| 1. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 2. |
- Niles, Andrea N., et al.
(författare)
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Internet-based cognitive behavior therapy for depression, social anxiety disorder, and panic disorder : Effectiveness and predictors of response in a teaching clinic
- 2021
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Ingår i: Behaviour Research and Therapy. - : Elsevier BV. - 0005-7967 .- 1873-622X. ; 136
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Tidskriftsartikel (refereegranskat)abstract
- Though therapist-guided Internet-based cognitive behavior therapy (ICBT) appears to be efficacious for depression, social anxiety disorder, and panic disorder, relatively little is known about real-world settings and predictors of treatment effects derived from cognitive-behavioral theory. We examined treatment effectiveness and predictors of improvement in a prospective cohort study where patients took part in 10 weeks of ICBT for depression (n = 114), social anxiety disorder (n = 150), or panic disorder (n = 106) at a teaching clinic. Patients self-reported symptoms before, during, and after treatment. Effect sizes were large for improvement in the primary symptom domain of each treatment group: depression (d = 1.48), social anxiety disorder (d = 1.01), and panic disorder (d = 1.15). In ICBT for depression, having no previous experience of psychological treatment (r = 0.21), and more frequent baseline negative automatic thoughts (r = 0.20) predicted larger improvement. In ICBT for panic disorder, having more baseline safety behaviors (r = 0.25) predicted larger improvement. Predictors remained significant when baseline symptoms were included in the statistical models. We conclude that ICBT can be effective in a real-world teaching clinic, and that patients with greater deficits at baseline benefit the most.
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| 3. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 4. |
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| 5. |
- Elks, Cathy E, et al.
(författare)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Tidskriftsartikel (refereegranskat)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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| 6. |
- Eriksson, Per-Erik, et al.
(författare)
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Managing short-term efficiency and long-term development through industrialized construction
- 2014
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Ingår i: Construction Management and Economics. - Abingdon, Oxon : Informa UK Limited. - 0144-6193 .- 1466-433X. ; 32:1-2, s. 97-108
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Tidskriftsartikel (refereegranskat)abstract
- There is a strong need for a productive and innovative infrastructure sector because of its monetary value and importance for the development of a sustainable society. An increased level of industrialization is often proposed as a way to improve efficiency and productivity in construction projects. In prior literature on industrialized construction, there are however neither many studies addressing more long-term aspects of innovation and sustainability nor studies within the infrastructure context. Organizational theory suggests that firms need to be ambidextrous and focus on both long-term exploration of new knowledge and technologies and short-term exploitation of current knowledge and technologies, in order to achieve sustainable development. Therefore, an investigation of how both short-term exploitative performance objectives and long-term explorative development can be addressed when implementing industrialized construction in infrastructure projects was conducted. A case study consisting of four infrastructure projects shows that the main drivers for increased industrialization are of an exploitative nature, focusing on cost savings and increased productivity through more efficient processes. The main barriers to increased industrialization are however related to both explorative and exploitative activities. Hence, by managing the identified barriers and explicitly addressing both exploitation and exploration, industrialized construction can improve both short-term efficiency and long-term innovation and sustainability.
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| 7. |
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| 8. |
- Hedman, Erik, et al.
(författare)
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Proteomic identification of glucocorticoid receptor interacting proteins
- 2006
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 6:10, s. 3114-26
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Tidskriftsartikel (refereegranskat)abstract
- The glucocorticoid receptor (GR) acts as a ligand dependent transcription factor but can also cross talk with other signaling pathways via protein-protein interactions. In this paper we describe methods to study novel cytosolic GR interacting proteins, using mAb based immunoaffinity chromatography of GR from rat liver cytosol. Co-purifying proteins were identified by 2-DE in combination with MALDI-TOF-MS. Non-liganded/non-activated and in vitro liganded/activated GR, respectively, co-purifies with specific sets of proteins. Of these 34 were conclusively identified, seven have previously been reported to be part of the GR-complex, revealing 27 new possible interacting candidates for the GR-complex. Of the novel GR interacting proteins the major vault protein, TATA binding interacting protein 49a and glycoprotein PP63 were of special interest. Furthermore, using 2-D DIGE we show that the set of proteins interacting with non-liganded GR is distinctly different in protein amount compared to the proteins found with liganded/activated GR. This suggests the presence of different GR complexes in the cell, which was further substantiated by the finding of several separate GR native protein complexes, "GR-receptosomes", using blue native gel electrophoresis. Our findings suggest the existence of several new mechanisms for GR signaling and regulation.
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| 9. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 10. |
- Järvenpää, Anna-Therése
(författare)
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How to promote innovation from an organizational control perspective : A case study of a public infrastructure client
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Within the infrastructure sector, a public client can have various roles and responsibilities that extend beyond its own organization, such as stimulating and supporting innovation. As an infrastructure project is seldom standardized, the client needs to procure each contract based on the relevant uncertainties and complexities for that specific context. To encourage a contractor’s compliance with the client’so bjectives, the client employs some degree of organizational control. When a public client procures all its infrastructure from contractors, it also needs to find ways of eliciting innovative solutions from the suppliers. Therefore, a public client needs strategies to both promote innovation by the contractors and direct and oversee the contractors’ work to ensure the deliverables meet the project’s objectives. The demands for increased innovation in the construction sector in general needs to be handled concomitant with the client’s need to check that the contractor delivers accordingly to the client’s objectives and demands. The overall purpose of this thesis is to explore the relationship between organizational control and promoting innovation by a public infrastructure client. More specifically, it explores how a public client can promote innovation by its contractors from an organizational control perspective. The theoretical background is provided by an organizational control framework (Ouchi, 1979; Aulakh et al., 1996), i.e. a client can manage and steer an agent via three different control systems: process, output, and social. The empirical data is derived from 47 semi-structured interviews, complemented by observations, from10 different infrastructure projects. The client (The Swedish Transport Administration; STA) is the same for each project, but the contractors differ. Two types of contractor are represented: contractors that have not worked with the STA before (“unfamiliar contractors”), and contractors that have worked with the STA before (“familiar contractors”). A majority of the contract type is design-build. Four appended papers, each presenting a public client perspective, provide the basis of the thesis. Previous findings that the client’s role is important for promoting innovation is explored further in this thesis from an organizational control perspective, emphasizing the role of the public client. It is important that during the procurement phase the client tries to find the right balance between achieving the intended objectives and creating space for innovation. Ex-ante planning is important, because how the client writes the control mechanisms into the procurement documents, and later the contract, has a direct effect on the opportunities for innovation by the contractors.In addition, the client has to manage the project in a way that does not cause irritation of frustration for the contractor, or hinder their work, thus supporting the view that organizational control should be enabling instead of coercive, so that the client’s input encourages innovation rather than creating obstacles. In addition, when adding a relationship history perspective on organizational control, an unfamiliar contractor (i.e. a contractor that has not worked with the client before) can find process control unsuitable and social control confusing, which means output control is probably the most appropriate approach to take when working with unfamiliar contractors. However, just relying on procurement strategies such as a design-build (DB)contract in combination with strict functional demands is not enough to promote innovation. Furthermore, a collaborative setting only seems to lead to innovative solutions if the client regards innovation as a mutual task and utilizes the collaborative setting for innovative co-creation. From the client’s perspective, the practical and managerial implication of this thesisis the importance of finding a balance between giving the contractor space to be innovative in the execution of the contract, and at the same time making sure that the requisite end product is delivered. The results of this thesis suggest that the client does not hand over the “how” to the contractor when it comes to executing the project, as would be expected in a DB contract. From the contractor’s perspective, the responsibility for innovation within a DB contract can be confounded by the client’s use of social control, by which the client may encourage discussions and collaboration regarding innovative solutions but blur the line over responsibilities. This could explain why social control often fails to have a positive impact on innovative output.
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| 11. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 12. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 13. |
- Lind, Lars, et al.
(författare)
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Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin.
- 2014
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding α1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.
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| 14. |
- Lu, Yingchang, et al.
(författare)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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| 15. |
- Marboe, Christian, et al.
(författare)
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The fate of the Konishi multiplet in the beta-deformed Quantum Spectral Curve
- 2020
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Ingår i: Journal of High Energy Physics (JHEP). - : SPRINGER. - 1126-6708 .- 1029-8479. ; :1
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the solution space of the beta-deformed Quantum Spectral Curve by studying a sample of solutions corresponding to single-trace operators that in the undeformed theory belong to the Konishi multiplet. We discuss how to set the precise boundary conditions for the leading Q-system for a given state, how to solve it, and how to build perturbative corrections to the P mu-system. We confirm and add several loop orders to known results in the literature.
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| 16. |
- Marboe, Christian, et al.
(författare)
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The fate of the Konishi multiplet in the β-deformed Quantum Spectral Curve
- 2020
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Ingår i: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :1
-
Tidskriftsartikel (refereegranskat)abstract
- We investigate the solution space of the β-deformed Quantum Spectral Curve by studying a sample of solutions corresponding to single-trace operators that in the undeformed theory belong to the Konishi multiplet. We discuss how to set the precise boundary conditions for the leading Q-system for a given state, how to solve it, and how to build perturbative corrections to the Pμ-system. We confirm and add several loop orders to known results in the literature.
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| 17. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 18. |
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| 19. |
- Prokopenko, Inga, et al.
(författare)
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A Central Role for GRB10 in Regulation of Islet Function in Man.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father.
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| 20. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 21. |
- Russo, Jorge G., et al.
(författare)
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N=2 phase transitions and holography
- 2019
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Ingår i: Journal of High Energy Physics (JHEP). - : SPRINGER. - 1126-6708 .- 1029-8479. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- We clarify the relationship between probe analysis of the supergravity al and the large-N solution of the localization matrix model for the anar N=2 super-Yang-Mills theory. A formalism inspired by supergravity lows us to systematically solve the matrix model at strong coupling. ite surprisingly, we find that quantum phase transitions, known to cur in the N=2 theory, start to be visible at the third order of the rong-coupling expansion and thus constitute a perturbative phenomenon the string worldsheet.
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| 22. |
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| 23. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 24. |
- Stolk, Lisette, et al.
(författare)
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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
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Tidskriftsartikel (refereegranskat)abstract
- To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
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| 25. |
- van der Valk, Ralf J P, et al.
(författare)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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| 26. |
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| 27. |
- Widen, Erik, 1986-
(författare)
-
Exact Results in Supersymmetric Field Theories : A dissertation on the defect and deformed
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Quantum field theories (QFTs) are the most precise descriptions of the physical reality that humanity has found. Yet exact predictions are often missing as most computations are notoriously difficult to carry out. One generally resorts to perturbation theory which immediately limits the regime of validity. The need of better computational techniques and a deeper understanding of quantum field theory is evident.The highly symmetric N=4 SYM theory offers guidance in this quest. The theory's maximal supersymmetry and conformal invariance have allowed for the development of several computational techniques, most notably the AdS/CFT correspondence, supersymmetric localization and applications of integrability. These methods provide the rarity of exact results in a fully interacting QFT and shine light on regimes inaccessible by traditional computations.The insights drawn from N=4 SYM can be extended into more general settings through deformations and modifications. Three such modifications are the β-deformation, the massive deformation N=2* and N=4 SYM with a defect. This thesis summarizes a number of exact results for these three settings through: i) a spin-chain analogy for two-point functions in the defect N=4 SYM, ii) a vacuum solution for the β-deformed defect N=4 SYM and its spin-chain interpretation of one-point functions, iii) a detailed study of the phase transitions in N=2* applying localization and iv) an adaptation of the Quantum Spectral Curve to explicit calculations of anomalous dimensions in β-deformed N=4 SYM.
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| 28. |
- Widén, Erik
(författare)
-
One-point functions in beta-deformed N=4 SYM with defect
- 2018
-
Ingår i: Journal of High Energy Physics (JHEP). - : SPRINGER. - 1126-6708 .- 1029-8479. ; :11
-
Tidskriftsartikel (refereegranskat)abstract
- We generalize earlier results on one-point functions in N = 4 SYM with a codimension one defect, dual to the D3-D5-brane setup in type IIB string theory on AdS(5)xS(5), to a similar setup in the beta-deformed version of the theory. The treelevel vacuum expectation values of single-trace operators in the two-scalar-subsector are expressed as overlaps between a matrix product state (MPS) and Bethe states in the corresponding twisted spin-chain picture. We comment on the properties of this MPS and present the simplest analytical overlaps and their behavior in a certain limit (of large k). Importantly, we note that the deformation alters earlier interpretations of the MPS as an integrable boundary state, seemingly obstructing simpli fi cations of the overlaps analogous to the compact determinant formula found in the non-deformed theory. The results are supplemented with some supporting numerical results for operators of length eight with four excitations.
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| 29. |
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| 30. |
- Widen, Erik
(författare)
-
Two-point functions of SU(2)-subsector and length-two operators in dCFT
- 2017
-
Ingår i: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 773, s. 435-439
-
Tidskriftsartikel (refereegranskat)abstract
- We consider a particular set of two-point functions in the setting of N=4SYM with a defect, dual to the fuzzy-funnel solution for the probe D5-D3-brane system. The two-point functions in focus involve a single trace operator in the SU(2)-subsector of arbitrary length and a length-two operator built out of any scalars. By interpreting the contractions as a spin-chain operator, simple expressions were found for the leading contribution to the two-point functions, mapping them to earlier known formulas for the one-point functions in this setting.
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| 31. |
- Widén, Joakim, 1980-, et al.
(författare)
-
Constructing load profiles for household electricity and hot water from time-use data-Modelling approach and validation
- 2009
-
Ingår i: Energy and Buildings. - : Elsevier BV. - 0378-7788 .- 1872-6178. ; 41:7, s. 753-768
-
Tidskriftsartikel (refereegranskat)abstract
- Time-use data, describing in detail the everyday life of household members as high-resolved activity sequences, have a largely unrealized potential of contributing to domestic energy demand modelling. A model for computation of daily electricity and hot-water demand profiles from time-use data was developed, using simple conversion schemes, mean appliance and water-tap data and general daylight availability distributions. Validation against detailed, end-use specific electricity measurements in a small sample of households reveals that the model for household electricity reproduces hourly load patterns with preservation of important qualitative features. The output from the model, when applied to a large data set of time use in Sweden, also shows correspondence to aggregate profiles for both household electricity and hot water from recent Swedish measurement surveys. Deviations on individual household level are predominantly due to occasionally ill-reported time-use data and on aggregate population level due to slightly non-representative samples. Future uses and developments are identified and it is suggested that modelling energy use from time-use data could be an alternative, or a complement, to energy demand measurements in households.
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| 32. |
- Widén, Åsa, et al.
(författare)
-
Environmental Flow Scenarios for a Regulated River System : Projecting Catchment-Wide Ecosystem Benefits and Consequences for Hydroelectric Production
- 2022
-
Ingår i: Water resources research. - : John Wiley & Sons. - 0043-1397 .- 1944-7973. ; 58:1
-
Tidskriftsartikel (refereegranskat)abstract
- To enable prioritization among measures for ecological restoration, knowing the expected benefits and consequences of implementation is imperative but rarely explicitly quantified. We developed a novel method to prioritize among environmental flow measures to rehabilitate ecosystems in the Ume River catchment in northern Sweden, a river system heavily regulated for hydropower production. Our strategy was to identify measures with minimal impact on hydropower production while providing substantial environmental benefits. Based on field surveys of remaining natural values and potential for ecological rehabilitation, we quantified the projected gain in habitat area of implementing environmental flows for target organism groups, for example, lotic fish species and riparian vegetation, along the whole river length. We quantified the consequences for hydropower production by identifying a set of hydropower operational rules reflecting the constraints added by environmental flows. We then used production optimization software to calculate changes in hydropower production and revenues. Implementing restrictions on zero-flow events by mandating minimum discharge at all run-of-river hydropower stations and allocating 1%–12% of mean annual discharge to bypassed reaches in the entire catchment would result in a 2.1% loss of annual electricity production. Adding flow to fishways would increase the loss to 3.1% per year. With implementation of more natural water-level fluctuations in run-of-river impoundments, the loss increases to 3.8%. These actions would increase the habitat for lotic species like the grayling Thymallus more than threefold and increase the area of riparian vegetation by about 66%. Our method forms a basis for ongoing implementation of nationwide environmental rehabilitation schemes.
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| 33. |
- Widén, Åsa, et al.
(författare)
-
Let it flow : Modeling ecological benefits and hydropower production impacts of banning zero-flow events in a large regulated river system
- 2021
-
Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 783
-
Tidskriftsartikel (refereegranskat)abstract
- Hydropeaking, defined as rapid and frequent changes in flow to optimize hydropower production, is an increasingly common procedure negatively affecting lotic habitats in riverine ecosystems. An important aspect of hydropeaking is zero-flow events, occurring when hydropower stations are stopped due to low energy demand or low electricity prices. We quantified the ecological benefits and consequences for hydropower production of restricting zero-flow events. The 19 major hydropower stations in the Ume River system in northern Sweden stand still with no discharge 9% to 55% of the time a hydrologically normal year, transforming lotic habitat to stagnant water. The duration of zero-flow events is exacerbated in dry years, with no discharge for 28% of the time in a typical station, to be compared with 7% in a wet year. Zero-flow events affect the behavior of fish, altering the fish community, and potentially result in low oxygen levels and low food supply to filter-feeding macroinvertebrates. We modelled the consequences of restricting zero-flow events by introducing minimum flows equaling mean annual low flow or higher for the entire Ume River catchment. The measure would result in an additional 240 ha of shallow lotic habitat with gravel to boulder streambeds having flow velocity exceeding 0.1 m/s, i.e. suitable for lotic species such as grayling Thymallus thymallus. In addition, the measure would enable creating another 107 ha of similar habitat after structural rehabilitation of river reaches. All measures would result in a mean loss of hydropower production of 0.5% per year for the entire river system, 98% of which would occur between May and October when the demand for electricity is lower. Hydropower production would also be partly moved from daytime to nighttime. As zero-flow events are common in several other river systems, restrictions on their frequency and duration could be implemented in many areas.
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| 34. |
- Widén, Åsa, et al.
(författare)
-
Ljungan inför miljöprövning av vattenkraften: naturvärden, flöden och strömhabitat samt möjliga miljönyttor
- 2022
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport utgör en beskrivning av dagens vattenkraftproduktion, återstående strömhabitat och nutida och dåtida naturvärden i Ljungan med förslag till miljöåtgärder och en skattning av kostnaderna (i form av kraftproduktion) och miljönyttorna (främst räknat som tillgängliggjort habitat). I arbetet, som följer de riktlinjer som presenteras i rapporter från forskningsprojektet Priokliv, ingår även en bristanalys där dagens situation jämförs med förhållanden innan vattenkraften byggdes ut. Därefter har vi utformat förslag på miljöanpassade flöden, öppnade vandringsvägar samt kompletterande åtgärder. Miljöåtgärderna fokuserar främst på ett antal scenarier med olika åtgärder där kostnader och miljönyttor jämförs med dagens situation. Arbetet fokuserar på huvudfårorna av Ljungan och Gimån i de vattenkraftpåverkade delarna. Vattensystemet har delats in i 20 dämningsområden, sträckor mellan kraftverk, där naturvärdet beskrivs utifrån habitat (strömsträckor, deltaområden, tillgång till biflöden, skyddad natur och kulturmiljöer) och förekommande arter. För de senare ligger fokus på arter som är rödlistade eller pekas ut i Art- och Habitatdirektivet eller Fågeldirektivet. Artuppgifterna kommer från standardiserad övervakning (fisk, flodpärlmussla) redovisad i offentliga databaser samt från rapporterade artförekomster till SLU:s Artportal. Analyserna visar att en stor påverkan skett av vattensystemet med förändrat flödesmönster, omfattande korttidsreglering och 18 torrfåror i området med en samlad areal av 219 hektar. Ett normalår är det nolltappning vid 175 tillfällen nedströms Flåsjön och 286 tillfällen nedom Holmsjön. Påverkan från korttidsreglering i älvsystemet är således omfattande, och åtgärder som kan lindra dess effekter har stor potential. Fiskfaunan har påverkats och laxens område utgör idag endast 7% av den forna längden. Endast 3% av avrinningsområdets dammar har fiskvägar. Sammanställningen visar samtidigt att det finns naturvärden kvar. Vid jämförelse med fallhöjd före regleringen av Ljungan med nuvarande förhållande visar analyserna att 16% av fallhöjden återstår. Beskrivningen av naturvärden visar att de är klart högst i de övre delarna av Ljungan och Gimån, dvs ovanför området där vattenkraftproduktion sker, men ett antal ekologiska värdekärnor har identifierats i de nedre delarna. Vi har även beaktat effekterna av det framtida klimatet. För år 2040 beräknas produktionen av elektricitet öka med i medel 3,1% jämfört med nuvarande förhållanden för hela avrinningsområdet. Vi förordar mer dynamiska modeller för att beskriva miljönyttorna som omfattar påverkan på processer i vattendraget, gynnad areal av bristhabitat, tillgängliggjord areal genom konnektivitet samt biologi som är kopplat till hydrologi på varierande skala gällande tidsupplösning och geografi. Nyttorna beskrivs genom tillgänglig gjord eller förbättrad areal av strömmande habitat, minskad påverkan av korttidsregleringseffekter, konnektivitet i form av tillgängliggjort habitat och vattendragslängd i denna rapport. Ekologisk reglering har modellerats med 13 scenarios och resultaten varierar gällande produktionspåverkan från att produktionen ökar med 1,2% (nolltappningsförbud nedströms Holmsjön i framtida klimat 2040) till en minskning av produktionen med 15,2% (statiska spill till torrfåror motsvarande medellågvattenföring (MLQ)). Samtliga scenarios med ekologisk reglering har påverkan på när produktionen av elektricitet sker över året, månad, vecka, dygn och timme. Det innebär att vi i modellerna flyttar produktionstillfället från tider med stora behov från samhället av elektricitet till tillfällen med lägre behov från samhället. Resultaten presenteras samlat mer utförligt i kapitel 8-9. Vi belyser betydelsen av noggranna och detaljerade beskrivningar av åtgärder, kostnader, miljönyttor och produktionspåverkan på energisystemet med avrinnesområdet som den minsta geografiska ytan.
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| 35. |
- Widén, Åsa, et al.
(författare)
-
Sveriges torrfåror : geografi, naturvärden och metoder för miljöförbättringar
- 2022
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med projektet var att ta fram metoder för att underlätta beslut om minimitappning och andra miljöförbättringsåtgärder för torrfåror, d.v.s. vattendragssträckor där vatten letts bort via kanaler eller tunnlar för att passera genom vattenkraftverks turbiner. Ibland sker även överledning från ett vattendrag till ett annat för att på så sätt öka produktionen av vattenkraft i vissa kraftverksanläggningar. Detta lämnar den ursprungliga fåran helt eller delvis torrlagd under stora delar av året. Vi har i denna rapport valt att använda begreppet ”torrfåror” för att indikera att det mest utmärkande draget är den reducerade vattenföringen. Många av dessa sträckor var ursprungligen forsar, och ekosystem och arter knutna till forsar har blivit sällsynta. Vi kartlade förekomsten av torrfåror i Sverige, och totalt identifierades och verifierades 972 torrfåror i en databas. 366 av dessa är belägna i Götaland, 323 i Svealand och 283 i Norrland. Den absoluta majoriteten av Sveriges torrfåror saknar bestämmelser om minimitappning. För de 622 torrfåror där vi hittat uppgifter om vattenföring, saknar 481 (77%) en tilldömd minimitappning. De 137 torrfårorna med minimitappning hade i genomsnitt en medelminimitappning på årsbasis på endast 3,6% av den naturliga årsmedelvattenföringen. I 63% av torrfårorna med minimitappning var denna lika med eller mindre än 5% av den naturliga årsmedelvattenföringen, och 48% var flödet lika med eller mindre än 0,5 m3/s. Analyser av fiskfaunan baserat på elfiskedata visar att torrfåror hade i genomsnitt lägre andel fiskar som hör till typiskt sett strömlevande arter och lägre total fiskabundans jämfört med av vattenkraft opåverkade referenslokaler. Torrfåror med minimitappning hade bättre status vad gäller fiskfaunan än de utan minimitappning vad gäller andel strömlevande arter, total fiskabundans och artrikedom av fisk. Andel individer av strömlevande fiskarter, total fiskabundans och fiskartrikedom ökade med ökande minimitappning i torrfårorna, men sambanden var icke-linjära och planade ut med ökande minimitappning. Torrfårornas medellutning var relativt hög (3,6%), och de representerar till övervägande del strömmande och forsande miljöer som helt eller delvis har torrlagts. Torrfårorna var i genomsnitt 1317 m, medan medianlängden endast var 319 m. De korta (50-100 m) och mycket korta (<50 m) torrfårorna var framför allt belägna i södra Sverige, medan långa (1-10 km) och mycket långa (>10 km) var vanligare i Norrlands inland. Majoriteten av torrfårorna i Sverige låg i vattendragens nedströmsdelar, i vattendragsordning 1 eller 2 räknat från mynningen. Miljöförbättringsåtgärder av olika slag, som mer naturliga vattenflöden, fiskvägar eller biotopvårdande åtgärder, har utförts vid 10% av torrfårorna sedan 1970. Av de 574 torrfåror där överensstämmelsen med vattenförekomster i VISS var god var 434 klassade som naturliga och 140 som kraftigt modifierade. I det senare fallet var den ekologiska potentialen enligt Vattendirektivet alltid klassificerad som måttlig eller sämre. Av de 434 som definierades som naturliga vattenförekomster hade de flesta givits måttlig ekologisk status. De största problemen i vattenförekomster som helt eller delvis motsvarar torrfåror är brister i konnektivitet och att den hydrologiska regimen är förändrad. Våra resultat visar att kortare torrfåror, som bara omfattar en del av en vattenförekomst, ofta förbises vid statusklassningen enligt Vattendirektivet, och att torrfåran ges samma ekologisk status som vattenförekomsten i stort. För att kunna välja ut vilka torrfåror som ska restaureras och genomföra restaureringsprojekt i torrfåror är fungerande samverkansprocess mellan berörda parter (t.ex. verksamhetsutövare, myndigheter, konsulter och ideella organisationer) viktig för att underlätta vägen från kartläggning till genomförande. Vi presenterar aspekter som underlättar, och kompetenser som behövs hos för att processen ska bli lyckosam. För att underlätta genomförandet av miljöförbättringsåtgärder i torrfåror presenterar vi ett metodiskt och strukturerat arbetssätt som ger en komplett kartläggning av torrfåran samt dess omgivande dämningsområden med biflöden, som leder fram till analyser av påverkansgraden, brister jämfört med opåverkade ekosystem, och åtgärdsbehov. Behov av åtgärder grundar sig på vilken restaureringspotential som finns baserat på förhållanden innan reglering och opåverkade referenslokaler. När man summerar naturvärden ger det en bild av vad som är möjligt att göra och vad som kan åstadkommas inom rimliga gränser med tanke på vattenkraftsproduktion. Målet är att detektera för vattenkraftsproduktion kostnadseffektiva och i det långa perspektivet resursanpassade åtgärder som gynnar ekosystemet och bevarar eller ökar naturvärdena. Som en grund för att kunna bestämma nivå på minimitappning presenterar vi en lista på vilka flöden eller aspekter av en naturlig flödesregim som krävs för att uppnå olika naturvärden (ökad biologisk mångfald av naturligt förekommande arter på en vattendragssträcka) eller ekosystemfunktioner. Denna kan hjälpa att bedöma vilka aspekter av naturliga flödesregimer som behövs för att erhålla önskade naturvärden, eller omvänt, att kunna ge en prognos för vilka naturvärden som kan förväntas vid en viss flödesregim, allt fokuserat på torrfåror. Vi presenterar också en metodik för att inventera torrfåror med kvantitativa metoder som bygger på att med hjälp av stickprov skatta hur mycket det finns av olika strukturer. Syftet med inventeringen är att kvantifiera strukturer i och kring vattendraget som kan vara viktiga för en bedömning av potentialen för att återskapa naturvärden (både akvatiska och i strandmiljön) vid olika möjliga flöden i torrfåror. Det finns flera fördelar med att ha en sådan samplingdesign (istället för kvalitativa metoder) i studier av ekologiska restaureringsprojekt. Det möjliggör att skatta t.ex. medelvärdet eller storleken på variabler som är av intresse, vare sig det är ytan av ett vegetationsbälte, mängden död ved eller fraktioner av sediment i fåran. Det kanske viktigaste skälet att göra det är att det möjliggör kvantitativ utvärdering av miljöförbättringsåtgärder, och avgöra om åtgärder har haft avsedd effekt. Miljödomar bör utformas för att vara långsiktigt hållbara för torrfårans ekosystem, d.v.s. vara relevanta under flera decennier trots att elsystemet och klimatet förändras. Få föreslagna åtgärder gällande torrfåror har genomförts praktiskt och att utreda genom uppföljning och belägga huruvida genomförda åtgärder faktiskt gett miljönytta är essentiellt. Uppföljning förutsätter att en vetenskaplig förstudie har genomförts (naturvärde, nuläge, påverkans- och bristanalys). Om det finns förstudier så finns goda förutsättningar att utvärdera effekterna, om tillräckligt lång tid efter restaurering har gått för att åtminstone initial ekologisk respons ska ha skett. Sammanfattningsvis konstaterar vi att de allra flesta torrfåror saknar minimitappning eller andra åtgärder för att förbättra den biologiska mångfalden och vattendragsekosystemen, men att det finns stöd för att sådana åtgärder är effektiva. Vår förhoppning är att de metoder vi presenterar ska underlätta beslut och genomförande av miljöförbättringsåtgärder i torrfåror.
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| 36. |
- Winkler, Charlotta, 1976-
(författare)
-
Client orchestration for the implementation of energy innovation in construction
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis aims to explore value creation from energy innovation in construction through implementation. The construction sector significantly impacts the environment. Buildings’ energy demand for heating and cooling accounts for 20% of annual global greenhouse gas emissions. Innovation is needed to reduce the sector’s contribution to climate change. This thesis focuses on energy-related innovations that reduce our dependency on fossil energy sources. For an innovation to give value, it must be put to use through implementation. In the construction context, the implementation takes place in inter-organisational and temporary project settings where interdependent actors collaborate to create value. The process of innovation implementation is affected by the innovation’s characteristics and the context of its implementation. The more complex the innovation, the more challenges the implementation process might involve.Clients in construction are central when it comes to change, and their ability to adapt to changing factors depends on their innovation capabilities. For the industry to meet climate-related challenges and contribute to the energy transition in the built environment, knowledge of the implementation of energy innovations and clients’ innovation capabilities must be developed.The aim of this thesis was realised by studying the characteristics and challenges of energy innovation implementation and clients’ innovation capabilities to orchestrate the activities required to meet these challenges. The characteristics and related challenges for implementation were explored by studying solar photovoltaic systems installed in the built environment (BEPV) as a case. The study identified several barriers to BEPV implementation and subsequent requirements for client orchestration. Due to a long history of implementing energy innovations, the real estate company of the municipality of Kungsbacka, Eksta Bostads AB, was chosen as a case in which to study client orchestration.This thesis draws on the literature on systemic innovation, innovation implementation, and ecosystem perspectives. The literature on systemic innovation helps us study and understand the implementation of energy innovations. The business ecosystem framework serves as a lens through which to study value co-creation in construction projects, and the innovation ecosystem perspective can be applied to study a client’s innovation capabilities to orchestrate activities for value creation. This thesis offers several contributions. First, it offers insights into systemic innovation implementation in construction by describing the characteristics of systemic energy innovations that display a high complexity requiring collaboration required in both the process and the innovation as such to implement systemic energy innovation in construction. Second, this change leads to the requirement that a client should act as a focal firm to orchestrate collaborative activities beyond project management. Third, this thesis offers empirical evidence that implementing energy innovations involves understanding implementation as part of a larger innovation process, not as an isolated process. Rather, the innovation process is highly dependent on the ecosystem orchestration, which in turn depends on a client’s innovation capabilities. As such, the thesis contributes to the ecosystem orchestration literature by demonstrating that client innovation capabilities enable orchestration that involves activities within and between projects and engagements across industry boundaries. In this way, the thesis builds our knowledge of the innovation process in construction, specifically, that the client is a central actor in realising value creation from innovation. The research shows how a client’s activities contribute to innovation diffusion in the construction industry and that these activities are anchored in a strong long-term strategy and a holistic view of sustainable development. These activities consist of formal and informal working methods and wholehearted engagements at an individual level, at which trust and long-term relationships are essential.Finally, by providing insights into the construction industry’s challenges in contributing to the energy transition in the built environment, this thesis offers policy suggestions regarding changes and adaptations in regulations and building norms to facilitate the implementation of energy innovations in construction projects, and to initiate educational arrangements and identify roles for key actors who can connect innovation development to innovation implementation for value creation.This thesis addresses the United Nations’s goals for sustainable development, specifically goals 7, ‘affordable and clean energy’, and 11, ‘sustainable cities and communities’.
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| 37. |
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| 38. |
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| 39. |
- Zillikens, M. C., et al.
(författare)
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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
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