| 1. |
- Weinstock, Joshua S, et al.
(författare)
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Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
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Ingår i: Nature. - 1476-4687. ; 616:7958, s. 755-763
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, butthis effect was not seen inclones withdriver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimentalknockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
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| 2. |
- Bangsbo, Jens, et al.
(författare)
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Copenhagen Consensus statement 2019 : physical activity and ageing
- 2019
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Ingår i: British Journal of Sports Medicine. - London : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 53:14, s. 856-858
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Tidskriftsartikel (refereegranskat)abstract
- From 19th to 22nd November 2018, 26 researchers representing nine countries and a variety of academic disciplines met in Snekkersten, Denmark, to reach evidence-based consensus about physical activity and older adults. It was recognised that the term ‘older adults’ represents a highly heterogeneous population. It encompasses those that remain highly active and healthy throughout the life-course with a high intrinsic capacity to the very old and frail with low intrinsic capacity. The consensus is drawn from a wide range of research methodologies within epidemiology, medicine, physiology, neuroscience, psychology and sociology, recognising the strength and limitations of each of the methods. Much of the evidence presented in the statements is based on longitudinal associations from observational and randomised controlled intervention studies, as well as quantitative and qualitative social studies in relatively healthy community-dwelling older adults. Nevertheless, we also considered research with frail older adults and those with age-associated neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, and in a few cases molecular and cellular outcome measures from animal studies. The consensus statements distinguish between physical activity and exercise. Physical activity is used as an umbrella term that includes both structured and unstructured forms of leisure, transport, domestic and work-related activities. Physical activity entails body movement that increases energy expenditure relative to rest, and is often characterised in terms of intensity from light, to moderate to vigorous. Exercise is defined as a subset of structured physical activities that are more specifically designed to improve cardiorespiratory fitness, cognitive function, flexibility balance, strength and/or power. This statement presents the consensus on the effects of physical activity on older adults’ fitness, health, cognitive functioning, functional capacity, engagement, motivation, psychological well-being and social inclusion. It also covers the consensus on physical activity implementation strategies. While it is recognised that adverse events can occur during exercise, the risk can be minimised by carefully choosing the type of activity undertaken and by consultation with the individual’s physician when warranted, for example, when the individual is frail, has a number of co-morbidities, or has exercise-related symptoms, such as chest pain, heart arrhythmia or dizziness. The consensus was obtained through an iterative process that began with the presentation of the state-of-the-science in each domain, followed by group and plenary discussions. Ultimately, the participants reached agreement on the 30-item consensus statements.
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| 3. |
- Bergström, Ilias, et al.
(författare)
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The Practices of Programming
- 2016
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Ingår i: 2016 IEEE SYMPOSIUM ON VISUAL LANGUAGES AND HUMAN-CENTRIC COMPUTING (VL/HCC). - : IEEE conference proceedings. - 9781509002528 ; , s. 190-198
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Konferensbidrag (refereegranskat)abstract
- How diverse are the ways that programming is done? While a variety of accounts exist, each appears in isolation, neither framed in terms of a distinct practice, nor as one of many such practices. In this work we explore accounts spanning software engineering, bricolage/tinkering, sketching, live coding, code-bending, and hacking. These practices of programming are analyzed in relation to ongoing research, and in particular HCI's 'practice turn', offering connections to accounts of practice in other contexts than programming. The conceptualization of practice helps to interpret recent interest in program code as craft material, and also offers potential to inform programming education, tools and work as well as future research.
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| 4. |
- Nilsson, Tommy, et al.
(författare)
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Applying Seamful Design in Location-Based Mobile Museum Applications
- 2016
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Ingår i: ACM Transactions on Multimedia Computing, Communications, and Applications (TOMCCAP). - : Association for Computing Machinery (ACM). - 1551-6857 .- 1551-6865. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- The application of mobile computing is currently altering patterns of our behavior to a greater degree than perhaps any other invention. In combination with the introduction of power-efficient wireless communication technologies, such as Bluetooth Low Energy (BLE), designers are today increasingly empowered to shape the way we interact with our physical surroundings and thus build entirely new experiences. However, our evaluations of BLE and its abilities to facilitate mobile location-based experiences in public environments revealed a number of potential problems. Most notably, the position and orientation of the user in combination with various environmental factors, such as crowds of people traversing the space, were found to cause major fluctuations of the received BLE signal strength. These issues are rendering a seamless functioning of any location-based application practically impossible. Instead of achieving seamlessness by eliminating these technical issues, we thus choose to advocate the use of a seamful approach, that is, to reveal and exploit these problems and turn them into a part of the actual experience. In order to demonstrate the viability of this approach, we designed, implemented, and evaluated the Ghost Detector-an educational location-based museum game for children. By presenting a qualitative evaluation of this game and by motivating our design decisions, this article provides insight into some of the challenges and possible solutions connected to the process of developing location-based BLE-enabled experiences for public cultural spaces.
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| 5. |
- Su, Zhan, et al.
(författare)
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Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
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Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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