| 1. |
- Roselli, Carolina, et al.
(author)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Journal article (peer-reviewed)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 2. |
- Galván, Ignacio Fdez., et al.
(author)
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OpenMolcas : From Source Code to Insight
- 2019
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In: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 15:11, s. 5925-5964
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Journal article (peer-reviewed)abstract
- In this Article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics, and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the Article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism, and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with postcalculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory, and new electronic and muonic basis sets.
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| 3. |
- Leebens-Mack, James H., et al.
(author)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Journal article (peer-reviewed)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 4. |
- Weng, Lu Chen, et al.
(author)
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Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation : The AFGen Consortium
- 2017
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Journal article (peer-reviewed)abstract
- It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10-5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10-8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.
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| 5. |
- Aldrin-Kirk, Patrick, et al.
(author)
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Chemogenetic modulation of cholinergic interneurons reveals their regulating role on the direct and indirect output pathways from the striatum
- 2018
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In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 109, s. 148-162
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Journal article (peer-reviewed)abstract
- The intricate balance between dopaminergic and cholinergic neurotransmission in the striatum has been thoroughly difficult to characterize. It was initially described as a seesaw with a competing function of dopamine versus acetylcholine. Recent technical advances however, have brought this view into question suggesting that the two systems work rather in concert with the cholinergic interneurons (ChIs) driving dopamine release. In this study, we have utilized two transgenic Cre-driver rat lines, a choline acetyl transferase ChAT-Cre transgenic rat and a novel double-transgenic tyrosine hydroxylase TH-Cre/ChAT-Cre rat to further elucidate the role of striatal ChIs in normal motor function and in Parkinson's disease. Here we show that selective and reversible activation of ChIs using chemogenetic (DREADD) receptors increases locomotor function in intact rats and potentiate the therapeutic effect of L-DOPA in the rats with lesions of the nigral dopamine system. However, the potentiation of the L-DOPA effect is accompanied by an aggravation of L-DOPA induced dyskinesias (LIDs). These LIDs appear to be driven primarily through the indirect striato-pallidal pathway since the same effect can be induced by the D2 agonist Quinpirole. Taken together, the results highlight the intricate regulation of balance between the two output pathways from the striatum orchestrated by the ChIs.
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| 6. |
- Andersson, Petra, et al.
(author)
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Innovativa elsystem i byggnader : konsekvenser för brandsäkerhet
- 2019
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Reports (other academic/artistic)abstract
- Det sker en snabb teknikutveckling i den elektriska miljön i byggnader, framförallt i våra bostäder. Ett exempel är lokal produktion av el, där solcellsinstallationer blir alltmer populära. Sådan elproduktion medför även förändringar i övriga delar av byggnaders elektriska infrastruktur, såsom DC-nät och i vissa fall energilagring i batterisystem. Utvecklingen sker till stor del som ett svar på behovet av mer hållbara lösningar, ur ett växthuseffektperspektiv, för vår elförsörjning, och förstärks bland annat av statligt stöd och ökad tillgänglighet på marknaden.Ny elektrisk teknologi kan leda till ökad brandrisk och denna förstudie har haft som mål att undersöka denna problematik. Metoden har varit workshops med intressenter och experter inom området, intervjuer, samt litteraturstudier.Av de studerade områdena förefaller solcellsanläggningar skapa störst utmaningar i framtiden om inget görs. Detta beror dels på bristfälligt regelverk men även på att dessa system är distribuerade i byggnaderna med flera delar som kan orsaka brand och att delar är exponerade för utomhusklimat vilket får stora konsekvenser vad gäller uppkomst av fel.Brandsäkerheten i samhället har sett ur ett långt tidsperspektiv väsentligt förbättrats. Detta har huvudsakligen drivits fram med hjälp av ett förbättrat regelverk, som ofta inkluderat förbättrade provnings- och kvalificeringsmetoder. En generell observation i detta projekt är att regelverket inte hinner utvecklas i samma takt som tekniken. Detta är en ofta återkommande utmaning inom brandsäkerhet, men gäller speciellt för de teknikområden som behandlas i denna rapport där utvecklingen går mycket snabbt, och de ingående komponenterna nästan uteslutande har stor inneboende brandpotential. Rapporten konstaterar att för att skapa ett relevant regelverk behövs tillämpad forskning, så kallad prenormativ forskning, inom prioriterade områden för att besvara de frågor som ställs vid formulerandet av nya regler och standarder. Exempel på områden som bör prioriteras är 1) komplettering av det än så länge magra statistiska underlaget för bränder i solcellsinstallationer med olycksutredningar, och studier av redan befintliga olycksutredningar, 2) studier av branddynamiken i solcellsinstallationer, såväl byggnadsapplicerade som integrerade, och såväl tak- som fasadmonterade sådana, 3) studier av ljusbågars uppkomst och hur dessa kan undvikas, alternativt hur det kan undvikas att de ger upphov till bränder, 4) skapa underlag för säker installation av batterilager, samt 5) kvalitetssäkring av så kallade second-life batterier, dvs. begagnade batterier, som används i batterilager.
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| 7. |
- Barkowsky, Marcus, et al.
(author)
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Objective Video Quality Assessment - Towards large scale video database enhanced model development
- 2015
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In: IEICE transactions on communications. - 0916-8516 .- 1745-1345. ; E98.B:1, s. 2-11
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Journal article (peer-reviewed)abstract
- The current development of video quality assessment algorithms suffers from the lack of available video sequences for training, verification and validation to determine and enhance the algorithm’s application scope. The Joint Effort Group of the Video Quality Experts Group (VQEG-JEG) is currently driving efforts towards the creation of large scale, reproducible, and easy to use databases. These databases will contain bitstreams of recent video encoders (H.264, H.265), packet loss impairment patterns and impaired bitstreams, pre-parsed bitstream information into files in XML syntax, and well-known objective video quality measurement outputs. The database is continuously updated and enlarged using reproducible processing chains. Currently, more than 70,000 sequences are available for statistical analysis of video quality measurement algorithms. New research questions are posed as the database is designed to verify and validate models on a very large scale, testing and validating various scopes of applications, while subjective assessment has to be limited to a comparably small subset of the database. Special focus is given on the principles guiding the database development, and some results are given to illustrate the practical usefulness of such a database with respect to the detailed new research questions.
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| 8. |
- Bianchi, Federica, et al.
(author)
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Benefit of Higher Maximum Force Output on Listening Effort in Bone-Anchored Hearing System Users: A Pupillometry Study
- 2019
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In: Ear and Hearing. - : LIPPINCOTT WILLIAMS & WILKINS. - 0196-0202 .- 1538-4667. ; 40:5, s. 1220-1232
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Journal article (peer-reviewed)abstract
- Objectives: The aim of this study was to compare listening effort, as estimated via pupillary response, during a speech-in-noise test in bone-anchored hearing system (BAHS) users wearing three different sound processors. The three processors, Ponto Pro (PP), Ponto 3 (P3), and Ponto 3 SuperPower (P3SP), differ in terms of maximum force output (MFO) and MFO algorithm. The hypothesis was that listeners would allocate lower listening effort with the P3SP than with the PP, as a consequence of a higher MFO and, hence, fewer saturation artifacts in the signal. Design: Pupil dilations were recorded in 21 BAHS users with a conductive or mixed hearing loss, during a speech-in-noise test performed at positive signal-to-noise ratios (SNRs), where the speech and noise levels were individually adjusted to lead to 95% correct intelligibility with the PP. The listeners had to listen to a sentence in noise, retain it for 3 seconds and then repeat it, while an eye-tracking camera recorded their pupil dilation. The three sound processors were tested in random order with a single-blinded experimental design. Two conditions were performed at the same SNR: Condition 1, where the speech level was designed to saturate the PP but not the P3SP, and condition 2, where the overall sound level was decreased relative to condition 1 to reduce saturation artifacts. Results: The P3SP led to higher speech intelligibility than the PP in both conditions, while the performance with the P3 did not differ from the performance with the PP and the P3SP. Pupil dilations were analyzed in terms of both peak pupil dilation (PPD) and overall pupil dilation via growth curve analysis (GCA). In condition 1, a significantly lower PPD, indicating a decrease in listening effort, was obtained with the P3SP relative to the PP. The PPD obtained with the P3 did not differ from the PPD obtained with the other two sound processors. In condition 2, no difference in PPD was observed across the three processors. The GCA revealed that the overall pupil dilation was significantly lower, in both conditions, with both the P3SP and the P3 relative to the PP, and, in condition 1, also with the P3SP relative to the P3. Conclusions: The overall effort to process a moderate to loud speech signal was significantly reduced by using a sound processor with a higher MFO (P3SP and P3), as a consequence of fewer saturation artifacts. These findings suggest that sound processors with a higher MFO may help BAHS users in their everyday listening scenarios, in particular in noisy environments, by improving sound quality and, thus, decreasing the amount of cognitive resources utilized to process incoming speech sounds.
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| 9. |
- Brange, Lisa, et al.
(author)
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Bottlenecks in district heating networks and how to eliminate them - A simulation and cost study
- 2017
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In: Energy. - : Elsevier BV. - 0360-5442. ; 137, s. 607-616
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Journal article (peer-reviewed)abstract
- To optimise district heating (DH) systems and simplify the transition towards the fourth generation of district heating, it is important to remove any bottlenecks existing in the DH network. DH bottlenecks are in this study defined as pipes with too high flow relative to the pipe diameter, resulting in difficulties to maintain sufficient differential pressure in the area beyond the pipe. The aim of this study is to investigate how well possible measures to solve bottleneck problems work in different DH network configurations and how much they cost. This was achieved by a simulation study and a cost analysis. The results showed that DH systems with a lower flow rate demanded more extensive measures than other systems and that different problems might arise in different types of networks. The economic results showed that a lot of varying parameters, such as the internal rate of return, the fuel and electricity prices and the annual utilisation time of the measure could have a large impact on the outcome. An increase of the supply temperature could however easily become very expensive. Before any bottleneck measures are implemented in a DH system, calculations and analysis based on the local situations should thus be performed.
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| 10. |
- Brange, Lisa, et al.
(author)
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Bottlenecks in district heating systems and how to address them
- 2017
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In: Energy Procedia. - : Elsevier BV. - 1876-6102. ; 116, s. 249-259
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Journal article (peer-reviewed)abstract
- Problems with bottlenecks in district heating networks occur when the pipes have too small dimensions to sufficiently meet customer needs. This may result in insufficient differential pressure in DH areas attached to these pipes. Bottlenecks are especially common in expanding DH networks, as previously sufficient pipe diameters may become too small when more DH consumers are connected to the DH network. Historically, bottlenecks have often been addressed by increasing the supply temperature or by exchanging the pipe to a larger dimension. Other techniques are however available to solve bottleneck problems. Such techniques are for example installation of local heat supply on the other side of the bottleneck (LHS), demand side management (DSM), or installation of thermal energy storage (TES). The aim of this study was to identify different techniques for addressing bottlenecks and to see what solutions were used by the DH companies in Sweden. A literature study of the different techniques available was performed and a survey study with the DH distribution companies in Sweden that are members of the Swedish DH association was carried out. The survey was sent out to in total 131 companies, of which 89 answered. The results showed that the most used techniques in Sweden are a higher supply temperature and installation of a new pipe to increase the pipe area, whereas for example DSM and TES were more rarely used techniques. This work is an introduction to the different techniques used to address bottleneck problems and shows the bottleneck situation in Swedish DH networks. More research and tests are however necessary in order to more thoroughly evaluate which techniques that should be used in different situations.
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