9 nm, which corresponds to one D6R or one unit cell along the < 001 > direction. The {100} face contains two distinct types of spirals. The first has a Burgers vector of 0.9 rim, or half a unit cell along < 100 >. This dislocation produces a change in the ""stacking"" sequence of the D6Rs generating all overgrowth with the AEI structure. The second type is an interlaced spiral and is generated by a dislocation with a Burgers vector of 1.8 nm or one unit cell, leading to the formation of two substeps each with a different growth anisotropy. This anisotropy is directed by the shape of the substep and the energetics of template attachment. The preponderance of a surface coating of a secondary phase will have significant consequences on applications reliant on intracrystalline diffusion, such as catalysis, where, owing to diffusion limitations, the outermost structure dominates the functional properties.
|
|
| 15. |
- Hung, Craig L. H., et al.
(författare)
-
An assessment of the risks associated with polychlorinated biphenyls found in the stomach contents of stranded Indo-Pacific Humpback Dolphins (Sousa chinensis) and Finless Porpoises (Neophocaena phocaenoides) from Hong Kong waters
- 2006
-
Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 63:5, s. 845-852
-
Tidskriftsartikel (refereegranskat)abstract
- The risks to Indo-Pacific Humpback Dolphins and Finless Porpoises associated with polychlorinated biphenyls (PCBs) were assessed. Stomach contents from twelve stranded Humpback Dolphins and sixteen stranded Finless Porpoises were collected. Concentrations of total and isomer-specific PCBs in the stomach contents were determined using dual-column gas chromatography equipped with electron capture detectors (GC-ECD). Risks due to the PCBs were assessed in three scenarios, based on total PCBs (summation of 41 PCB congeners), total toxicity equivalency (TEQs) and PCB 118, using the toxicity reference values (TRVs) as the threshold effects benchmarks. The calculated risk quotients (RQs) showed that risks due to PCBs were generally low or negligible. Specifically, RQs from total TEQs and total PCBs for Finless Porpoises are below one, suggesting that PCBs should be a low risk for the Finless Porpoise in Hong Kong waters. However, the Humpback Dolphin has RQs larger than 1 for total TEQs and total PCBs when the 95th percentile data were used in the evaluation. This indicates that further investigation may be needed to examine more closely the potential impact of toxic contaminants in the habitat of the Humpback Dolphin.
|
|
| 16. |
- Richards, Stephen, et al.
(författare)
-
The genome of the model beetle and pest Tribolium castaneum.
- 2008
-
Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
-
Tidskriftsartikel (refereegranskat)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Aksentijevich, Ivona, et al.
(författare)
-
An Autoinflammatory Disease with Deficiency of the Interleukin-1-Receptor Antagonist
- 2009
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 360:23, s. 2426-2437
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T cells. We report a disorder caused by mutations of IL1RN, which encodes the interleukin-1-receptor antagonist, with prominent involvement of skin and bone. METHODS We studied nine children from six families who had neonatal onset of sterile multifocal osteomyelitis, periostitis, and pustulosis. Response to empirical treatment with the recombinant interleukin-1-receptor antagonist anakinra in the first patient prompted us to test for the presence of mutations and changes in proteins and their function in interleukin-1-pathway genes including IL1RN. RESULTS We identified homozygous mutations of IL1RN in nine affected children, from one family from Newfoundland, Canada, three families from the Netherlands, and one consanguineous family from Lebanon. A nonconsanguineous patient from Puerto Rico was homozygous for a genomic deletion that includes IL1RN and five other interleukin-1-family members. At least three of the mutations are founder mutations; heterozygous carriers were asymptomatic, with no cytokine abnormalities in vitro. The IL1RN mutations resulted in a truncated protein that is not secreted, thereby rendering cells hyperresponsive to interleukin-1 beta stimulation. Patients treated with anakinra responded rapidly. CONCLUSIONS We propose the term deficiency of the interleukin-1-receptor antagonist, or DIRA, to denote this autosomal recessive autoinflammatory disease caused by mutations affecting IL1RN. The absence of interleukin-1-receptor antagonist allows unopposed action of interleukin-1, resulting in life-threatening systemic inflammation with skin and bone involvement. (ClinicalTrials.gov number, NCT00059748.)
|
|
| 20. |
- Ben Rayana, Mohammed C., et al.
(författare)
-
IFCC guideline for sampling, measuring and reporting ionized magnesium in plasma
- 2008
-
Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 46:1, s. 21-26
-
Tidskriftsartikel (refereegranskat)abstract
- Analyzers with ion-selective electrodes (ISEs) for ionized magnesium (iMg) should yield comparable and unbiased results for iMg. This IFCC guideline on sampling, measuring and reporting iMg in plasma provides a prerequisite to achieve this goal [in this document, "plasma" refers to circulating plasma and the forms in which it is sampled, namely the plasma phase of anticoagulated whole blood (or "blood"), plasma separated from blood cells, or serum]. The guideline recommends measuring and reporting ionized magnesium as a substance concentration relative to the substance concentration of magnesium in primary aqueous calibrants with magnesium, sodium, and calcium chloride of physiological ionic strength. The recommended name is "the concentration of ionized magnesium in plasma". Based on this guideline, results will be approximately 3% higher than the true substance concentration and 4% lower than the true molality in plasma. Calcium ions interfere with all current magnesium ion-selective electrodes (Mg-ISEs), and thus it is necessary to determine both ions simultaneously in each sample and correct the result for Ca2+ interference. Binding of Mg in plasma is pH-dependent. Therefore, pH should be measured simultaneously with iMg to allow adjustment of the result to pH 7.4. The concentration of iMg in plasma may be physiologically and clinically more relevant than the concentration of total magnesium. Furthermore, blood-gas analyzers or instruments for point-of-care testing are able to measure plasma iMg using whole blood (with intact blood cells) as the sample, minimizing turnaround time compared to serum and plasma, which require removal of blood cells.
|
|
| 21. |
- Ben Rayana, Mohammed C, et al.
(författare)
-
Recommendation for measuring and reporting chloride by ISEs in undiluted serum, plasma or blood
- 2006
-
Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 44:3, s. 346-352
-
Tidskriftsartikel (refereegranskat)abstract
- The proposed recommendation for measuring and reporting chloride in undiluted plasma† or blood by ion-selective electrodes (ISEs) will provide results that are identical to chloride concentrations measured by coulometry for standardized normal plasma or blood samples. It is applicable to all current ISEs dedicated to chloride measurement in undiluted samples that meet the requirements. However, in samples with reduced water concentration, results by coulometry are lower than by ion-selective electrode due to volume displacement. The quantity measured by this standardized ISE procedure is called the ionized chloride concentration. It may be clinically more relevant than the chloride concentration as determined by coulometry, photometry or by ISE after dilution of the sample. © 2006 by Walter de Gruyter.
|
|
| 22. |
- 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.
|
|
| 23. |
- Buitenhuis, Miranda, et al.
(författare)
-
Protein kinase B (c-akt) regulates hematopoietic lineage choice decisions during myelopoiesis
- 2008
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 111:1, s. 112-121
-
Tidskriftsartikel (refereegranskat)abstract
- Hematopoiesis is a highly regulated process resulting in the formation of all blood lineages. Aberrant regulation of phosphatidylinositol-3-kinase (PI3K) signaling has been observed in hematopoietic malignancies, suggesting that regulated PI3K signaling is critical for regulation of blood cell production. An ex vivo differentiation system was used to investigate the role of PI3K and its downstream effector, protein kinase B (PKB/c-akt) in myelopoiesis. PI3K activity was essential for hematopoietic progenitor survival. High PKB activity was found to promote neutrophil and monocyte development, while, conversely, reduction of PKB activity was required to induce optimal eosinophil differentiation. In addition, transplantation of beta2-microglobulin (-/-) NOD/SCID mice with CD34(+) cells ectopically expressing constitutively active PKB resulted in enhanced neutrophil and monocyte development, whereas ectopic expression of dominant-negative PKB induced eosinophil development in vivo. Inhibitory phosphorylation of C/EBPalpha on Thr222/226 was abrogated upon PKB activation in hematopoietic progenitors. Ectopic expression of a nonphosphorylatable C/EBPalpha mutant inhibited eosinophil differentiation ex vivo, whereas neutrophil development was induced, demonstrating the importance of PKB-mediated C/EBPalpha phosphorylation in regulation of granulopoiesis. These results identify an important novel role for PKB in regulation of cell fate choices during hematopoietic lineage commitment.
|
|
| 24. |
- Carter, Andrew T., et al.
(författare)
-
Independent evolution of neurotoxin and flagellar genetic loci in proteolytic Clostridium botulinum
- 2009
-
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Proteolytic Clostridium botulinum is the causative agent of botulism, a severe neuroparalytic illness. Given the severity of botulism, surprisingly little is known of the population structure, biology, phylogeny or evolution of C. botulinum. The recent determination of the genome sequence of C. botulinum has allowed comparative genomic indexing using a DNA microarray. Results: Whole genome microarray analysis revealed that 63% of the coding sequences (CDSs) present in reference strain ATCC 3502 were common to all 61 widely-representative strains of proteolytic C. botulinum and the closely related C. sporogenes tested. This indicates a relatively stable genome. There was, however, evidence for recombination and genetic exchange, in particular within the neurotoxin gene and cluster (including transfer of neurotoxin genes to C. sporogenes), and the flagellar glycosylation island (FGI). These two loci appear to have evolved independently from each other, and from the remainder of the genetic complement. A number of strains were atypical; for example, while 10 out of 14 strains that formed type A1 toxin gave almost identical profiles in whole genome, neurotoxin cluster and FGI analyses, the other four strains showed divergent properties. Furthermore, a new neurotoxin sub-type (A5) has been discovered in strains from heroin-associated wound botulism cases. For the first time, differences in glycosylation profiles of the flagella could be linked to differences in the gene content of the FGI. Conclusion: Proteolytic C. botulinum has a stable genome backbone containing specific regions of genetic heterogeneity. These include the neurotoxin gene cluster and the FGI, each having evolved independently of each other and the remainder of the genetic complement. Analysis of these genetic components provides a high degree of discrimination of strains of proteolytic C. botulinum, and is suitable for clinical and forensic investigations of botulism outbreaks.
|
|
| 25. |
- Chang, Wei-Ching, et al.
(författare)
-
Forecasting mortality : dynamic assessment of risk in ST-segment elevation acute myocardial infarction
- 2006
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:4, s. 419-426
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: To demonstrate the feasibility and clinical utility of developing dynamic risk assessment models for ST-segment elevation myocardial infarction (STEMI) patients. METHODS AND RESULTS: In 6066 STEMI patients enrolled in the Assessment of the Safety and Efficacy of a New Thrombolytic-3 (ASSENT-3) trial with complete electrocardiographic data, we assessed the probability of 30-day mortality over the following forecasting periods beginning at day 0 (baseline), 3 h, day 2, and day 5 using multiple-logistic regression. These models were validated and simplified in independent samples of 1622 similar fibrinolytic-treated patients from the ASSENT-3 PLUS trial and in 814 STEMI patients undergoing primary percutaneous coronary intervention in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial. The discriminatory power of these predictive models, from baseline to day 5, was excellent (c-statistics 0.80 to 0.87); and their predictive ability was supported by strong gradients in mortality outcomes as the risk score increased. Dynamic modelling also provided information on the change in prognosis over time which may be used to advise more appropriate therapeutic decisions, e.g. the identification of high-risk patients for possible co-interventions. CONCLUSION: Dynamic modelling for STEMI patients enhances the risk assessment and stratification and should provide valuable ongoing guidance for their management.
|
|
