| 1. |
- Schael, S., et al.
(författare)
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Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
- 2013
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
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Forskningsöversikt (refereegranskat)abstract
- Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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| 9. |
- Fomichev, A. S., et al.
(författare)
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Status of the ACCULINNA-2 project at FLNR
- 2012
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 337:1, s. Art. no. 012025-
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Konferensbidrag (refereegranskat)abstract
- The project of a new and more powerful in-flight fragment separator ACCULINNA-2 at U-400M cyclotron in FLNR, JINR planned to build in addition to the existing separator ACCULINNA is presented. The new separator will provide high intensity RIBs in the lowest energy range (5÷50 MeV/nucleon) which is attainable for in-flight separators. The possibilities for the astrophysics studies at the proposed device are presented. ACCULINNA-2 separator is planned to be constructed in the years 2010-2015. The current status of the project is reported.
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| 12. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 13. |
- Pinto, Dalila, et al.
(författare)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Tidskriftsartikel (refereegranskat)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 14. |
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| 15. |
- Fomichev, A. S., et al.
(författare)
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Long range plan with radioactive beams at Dubna
- 2010
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Ingår i: 3rd International Conference on Current Problems in Nuclear Physics and Atomic Energy, NPAE 2010; Kyiv; Ukraine; 7 June 2010 through 12 June 2010. ; , s. 64-69
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Konferensbidrag (refereegranskat)abstract
- A program for upgrade of existing radioactive ion beams facilities at Flerov Laboratory of Nuclear Reactions, JINR Dubna is presented. A project of a new in-flight fragment separator ACCULINNA-2 is proposed. It is expected the new instrument will be more universal and powerful than the existing nowadays. The beam intensity should be increased by factor 10-15, its optical quality greatly improved and the range of the accessible secondary radioactive beams broadened up to Z∼20. Main ion-optical characteristics, operating principles and a tentative plan for the project realization are included. An extensive research program based on local experiments made so far and international proposals for these equipments is discussed.
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| 16. |
- Fomichev, A. S., et al.
(författare)
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The Suggested New Fragment Separator ACCULINNA-2
- 2010
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Ingår i: Acta Physica Polonica, Series B.. - 1509-5770 .- 0587-4254. ; 41:2, s. 475-480
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Tidskriftsartikel (refereegranskat)abstract
- We present new project of fragment separator ACCULINNA-2 that is being planned to be constructed in Flerov Laboratory of Nuclear Reaction, JINR. The ACCULINNA-2 facility is not, intended to compete with the, new large in-flight RIB facilities. It, should complement the existing/constructed facilities in certain fields. Namely, ACCULINNA-2 should provide high intensity RIBs in the lowest energy range attainable for in-flight separators.
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| 17. |
- Krupko, S. A., et al.
(författare)
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Fragment separator ACCULINNA-2
- 2010
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Ingår i: AIP Conference Proceedings. - : AIP. - 1551-7616 .- 0094-243X. - 9780735407688 ; 1224, s. 516-521
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 22. |
- Scott, James S., et al.
(författare)
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Circumventing seizure activity in a series of G protein coupled receptor 119 (GPR119) agonists
- 2014
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society. - 0022-2623 .- 1520-4804. ; 57:21, s. 8984-8998
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Tidskriftsartikel (refereegranskat)abstract
- Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group. Subsequent optimization to improve the overall profile, specifically with regard to hERG activity, led to alkyl sulfone 16. This compound did not cause tonic-clonic convulsions in mice, had a good pharmacokinetic profile, and displayed in vivo efficacy in murine models. Importantly, it was shown to be effective in wild-type (WT) but not GPR119 knockout (KO) animals, consistent with the pharmacology observed being due to agonism of GPR119.
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| 23. |
- Theorell, Töres, et al.
(författare)
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Job strain in relation to body mass index : pooled analysis of 160 000 adults from 13 cohort studies
- 2012
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 272:1, s. 65-73
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Tidskriftsartikel (refereegranskat)abstract
- Job strain in relation to body mass index: pooled analysis of 160 000 adults from 13 cohort studies. J Intern Med 2012; 272: 6573. Background. Evidence of an association between job strain and obesity is inconsistent, mostly limited to small-scale studies, and does not distinguish between categories of underweight or obesity subclasses. Objectives. To examine the association between job strain and body mass index (BMI) in a large adult population. Methods. We performed a pooled cross-sectional analysis based on individual-level data from 13 European studies resulting in a total of 161 746 participants (49% men, mean age, 43.7 years). Longitudinal analysis with a median follow-up of 4 years was possible for four cohort studies (n = 42 222). Results. A total of 86 429 participants were of normal weight (BMI 18.524.9 kg m-2), 2149 were underweight (BMI < 18.5 kg m-2), 56 572 overweight (BMI 25.029.9 kg m-2) and 13 523 class I (BMI 3034.9 kg m-2) and 3073 classes II/III (BMI = 35 kg m-2) obese. In addition, 27 010 (17%) participants reported job strain. In cross-sectional analyses, we found increased odds of job strain amongst underweight [odds ratio 1.12, 95% confidence interval (CI) 1.001.25], obese class I (odds ratio 1.07, 95% CI 1.021.12) and obese classes II/III participants (odds ratio 1.14, 95% CI 1.011.28) as compared with participants of normal weight. In longitudinal analysis, both weight gain and weight loss were related to the onset of job strain during follow-up. Conclusions. In an analysis of European data, we found both weight gain and weight loss to be associated with the onset of job strain, consistent with a U-shaped cross-sectional association between job strain and BMI. These associations were relatively modest; therefore, it is unlikely that intervention to reduce job strain would be effective in combating obesity at a population level.
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| 24. |
- Kivimäki, M., et al.
(författare)
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Job strain as a risk factor for coronary heart disease : A collaborative meta-analysis of individual participant data
- 2012
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 380:9852, s. 1491-1497
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Tidskriftsartikel (refereegranskat)abstract
- Background Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. Methods We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. Findings 30 214 (15%) of 197 473 participants reported job strain. In 1•49 million person-years at risk (mean follow-up 7•5 years [SD 1•7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1•23 (95% CI 1•10-1•37). This effect estimate was higher in published (1•43, 1•15-1•77) than unpublished (1•16, 1•02-1•32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1•31, 1•15-1•48) and 5 years (1•30, 1•13-1•50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3•4%. Interpretation Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. Funding Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.
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| 25. |
- Zabriskie, Matthew S., et al.
(författare)
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BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia
- 2014
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 26:3, s. 428-442
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Tidskriftsartikel (refereegranskat)abstract
- Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph+) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph+ leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome.
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| 26. |
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| 27. |
- Heikkilä, K., et al.
(författare)
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Job strain and health-related lifestyle : Findings from an individual-participant meta-analysis of 118 000 working adults
- 2013
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Ingår i: American Journal of Public Health. - 0090-0036 .- 1541-0048. ; 103:11, s. 2090-2097
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. We examined the associations of job strain, an indicator of work-related stress, with overall unhealthy and healthy lifestyles. Methods. We conducted a meta-analysis of individual-level data from 11 European studies (cross-sectional data: n = 118 701; longitudinal data: n = 43 971). We analyzed job strain as a set of binary (job strain vs no job strain) and categorical (high job strain, active job, passive job, and low job strain) variables. Factors used to define healthy and unhealthy lifestyles were body mass index, smoking, alcohol intake, and leisure-time physical activity. Results. Individuals with job strain were more likely than those with no job strain to have 4 unhealthy lifestyle factors (odds ratio [OR] = 1.25; 95% confidence interval [CI] = 1.12, 1.39) and less likely to have 4 healthy lifestyle factors (OR = 0.89; 95% CI = 0.80, 0.99). The odds of adopting a healthy lifestyle during study follow-up were lower among individuals with high job strain than among those with low job strain (OR = 0.88; 95% CI = 0.81, 0.96). Conclusions. Work-related stress is associated with unhealthy lifestyles and the absence of stress is associated with healthy lifestyles, but longitudinal analyses suggest no straightforward cause-effect relationship between workrelated stress and lifestyle. Copyright © 2013 by the American Public Health Association®.
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| 29. |
- Stajich, Jason E., et al.
(författare)
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Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom Coprinopsis cinerea (Coprinus cinereus)
- 2010
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 107:26, s. 11889-11894
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Tidskriftsartikel (refereegranskat)abstract
- The mushroom Coprinopsis cinerea is a classic experimental model for multicellular development in fungi because it grows on defined media, completes its life cycle in 2 weeks, produces some 10(8) synchronized meiocytes, and can be manipulated at all stages in development by mutation and transformation. The 37-megabase genome of C. cinerea was sequenced and assembled into 13 chromosomes. Meiotic recombination rates vary greatly along the chromosomes, and retrotransposons are absent in large regions of the genome with low levels of meiotic recombination. Single-copy genes with identifiable orthologs in other basidiomycetes are predominant in low-recombination regions of the chromosome. In contrast, paralogous multicopy genes are found in the highly recombining regions, including a large family of protein kinases (FunK1) unique to multicellular fungi. Analyses of P450 and hydrophobin gene families confirmed that local gene duplications drive the expansions of paralogous copies and the expansions occur in independent lineages of Agaricomycotina fungi. Gene-expression patterns from microarrays were used to dissect the transcriptional program of dikaryon formation (mating). Several members of the FunK1 kinase family are differentially regulated during sexual morphogenesis, and coordinate regulation of adjacent duplications is rare. The genomes of C. cinerea and Laccaria bicolor, a symbiotic basidiomycete, share extensive regions of synteny. The largest syntenic blocks occur in regions with low meiotic recombination rates, no transposable elements, and tight gene spacing, where orthologous single-copy genes are overrepresented. The chromosome assembly of C. cinerea is an essential resource in understanding the evolution of multicellularity in the fungi.
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| 30. |
- Goldberg, K., et al.
(författare)
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Diagenesis of Paleozoic playa-lake and ephemeral-stream deposits from the Pimenta Bueno Formation, Siluro-Devonian (?) of the Parecis Basin, central Brazil
- 2011
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Ingår i: Journal of South American Earth Sciences. - : Elsevier BV. - 0895-9811 .- 1873-0647. ; 32:1, s. 58-74
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Tidskriftsartikel (refereegranskat)abstract
- The Parecis Basin is a large intracratonic rift located in central Brazil and filled with Paleozoic carbonate, evaporite and siliciclastic sediments. The occurrence of gas seeps has recently attracted significant exploration interest by the Brazilian petroleum agency and by Petrobras. The continuously cored PB-01-RO well provided the first opportunity to study the depositional environments, diagenetic evolution and hydrocarbon potential of the largely unknown sedimentary successions of the Parecis Basin. The cored lithologies, belonging to the Siluro-Devonian (?) Pimenta Bueno Formation, are interpreted as deposited in playa-lake and ephemeral-stream environments. The deposits display a strong fades control on the diagenetic mineral assemblages and evolution. Diagenetic minerals in the ephemeral-stream deposits include eogenetic hematite and smectitic clay coats and quartz cement, and the mesogenetic process includes precipitation of sulfates (anhydrite and barite) and carbonates (calcite, dolomite and kutnahorite-ankerite-huntite), followed by partial dissolution of these carbonates and sulfates, and of feldspar grains. Telogenetic processes include the precipitation of hematite and kaolinite within secondary pores, and the replacement of anhydrite by gypsum. A second burial phase and mesodiagenesis is indicated by the precipitation of discrete K-feldspar crystals within moldic pores after dissolved feld-spars, and by the illitization of etched, telogenetic kaolinite. The playa-lake deposits show early diagenetic dolomitization of lime mud, precipitation of anhydrite nodules and extensive silicification. The anhydrite nodules were replaced by gypsum and chalcedony during telodiagenesis. Potential source rocks are locally represented by organic shales. The fluvial sandstones show fair reservoir quality and limited compaction, as indicated by their intergranular volume, suggesting that the succession has undergone moderate burial. Potential seals for hydrocarbon accumulations are provided by the evaporites and playa-lake mudstones. The presence of an active petroleum system in the basin, as indicated by the gas seeps, suggests a good hydrocarbon exploration potential for the Parecis Basin, gas and stresses the importance of studying the depositional and diagenetic evolution of its sedimentary successions.
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| 32. |
- Schiffman, E, et al.
(författare)
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Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications : recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group
- 2014
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Ingår i: Journal of oral & facial pain and headache. - : Quintessence. - 2333-0384 .- 2333-0376. ; 28:1, s. 6-27
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The original Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I diagnostic algorithms have been demonstrated to be reliable. However, the Validation Project determined that the RDC/TMD Axis I validity was below the target sensitivity of ≥ 0.70 and specificity of ≥ 0.95. Consequently, these empirical results supported the development of revised RDC/TMD Axis I diagnostic algorithms that were subsequently demonstrated to be valid for the most common pain-related TMD and for one temporomandibular joint (TMJ) intra-articular disorder. The original RDC/TMD Axis II instruments were shown to be both reliable and valid. Working from these findings and revisions, two international consensus workshops were convened, from which recommendations were obtained for the finalization of new Axis I diagnostic algorithms and new Axis II instruments. METHODS: Through a series of workshops and symposia, a panel of clinical and basic science pain experts modified the revised RDC/TMD Axis I algorithms by using comprehensive searches of published TMD diagnostic literature followed by review and consensus via a formal structured process. The panel's recommendations for further revision of the Axis I diagnostic algorithms were assessed for validity by using the Validation Project's data set, and for reliability by using newly collected data from the ongoing TMJ Impact Project-the follow-up study to the Validation Project. New Axis II instruments were identified through a comprehensive search of the literature providing valid instruments that, relative to the RDC/TMD, are shorter in length, are available in the public domain, and currently are being used in medical settings. RESULTS: The newly recommended Diagnostic Criteria for TMD (DC/TMD) Axis I protocol includes both a valid screener for detecting any pain-related TMD as well as valid diagnostic criteria for differentiating the most common pain-related TMD (sensitivity ≥ 0.86, specificity ≥ 0.98) and for one intra-articular disorder (sensitivity of 0.80 and specificity of 0.97). Diagnostic criteria for other common intra-articular disorders lack adequate validity for clinical diagnoses but can be used for screening purposes. Inter-examiner reliability for the clinical assessment associated with the validated DC/TMD criteria for pain-related TMD is excellent (kappa ≥ 0.85). Finally, a comprehensive classification system that includes both the common and less common TMD is also presented. The Axis II protocol retains selected original RDC/TMD screening instruments augmented with new instruments to assess jaw function as well as behavioral and additional psychosocial factors. The Axis II protocol is divided into screening and comprehensive self report instrument sets. The screening instruments' 41 questions assess pain intensity, pain-related disability, psychological distress, jaw functional limitations, and parafunctional behaviors, and a pain drawing is used to assess locations of pain. The comprehensive instruments, composed of 81 questions, assess in further detail jaw functional limitations and psychological distress as well as additional constructs of anxiety and presence of comorbid pain conditions. CONCLUSION: The recommended evidence-based new DC/TMD protocol is appropriate for use in both clinical and research settings. More comprehensive instruments augment short and simple screening instruments for Axis I and Axis II. These validated instruments allow for identification of patients with a range of simple to complex TMD presentations
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