| 1. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 2. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 3. |
- Appelqvist, Christin, 1972, et al.
(författare)
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Climate envelope modeling and dispersal simulations show little risk of range extension of the shipworm, Teredo navalis (L.), in the Baltic Sea
- 2015
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- The shipworm, Teredo navalis , is absent from most of the Baltic Sea. In the last 20 years, increased frequency of T. navalis has been reported along the southern Baltic Sea coasts of Denmark, Germany, and Sweden, indicating possible range-extensions into previously unoccupied areas. We evaluated the effects of historical and projected near-future changes in salinity, temperature, and oxygen on the risk of spread of T. navalis in the Baltic. Specifically, we developed a simple, GIS-based, mechanistic climate envelope model to predict the spatial distribution of favourable conditions for adult reproduction and larval metamorphosis of T. navalis, based on published environmental tolerances to these factors. In addition, we used a high-resolution three-dimensional hydrographic model to simulate the probability of spread of T. navalis larvae within the study area. Climate envelope modeling showed that projected near-future climate change is not likely to change the overall distribution of T. navalis in the region, but will prolong the breeding season and increase the risk of shipworm establishment at the margins of the current range. Dispersal simulations indicated that the majority of larvae were philopatric, but those that spread over a wider area typically spread to areas unfavourable for their survival. Overall, therefore, we found no substantive evidence for climate-change related shifts in the distribution of T. navalis in the Baltic Sea, and no evidence for increased risk of spread in the near-future. © 2015 Appelqvist et al.
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| 4. |
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| 5. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 6. |
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| 7. |
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| 8. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 9. |
- Dobsicek Trefna, Hana, 1979, et al.
(författare)
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Antenna Applicator for Microwave Hyperthermia Treatment of Pediatric Brain Cancer
- 2014
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Ingår i: 8th European Conference on Antennas and Propagation, EuCAP 2014, The Hague, The Netherlands 6-11 April 2014. - 9788890701849
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A novel antenna applicator for microwave hyperthermia allowing treatment of deep brain tumors is proposed. The applicator consists of up to 16 antennas placed around the head in a helmet-like set-up and operates at a frequency range of 430-1000~MHz. The self-grounded bow-tie antennas are housed in a molded plastic enclosure with the shape of a truncated cone. The inner space of the enclosure is filled with distilled water. The antennas are attached to a perimetric water bolus with a thickness of 2 cm and aligned with the head shape. The focusing ability of the applicator was investigated on a homogeneous SAM model and on a model of a 13-year old patient containing a spherical tumor of 2 cm radius. Two different tumor positions were investigated: the right frontal lobe and the central brain. The obtained SAR distributions are favorable, although a relatively high level of energy is also absorbed on the surface of the body. This heating is however not expected to cause problems as it can be cooled by blood perfusion and water bolus. Our results show that focused microwave heating in the brain is feasible and warrants further verification on phantoms.
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| 10. |
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| 11. |
- Ejenstam, Jesper, et al.
(författare)
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Oxidation studies of Fe10CrAl-RE alloys exposed to Pb at 550 degrees C for 10,000 h
- 2013
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 443:1-3, s. 161-170
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Tidskriftsartikel (refereegranskat)abstract
- Five experimental FeCrAl-RE alloys have been exposed up to 10,000 h in stagnant liquid Pb at 550 C. The test matrix consisted of three 10 wt.% Cr alloys, with an Al content ranging from 4 to 8 wt.% (10Cr-4Al, 10Cr-6Al and 10Cr-8Al), one alloy without additions of reactive elements (RE) (10Cr-6Al), and one reference alloy with 21 wt.% Cr and 5 wt.% Al (21Cr-5Al). The evaluation showed a clear difference in oxidation properties, and it was possible to divide the alloys into two distinct groups. A critical Al concentration in the interval of 4-6 wt.% at the given RE content was required to form a thin protective oxide. However, the absence of RE addition in one of the two 10Cr-6Al alloys resulted in a significant reduction in oxidation resistance, comparable with 10Cr-4Al. None of the alloys were severely corroded, however Pb penetrated to a relatively large extent into the porous oxide of the low performing alloys. A 100 nm thick oxide scale, partly consisting of alumina (Al2O3), was observed for the high performing 10Cr-6Al alloy. The Fe10CrAl-RE alloys showed overall very good corrosion resistance and are hence a promising new alloy category for liquid Pb applications. (C) 2013 Elsevier B.V. All rights reserved.
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| 12. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 13. |
- Gamfeldt, Lars, 1975, et al.
(författare)
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Increasing intraspecific diversity enhances settling success in a marine invertebrate
- 2005
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Ingår i: Ecology. - : Wiley. - 0012-9658. ; 86:12, s. 3219-3224
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Tidskriftsartikel (refereegranskat)abstract
- Theoretical and empirical research during the last decade suggests that increasing species richness often enhances ecosystem processes Such as productivity, nutrient cycling. or resistance to disturbance. By analogous reasoning, it can be hypothesized that genetic diversity within species will have equivalent effects; however, this hypothesis has rarely been tested. We present experimental support for the positive effects of intraspecific diversity on a key trait: larval settlement in a marine invertebrate, the barnacle Balanus improvisus. Varying within-species diversity levels of an animal over nine experiments, We found increasing larval settlement with increasing diversity (one, two, or three parental broods). Possible mechanisms explaining this pattern include: (1) facilitation of gregarious response through the presence of founder genotypes, and (2) ensuring genetic complementarity to increase future reproductive potential. Our results indicate that changing intraspecific genetic diversity could have hitherto unrecognized community-scale implications for larval recruitment and space occupancy.
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| 14. |
- Hellman, A, et al.
(författare)
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Predicting catalysis : understanding ammonia synthesis from first-principles calculations
- 2006
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Ingår i: Journal of Physical Chemistry B. - 1520-6106 .- 1520-5207. ; 110, s. 17719-17735
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Tidskriftsartikel (refereegranskat)abstract
- Here, we give a full account of a large collaborative effort toward an atomic-scale understanding of modern industrial ammonia production over ruthenium catalysts. We show that overall rates of ammonia production can be determined by applying various levels of theory (including transition state theory with or without tunneling corrections, and quantum dynamics) to a range of relevant elementary reaction steps, such as N(2) dissociation, H(2) dissociation, and hydrogenation of the intermediate reactants. A complete kinetic model based on the most relevant elementary steps can be established for any given point along an industrial reactor, and the kinetic results can be integrated over the catalyst bed to determine the industrial reactor yield. We find that, given the present uncertainties, the rate of ammonia production is well-determined directly from our atomic-scale calculations. Furthermore, our studies provide new insight into several related fields, for instance, gas-phase and electrochemical ammonia synthesis. The success of predicting the outcome of a catalytic reaction from first-principles calculations supports our point of view that, in the future, theory will be a fully integrated tool in the search for the next generation of catalysts.
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| 15. |
- Johannesdottir, Fjola, et al.
(författare)
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Distribution of cortical bone in the femoral neck and hip fracture: A prospective case-control analysis of 143 incident hip fractures; the AGES-REYKJAVIK Study
- 2011
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 48:6, s. 1268-1276
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Tidskriftsartikel (refereegranskat)abstract
- In this prospective nested case-control study we analyzed the circumferential differences in estimated cortical thickness (Est CTh) of the mid femoral neck as a risk factor for osteoporotic hip fractures in elderly women and men. Segmental QCT analysis of the mid femoral neck was applied to assess cortical thickness in anatomical quadrants. The superior region of the femoral neck was a stronger predictor for hip fracture than the inferior region, particularly in men. There were significant gender differences in Est CTh measurements in the control group but not in the case group. In multivariable analysis for risk of femoral neck (FN) fracture, Est CTh in the supero-anterior (SA) quadrant was significant in both women and men, and remained a significant predictor after adjustment for FN areal BMD (aBMD, dimensions g/cm(2), DXA-like), (p = 0.05 and p<0.0001, respectively). In conclusion, Est CTh in the SA quadrant best discriminated cases (n = 143) from controls (n = 298), especially in men. Cortical thinning superiorly in the hip might be of importance in determining resistance to fracture. (C) 2011 Elsevier Inc. All rights reserved.
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| 16. |
- Johannesson, Kerstin, 1955, et al.
(författare)
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Indiscriminate Males: Mating Behaviour of a Marine Snail Compromised by a Sexual Conflict?
- 2010
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 5:8, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Background In promiscuous species, male fitness is expected to increase with repeated matings in an open-ended fashion (thereby increasing number of partners or probability of paternity) whereas female fitness should level out at some optimal number of copulations when direct and indirect benefits still outweigh the costs of courtship and copulation. After this fitness peak, additional copulations would incur female fitness costs and be under opposing selection. Hence, a sexual conflict over mating frequency may evolve in species where females are forced to engage in costly matings. Under such circumstance, if females could avoid male detection, significant fitness benefits from such avoidance strategies would be predicted. Methodology/Principal Findings Among four Littorina species, one lives at very much higher densities and has a longer mating season than the other three species. Using video records of snail behaviour in a laboratory arena we show that males of the low-density species discriminate among male and female mucous trails, trailing females for copulations. In the high-density species, however, males fail to discriminate between male and female trails, not because males are unable to identify female trails (which we show using heterospecific females), but because females do not, as the other species, add a gender-specific cue to their trail. Conclusions/Significance We conclude that there is likely a sexual conflict over mating frequency in the high-density species (L. saxatilis) owing to females most likely being less sperm-limited in this species. This has favoured the evolution of females that permanently or optionally do not release a cue in the mucus to decrease excessive and costly matings resulting in unusually high frequencies of male-male copulating attempts in the wild. This is one of few examples of masking gender identity to obtain fewer matings.
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| 17. |
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| 18. |
- Johannesson, Kerstin, 1955, et al.
(författare)
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Oceanographic barriers to gene flow promote genetic subdivision of the tunicate Ciona intestinalis in a North Sea archipelago
- 2018
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Ingår i: Marine Biology. - : Springer Science and Business Media LLC. - 0025-3162 .- 1432-1793. ; 165:8
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Tidskriftsartikel (refereegranskat)abstract
- Pelagic larval development has the potential to connect populations over large geographic distances and prevent genetic structuring. The solitary tunicate Ciona intestinalis has pelagic eggs and a swimming larval stage lasting for maximum a few days, with the potential for a homogenizing gene flow over relatively large areas. In the eastern North Sea, it is found in a geomorphologically complex archipelago with a mix of fjords and open costal habitats. Here, the coastal waters are also stratified with a marked pycnocline driven by salinity and temperature differences between shallow and deep waters. We investigated the genetic structure of C. intestinalis in this area and compared it with oceanographic barriers to dispersal that would potentially reduce connectivity among local populations. Genetic data from 240 individuals, sampled in 2 shallow, and 4 deep-water sites, showed varying degrees of differentiation among samples (F (ST) = 0.0-0.11). We found no evidence for genetic isolation by distance, but two distant deep-water sites from the open coast were genetically very similar indicating a potential for long-distance gene flow. However, samples from different depths from the same areas were clearly differentiated, and fjord samples were different from open-coast sites. A biophysical model estimating multi-generation, stepping-stone larval connectivity, and empirical data on fjord water mass retention time showed the presence of oceanographic barriers that explained the genetic structure observed. We conclude that the local pattern of oceanographic connectivity will impact on the genetic structure of C. intestinalis in this region.
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| 19. |
- Johannesson, Kerstin, 1955, et al.
(författare)
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Ten years of marine evolutionary biology - challenges and achievements of a multidisciplinary research initiative
- 2023
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Ingår i: Evolutionary Applications. - : Wiley. - 1752-4571. ; 16:2, s. 530-41
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Tidskriftsartikel (refereegranskat)abstract
- The Centre for Marine Evolutionary Biology (CeMEB) at the University of Gothenburg, Sweden, was established in 2008 through a 10-year research grant of 8.7 m€ to a team of senior researchers. Today, CeMEB members have contributed >500 scientific publications, 30 PhD theses and have organised 75 meetings and courses, including 18 three-day meetings and four conferences. What are the footprints of CeMEB, and how will the centre continue to play a national and international role as an important node of marine evolutionary research? In this perspective arcticle we first look back over the 10 years of CeMEB activities and briefly survey some of the many achievements of CeMEB. We furthermore compare the initial goals, as formulated in the grant application, with what has been achieved, and discuss challenges and milestones along the way. Finally, we bring forward some general lessons that can be learnt from a research funding of this type, and we take also look ahead, discussing how CeMEB’s achievements and lessons can be used as a springboard to the future of marine evolutionary biology.
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| 20. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 21. |
- Jonsson, Amanda, et al.
(författare)
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Bioelectronic neural pixel: Chemical stimulation and electrical sensing at the same site
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:34, s. 9440-9445
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Tidskriftsartikel (refereegranskat)abstract
- Local control of neuronal activity is central to many therapeutic strategies aiming to treat neurological disorders. Arguably, the best solution would make use of endogenous highly localized and specialized regulatory mechanisms of neuronal activity, and an ideal therapeutic technology should sense activity and deliver endogenous molecules at the same site for the most efficient feedback regulation. Here, we address this challenge with an organic electronic multifunctional device that is capable of chemical stimulation and electrical sensing at the same site, at the single-cell scale. Conducting polymer electrodes recorded epileptiform discharges induced in mouse hippocampal preparation. The inhibitory neurotransmitter, γ-aminobutyric acid (GABA), was then actively delivered through the recording electrodes via organic electronic ion pump technology. GABA delivery stopped epileptiform activity, recorded simultaneously and colocally. This multifunctional “neural pixel” creates a range of opportunities, including implantable therapeutic devices with automated feedback, where locally recorded signals regulate local release of specific therapeutic agents.
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| 22. |
- Jonsson, Henric
(författare)
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Towards a Framework for Production Strategy in Construction
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The problem with low productivity increase in the construction industry is highlighted in many studies and in Sweden the need to improve productivity and client satisfaction in the construction industry has promoted a number of government investigations. One suggested way of improving productivity and client satisfaction is to move value adding activities offsite, to a more industrial environment. Compared to traditional on-site production, off-site production has been said to have many advantages such as: higher productivity, lower production cost, higher quality and shorter lead times. The trade-off when increasing the degree of off-site production is the reduced product and process flexibility. The trade-off between productivity and flexibility indicates that different production systems perform well in different areas of competition.The purpose of this research is to develop a production strategy framework for the construction industry, and more specifically for the production of multifamily residences. This framework can help construction firms to design the production system and find the right balance between productivity and flexibility. For the manufacturing industry, production strategy frameworks have been developed and shown useful when designing new or redesigning existing production systems. A corresponding framework adapted to the construction industry would be useful for construction firms when designing production systems to meet the targeted market in the most efficient way.Production strategy theory is traditionally built around two broad groups, decision categories and competitive priorities. Decision categories are areas in which a company must make decisions that are of long term importance for the production function. In this thesis focus is on the decision category traditionally named product/process technology and more specifically on the so called process choice i.e. choosing a production system that meets the demands from the targeted market in the most efficient way. To do this a classification matrix is developed that classify production systems along two dimensions, the degree of off-site assembly in one dimension and the degree of product standardisation in the other. This way of visualising the process and product characteristic has been used before, in traditional production strategy frameworks, to facilitate the process choice.For the classification matrix to be useful, the positions in the suggested classification matrix must be linked to the ability of different production systems to deliver manufacturing outputs. Therefor a performance measurement system is developed. In the process of developing classification matrix and the performance measurement system three research questions are addressed:RQ1. What dimensions can be useful, from a production strategy perspective, when classifying different production systems for the production of multifamily residences?RQ2. What manufacturing outputs/competitive priorities have to be taken into consideration when evaluating different production systems forproduction of multifamily residences?RQ3. How should the ability of a production system to deliver manufacturing outputs be measured?To answer the research questions an abductive approach has been used. The results from a literature review have been used to develop theoretical constructs. Case studies have then been used to empirically test the constructs. Thereafter the empirical data and information from additional literature reviews has then been used to further develop and refine the theoretical constructs. The findings of this research are thereby grounded in both theory and practise.There are two main contributions in this thesis. The first one is the proposed classification matrix for production systems producing multifamily residences. The classification matrix can be used as a base for production strategy reasoning in the construction industry. The second contribution is the suggested performance measurement system in which KPIs for measuring quality, delivery (speed and dependability), cost (level and dependability) and flexibility (volume, mix and expansion) have been defined.By positioning different production systems in the classification matrix and then use the defined performance measurement system, relative differences between the ability of different production systems to deliver manufacturing outputs can be exposed. The classification matrix can help companies to work with production strategy in a structured way, and to visualize the link between the market strategy and the production function of the firm in order to meet the demands from the targeted market in the most efficient way.
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| 23. |
- Jonsson, Jonathan, 1989, et al.
(författare)
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The Effect of Advanced Automatic Collision Notification (AACN) on Road Fatality Reduction in Sweden
- 2015
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Ingår i: Proceedings of the 3rd International Symposium on Future Active Safety Technology Towards Zero Traffic Accidents (FAST-zero 2015).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper aims at estimating the effect of the Advanced Automatic Collision Notification (AACN) post–crash system on road fatality reduction in Sweden. The analysis was based on the Swedish Traffic Accident Data Acquisition (STRADA) database in combination with in-depth studies of fatal accidents. Logistic regression with backward selection was used to identify relevant variables and develop a statistical model. The variables ‘admission to trauma center’, ‘age’ and ‘injury severity’ were identified as significant and by applying the final model on fatalities in passenger cars the estimated fatality reduction due to AACN was calculated. AACN was estimated to potentially reduce road fatalities by 9.6% (95% CI = -0.1-18.4%)
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| 24. |
- Jonsson, William O, et al.
(författare)
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Changes in plasma concentration of kynurenine following intake of branched-chain amino acids are not caused by alterations in muscle kynurenine metabolism.
- 2022
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Ingår i: American Journal of Physiology - Cell Physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 322, s. C49-C62
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Tidskriftsartikel (refereegranskat)abstract
- Administration of branched-chain amino acids (BCAA) has been suggested to enhance mitochondrial biogenesis, including levels of PGC-1α, which may, in turn, alter kynurenine metabolism. Ten healthy subjects performed 60 min of dynamic one-leg exercise at ~70% of Wmax on two occasions. They were in random order supplied either a mixture of BCAA or flavored water (placebo) during the experiment. Blood samples were collected during exercise and recovery, and muscle biopsies were taken from both legs before, after and 90 and 180 min following exercise. Ingestion of BCAA doubled their concentration in both plasma and muscle while causing a 30-40% reduction (P<0.05 vs. placebo) in levels of aromatic amino acids in both resting and exercising muscle during 3-h recovery. The muscle concentration of kynurenine decreased by 25% (P<0.05) during recovery, similar in both resting and exercising leg and with both supplements, although plasma concentration of kynurenine during recovery was 10% lower (P<0.05) when BCAA were ingested. Ingestion of BCAA reduced the plasma concentration of kynurenic acid by 60% (P<0.01) during exercise and recovery, while the level remained unchanged with placebo. Exercise induced a 3-4-fold increase (P<0.05) in muscle content of PGC-1a1 mRNA after 90 min of recovery under both conditions, whereas levels of KAT4 mRNA and protein were unaffected by exercise or supplement. In conclusion, the reduction of plasma levels of kynurenine and kynurenic acid caused by BCAA were not associated with any changes in the level of muscle kynurenine, suggesting that kynurenine metabolism was altered in tissues other than muscle.
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| 25. |
- Jonsson, Åsa M., 1976, et al.
(författare)
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Size‐resolved particle emission factors for individual ships
- 2011
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 38
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Tidskriftsartikel (refereegranskat)abstract
- In these experiments size‐resolved emission factors for particle number (EFPN) and mass (EFPM) have been determined for 734 individual ship passages for real‐world dilution. The method used is an extractive sampling method of the passing ship plumes where particle number/mass and CO2 were measured with high time resolution (1 Hz). The measurements were conducted on a small island located in the entrance to the port of Gothenburg (N57.6849, E11.838), the largest harbor in Scandinavia. This is an emission control area (ECA) and in close vicinity to populated areas. The average EFPN and EFPM were 2.55 ± 0.11 × 1016 (kg fuel)−1 and 2050 ± 110 mg (kg fuel)−1, respectively. The determined EF for ships with multiple passages showed a great reproducibility. Size‐resolved EFPN were peaking at small particle sizes ∼35 nm. Smaller particle sizes and hence less mass were observed by a gas turbine equipped ship compared to diesel engine equipped ships. On average 36 to 46% of the emitted particles by number were non‐volatile and 24% by mass (EFPN 1.16 ± 0.19 × 1016 [kg fuel]−1 and EFPM 488 ± 73 mg [kg fuel]−1, respectively). This study shows a great potential to gain large data‐sets regarding ship emission determining parameters that can improve current dispersion modeling for health assessments on local and regional scales. The global contributions of total and non‐volatile particle mass from shipping using this extensive data‐set from an ECA were estimated to be at least 0.80 Tgy−1 and 0.19 Tgy−1.
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| 26. |
- Kaldvee, Billy, et al.
(författare)
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Room-Fire Characterization Using Highly Range-Resolved Picosecond Lidar Diagnostics and CFD Simulations
- 2013
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Ingår i: Combustion Science and Technology. - : Informa UK Limited. - 1563-521X .- 0010-2202. ; 185:5, s. 749-765
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Tidskriftsartikel (refereegranskat)abstract
- In fire safety engineering, the use of computational fluid dynamics (CFD) allows for detailed multidimensional calculations of important parameters, for example, temperature. However, increasing use of CFD models puts requirements on experimental validation, a challenge for many measurement techniques under harsh fire conditions. In this work, laser-based picosecond light detection and ranging (ps-lidar) was used for remote measurements in a 1/2-scale ISO 9705 room containing either a methanol pool fire or a methane diffusion flame. Spatially resolved Rayleigh thermometry was conducted in the vertical door plane and in a horizontal plane inside the room. Temperatures obtained by ps-lidar are compared with values from thermocouples located in the doorway as well as results from CFD simulations. The technique allows for quantitative thermometry provided that minimal particle scattering interferences are present. Measurements of detailed distributions of temperature and particulates clearly demonstrate the potential of ps-lidar for diagnostics in large-scale combustion.
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| 27. |
- Kaushik, Sandeep S., et al.
(författare)
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Region of interest focused MRI to synthetic CT translation using regression and segmentation multi-task network
- 2023
-
Ingår i: Physics in Medicine and Biology. - : Institute of Physics (IOP). - 0031-9155 .- 1361-6560. ; 68:19
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: In MR-only clinical workflow, replacing CT with MR image is of advantage for workflow efficiency and reduces radiation to the patient. An important step required to eliminate CT scan from the workflow is to generate the information provided by CT via an MR image. In this work, we aim to demonstrate a method to generate accurate synthetic CT (sCT) from an MR image to suit the radiation therapy (RT) treatment planning workflow. We show the feasibility of the method and make way for a broader clinical evaluation.Approach: We present a machine learning method for sCT generation from zero-echo-time (ZTE) MRI aimed at structural and quantitative accuracies of the image, with a particular focus on the accurate bone density value prediction. The misestimation of bone density in the radiation path could lead to unintended dose delivery to the target volume and results in suboptimal treatment outcome. We propose a loss function that favors a spatially sparse bone region in the image. We harness the ability of the multi-task network to produce correlated outputs as a framework to enable localization of region of interest (RoI) via segmentation, emphasize regression of values within RoI and still retain the overall accuracy via global regression. The network is optimized by a composite loss function that combines a dedicated loss from each task.Main results: We have included 54 brain patient images in this study and tested the sCT images against reference CT on a subset of 20 cases. A pilot dose evaluation was performed on 9 of the 20 test cases to demonstrate the viability of the generated sCT in RT planning. The average quantitative metrics produced by the proposed method over the test set were-(a) mean absolute error (MAE) of 70 ± 8.6 HU; (b) peak signal-to-noise ratio (PSNR) of 29.4 ± 2.8 dB; structural similarity metric (SSIM) of 0.95 ± 0.02; and (d) Dice coefficient of the body region of 0.984 ± 0.Significance: We demonstrate that the proposed method generates sCT images that resemble visual characteristics of a real CT image and has a quantitative accuracy that suits RT dose planning application. We compare the dose calculation from the proposed sCT and the real CT in a radiation therapy treatment planning setup and show that sCT based planning falls within 0.5% target dose error. The method presented here with an initial dose evaluation makes an encouraging precursor to a broader clinical evaluation of sCT based RT planning on different anatomical regions.
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| 28. |
- Kinnby, Alexandra, 1990, et al.
(författare)
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Factors affecting formation of adventitious branches in the seaweeds Fucus vesiculosus and F. radicans
- 2019
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Ingår i: Bmc Ecology. - : Springer Science and Business Media LLC. - 1472-6785. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn the brackish Baltic Sea, shedding of adventitious branches is central to asexual recruitment of new thalli in the brown algae Fucus vesiculosus and F. radicans. To test which factors influence the formation of adventitious branches in brackish and in more marine conditions, we sampled 29 Fucus sites in the Baltic Sea (salinity 3-11) and 18 sites from the Danish straits, Kattegat, Skagerrak, and the North Sea (salinity 15-35). Separately for each area, we used structural equation modelling to determine which of eight predictor factors (phosphate, nitrate, chlorophyll-a (as a proxy for turbidity), temperature, salinity, oxygen, grazing pressure, and thallus area) best explained observed numbers of adventitious branches.ResultsIn more marine waters, high yearly average values of phosphate, salinity and turbidity had positive effects on the formation of adventitious branches. In brackish-waters, however, high numbers of adventitious branches were found in areas with low yearly average values of temperature, salinity and oxygen. Grazing intensity had no significant effect in either of the two study areas, contrasting findings from studies in other areas. In areas with both sexually and asexually reproducing Fucus individuals, clones had on average more adventitious branches than unique genotypes, although there was strong variation among clonal lineages.ConclusionThis study is the first to investigate multiple potential drivers of formation of adventitious branches in natural populations of Fucus. Our results suggest that several different factors synergistically and antagonistically affect the growth of adventitious branches in a complex way, and that the same factor (salinity) can have opposing effects in different areas.
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| 29. |
- Koch, Alina, 1990-
(författare)
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Characterisation of PFASs and Organofluorine in Freshwater Environments : Transfer from water to land via emergent aquatic insects
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Per- and polyfluoroalkyl substances (PFASs) are anthropogenic contaminants of emerging concern, because many are highly persistent to degradation and have been linked to adverse effects in humans as well as their ubiquitous spread in aquatic environments. This thesis investigated distribution of PFASs and organofluorine in freshwater environments impacted by PFAS point sources. The main focus was to study potential transfer of PFASs from freshwater systems to riparian zones via emergent aquatic insects as well as potential impacts on riparian invertebrate consumers.Comprehensive sets of samples, such as aquatic insect larvae, emergent aquatic insects, terrestrial invertebrate consumers and water were collected from mainly two sites in Sweden, Ronneby Airport and Kvarntorp industrial area. Homologue and branched isomer profiles, estimates of mass discharges, bioaccumulation factors, stable isotope analysis of carbon and nitrogen as well as organofluorine mass balance and suspect screening analysis were used to characterize the distribution of PFASs in these freshwater environments including their aquatic and terrestrial invertebrate food webs.Results revealed elevated PFAS concentrations in emergent aquatic insects and riparian invertebrate consumers, especially in spiders. Calculated biodriven transfers indicated that impact on riparian insectivores could be substantial on a local and seasonal scale. Furthermore, PFAS concentrations in terrestrial consumers were related to aquatic-based diet and trophic levels, indicating that biomagnification was a major pathway of uptake for some PFASs. Organofluorine mass balance could be closed for most aquatic and for some terrestrial invertebrates from the Ronneby site by target PFAS analysis, whereas a fraction of ~50% in surface water was unidentified organofluorine. Most new PFASs, tentatively identified by suspect screening, were found in water samples and given that contamination occurred decades ago suggested that those PFASs, mainly perfluoroalkyl sulfonamide-based PFASs, are highly water soluble and persistent.
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| 30. |
- Leander, Johan, et al.
(författare)
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Guiding downstream migrating Atlantic salmon (Salmo salar) and brown trout (Salmo trutta) of different life stages in a large river using bubbles
- 2024
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Ingår i: Rivers Research and Applications. - : John Wiley & Sons. - 1535-1459 .- 1535-1467. ; 40:1, s. 107-115
-
Tidskriftsartikel (refereegranskat)abstract
- Salmonid repeat spawners are precious individuals for wild populations due to their high fecundity and previous spawning experience, making them important in environmental policy. However, repeat spawners rarely exist above hydropower dams in regulated rivers as the mortality of post-spawners (kelts) when passing through turbines during downstream migration is very high. To mitigate this problem, there are different technical solutions that potentially guide fish toward available fishways. Bubble barriers represent one alternative to costly physical guiding structures, but the efficiency of bubbles for guiding downstream migrating kelts has not been tested. In this study, we evaluate a 100 m long bubble barrier in guiding salmonids—both smolts and kelts—away from the main current and toward an alternative fishway in Ume River, a large regulated river in northern Sweden. We used both acoustic telemetry and sonar to measure the guiding effect of the bubble barrier for downstream migrating fish. We found that more than twice as many salmonids chose the alternative fishway when the bubble barrier was turned on. This was true both for smolts and kelts, suggesting that bubble barriers can be used to guide salmonids of different life stages in rivers with flow rates over 500 m3 s−1. Indeed, our study indicates that bubble barriers are low-cost structures that could be rapidly applied in many regulated rivers to support salmonid migration.
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| 31. |
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| 32. |
- Lessard, Christopher J., et al.
(författare)
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Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome
- 2013
-
Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA. - 1061-4036 .- 1546-1718. ; 45:11, s. 1284-
-
Tidskriftsartikel (refereegranskat)abstract
- Sjogrens syndrome is a common autoimmune disease (affecting similar to 0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjogrens syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (P-meta = 7.65 x 10(-114)), we establish associations with IRF5-TNPO3 (P-meta = 2.73 x 10(-19)), STAT4 (Pmeta = 6.80 x 10-15), IL12A (P-meta = 1.17 x 10(-10)), FAM167ABLK (P-meta = 4.97 x 10(-10)), DDX6-CXCR5 (P-meta = 1.10 x 10(-8)) and TNIP1 (P-meta = 3.30 x 10(-8)). We also observed suggestive associations (P-meta andlt; 5 x 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjogrens syndrome.
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| 33. |
- Lind, Ulrika, et al.
(författare)
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Analysis of aquaporins from the euryhaline barnacle Balanus improvisus reveals differential expression in response to changes in salinity
- 2017
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Barnacles are sessile macro-invertebrates, found along rocky shores in coastal areas worldwide. The euryhaline bay barnacle Balanus improvisus (Darwin, 1854) (= Amphibalanus improvisus) can tolerate a wide range of salinities, but the molecular mechanisms underlying the osmoregulatory capacity of this truly brackish species are not well understood. Aquaporins are pore-forming integral membrane proteins that facilitate transport of water, small solutes and ions through cellular membranes, and that have been shown to be important for osmoregulation in many organisms. The knowledge of the function of aquaporins in crustaceans is, however, limited and nothing is known about them in barnacles. We here present the repertoire of aquaporins from a thecostracan crustacean, the barnacle B. improvisus, based on genome and transcriptome sequencing. Our analyses reveal that B. improvisus contains eight genes for aquaporins. Phylogenetic analysis showed that they represented members of the classical water aquaporins (Aqp1, Aqp2), the aquaglyceroporins (Glp1, Glp2), the unorthodox aquaporin (Aqp12) and the arthropod-specific big brain aquaporin (Bib). Interestingly, we also found two big brain-like proteins (BibL1 and BibL2) constituting a new group of aquaporins not yet described in arthropods. In addition, we found that the two water-specific aquaporins were expressed as C-terminal splice variants. Heterologous expression of some of the aquaporins followed by functional characterization showed that Aqp1 transported water and Glp2 water and glycerol, agreeing with the predictions of substrate specificity based on 3D modeling and phylogeny. To investigate a possible role for the B. improvisus aquaporins in osmoregulation, mRNA expression changes in adult barnacles were analysed after long-term acclimation to different salinities. The most pronounced expression difference was seen for AQP1 with a substantial (>100-fold) decrease in the mantle tissue in low salinity (3 PSU) compared to high salinity (33 PSU). Our study provides a base for future mechanistic studies on the role of aquaporins in osmoregulation. © 2017 Lind et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 34. |
- Lind, Ulrika, et al.
(författare)
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Molecular Characterization of the alpha-Subunit of Na+/K+ ATPase from the Euryhaline Barnacle Balanus improvisus Reveals Multiple Genes and Differential Expression of Alternative Splice Variants
- 2013
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10
-
Tidskriftsartikel (refereegranskat)abstract
- The euryhaline bay barnacle Balanus improvisus has one of the broadest salinity tolerances of any barnacle species. It is able to complete its life cycle in salinities close to freshwater (3 PSU) up to fully marine conditions (35 PSU) and is regarded as one of few truly brackish-water species. Na+/K+ ATPase (NAK) has been shown to be important for osmoregulation when marine organisms are challenged by changing salinities, and we therefore cloned and examined the expression of different NAKs from B. improvisus. We found two main gene variants, NAK1 and NAK2, which were approximately 70% identical at the protein level. The NAK1 mRNA existed in a long and short variant with the encoded proteins differing only by 27 N-terminal amino acids. This N-terminal stretch was coded for by a separate exon, and the two variants of NAK1 mRNAs appeared to be created by alternative splicing. We furthermore showed that the two NAK1 isoforms were differentially expressed in different life stages and in various tissues of adult barnacle, i.e the long isoform was predominant in cyprids and in adult cirri. In barnacle cyprid larvae that were exposed to a combination of different salinities and pCO(2) levels, the expression of the long NAK1 mRNA increased relative to the short in low salinities. We suggest that the alternatively spliced long variant of the Nak1 protein might be of importance for osmoregulation in B. improvisus in low salinity conditions.
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| 35. |
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| 36. |
- Lyamin, Nikita, 1989-, et al.
(författare)
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Real-time Detection of Denial-of-Service Attacks in IEEE 802.11p Vehicular Networks
- 2014
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Ingår i: IEEE Communications Letters. - Piscataway, NJ : IEEE Press. - 1089-7798 .- 1558-2558. ; 18:1, s. 110-113
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Tidskriftsartikel (refereegranskat)abstract
- A method for real-time detection of Denial-of-Service (DoS) attacks in IEEE 802.11p vehicular ad-hoc networks (VANETs) is proposed. The study is focused on the "jamming" of periodic position messages (beacons) exchanged by vehicles in a platoon. Probabilities of attack detection and false alarm are estimated for two different attacker models. © 2014 IEEE
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| 37. |
- Metzger, Jonathan, 1978-
(författare)
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I köttbullslandet : Konstruktionen av svenskt och utländskt på det kulinariska fältet
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this doctorate thesis is to investigate the historical discursive construction of swedishness and foreignness in the Swedish culinary field, primarily during the period of 1900-1970, and to relate the changes in the articulation of these concepts to the overarching ideological shifts during this time-period. To achieve this objective a conceptual apparatus inspired by cultural studies, discourse analysis and rhetorical analysis is employed upon the primary material, which consists of Swedish- and foreign-signified cookbooks published in Sweden during the period of 1600-1970. It is further argued that communities of consumption, such as nationalized culinary cultures, are discursive constructions and that actors attempt to write individuals into these communities through the articulation of nationalized subject positions. In the thesis it is thus investigated how, when and perhaps why certain actors on a field attempt to discursively construct such communities of consumption during a certain era. The chapters 2-5 of the thesis contain analyses of the historical construction of foreignness on the Swedish cultural field. Here various trends are traced in the construction of individual foreign cuisines, both in relation to each other and to the concept of culinary swedishness. An analysis is also made of the varied rhetoric that is used to promote foreign-signified cooking to the Swedish public during the examined time-period. It is concluded that the variations in rhetoric seem to covariate with larger ideological shifts in Swedish society. Chapters 6 and 7 specifically examine the construction of swedishness in the culinary field by focusing on the construction of national culinary icons such as the Smörgåsbord and Husmanskost and also on the evolution of the ideas of a distinct Swedish palate and a Swedish national cuisine. As a result of this investigation the perhaps surprisingly late codification of a Swedish national cuisine during the 1960’s is noted. It is further argued that this development coincides with a shift in the popular mood, where “the Swedish way of life” increasingly comes to be seen as threatened by external forces such as foreign influences and modernity, why certain actors on the culinary field express a necessity for the codification of what is perceived of as the “true Swedish cuisine”. A paradoxical result of this urge for preservation is the construction of new cultural phenomena dressed in a traditionalist and nationalist rhetoric that anchors them in a distant past.
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| 38. |
- Rosengren, Anders, et al.
(författare)
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Reduced Insulin Exocytosis in Human Pancreatic β-cells With Gene Variants Linked to Type 2 Diabetes.
- 2012
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 61:7, s. 1726-1733
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Tidskriftsartikel (refereegranskat)abstract
- The majority of genetic risk variants for type 2 diabetes (T2D) affect insulin secretion, but the mechanisms through which they influence pancreatic islet function remain largely unknown. We functionally characterized human islets to determine secretory, biophysical, and ultrastructural features in relation to genetic risk profiles in diabetic and nondiabetic donors. Islets from donors with T2D exhibited impaired insulin secretion, which was more pronounced in lean than obese diabetic donors. We assessed the impact of 14 disease susceptibility variants on measures of glucose sensing, exocytosis, and structure. Variants near TCF7L2 and ADRA2A were associated with reduced glucose-induced insulin secretion, whereas susceptibility variants near ADRA2A, KCNJ11, KCNQ1, and TCF7L2 were associated with reduced depolarization-evoked insulin exocytosis. KCNQ1, ADRA2A, KCNJ11, HHEX/IDE, and SLC2A2 variants affected granule docking. We combined our results to create a novel genetic risk score for β-cell dysfunction that includes aberrant granule docking, decreased Ca(2+) sensitivity of exocytosis, and reduced insulin release. Individuals with a high risk score displayed an impaired response to intravenous glucose and deteriorating insulin secretion over time. Our results underscore the importance of defects in β-cell exocytosis in T2D and demonstrate the potential of cellular phenotypic characterization in the elucidation of complex genetic disorders.
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| 39. |
- Sandell, Mikael, et al.
(författare)
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Endovascular Device for Endothelial Cell Sampling
- 2022
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Ingår i: Advanced NanoBiomed Research. - : Wiley. - 2699-9307 .- 2699-9307. ; 2:10, s. 2200023-2200023
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial cells play an important role in several vascular diseases, and molecular analysis of these cells could provide valuable information on underlying tissue status. However, no clinically established procedure for harvesting endothelial cells exists. A micro-3D-printed device adapted for endovascular techniques to harvest endothelial cells for transcriptomic analysis is presented. In vivo evaluation in swine (n = 6) yielded tissue samples in 60 out of 65 cases, of which 80% show a substantial amount of tissue. The cytological evaluation indicates high selectivity towards endothelial cells, and RNA-sequencing shows gene expression signatures consistent with vascular tissue. It is found that there are no short-term safety risks compared to operation with a control wire of equal dimensions and acute complications are not detected. If translated to clinical use, the device could enable increased understanding of early-stage endothelial cell-mediated disease progression and earlier diagnosis of diseases such as atherosclerosis.
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| 40. |
- Taneera, Jalal, et al.
(författare)
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A Systems Genetics Approach Identifies Genes and Pathways for Type 2 Diabetes in Human Islets
- 2012
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 16:1, s. 122-134
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Tidskriftsartikel (refereegranskat)abstract
- Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Using 48 genes located near T2D risk variants, we identified gene coexpression and protein-protein interaction networks that were strongly associated with islet insulin secretion and HbA(1c). We integrated our data to form a rank list of putative T2D genes, of which CHL1, LRFN2, RASGRP1, and PPM1K were validated in INS-1 cells to influence insulin secretion, whereas GPR120 affected apoptosis in islets. Expression variation of the top 20 genes explained 24% of the variance in HbA(1c) with no claim of the direction. The data present a global map of genes associated with islet dysfunction and demonstrate the value of systems genetics for the identification of genes potentially involved in T2D.
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| 41. |
- Thakur, Rohit, et al.
(författare)
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Transcriptomic analysis reveals prognostic molecular signatures of stage I melanoma
- 2019
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 25:24, s. 7424-7435
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Previously identified transcriptomic signatures have been based on primary and metastatic melanomas with relatively few American Joint Committee on Cancer (AJCC) stage I tumors, given difficulties in sampling small tumors. The advent of adjuvant therapies has highlighted the need for better prognostic and predictive biomarkers, especially for AJCC stage I and stage II disease. Experimental Design: A total of 687 primary melanoma transcriptomes were generated from the Leeds Melanoma Cohort (LMC). The prognostic value of existing signatures across all the AJCC stages was tested. Unsupervised clustering was performed, and the prognostic value of the resultant signature was compared with that of sentinel node biopsy (SNB) and tested as a biomarker in three published immunotherapy datasets. Results: Previous Lund and The Cancer Genome Atlas signatures predicted outcome in the LMC dataset (P = 10¯8 to 10¯4) but showed a significant interaction with AJCC stage (P = 0.04) and did not predict outcome in stage I tumors (P = 0.3–0.7). Consensus-based classification of the LMC dataset identified six classes that predicted outcome, notably in stage I disease. LMC class was a similar indicator of prognosis when compared with SNB, and it added prognostic value to the genes reported by Gerami and colleagues. One particular LMC class consistently predicted poor outcome in patients receiving immunotherapy in two of three tested datasets. Biological characterization of this class revealed high JUN and AXL expression and evidence of epithelial-to-mesenchymal transition. Conclusions: A transcriptomic signature of primary melanoma was identified with prognostic value, including in stage I melanoma and in patients undergoing immunotherapy.
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| 42. |
- Venermo, Maarit, et al.
(författare)
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Sex Related Differences in Indication and Procedural Outcomes of Carotid interventions in VASCUNET
- 2023
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 66:1, s. 7-14
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Tidskriftsartikel (refereegranskat)abstract
- Objective:It has been suggested that peri-operative complications after carotid surgery may be higher in women than in men. This assumption may affect the treatment patterns, and it is thus possible that carotid endarterectomy (CEA) is provided to women less often. The aim of the current VASCUNET study was to determine sex related differences in operative risk in routine clinical practice among non-selected patients undergoing carotid revascularisation.Methods:Data on CEA and carotid artery stenting (CAS) from 14 vascular registries were collected and amalgamated. Comprehensive data were available for 223 626 carotid artery procedures; these were analysed overall and by country. The primary outcome was any stroke and or death within 30 days of carotid revascularisation. Secondary outcomes were stroke, death, or any major cardiac event or haemorrhage leading to re-operation.Results:Of the procedures, 34.8% were done in women. The proportion of CEA for asymptomatic stenosis compared with symptomatic stenosis was significantly higher among women than men (38.4% vs. 36.9%, p < .001).The proportion of octogenarians was higher among women than men who underwent CEA in both asymptomatic (21.2% vs. 19.9%) and symptomatic patients (24.3% vs. 21.4%). In the unadjusted analysis of symptomatic and asymptomatic patients, there were no significant differences between men and women in the rate of post-operative combined stroke and or death, any major cardiac event, or combined death, stroke, and any major cardiac event after CEA. Also, after stenting for asymptomatic or symptomatic carotid stenosis, there were no significant differences between men and women in the rate of post-operative complications. In adjusted analyses, sex was not significantly associated with any of the end points. Higher age and CAS vs. CEA were independently associated with all four end points.Conclusion:This study confirmed that, in a large registry among non-selected patients, no significant sex related differences were found in peri-operative complication rates after interventions for carotid stenosis.
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| 43. |
- Wain, Louise V, et al.
(författare)
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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
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| 44. |
- Williamson, Adam, et al.
(författare)
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Controlling Epileptiform Activity with Organic Electronic Ion Pumps
- 2015
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Ingår i: Advanced Materials. - : Wiley-VCH Verlag. - 0935-9648 .- 1521-4095. ; 27:20, s. 3138-3144
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Tidskriftsartikel (refereegranskat)abstract
- In treating epilepsy, the ideal solution is to act at a seizure's onset, but only in the affected regions of the brain. Here, an organic electronic ion pump is demonstrated, which directly delivers on-demand pure molecules to specific brain regions. State-of-the-art organic devices and classical pharmacology are combined to control pathological activity in vitro, and the results are verified with electrophysiological recordings.
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| 45. |
- Wrange, Anna-Lisa, 1981, et al.
(författare)
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Importance of plasticity and local adaptation for coping with changing salinity in coastal areas: a test case with barnacles in the Baltic Sea
- 2014
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Salinity plays an important role in shaping coastal marine communities. Near-future climate predictions indicate that salinity will decrease in many shallow coastal areas due to increased precipitation; however, few studies have addressed this issue. The ability of ecosystems to cope with future changes will depend on species’ capacities to acclimatise or adapt to new environmental conditions. Here, we investigated the effects of a strong salinity gradient (the Baltic Sea system – Baltic, Kattegat, Skagerrak) on plasticity and adaptations in the euryhaline barnacle Balanus improvisus. We used a common-garden approach, where multiple batches of newly settled barnacles from each of three different geographical areas along the Skagerrak-Baltic salinity gradient were exposed to corresponding native salinities (6, 15 and 30 PSU), and phenotypic traits including mortality, growth, shell strength, condition index and reproductive maturity were recorded. Results We found that B. improvisus was highly euryhaline, but had highest growth and reproductive maturity at intermediate salinities. We also found that low salinity had negative effects on other fitness-related traits including initial growth and shell strength, although mortality was also lowest in low salinity. Overall, differences between populations in most measured traits were weak, indicating little local adaptation to salinity. Nonetheless, we observed some population-specific responses – notably that populations from high salinity grew stronger shells in their native salinity compared to the other populations, possibly indicating adaptation to differences in local predation pressure. Conclusions Our study shows that B. improvisus is an example of a true brackish-water species, and that plastic responses are more likely than evolutionary tracking in coping with future changes in coastal salinity.
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| 46. |
- Wrange, Anna-Lisa, 1981, et al.
(författare)
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The Story of a Hitchhiker: Population Genetic Patterns in the Invasive Barnacle Balanus (Amphibalanus) improvisus Darwin 1854
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the ecological and evolutionary forces that determine the genetic structure and spread of invasive species is a key component of invasion biology. The bay barnacle, Balanus improvisus (= Amphibalanus improvisus), is one of the most successful aquatic invaders worldwide, and is characterised by broad environmental tolerance. Although the species can spread through natural larval dispersal, human-mediated transport through (primarily) shipping has almost certainly contributed to the current global distribution of this species. Despite its worldwide distribution, little is known about the phylogeography of this species. Here, we characterize the population genetic structure and model dispersal dynamics of the barnacle B. improvisus, and describe how human-mediated spreading via shipping as well as natural larval dispersal may have contributed to observed genetic variation. We used both mitochondrial DNA (cytochrome c oxidase subunit I: COI) and nuclear microsatellites to characterize the genetic structure in 14 populations of B. improvisus on a global and regional scale (Baltic Sea). Genetic diversity was high in most populations, and many haplotypes were shared among populations on a global scale, indicating that longdistance dispersal (presumably through shipping and other anthropogenic activities) has played an important role in shaping the population genetic structure of this cosmopolitan species. We could not clearly confirm prior claims that B. improvisus originates from the western margins of the Atlantic coasts; although there were indications that Argentina could be part of a native region. In addition to dispersal via shipping, we show that natural larval dispersal may play an important role for further colonisation following initial introduction.
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