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| 11. |
- Aaron, F. D., et al.
(författare)
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Combined measurement and QCD analysis of the inclusive e(+/-)p scattering cross sections at HERA
- 2010
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :1
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Tidskriftsartikel (refereegranskat)abstract
- A combination is presented of the inclusive deep inelastic cross sections measured by the H1 and ZEUS Collaborations in neutral and charged current unpolarised e(+/-)p scattering at HERA during the period 1994-2000. The data span six orders of magnitude in negative four-momentum-transfer squared, Q(2), and in Bjorken x. The combination method used takes the correlations of systematic uncertainties into account, resulting in an improved accuracy. The combined data are the sole input in a NLO QCD analysis which determines a new set of parton distributions, HERAPDF1.0, with small experimental uncertainties. This set includes an estimate of the model and parametrisation uncertainties of the fit result.
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| 12. |
- Aaron, F. D., et al.
(författare)
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Events with an isolated lepton and missing transverse momentum and measurement of W production at HERA
- 2010
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; 2010:3, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- A search for events containing an isolated electron or muon and missing trans verse momentum produced in e(+/-)p collisions is performed with the H1 and ZEUS detectors at HERA. The data were taken in the period 1994-2007 and correspond to an integrated luminosity of 0.98 fb(-1). The observed event yields are in good overall agreement with the Standard Model prediction, which is dominated by single W production. In the e(+)p data, at large hadronic transverse momentum P-T(X) > 25GeV, a total of 23 events are observed compared to a prediction of 14.0 +/- 1.9. The total single W boson production cross section is measured as 1.06 +/- 0.16 (stat.) +/- 0.07 (sys.) pb, in agreement with an Standard Model (SM) expectation of 1.26 +/- 0.19 pb.
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| 13. |
- Aaron, F. D., et al.
(författare)
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Multi-leptons with high transverse momentum at HERA
- 2009
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Ingår i: Journal of High Energy Physics. - : Springer Science and Business Media LLC. - 1029-8479. ; :10
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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.
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| 14. |
- Aaron, F. D., et al.
(författare)
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Combined inclusive diffractive cross sections measured with forward proton spectrometers in deep inelastic ep scattering at HERA
- 2012
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 72:10
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Tidskriftsartikel (refereegranskat)abstract
- A combination of the inclusive diffractive cross section measurements made by the H1 and ZEUS Collaborations at HERA is presented. The analysis uses samples of diffractive deep inelastic ep scattering data at a centre-of-mass energy root s = 318 GeV where leading protons are detected by dedicated spectrometers. Correlations of systematic uncertainties are taken into account, resulting in an improved precision of the cross section measurement which reaches 6 % for the most precise points. The combined data cover the range 2.5 < Q(2) < 200 GeV2 in photon virtuality, 0.00035 < x(P) < 0.09 in proton fractional momentum loss, 0.09 < vertical bar t vertical bar < 0.55 GeV2 in squared four-momentum transfer at the proton vertex and 0.0018 < beta < 0.816 in beta = x/x(P), where x is the Bjorken scaling variable.
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| 15. |
- Abramowicz, H., et al.
(författare)
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Combination and QCD analysis of charm production cross section measurements in deep-inelastic ep scattering at HERA
- 2013
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 73:2
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of open charm production cross sections in deep-inelastic ep scattering at HERA from the H1 and ZEUS Collaborations are combined. Reduced cross sections sigma(c (c) over bar)(red) for charm production are obtained in the kinematic range of photon virtuality 2.5 <= Q(2) <= 2000 GeV2 and Bjorken scaling variable 3 . 10(-5) <= x <= 5 . 10(-2). The combination method accounts for the correlations of the systematic uncertainties among the different data sets. The combined charm data together with the combined inclusive deep-inelastic scattering cross sections from HERA are used as input for a detailed NLO QCD analysis to study the influence of different heavy flavour schemes on the parton distribution functions. The optimal values of the charm mass as a parameter in these different schemes are obtained. The implications on the NLO predictions for W-+/- and Z production cross sections at the LHC are investigated. Using the fixed flavour number scheme, the running mass of the charm quark is determined.
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| 16. |
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| 17. |
- Carmona-Gutierrez, D., et al.
(författare)
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Guidelines and recommendations on yeast cell death nomenclature
- 2018
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Ingår i: Microbial Cell. - : Shared Science Publishers OG. - 2311-2638. ; 5:1, s. 4-31
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Forskningsöversikt (refereegranskat)abstract
- Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.
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| 18. |
- Tomas, C, et al.
(författare)
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Autosomal SNP typing of forensic samples with the GenPlex (TM) HID System: Results of a collaborative study
- 2011
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 5:5, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- The GenPlex (TM) HID System (Applied Biosystems - AB) offers typing of 48 of the 52 SNPforID SNPs and amelogenin. Previous studies have shown a high reproducibility of the GenPlex (TM) HID System using 250500 pg DNA of good quality. An international exercise was performed by 14 laboratories (9 in Europe and 5 in the US) in order to test the robustness and reliability of the GenPlex (TM) HID System on forensic samples. Three samples with partly degraded DNA and 10 samples with low amounts of DNA were analyzed in duplicates using various amounts of DNA. In order to compare the performance of the GenPlex (TM) HID System with the most commonly used STR kits, 500 pg of partly degraded DNA from three samples was typed by the laboratories using one or more STR kits. The median SNP typing success rate was 92.3% with 500 pg of partly degraded DNA. Three of the fourteen laboratories counted for more than two thirds of the locus dropouts. The median percentage of discrepant results was 0.2% with 500 pg degraded DNA. An increasing percentage of locus dropouts and discrepant results were observed when lower amounts of DNA were used. Different success rates were observed for the various SNPs. The rs763869 SNP was the least successful. With the exception of the MiniFiler (TM) kit (AB), GenPlex (TM) HID performed better than five other tested STR kits. When partly degraded DNA was analyzed, GenPlex (TM) HID showed a very low mean mach probability, while all STR kits except MiniFiler (TM) had very limited discriminatory power.
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| 22. |
- Nechushtai, Rachel, et al.
(författare)
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Allostery in the ferredoxin protein motif does not involve a conformational switch
- 2011
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Science Sessions. - 0027-8424 .- 1091-6490. ; 108:6, s. 2240-2245
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Tidskriftsartikel (refereegranskat)abstract
- Regulation of protein function via cracking, or local unfolding and refolding of substructures, is becoming a widely recognized mechanism of functional control. Oftentimes, cracking events are localized to secondary and tertiary structure interactions between domains that control the optimal position for catalysis and/or the formation of protein complexes. Small changes in free energy associated with ligand binding, phosphorylation, etc., can tip the balance and provide a regulatory functional switch. However, understanding the factors controlling function in single-domain proteins is still a significant challenge to structural biologists. We investigated the functional landscape of a single-domain plant-type ferredoxin protein and the effect of a distal loop on the electron-transfer center. We find the global stability and structure are minimally perturbed with mutation, whereas the functional properties are altered. Specifically, truncating the L1,2 loop does not lead to large-scale changes in the structure, determined via X-ray crystallography. Further, the overall thermal stability of the protein is only marginally perturbed by the mutation. However, even though the mutation is distal to the iron-sulfur cluster (∼20 Å), it leads to a significant change in the redox potential of the iron-sulfur cluster (57 mV). Structure-based all-atom simulations indicate correlated dynamical changes between the surface-exposed loop and the iron-sulfur cluster-binding region. Our results suggest intrinsic communication channels within the ferredoxin fold, composed of many short-range interactions, lead to the propagation of long-range signals. Accordingly, protein interface interactions that involve L1,2 could potentially signal functional changes in distal regions, similar to what is observed in other allosteric systems.
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| 23. |
- Carmona-Gutierrez, D, et al.
(författare)
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The flavonoid 4,4'-dimethoxychalcone promotes autophagy-dependent longevity across species
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 651-
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Tidskriftsartikel (refereegranskat)abstract
- Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4′-dimethoxychalcone (DMC) as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescence of human cell cultures, and protects mice from prolonged myocardial ischaemia. Concomitantly, DMC induces autophagy, which is essential for its cytoprotective effects from yeast to mice. This pro-autophagic response induces a conserved systemic change in metabolism, operates independently of TORC1 signalling and depends on specific GATA transcription factors. Notably, we identify DMC in the plant Angelica keiskei koidzumi, to which longevity- and health-promoting effects are ascribed in Asian traditional medicine. In summary, we have identified and mechanistically characterised the conserved longevity-promoting effects of a natural anti-ageing drug.
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| 26. |
- Al-Hashimi, Ibtisam, et al.
(författare)
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Oral lichen planus and oral lichenoid lesions: diagnostic and therapeutic considerations.
- 2007
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Ingår i: Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. - : Elsevier BV. - 1528-395X .- 1079-2104. ; 103 Suppl
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Tidskriftsartikel (refereegranskat)abstract
- Several therapeutic agents have been investigated for the treatment of oral lichen planus (OLP). Among these are corticosteroids, retinoids, cyclosporine, and phototherapy, in addition to other treatment modalities. A systematic review of clinical trials showed that particularly topical corticosteroids are often effective in the management of symptomatic OLP lichen planus. Systemic corticosteroids should be only considered for severe widespread OLP and for lichen planus involving other mucocutaneous sites. Because of the ongoing controversy in the literature about the possible premalignant character of OLP, periodic follow-up is recommended. There is a spectrum of oral lichen planus-like ("lichenoid") lesions that may confuse the differential diagnosis. These include lichenoid contact lesions, lichenoid drug reactions and lichenoid lesions of graft-versus-host disease. In regard to the approach to oral lichenoid contact lesions the value of patch testing remains controversial. Confirmation of the diagnosis of an oral lichenoid drug reaction may be difficult, since empiric withdrawal of the suspected drug and/or its substitution by an alternative agent may be complicated. Oral lichenoid lesions of graft-versus-host disease (OLL-GVHD) are recognized to have an association with malignancy. Local therapy for these lesions rests in topical agents, predominantly corticosteroids.
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| 27. |
- Almqvist, E, et al.
(författare)
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Risk reversals in predictive testing for Huntington disease.
- 1997
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 61:4, s. 945-52
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Tidskriftsartikel (refereegranskat)abstract
- The first predictive testing for Huntington disease (HD) was based on analysis of linked polymorphic DNA markers to estimate the likelihood of inheriting the mutation for HD. Limits to accuracy included recombination between the DNA markers and the mutation, pedigree structure, and whether DNA samples were available from family members. With direct tests for the HD mutation, we have assessed the accuracy of results obtained by linkage approaches when requested to do so by the test individuals. For six such individuals, there was significant disparity between the tests. Three went from a decreased risk to an increased risk, while in another three the risk was decreased. Knowledge of the potential reasons for these changes in results and impact of these risk reversals on both patients and the counseling team can assist in the development of strategies for the prevention and, where necessary, management of a risk reversal in any predictive testing program.
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| 28. |
- Brennan, Michael, et al.
(författare)
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Management of oral epithelial dysplasia: a review.
- 2007
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Ingår i: Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. - : Elsevier BV. - 1528-395X .- 1079-2104. ; 103 Suppl
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Tidskriftsartikel (refereegranskat)abstract
- One of the goals of the fourth meeting of The World Workshop on Oral Medicine (WWOM IV) included a review of the pathophysiology and future directions for the clinical management of patients with oral epithelial dysplasia, excluding the lips and oropharynx. In the pathophysiology review of dysplasia since WWOM III (1998-2006), a wide range of molecular changes associated with progression of dysplasia to squamous cell carcinoma were found. These include loss of heterozygosity, dysregulation of apoptosis, aberrant DNA expression, and altered expression of numerous tissue markers. Based on the literature search, no single molecular pathway has been identified as the primary factor in progression of dysplasia to squamous cell carcinoma. A systematic review of medical (i.e., nonsurgical) management strategies for the treatment of dysplastic lesions has shown promising results in short-term resolution of dysplasia in the small number of studies that met eligibility criteria for review. However, because of the limited periods of follow-up reported in these studies, it remains unclear as whether resolution of dysplasia would actually be a long-term benefit of these interventions. This question is particularly germane when it is considered in the context of prevention of future development of squamous cell carcinoma. Because of the lack of randomized controlled trials that have shown effectiveness in the prevention of malignant transformation, no recommendations can be provided for specific surgical interventions of dysplastic oral lesions either.
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| 30. |
- Campbell, Benjamin, et al.
(författare)
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The 7R polymorphism in the dopamine receptor D(4) gene (DRD4) is associated with financial risk taking in men
- 2009
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Ingår i: Evolution and Human Behavior. - : Elsevier. - 1090-5138. ; 30:2, s. 85-92
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Tidskriftsartikel (refereegranskat)abstract
- Individuals exhibit substantial heterogeneity in financial risk aversion. Recent work on twins demonstrated that some variation is influenced by individual heritable differences. Despite this, there has been no study investigating possible genetic loci associated with financial risk taking in healthy individuals. Here, we examined whether there is an association between financial risk preferences, elicited experimentally in a game with real monetary payoffs, and the presence of the 7-repeat allele (7R+) in the dopamine receptor D(4) gene as well as the presence of the Al allele (Al+) in the dopamine receptor D(2) gene in 94 young men. Although we found no association between the Al allele and risk preferences, we did find that 7R+ men are significantly more risk loving than 7R- men. This polymorphism accounts for roughly 20% of the heritable variation in financial risk taking. We suggest that selection for the 7R allele may be for a behavioral phenotype associated with risk taking. This is consistent with previous evolutionary explanations suggesting that selection for this allele was for behaviors associated with migration and male competition, both of which entail an element of risk. (C) 2009 Elsevier Inc. All rights reserved.
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| 33. |
- Di Giunta, Laura, et al.
(författare)
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Longitudinal associations between mothers' and fathers' anger/irritability expressiveness, harsh parenting, and adolescents' socioemotional functioning in nine countries.
- 2020
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Ingår i: Developmental Psychology. - : American Psychological Association (APA). - 0012-1649 .- 1939-0599. ; 56:3, s. 458-474
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Tidskriftsartikel (refereegranskat)abstract
- The present study examines parents' self-efficacy about anger regulation and irritability as predictors of harsh parenting and adolescent children's irritability (i.e., mediators), which in turn were examined as predictors of adolescents' externalizing and internalizing problems. Mothers, fathers, and adolescents (N = 1,298 families) from 12 cultural groups in 9 countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, and United States) were interviewed when children were about 13 years old and again 1 and 2 years later. Models were examined separately for mothers and fathers. Overall, cross-cultural similarities emerged in the associations of both mothers' and fathers' irritability, as well as of mothers' self-efficacy about anger regulation, with subsequent maternal harsh parenting and adolescent irritability, and in the associations of the latter variables with adolescents' internalizing and externalizing problems. The findings suggest that processes linking mothers' and fathers' emotion socialization and emotionality in diverse cultures to adolescent problem behaviors are somewhat similar.
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| 34. |
- Dreber Almenberg, Anna, et al.
(författare)
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Ancestry and allelic variation of the dopamine receptor D4 (DRD4) gene
- 2010
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Ingår i: Social Cognitive and Affective Neuroscience. - : Oxford University Press. - 1749-5016 .- 1749-5024. ; 5:2-3, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- The 7 repeat (7R) allele of the dopamine receptor D4 gene has been associated with attention deficit hyperactivity disorder and risk taking. On the cross-population scale, 7R allele frequencies have been shown to be higher in populations with more of a history of long-term migrations. It has also been shown that the 7R allele is associated with individuals having multiple ancestries. Here, we conduct a replication of this latter finding with two independent samples. Measures of subjects’ ancestry are used to examine past reproductive bonds. The individuals’ history of interracial/ancestral dating and their feelings about this are also assessed. Tentative support for an association between multiple ancestries and the 7R allele was found. These results are dependent upon the method of questioning subjects about their ancestries, with only finer-scale measures of ancestry being associated with 7R. Interracial dating and feelings about interracial pairing were not related to the presence of the 7R allele. This study provides continued support for a role for the 7R allele in migration and/or mate choice patterns. However, replications and extensions of this study are needed and the way ancestry/race is assessed must be carefully considered.
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| 35. |
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| 36. |
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| 37. |
- Eisenberg, Dan T.A., et al.
(författare)
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Assortative Human Pair-Bonding for Partner Ancestry and Allelic Variation of the Dopamine Receptor D4 (DRD4) Gene
- 2010
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Ingår i: Social Cognitive and Affective Neuroscience. - : Oxford University Press (OUP): Policy C - Option D. - 1749-5016 .- 1749-5024. ; 5:2-3, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- The 7 repeat (7R) allele of the dopamine receptor D4 gene has been associated with attention deficit hyperactivity disorder and risk taking. On the cross-population scale, 7R allele frequencies have been shown to be higher in populations with more of a history of long-term migrations. It has also been shown that the 7R allele is associated with individuals having multiple ancestries. Here, we conduct a replication of this latter finding with two independent samples. Measures of subjects' ancestry are used to examine past reproductive bonds. The individuals' history of interracial/ancestral dating and their feelings about this are also assessed. Tentative support for an association between multiple ancestries and the 7R allele was found. These results are dependent upon the method of questioning subjects about their ancestries, with only finer-scale measures of ancestry being associated with 7R. Interracial dating and feelings about interracial pairing were not related to the presence of the 7R allele. This study provides continued support for a role for the 7R allele in migration and/or mate choice patterns. However, replications and extensions of this study are needed and the way ancestry/race is assessed must be carefully considered.
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| 38. |
- Eisenberg, Tobias, et al.
(författare)
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Cardioprotection and lifespan extension by the natural polyamine spermidine
- 2016
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 22:12, s. 1428-1438
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Tidskriftsartikel (refereegranskat)abstract
- Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease.
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| 41. |
- Jeffet, Jonathan, et al.
(författare)
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Super-Resolution Genome Mapping in Silicon Nanochannels
- 2016
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 10:11, s. 9823-9830
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Tidskriftsartikel (refereegranskat)abstract
- Optical genome mapping in nanochannels is a powerful genetic analysis method, complementary to deoxyribonucleic acid (DNA) sequencing. The method is based on detecting a pattern of fluorescent labels attached along individual DNA molecules. When such molecules are extended in nanochannels, the labels create a fluorescent genetic barcode that is used for mapping the DNA molecule to its genomic locus and identifying large-scale variation from the genome reference. Mapping resolution is currently limited by two main factors: the optical diffraction limit and the thermal fluctuations of DNA molecules suspended in the nanochannels. Here, we utilize single-molecule tracking and super-resolution localization in order to improve the mapping accuracy and resolving power of this genome mapping technique and achieve a 15-fold increase in resolving power compared to currently practiced methods. We took advantage of a naturally occurring genetic repeat array and labeled each repeat with custom-designed Trolox conjugated fluorophores for enhanced photostability. This model system allowed us to acquire extremely long image sequences of the equally spaced fluorescent markers along DNA molecules, enabling detailed characterization of nanoconfined DNA dynamics and quantitative comparison to the Odijk theory for confined polymer chains. We present a simple method to overcome the thermal fluctuations in the nanochannels and exploit single-step photobleaching to resolve subdiffraction spaced fluorescent markers along fluctuating DNA molecules with ∼100 bp resolution. In addition, we show how time-averaging over just ∼50 frames of 40 ms enhances mapping accuracy, improves mapping P-value scores by 3 orders of magnitude compared to nonaveraged alignment, and provides a significant advantage for analyzing structural variations between DNA molecules with similar sequence composition.
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| 42. |
- Koroidov, Sergey, et al.
(författare)
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Probing the Electron Accepting Orbitals of Ni-Centered Hydrogen Evolution Catalysts with Noninnocent Ligands by Ni L-Edge and S K-Edge X-ray Absorption
- 2018
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Ingår i: Inorganic Chemistry. - : AMER CHEMICAL SOC. - 0020-1669 .- 1520-510X. ; 57:21, s. 13167-13175
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Tidskriftsartikel (refereegranskat)abstract
- The valence electronic structure of several square planar Ni-centered complexes, previously shown to catalyze the hydrogen evolution reaction, are characterized using S K-edge and Ni L-edge X-ray absorption spectroscopy and electronic structure calculations. Measurement of the atomic Ni 3d and S 3p contributions enables assessment of the metal-ligand covalency of the electron accepting valence orbitals and yields insight into the ligand-dependent reaction mechanisms proposed for the catalysts. The electron accepting orbital of the Ni(abt)(2) (abt = 2-aminobenzenethiolate) catalyst is found to have large ligand character (80%), with only 9% S 3p (per S) character, indicating delocalization over the entire abt ligand. Upon two proton-coupled reductions to form the Ni(abt-H)(2) intermediate, the catalyst stores 1.8 electrons on the abt ligand, and the ligand N atoms are protonated, thus supporting its role as an electron and proton reservoir. The electron accepting orbitals of the Ni(abt-H)(2) intermediate and Ni(mpo)(2) (mpo = 2-mercaptopyridyl-N-oxide) catalyst are found to have considerably larger Ni 3d (46-47%) and S 3p (17-18% per S) character, consistent with an orbital localized on the metal-ligand bonds. This finding supports the possibility of metal-based chemistry, resulting in Ni-H bond formation for the reduced Ni(abt-H)(2) intermediate and Ni(mpo)(2) catalyst, a critical reaction intermediate in H-2 generation.
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| 43. |
- Krotee, Pascal, et al.
(författare)
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Atomic structures of fibrillar segments of hIAPP suggest tightly mated beta-sheets are important or cytotoxicity
- 2017
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Ingår i: eLIFE. - 2050-084X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- hIAPP fibrils are associated with Type-II Diabetes, but the link of hIAPP structure to islet cell death remains elusive. Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic beta-cells, leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP. Using the cryoEM method MicroED, we discover that one segment, 19-29 S20G, forms pairs of beta-sheets mated by a dry interface that share structural features with and are similarly cytotoxic to full-length hIAPP fibrils. In contrast, a second segment, 15-25 WT, forms non-toxic labile beta-sheets. These segments possess different structures and cytotoxic effects, however, both can seed full-length hIAPP, and cause hIAPP to take on the cytotoxic and structural features of that segment. These results suggest that protein segment structures represent polymorphs of their parent protein and that segment 19-29 S20G may serve as a model for the toxic spine of hIAPP.
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| 44. |
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| 45. |
- Maji, Samir K, et al.
(författare)
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Functional Amyloids As Natural Storage of Peptide Hormones in Pituitary Secretory Granules
- 2009
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Ingår i: SCIENCE. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5938, s. 328-332
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Tidskriftsartikel (refereegranskat)abstract
- Amyloids are highly organized cross-beta-sheet-rich protein or peptide aggregates that are associated with pathological conditions including Alzheimers disease and type II diabetes. However, amyloids may also have a normal biological function, as demonstrated by fungal prions, which are involved in prion replication, and the amyloid protein Pmel17, which is involved in mammalian skin pigmentation. We found that peptide and protein hormones in secretory granules of the endocrine system are stored in an amyloid-like cross-beta-sheet-rich conformation. Thus, functional amyloids in the pituitary and other organs can contribute to normal cell and tissue physiology.
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| 46. |
- Parès, Yves, et al.
(författare)
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Composing Effects into Tasks and Workflows
- 2020
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Ingår i: Proceedings of the 13th ACM SIGPLAN International Haskell Symposium (Haskell’20), August 27, 2020, Virtual Event, New York, USA. - New York : Association for Computing Machinery. - 9781450380508
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Konferensbidrag (refereegranskat)abstract
- Data science applications tend to be built by composing tasks: discrete manipulations of data. These tasks are arranged in directed acyclic graphs, and many frameworks exist within the data science community supporting such a structure, which is called a workflow. In realistic applications, we want to be able to both analyze a workflow in the absence of data, and to execute the workflow with data. This paper combines effect handlers with arrow-like structures to abstract out data science tasks. This combination of techniques enables a modular design of workflows. Additionally, these workflows can both be analyzed prior to running (e.g., to provide early failure) and run conveniently. Our work is directly motivated by real-world scenarios, and we believe that our approach is applicable to new data science and machine learning applications and frameworks.
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| 47. |
- Popp, David, et al.
(författare)
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Flow-aligned, single-shot fiber diffraction using a femtosecond X-ray free-electron laser
- 2017
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Ingår i: CYTOSKELETON. - : WILEY. - 1949-3584 .- 1949-3592. ; 74:12, s. 472-481
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Tidskriftsartikel (refereegranskat)abstract
- A major goal for X-ray free-electron laser (XFEL) based science is to elucidate structures of biological molecules without the need for crystals. Filament systems may provide some of the first single macromolecular structures elucidated by XFEL radiation, since they contain one-dimensional translational symmetry and thereby occupy the diffraction intensity region between the extremes of crystals and single molecules. Here, we demonstrate flow alignment of as few as 100 filaments (Escherichia coli pili, F-actin, and amyloid fibrils), which when intersected by femtosecond X-ray pulses result in diffraction patterns similar to those obtained from classical fiber diffraction studies. We also determine that F-actin can be flow-aligned to a disorientation of approximately 5 degrees. Using this XFEL-based technique, we determine that gelsolin amyloids are comprised of stacked -strands running perpendicular to the filament axis, and that a range of order from fibrillar to crystalline is discernable for individual -synuclein amyloids.
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| 48. |
- Priskorn, Lærke, et al.
(författare)
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RUBIC (ReproUnion Biobank and Infertility Cohort) : A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity
- 2021
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Ingår i: Andrology. - : Wiley. - 2047-2919 .- 2047-2927. ; 9:6, s. 1828-1842
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Tidskriftsartikel (refereegranskat)abstract
- Background: Infertility affects 15%–25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth. Objectives: Three overall questions will be studied: (1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? (2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And (3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up?. Material and Methods: ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skåne University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of biospecimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem.
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| 49. |
- Spiwack, Arnaud, et al.
(författare)
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Linearly Qualified Types: Generic inference for capabilities and uniqueness
- 2022
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Ingår i: Proceedings of the ACM on Programming Languages (PACMPL). - : Association for Computing Machinery (ACM). - 2475-1421. ; 6:ICFP
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Tidskriftsartikel (refereegranskat)abstract
- A linear parameter must be consumed exactly once in the body of its function. When declaring resources such as file handles and manually managed memory as linear arguments, a linear type system can verify that these resources are used safely. However, writing code with explicit linear arguments requires bureaucracy. This paper presents linear constraints, a front-end feature for linear typing that decreases the bureaucracy of working with linear types. Linear constraints are implicit linear arguments that are filled in automatically by the compiler. We present linear constraints as a qualified type system, together with an inference algorithm which extends GHC's existing constraint solver algorithm. Soundness of linear constraints is ensured by the fact that they desugar into Linear Haskell.
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| 50. |
- Topooco, Naira, et al.
(författare)
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Digital interventions to address mental health needs in colleges : Perspectives of student stakeholders
- 2022
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Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 28
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The need for clinical services in U.S. colleges exceeds the supply. Digital Mental health Interventions (DMHIs) are a potential solution, but successful implementation depends on stakeholder acceptance. This study investigated the relevance of DMHIs from students perspectives. Methods: In 2020-2021, an online cross-sectional survey using mixed methods was conducted with 479 students at 23 colleges and universities. Respondents reported views and use of standard mental health services and DMHIs and rated the priority of various DMHIs to be offered through campus services. Qualitative data included open-ended responses. Findings: Among respondents, 91% reported having experienced mental health problems, of which 91% reported barriers to receiving mental health services. Students highlighted therapy and counseling as desired and saw flexible access to services as important. With respect to DMHIs, respondents had the most experience with physical health apps (46%), mental health questionnaires (41%), and mental well-being apps (39%). Most were unaware of or had not used apps or self-help programs for mental health problems. Students were most likely to report the following DMHIs as high priorities: a crisis text line (76%), telehealth (66%), websites for connecting to services (62%), and text/messaging with counselors (62%). They considered a self-help program with coach support to be convenient but some also perceived such services to be possibly less effective than in-person therapy. Conclusions: Students welcome DMHIs on campus and indicate preference for mental health services that include human support. The findings, with particular focus on characteristics of the DMHIs prioritized, and students awareness and perceptions of scalable DMHIs emphasized by policymakers, should inform schools looking to implement DMHIs.
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