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1.	Frazier-Wood, Alexis C., et al. (författare) Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses 2016 Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624- Tidskriftsartikel (refereegranskat)abstract Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
2.	Hardman, Scott, et al. (författare) Driving the Market for Plug-in Vehicles - Understanding Financial Purchase Incentives 2017 Ingår i: UC Davis, International EV Policy Council. Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
3.	Hardman, Scott, et al. (författare) Exploring the Role of Plug-In Hybrid Electric Vehicles in Electrifying Passenger Transportation 2019 Rapport (övrigt vetenskapligt/konstnärligt)
4.	Mattsson, Johanna S. M., et al. (författare) ALK Rearrangements in Non-Small Cell Lung Cancer : Comprehensive Integration of Genomic, Gene Expression and Protein Analysis 2015 Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 10:9, s. S298-S298 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
5.	Mattsson, Johanna Sofia Margareta, 1985-, et al. (författare) Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer 2016 Ingår i: BMC Cancer. - London, United Kingdom : Springer Science and Business Media LLC. - 1471-2407. ; 16 Tidskriftsartikel (refereegranskat)abstract Background: Identification of targetable EML4-ALK fusion proteins has revolutionized the treatment of a minor subgroup of non-small cell lung cancer (NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded as the gold standard for detection of ALK rearrangements, ALK immunohistochemistry (IHC) is often used as screening tool in clinical practice. In order to unbiasedly analyze the diagnostic impact of such a screening strategy, we compared ALK IHC with ALK FISH in three large representative Swedish NSCLC cohorts incorporating clinical parameters and gene expression data.Methods: ALK rearrangements were detected using FISH on tissue microarrays (TMAs), including tissue from 851 NSCLC patients. In parallel, ALK protein expression was detected using IHC, applying the antibody clone D5F3 with two different protocols (the FDA approved Ventana CDx assay and our in house Dako IHC protocol). Gene expression microarray data (Affymetrix) was available for 194 patients.Results: ALK rearrangements were detected in 1.7% in the complete cohort and 2.0% in the non-squamous cell carcinoma subgroup. ALK protein expression was observed in 1.9% and 1.5% when applying the Ventana assay or the in house Dako protocol, respectively. The specificity and accuracy of IHC was high (>99%), while the sensitivity was between 69% (Ventana) and 62% (in house Dako protocol). Furthermore, only 67% of the ALK IHC positive cases were positive in both IHC assays. Gene expression analysis revealed that 6/194 (3%) tumors showed high ALK gene expression (≥6AU) and of them only three were positive by either FISH or IHC.Conclusion: The overall frequency of ALK rearrangements based on FISH was lower than previously reported. The sensitivity of both IHC assays was low, and the concordance between the FISH and the IHC assays poor, questioning current strategies to screen with IHC prior to FISH or completely replace FISH by IHC.
6.	Mattsson, Johanna Sofia Margareta, 1985-, et al. (författare) Prognostic impact of COX-2 in non-small cell lung cancer : a comprehensive compartment-specific evaluation of tumor and stromal cell expression 2015 Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 356:2, s. 837-845 Tidskriftsartikel (refereegranskat)abstract Cyclooxygenase-2 (COX-2) is an enzyme that has been extensively investigated as a prognostic marker in cancer. In non-small cell lung cancer (NSCLC) previous results regarding the prognostic impact of COX-2 expression are inconsistent. Therefore we evaluated the association between transcript levels and overall survival in nine publicly available gene expression data sets (total n = 1337) and determined in situ compartment-specific tumor and stromal cell protein expression in two independent cohorts (n = 616). Gene expression did not show any correlation with clinical parameters or with overall survival. Protein expression in tumor and stromal cells did not correlate with any clinical parameter or with overall survival in one of the analyzed cohorts, while a significant association of high stromal expression with longer survival was observed in both univariate and multivariate analysis in the other cohort. Stromal expression of COX-2 has not been separately evaluated in NSCLC previously and may be a subject of further investigation, whereas the presented findings from this comprehensive compartment specific evaluation clearly reject the hypothesis of COX-2 tumor cell expression having a prognostic value in NSCLC. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
7.	Smith, Jennifer A, et al. (författare) Genome-wide association study identifies 74 loci associated with educational attainment 2016 Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542 Tidskriftsartikel (refereegranskat)abstract Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
8.	Adams Lyngbäck, Liz, 1966- (författare) Experiences, networks and uncertainty : parenting a child who uses a cochlear implant 2016 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The aim of this dissertation project is to describe the ways people experience parenting a deaf child who uses a cochlear implant. Within a framework of social science studies of disability this is done by combining approaches using ethnographic and netnographic methods of participant observation with an interview study. Interpretations are based on the first-person perspective of 19 parents against the background of their related networks of social encounters of everyday life. The netnographic study is presented in composite conversations building on exchanges in 10 social media groups, which investigates the parents’ meaning-making in interaction with other parents with similar living conditions. Ideas about language, technology, deafness, disability, and activism are explored. Lived parenting refers to the analysis of accounts of orientation and what 'gets done' in respect to these ideas in situations where people utilize the senses differently. In the results, dilemmas surrounding language, communication and cochlear implantation are identified and explored. The dilemmas extend from if and when to implant, to decisions about communication modes, intervention approaches, and schools. An important finding concerns the parents’ orientations within the dilemmas, where most parents come up against antagonistic conflicts. There are also examples found of a development process in parenting based on lived, in-depth experiences of disability and uncertainty which enables parents to transcend the conflictive atmosphere. This process is analyzed in terms of a social literacy of dis/ability.
9.	Ahnesjö, Jonas, 1969-, et al. (författare) Benefits of outdoor exercise and recovery outdoors in elderly 2019 Ingår i: HEPA Europe, Odense, Denmark, August 28-30, 2019. ; , s. 38-38 Konferensbidrag (refereegranskat)abstract Purpose: The purpose of this study was to test the hypothesis that the ”outdoors” has an added health effect on top of that of physical activity. This hypothesis is based on the fairly extensive volume of evidens suggesting that the outdoor environment is beneficial for overall health. We, however, consider most previous studies insufficiently designed in order to draw causal relationship between spending time outdoors and examined health parameters. In this study we state that our experimental design allows us to do just that. Methods:In this randomized cross-over experimental design, 49 healthy subjects (+65 years, 27 female) performed a standardized submaximal bike ergometer test in three different environments (indoors, simulated outdoors and outdoors). The test consisted of 20 minutes cycling and subjects were instructed to stay between 11-13 at the Borg RPE scale (i.e. moderate intensity). Each test was followed by two hours of passive recovery. We measured power output, heart rate, lactate and counts of five fractions (lymphocytes, monocytes, neutrophiles, basophiles and eosinophiles) of white blood cells (leukocytes) in circulation. Results:Our results revealed that the outdoor treatment resulted in higher levels of lactate, higher heart rate and higher power output despite that there were no differences in Borg RPE-rating between the treatments. The white blood cell analysis showed an increase of circulating leukocytes in almost all fractions immediately post exercise in all treatments. Numbers decreased rapidly post exercise and the lymphocyte numbers stayed well under baseline for more than one hour during recovery. This is referred to as an “open window” where the immune function is temporarily suppressed and there is an elevated risk of infection of primarily URTI. Conclusions:Our results not only suggest that exercise is more efficient out of doors such that more exercise/effort is obtained but also that recovery outdoors may be a way to decrease the risk of infections due to exercise induced immune suppression. The risk of getting an infection is known to be generally lower out of doors. Taken together, our results support the notion that exercising and spending time outdoors indeed is beneficial for health in senior citizens.
10.	Andersson, Evelyn, et al. (författare) Genetics of response to cognitive behavior therapy in adults with major depression : a preliminary report 2019 Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 24:4, s. 484-490 Tidskriftsartikel (refereegranskat)abstract Major depressive disorder is heritable and a leading cause of disability. Cognitive behavior therapy is an effective treatment for major depression. By quantifying genetic risk scores based on common genetic variants, the aim of this report was to explore the utility of psychiatric and cognitive trait genetic risk scores, for predicting the response of 894 adults with major depressive disorder to cognitive behavior therapy. The participants were recruited in a psychiatric setting, and the primary outcome score was measured using the Montgomery Asberg Depression Rating Scale-Self Rated. Single-nucleotide polymorphism genotyping arrays were used to calculate the genomic risk scores based on large genetic studies of six phenotypes: major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, intelligence, and educational attainment. Linear mixed-effect models were used to test the relationships between the six genetic risk scores and cognitive behavior therapy outcome. Our analyses yielded one significant interaction effect (B = 0.09, p < 0.001): the autism spectrum disorder genetic risk score correlated with Montgomery Asberg Depression Rating Scale-Self Rated changes during treatment, and the higher the autism spectrum disorder genetic load, the less the depressive symptoms decreased over time. The genetic risk scores for the other psychiatric and cognitive traits were not related to depressive symptom severity or change over time. Our preliminary results indicated, as expected, that the genomics of the response of patients with major depression to cognitive behavior therapy were complex and that future efforts should aim to maximize sample size and limit subject heterogeneity in order to gain a better understanding of the use of genetic risk factors to predict treatment outcome.
11.	Brouder, Patrick, et al. (författare) Hyper-production : a new metric of multifinctionality 2015 Ingår i: European Countryside. - : Walter de Gruyter. - 1803-8417. ; 7:3, s. 134-143 Tidskriftsartikel (refereegranskat)abstract Multifunctionality has emerged as the dominant framework for understanding rural socioeconomic landscapes. The central claim of multifunctionality – that rural regions need to be understood as being made up of more than just traditional uses – has led to the incorporation of new rural activities into regional development plans, e.g., tourism. In some places, such post-productive activity is perceived to be slowly replacing productive uses of the land, e.g., agriculture/forestry. However, there is limited empirical evidence to support such claims. Drawing on previous research and data from the Swedish countryside this paper shows that, even as the number of persons employed within traditional activities decreases, the economic output per areal unit and per labour hour is increasing over time and traditional uses still occupy the majority of rural space. Hyper-production is introduced as a new metric for understanding multifunctional regions going forward. The complementary union of economic mainstays, such as agriculture, and newer activities with more quality-of-life benefits, such as tourism, is highlighted in terms of economic diversification, job creation and local social capital development, while the conflict-prone intersection of these two modes is also acknowledged. Understanding hyper-production as a key metric of multifunctionality is thus argued as integral to planning and developing resilient rural regions now and for the future.
12.	Colleoni, Marco, et al. (författare) Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. 2018 Ingår i: The Lancet. Oncology. - : Elsevier. - 1474-5488 .- 1470-2045. ; 19:1, s. 127-138 Tidskriftsartikel (refereegranskat)abstract In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women.We did the multicentre, open-label, randomised, parallel, phase 3 SOLE trial in 240 centres (academic, primary, secondary, and tertiary care centres) in 22 countries. We enrolled postmenopausal women of any age with hormone receptor-positive, lymph node-positive, and operable breast cancer for which they had undergone local treatment (surgery with or without radiotherapy) and had completed 4-6 years of adjuvant endocrine therapy. They had to be clinically free of breast cancer at enrolment and without evidence of recurrent disease at any time before randomisation. We randomly assigned women (1:1) to treatment groups of either continuous use of letrozole (2·5 mg/day orally for 5 years) or intermittent use of letrozole (2·5 mg/day orally for 9 months followed by a 3-month break in years 1-4 and then 2·5 mg/day during all 12 months of year 5). Randomisation was done by principal investigators or designee at respective centres through the internet-based system of the International Breast Cancer Study Group, was stratified by type of previous endocrine therapy (aromatase inhibitors only vs selective oestrogen receptor modulators only vs both therapies), and used permuted block sizes of four and institutional balancing. No one was masked to treatment assignment. The primary endpoint was disease-free survival, analysed by the intention-to-treat principle using a stratified log-rank test. All patients in the intention-to-treat population who initiated protocol treatment during their period of trial participation were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00553410, and EudraCT, number 2007-001370-88; and long-term follow-up of patients is ongoing.Between Dec 5, 2007, and Oct 8, 2012, 4884 women were enrolled and randomised after exclusion of patients at a non-adherent centre, found to have inadequate documentation of informed consent, immediately withdrew consent, or randomly assigned to intervention groups in error. 4851 women comprised the intention-to-treat population that compared extended intermittent letrozole use (n=2425) with continuous letrozole use (n=2426). After a median follow-up of 60 months (IQR 53-72), disease-free survival was 85·8% (95% CI 84·2-87·2) in the intermittent letrozole group compared with 87·5% (86·0-88·8) in the continuous letrozole group (hazard ratio 1·08, 95% CI 0·93-1·26; p=0·31). Adverse events were reported as expected and were similar between the two groups. The most common grade 3-5 adverse events were hypertension (584 [24%] of 2417 in the intermittent letrozole group vs 517 [21%] of 2411 in the continuous letrozole group) and arthralgia (136 [6%] vs 151 [6%]). 54 patients (24 [1%] in the intermittent letrozole group and 30 [1%] in the continuous letrozole group) had grade 3-5 CNS cerebrovascular ischaemia, 16 (nine [<1%] vs seven [<1%]) had grade 3-5 CNS haemorrhage, and 40 (19 [1%] vs 21 [1%]) had grade 3-5 cardiac ischaemia. In total, 23 (<1%) of 4851 patients died while on trial treatment (13 [<1%] of 2417 patients in the intermittent letrozole group vs ten [<1%] of 2411 in the continuous letrozole group).In postmenopausal women with hormone receptor-positive breast cancer, extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole. An alternative schedule of extended adjuvant endocrine therapy with letrozole, including intermittent administration, might be feasible and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them.Novartis and the International Breast Cancer Study Group.
13.	David, Jennifer, 1987-, et al. (författare) Design and Development of a Hexacopter for the Search and Rescue of a Lost Drone 2019 Konferensbidrag (refereegranskat)abstract Search and rescue with an autonomous robot is an attractive and challenging task within the research community. This paper presents the development of an autonomous hexacopter that is designed for retrieving a lost object, like a drone, from a vast-open space, like a desert area. Navigating its path with a proposed coverage path planning strategy, the hexacopter can efficiently search for a lost target and locate it using an image-based object detection algorithm. Moreover, after the target is located, our hexacopter can grasp it with a customised gripper and transport it back to a destined location. It is also capable of avoiding static obstacles and dynamic objects. The proposed system was realised in simulations before implementing it in a real hardware setup, i.e. assembly of the drone, crafting of the gripper, software implementation and testing under real-world scenarios. The designed hexacopter won the best UAV design award at the CPS-VO 2018 Competition held in Arizona, USA.
14.	Escaned, Javier, et al. (författare) Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes 2018 Ingår i: JACC. - : Elsevier. - 1936-8798 .- 1876-7605. ; 11:15, s. 1437-1449 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
15.	Falck, Peter, et al. (författare) Arabinoxylanase from glycoside hydrolase family 5 is a selective enzyme for production of specific arabinoxylooligosaccharides 2018 Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146. ; 242, s. 579-584 Tidskriftsartikel (refereegranskat)abstract An arabinose specific xylanase from glycoside hydrolase family 5 (GH5) was used to hydrolyse wheat and rye arabinoxylan, and the product profile showed that it produced arabinose substituted oligosaccharides (AXOS) having 2-10 xylose residues in the main chain but no unsubstituted xylooligosaccharides (XOS). Molecular modelling showed that the active site has an open structure and that the hydroxyl groups of all xylose residues in the active site are solvent exposed, indicating that arabinose substituents can be accommodated in the glycone as well as the aglycone subsites. The arabinoxylan hydrolysates obtained with the GH5 enzyme stimulated growth of Bifidobacterium adolescentis but not of Lactobacillus brevis. This arabinoxylanase is thus a good tool for the production of selective prebiotics.
16.	Falck, Peter, et al. (författare) Characterization of a family 43 β-xylosidase from the xylooligosaccharide utilizing putative probiotic Weissella sp. strain 92. 2015 Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 26:2, s. 193-202 Tidskriftsartikel (refereegranskat)abstract In this work we present the first XOS degrading glycoside hydrolase from Weissella, WXyn43, a two-domain enzyme from GH43. The gene was amplified from genomic DNA of the XOS utilizing Weissella strain 92, classified under the species pair Weissella cibaria/W.confusa, and expressed in Escherichia coli. The enzyme is lacking a putative signal peptide and is, from a homology model, shown to be composed of an N-terminal 5-fold ß-propeller catalytic domain and a C-terminal ß-sandwich domain of unknown function. WXyn43 hydrolysed short (1-4)-β-D-xylooligosaccharides, with similar kcat/KM for Xylobiose (X2) and xylotriose (X3) and clearly lower efficiency in xylotetraose (X4) conversion. WXyn43 displays the highest reported kcat for conversion of X3 (900 s(-1) at 37°C) and X4 (770 s(-1)), and kcat for hydrolysis of X2 (907 s(-1)) is comparable to or greater than the highest previously reported. The purified enzyme adopted a homotetrameric state in solution, while a truncated form with isolated N-terminal catalytic domain adopted a mixture of oligomeric states and lacked detectable activity. The homology model shows that residues from both domains are involved in monomer-monomer hydrogen bonds, while the bonds creating dimer-dimer interactions only involved residues from the N-terminal domain. Docking of X2 and X3 in the active site show interactions corresponding to sub-sites -1 and +1, while presence of a third subsite is unclear, but interactions between a loop and the reducing-end xylose of X3 may be present.
17.	Feng, Zhaozhong, et al. (författare) A unifying explanation for variation in ozone sensitivity among woody plants 2018 Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 24:1, s. 78-84 Tidskriftsartikel (refereegranskat)abstract Tropospheric ozone is considered the most detrimental air pollutant for vegetation at the global scale, with negative consequences for both provisioning and climate regulating ecosystem services. In spite of recent developments in ozone exposure metrics, from a concentration-based to a more physiologically relevant stomatal flux-based index, large-scale ozone risk assessment is still complicated by a large and unexplained variation in ozone sensitivity among tree species. Here, we explored whether the variation in ozone sensitivity among woody species can be linked to interspecific variation in leaf morphology. We found that ozone tolerance at the leaf level was closely linked to leaf dry mass per unit leaf area (LMA) and that whole-tree biomass reductions were more strongly related to stomatal flux per unit leaf mass (r 2 =0.56) than to stomatal flux per unit leaf area (r 2 =0.42). Furthermore, the interspecific variation in slopes of ozone flux–response relationships was considerably lower when expressed on a leaf mass basis (coefficient of variation, CV=36%) than when expressed on a leaf area basis (CV=66%), and relationships for broadleaf and needle-leaf species converged when using the mass-based index. These results show that much of the variation in ozone sensitivity among woody plants can be explained by interspecific variation in LMA and that large-scale ozone impact assessment could be greatly improved by considering this well-known and easily measured leaf trait.
18.	Freire, Sergio Miranda, et al. (författare) Comparing the Performance of NoSQL Approaches for Managing Archetype-Based Electronic Health Record Data 2016 Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 11:3 Tidskriftsartikel (refereegranskat)abstract This study provides an experimental performance evaluation on population-based queries of NoSQL databases storing archetype-based Electronic Health Record (EHR) data. There are few published studies regarding the performance of persistence mechanisms for systems that use multilevel modelling approaches, especially when the focus is on population-based queries. A healthcare dataset with 4.2 million records stored in a relational database (MySQL) was used to generate XML and JSON documents based on the openEHR reference model. Six datasets with different sizes were created from these documents and imported into three single machine XML databases (BaseX, eXistdb and Berkeley DB XML) and into a distributed NoSQL database system based on the MapReduce approach, Couchbase, deployed in different cluster configurations of 1, 2, 4, 8 and 12 machines. Population-based queries were submitted to those databases and to the original relational database. Database size and query response times are presented. The XML databases were considerably slower and required much more space than Couchbase. Overall, Couchbase had better response times than MySQL, especially for larger datasets. However, Couchbase requires indexing for each differently formulated query and the indexing time increases with the size of the datasets. The performances of the clusters with 2, 4, 8 and 12 nodes were not better than the single node cluster in relation to the query response time, but the indexing time was reduced proportionally to the number of nodes. The tested XML databases had acceptable performance for openEHR-based data in some querying use cases and small datasets, but were generally much slower than Couchbase. Couchbase also outperformed the response times of the relational database, but required more disk space and had a much longer indexing time. Systems like Couchbase are thus interesting research targets for scalable storage and querying of archetype-based EHR data when population-based use cases are of interest.
19.	Gulshan Kazi, Zubaida, et al. (författare) A CGTase with high coupling activity using γ-cyclodextrin isolated from a novel strain clustering under the genus Carboxydocella. 2015 Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 25:5, s. 514-523 Tidskriftsartikel (refereegranskat)abstract Cyclodextrin glucanotransferases (CGTases; EC 2.4.1.19) have mainly been characterized for their ability to produce cyclodextrins (CDs) from starch in an intramolecular transglycosylation reaction (cyclization). However, this class of enzymes can also catalyze intermolecular transglycosylation via disproportionation or coupling reactions onto a wide array of acceptors and could therefore be valuable as a tool for glycosylation. In this paper, we report the gene isolation, via the CODEHOP-strategy, expression and characterization of a novel CGTase (CspCGT13) from a Carboxydocella sp. This enzyme is the first glycoside hydrolase isolated from the genus, indicating starch degradation via cyclodextrin production in the Carboxydocella strain. The fundamental reactivities of this novel CGTase are characterized and compared to two commercial CGTases, assayed under identical condition, in order to facilitate interpretation of the results. The comparison showed that the enzyme, CspCGT13, displayed high coupling activity using γ-CD as donor, despite preferentially forming α and β-CD in the cyclization reaction using wheat starch as substrate. Comparison of subsite conservation within previously characterized CGTases showed significant sequence variation in subsite -3 and -7, which may be important for the coupling activity.
20.	Haghighi, Mona, et al. (författare) A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study 2016 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6 Tidskriftsartikel (refereegranskat)abstract Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
21.	Hardman, Scott, et al. (författare) Driving the Market for Plug-in Vehicles - Understanding Reoccurring Incentives 2017 Ingår i: UC Davis, International EV Policy Council. Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
22.	Jakobsson, Niklas, 1985, et al. (författare) Are multi-car households better suited for battery electric vehicles? - Driving patterns and economics in Sweden and Germany 2016 Ingår i: Transportation Research, Part C: Emerging Technologies. - : Elsevier BV. - 0968-090X. ; 65, s. 1-15 Tidskriftsartikel (refereegranskat)abstract Battery electric vehicles (BEVs) could reduce CO2 emissions from the transport sector but their limited electric driving range diminishes their utility to users. The effect of the limited driving range can be reduced in multi-car households where users could choose between a BEV and a conventional car for long-distance travel. However, to what extent the driving patterns of different cars in a multi-car household’s suit the characteristics of a BEV needs further analysis. In this paper we analyse the probability of daily driving above a fixed threshold for conventional cars in current Swedish and German car driving data. We find second cars in multi-car households to require less adaptation and to be better suited for BEV adoption compared to first cars in multi-car households as well as to cars in single-car households. Specifically, the share of second cars that could fulfil all their driving is 20 percentage points higher compared to first cars and cars from single-car households. This result is stable against variation of driving range and of the tolerated number of days requiring adaptation. Furthermore, the range needed to cover all driving needs for about 70% of the vehicles is only 220 km for second cars compared to 390 km for the average car. We can further confirm that second cars have higher market viability from a total cost of ownership perspective. Here, the second cars achieve a 10 percentage points higher market share compared to first cars, and to cars in single-car households for Swedish economic conditions, while for Germany the corresponding figure is 2 percentage points. Our results are important for understanding the market viability of current and near-future BEVs.
23.	Karlsson, Anna, et al. (författare) A combined gene expression tool for parallel histological prediction and gene fusion detection in non-small cell lung cancer 2019 Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9 Tidskriftsartikel (refereegranskat)abstract Accurate histological classification and identification of fusion genes represent two cornerstones of clinical diagnostics in non-small cell lung cancer (NSCLC). Here, we present a NanoString gene expression platform and a novel platform-independent, single sample predictor (SSP) of NSCLC histology for combined, simultaneous, histological classification and fusion gene detection in minimal formalin fixed paraffin embedded (FFPE) tissue. The SSP was developed in 68 NSCLC tumors of adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large-cell neuroendocrine carcinoma (LCNEC) histology, based on NanoString expression of 11 (CHGA, SYP, CD56, SFTPG, NAPSA, TTF-1, TP73L, KRT6A, KRT5, KRT40, KRT16) relevant genes for IHC-based NSCLC histology classification. The SSP was combined with a gene fusion detection module (analyzing ALK, RET, ROS1, MET, NRG1, and NTRK1) into a multicomponent NanoString assay. The histological SSP was validated in six cohorts varying in size (n = 11-199), tissue origin (early or advanced disease), histological composition (including undifferentiated cancer), and gene expression platform. Fusion gene detection revealed five EML4-ALK fusions, four KIF5B-RET fusions, two CD74-NRG1 fusion and three MET exon 14 skipping events among 131 tested cases. The histological SSP was successfully trained and tested in the development cohort (mean AUC = 0.96 in iterated test sets). The SSP proved successful in predicting histology of NSCLC tumors of well-defined subgroups and difficult undifferentiated morphology irrespective of gene expression data platform. Discrepancies between gene expression prediction and histologic diagnosis included cases with mixed histologies, true large cell carcinomas, or poorly differentiated adenocarcinomas with mucin expression. In summary, we present a proof-of-concept multicomponent assay for parallel histological classification and multiplexed fusion gene detection in archival tissue, including a novel platform-independent histological SSP classifier. The assay and SSP could serve as a promising complement in the routine evaluation of diagnostic lung cancer biopsies.
24.	Karlsson, Anna, et al. (författare) Gene Expression Profiling of Large Cell Lung Cancer Links Transcriptional Phenotypes to the New Histological WHO 2015 Classification 2017 Ingår i: Journal of Thoracic Oncology. - : ELSEVIER SCIENCE INC. - 1556-0864 .- 1556-1380. ; 12:8, s. 1257-1267 Tidskriftsartikel (refereegranskat)abstract Introduction: Large cell lung cancer (LCLC) and large cell neuroendocrine carcinoma (LCNEC) constitute a small proportion of NSCLC. The WHO 2015 classification guidelines changed the definition of the debated histological subtype LCLC to be based on immunomarkers for adenocarcinoma and squamous cancer. We sought to determine whether these new guidelines also translate into the transcriptional landscape of lung cancer, and LCLC specifically.Methods: Gene expression profiling was performed by using Illumina V4 HT12 microarrays (Illumina, San Diego, CA) on samples from 159 cases (comprising all histological subtypes, including 10 classified as LCLC WHO 2015 and 14 classified as LCNEC according to the WHO 2015 guidelines), with complimentary mutational and immunohistochemical data. Derived transcriptional phenotypes were validated in 199 independent tumors, including six WHO 2015 LCLCs and five LCNECs.Results: Unsupervised analysis of gene expression data identified a phenotype comprising 90% of WHO 2015 LCLC tumors, with characteristics of poorly differentiated proliferatiVe cancer, a 90% tumor protein p53 gene (TP53) mutation rate, and lack of well-known NSCLC oncogene driver alterations. Validation in independent data confirmed aggregation of WHO 2015 LCLCs in the specific phenotype. For LCNEC tumors, the unsupervised gene expression analysis suggested two different transcriptional patterns corresponding to a proposed genetic division of LCNEC tumors into SCLC-like and NSCLC-like cancer on the basis of TP53 and retinoblastoma 1 gene (RB1) alteration patterns.Conclusions: Refined classification of LCLC has implications for diagnosis, prognostics, and therapy decisions. Our molecular analyses support the WHO 2015 classification of LCLC and LCNEC tumors, which herein follow different tumorigenic paths and can accordingly be stratified into different transcriptional subgroups, thus linking diagnostic immunohistochemical staining driven classification with the transcriptional landscape of lung cancer.
25.	Karlsson, Christoffer, et al. (författare) Stable Deep Doping of Vapor-Phase Polymerized Poly(3,4-ethylenedioxythiophene)/Ionic Liquid Supercapacitors. 2016 Ingår i: ChemSusChem. - : Wiley. - 1864-5631 .- 1864-564X. ; 9:16, s. 2112-2121 Tidskriftsartikel (refereegranskat)abstract Liquid-solution polymerization and vapor-phase polymerization (VPP) have been used to manufacture a series of chloride- and tosylate-doped poly(3,4-ethylenedioxythiophene) (PEDOT) carbon paper electrodes. The electrochemistry, specific capacitance, and specific charge were determined for single electrodes in 1-ethyl-3-methylimidazolium dicyanamide (emim dca) ionic liquid electrolyte. VPP-PEDOT exhibits outstanding properties with a specific capacitance higher than 300 F g(-1) , the highest value reported for a PEDOT-based conducting polymer, and doping levels as high as 0.7 charges per monomer were achieved. Furthermore, symmetric PEDOT supercapacitor cells with the emim dca electrolyte exhibited a high specific capacitance (76.4 F g(-1) ) and high specific energy (19.8 Wh kg(-1) ). A Ragone plot shows that the VPP-PEDOT cells combine the high specific power of conventional ("pure") capacitors with the high specific energy of batteries, a highly sought-after target for energy storage.
26.	Karlsson, Terese, 1979-, et al. (författare) LMO7 and LIMCH1 interact with LRIG proteins in lung cancer, with prognostic implications for early-stage disease 2018 Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 125, s. 174-184 Tidskriftsartikel (refereegranskat)abstract Objectives: The human leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family comprises the integral membrane proteins LRIG1, LRIG2 and LRIG3. LRIG1 is frequently down-regulated in human cancer, and high levels of LRIG1 in tumor tissue are associated with favorable clinical outcomes in several tumor types including non-small cell lung cancer (NSCLC). Mechanistically, LRIG1 negatively regulates receptor tyrosine kinases and functions as a tumor suppressor. However, the details of the molecular mechanisms involved are poorly understood, and even less is known about the functions of LRIG2 and LRIG3. The aim of this study was to further elucidate the functions and molecular interactions of the LRIG proteins.Materials and methods: A yeast two-hybrid screen was performed using a cytosolic LRIG3 peptide as bait. In transfected human cells, co-immunoprecipitation and co-localization experiments were performed. Proximity ligation assay was performed to investigate interactions between endogenously expressed proteins. Expression levels of LMO7 and LIMCH1 in normal and malignant lung tissue were investigated using qRT-PCR and through in silico analyses of public data sets. Finally, a clinical cohort comprising 355 surgically treated NSCLC cases was immunostained for LMO7.Results: In the yeast two-hybrid screen, the two paralogous proteins LMO7 and LIMCH1 were identified as interaction partners to LRIG3. LMO7 and LIMCH1 co-localized and co-immunoprecipitated with both LRIG1 and LRIG3. Endogenously expressed LMO7 was in close proximity of both LRIG1 and LRIG3. LMO7 and LIMCH1 were highly expressed in normal lung tissue and down-regulated in malignant lung tissue. LMO7 immunoreactivity was shown to be a negative prognostic factor in LRIG1 positive tumors, predicting poor patient survival.Conclusion: These findings suggest that LMO7 and LIMCH1 physically interact with LRIG proteins and that expression of LMO7 is of clinical importance in NSCLC.
27.	Kvarnbrink, Samuel, et al. (författare) LRIG1 is a prognostic biomarker in non-small cell lung cancer 2015 Ingår i: Acta Oncologica. - : Taylor & Francis. - 1651-226X .- 0284-186X. ; 54:8, s. 1113-1119 Tidskriftsartikel (refereegranskat)abstract Background. The leucine-rich repeats and immunoglobulin-like domains (LRIG) family of transmembrane proteins are involved in the regulation of cellular signal transduction. LRIG1 is an endogenous inhibitor of receptor tyrosine kinases (RTKs) and an emerging tumor suppressor. In the lung epithelium, the expression of LRIG1 is downregulated by tobacco smoking, and further downregulated in lung squamous cell carcinoma. Material and methods. The expression of LRIG proteins were analyzed in 347 cases of non-small cell lung cancer (NSCLC) by immunohistochemistry, and LRIG1 mRNA expression was evaluated in 807 lung cancer samples in silico in the Oncomine database. Potential associations between the expression data and the clinical parameters, including patient survival, were investigated. Results. Expression of the LRIG1 protein was found to be an independent prognostic factor in NSCLC, whereas expression of LRIG2 or LRIG3 did not correlate with patient survival. The levels of LRIG1 mRNA also correlated with the survival of NSCLC patients. Conclusion. These findings demonstrate that LRIG1 is an independent prognostic factor in patients with NSCLC that could be important in future decision-making algorithms for adjuvant lung cancer treatment.
28.	La Fleur, Linnea, et al. (författare) Expression of scavenger receptor MARCO defines a targetable tumor-associated macrophage subset in non-small cell lung cancer 2018 Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 143:7, s. 1741-1752 Tidskriftsartikel (refereegranskat)abstract Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n=352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n=199) with available RNA-seq data. We observed a large variation in macrophage density between cases and a strong correlation between CD68 and CD163, suggesting that the majority of TAMs present in NSCLC exhibit a protumor phenotype. Correlation to clinical data only showed a weak trend toward worse survival for patients with high macrophage infiltration. Interestingly, MARCO was expressed on a distinct subpopulation of TAMs, which tended to aggregate in close proximity to tumor cell nests. On the transcriptomic level, we found a positive association between MARCO gene expression and general immune response pathways including strong links to immunosuppressive TAMs, T-cell infiltration and immune checkpoint molecules. Indeed, a higher macrophage infiltration was seen in tumors expressing PD-L1, and macrophages residing within tumor cell nests co-expressed MARCO and PD-L1. Thus, MARCO is a potential new immune target for anti-TAM treatment in a subset of NSCLC patients, possibly in combination with available immune checkpoint inhibitors.
29.	Lee, James J, et al. (författare) Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. 2018 Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 50:8, s. 1112-1121 Tidskriftsartikel (refereegranskat)abstract Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1million individuals and identify 1,271independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.
30.	Li, Daniel Y., et al. (författare) H19 Induces Abdominal Aortic Aneurysm Development and Progression 2018 Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 138:15, s. 1551-1568 Tidskriftsartikel (refereegranskat)abstract Background: Long noncoding RNAs have emerged as critical molecular regulators in various biological processes and diseases. Here we sought to identify and functionally characterize long noncoding RNAs as potential mediators in abdominal aortic aneurysm development. Methods: We profiled RNA transcript expression in 2 murine abdominal aortic aneurysm models, Angiotensin II (ANGII) infusion in apolipoprotein E-deficient (ApoE(-/-)) mice (n=8) and porcine pancreatic elastase instillation in C57BL/6 wild-type mice (n=12). The long noncoding RNA H19 was identified as 1 of the most highly upregulated transcripts in both mouse aneurysm models compared with sham-operated controls. This was confirmed by quantitative reverse transcription-polymerase chain reaction and in situ hybridization. Results: Experimental knock-down of H19, utilizing site-specific antisense oligonucleotides (LNA-GapmeRs) in vivo, significantly limited aneurysm growth in both models. Upregulated H19 correlated with smooth muscle cell (SMC) content and SMC apoptosis in progressing aneurysms. Importantly, a similar pattern could be observed in human abdominal aortic aneurysm tissue samples, and in a novel preclinical LDLR-/- (low-density lipoprotein receptor) Yucatan mini-pig aneurysm model. In vitro knock-down of H19 markedly decreased apoptotic rates of cultured human aortic SMCs, whereas overexpression of H19 had the opposite effect. Notably, H19-dependent apoptosis mechanisms in SMCs appeared to be independent of miR-675, which is embedded in the first exon of the H19 gene. A customized transcription factor array identified hypoxia-inducible factor 1 as the main downstream effector. Increased SMC apoptosis was associated with cytoplasmic interaction between H19 and hypoxia-inducible factor 1 and sequential p53 stabilization. Additionally, H19 induced transcription of hypoxia-inducible factor 1 via recruiting the transcription factor specificity protein 1 to the promoter region. Conclusions: The long noncoding RNA H19 is a novel regulator of SMC survival in abdominal aortic aneurysm development and progression. Inhibition of H19 expression might serve as a novel molecular therapeutic target for aortic aneurysm disease.
31.	Linares-Pastén, Javier A., et al. (författare) Three-dimensional structures and functional studies of two GH43 arabinofuranosidases from Weissella sp. strain 142 and Lactobacillus brevis 2017 Ingår i: The FEBS Journal. - : Wiley. - 1742-464X. ; 284:13, s. 2019-2036 Tidskriftsartikel (refereegranskat)abstract Arabinofuranosidases degrade arabinose-containing oligo and polysaccharides, releasing l-arabinose, which is a potentially useful sugar, shown to reduce glycemic response under certain conditions. Arabinofuranosidases (Arafs) are frequently found in GH43, one of the most common GH-families encoded in genomes in gut microbiota, and hence it is of interest to increase understanding of the function of these enzymes in species occurring in the gut. Here we have produced, characterized and solved the three-dimensional structures, at 1.9 and 2.0 Å resolution respectively, of two homologous GH43 enzymes, classified under subfamily 26, from Lactobacillus brevis DSM1269 (LbAraf43) and Weissella strain 142 (WAraf43), respectively. The enzymes, with 74% sequence identity to each other, are composed of a single catalytic module with a β-propeller structure typical of GH43, and an active-site pocket with three identifiable subsites (−1, +1, and +2). According to size exclusion chromatography, native WAraf43 is a dimer, while LbAraf43 is a tetramer in solution. Both of them show activity with similar catalytic efficiency on 1,5-α-l-arabinooligosaccharides with a degree of polymerization (DP) of 2–3. Activity is restricted to substrates of low DP, and the reason for this is believed to be an extended loop at the entrance to the active site, creating interactions in the +2 subsite. Database: Structural data are available in the PDB under the accession numbers 5M8B (LbAraf43) and 5M8E (WAraf43).
32.	Lundemo, Pontus, et al. (författare) Eliminating hydrolytic activity without affecting the transglycosylation of a GH1 β-glucosidase 2017 Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 0175-7598 .- 1432-0614. ; 101:3, s. 1121-1131 Tidskriftsartikel (refereegranskat)abstract Unveiling the determinants for transferase and hydrolase activity in glycoside hydrolases would allow using their vast diversity for creating novel transglycosylases, thereby unlocking an extensive toolbox for carbohydrate chemists. Three different amino acid substitutions at position 220 of a GH1 β-glucosidase from Thermotoga neapolitana caused an increase of the ratio of transglycosylation to hydrolysis (rs/rh) from 0.33 to 1.45–2.71. Further increase in rs/rh was achieved by modulation of pH of the reaction medium. The wild-type enzyme had a pH optimum for both hydrolysis and transglycosylation around 6 and reduced activity at higher pH. Interestingly, the mutants had constant transglycosylation activity over a broad pH range (5–10), while the hydrolytic activity was largely eliminated at pH 10. The results demonstrate that a combination of protein engineering and medium engineering can be used to eliminate the hydrolytic activity without affecting the transglycosylation activity of a glycoside hydrolase. The underlying factors for this success are pursued, and perturbations of the catalytic acid/base in combination with flexibility are shown to be important factors.
33.	Marques, André R A, et al. (författare) Glucosylated cholesterol in mammalian cells and tissues: formation and degradation by multiple cellular β-glucosidases. 2016 Ingår i: Journal of Lipid Research. - 1539-7262. ; 57, s. 451-463 Tidskriftsartikel (refereegranskat)abstract The membrane lipid glucosylceramide (GlcCer) is continuously formed and degraded. Cells express two GlcCer-degrading β-glucosidases, GBA and GBA2, located in and outside the lysosome, respectively. Here we demonstrate that through transglucosylation both GBA and GBA2 are able to catalyze in vitro the transfer of glucosyl-moieties from GlcCer to cholesterol, and vice versa. Furthermore, the natural occurrence of 1-O-cholesteryl-β-D-glucopyranoside (GlcChol) in mouse tissues and human plasma is demonstrated using LC-MS/MS and 13C6-labelled GlcChol as internal standard. In cells the inhibition of GBA increases GlcChol, whereas inhibition of GBA2 decreases glucosylated sterol. Similarly, in GBA2-deficient mice GlcChol is reduced. Depletion of GlcCer by inhibition of GlcCer synthase decreases GlcChol in cells and likewise in plasma of inhibitor-treated Gaucher disease patients. In tissues of mice with Niemann-Pick type C, a condition characterized by intralysosomal accumulation of cholesterol, marked elevations in GlcChol occur as well. When lysosomal accumulation of cholesterol is induced in cultured cells, GlcChol is formed via lysosomal GBA. This illustrates that reversible transglucosylation reactions are highly dependent on local availability of suitable acceptors. In conclusion, mammalian tissues contain GlcChol formed by transglucosylation through β-glucosidases using GlcCer as donor. Our findings reveal a novel metabolic function for GlcCer.
34.	Mathew, Sindhu, et al. (författare) Extraction of soluble arabinoxylan from enzymatically pretreated wheat bran and production of short xylo-oligosaccharides and arabinoxylo-oligosaccharides from arabinoxylan by glycoside hydrolase family 10 and 11 endoxylanases 2017 Ingår i: Journal of Biotechnology. - : Elsevier BV. - 0168-1656. ; 260, s. 53-61 Tidskriftsartikel (refereegranskat)abstract The enzymatic, ecofriendly pretreatment of wheat bran with α-amylase from Bacillus amyloliquifaciens or B. licheniformis at 90 °C for 1.5 h followed by Neutrase at 50 °C for 4 h, aqueous liquefaction at 121 °C for 15 h and ethanol precipitation enabled the production of soluble arabinoxylan (AX) with purity of 70.9% and 68.4% (w/w) respectively. Process alternatives tried, to simplify the process and curtail the cost resulted in AX products with different purities, yields and arabinose to xylose ratio (A/X). Among the two glycoside hydrolase (GH) family endoxylanases evaluated, GH10 family hydrolysed soluble AX more efficiently with xylanase from Geobacillus stearothermophilus T-6 (GsXyn10A) producing maximum amount of quantifiable short xylo-oligosaccharides (XOS) and arabinoxylo-oligosaccharides (AXOS) (53% w/w) followed by the catalytic module of Rhodothermus marinus Xyn10A (RmXyn10A-CM) with 37% (w/w) conversion. The GH11 family endoxylanases, from Thermomyces lanuginosus (Pentopan Mono BG™) and Neocallimastix patriciarum (NpXyn11A) gave conversions of 21% and 22% (w/w) of the soluble AX, respectively (major AXOS products were not quantified). In addition to the XOS formed such as X2, X3 and X4, the AXOS products identified were A3X and A2XX in the case of GsXyn10A and RmXyn10A-CM while Pentopan Mono BG and NpXyn11A produced XA3XX as the major AXOS product.
35.	Mathew, Sindhu, et al. (författare) Xylo- and arabinoxylooligosaccharides from wheat bran by endoxylanases, utilisation by probiotic bacteria, and structural studies of the enzymes 2018 Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 0175-7598 .- 1432-0614. ; 102:7, s. 3105-3120 Tidskriftsartikel (refereegranskat)abstract Xylooligosaccharides (XOS) and arabinoxylooligosaccharides (AXOS) were produced from the insoluble arabinoxylan fraction of pretreated wheat bran by endoxylanases. The glycoside hydrolase (GH) family 10 xylanases GsXyn10A from Geobacillus stearothermophilus and RmXyn10A-CM from Rhodothermus marinus produced the AXOS A3X, A2XX and A2 + 3XX in addition to XOS. RmXyn10A-CM also produced XA2 + 3XX due to its non-conserved aglycone region accommodating additional arabinose substitutions in subsite +2. The GH11 enzymes, Pentopan from Thermomyces lanuginosus and NpXyn11A from Neocallimastix patriciarum had minor structural differences affecting hydrogen bonds in subsites −3 and +3, with similar hydrolysis profiles producing XA3XX as major AXOS and minor amounts of XA2XX but different ratios of X3/X2. In vitro analysis of the prebiotic properties of (A)XOS produced by Pentopan revealed nearly complete uptake of X2 and X3 by the probiotic bacteria Lactobacillus brevis and Bifidobacterium adolescentis. In contrast to previous reports, the GH43 arabinofuranosidase BaAXHd-3 from B. adolescentis cleaved α-1,3-linked arabinose on some single substituted AXOS.
36.	McNamee, Margaret, et al. (författare) IAFSS agenda 2030 for a fire safe world 2019 Ingår i: Fire Safety Journal. - : Elsevier BV. - 0379-7112. ; 110 Tidskriftsartikel (refereegranskat)abstract The International Association of Fire Safety Science (IAFSS) is comprised of members from some 40 countries. This paper presents the Association's thinking, developed by the Management Committee, concerning pressing research needs for the coming 10 years presented as the IAFSS Agenda 2030 for a Fire Safe World. The research needs are couched in terms of two broad Societal Grand Challenges: (1) climate change, resiliency and sustainability and (2) population growth, urbanization and globalization. The two Societal Grand Challenges include significant fire safety components, that lead both individually and collectively to the need for a number of fire safety and engineering research activities and actions. The IAFSS has identified a list of areas of research and actions in response to these challenges. The list is not exhaustive, and actions within actions could be defined, but this paper does not attempt to cover all future needs.
37.	Morrill, Johan, et al. (författare) β-Mannanase-catalyzed synthesis of alkyl mannooligosides 2018 Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 0175-7598 .- 1432-0614. ; 102:12, s. 5149-5163 Tidskriftsartikel (refereegranskat)abstract β-Mannanases catalyze the conversion and modification of β-mannans and may, in addition to hydrolysis, also be capable of transglycosylation which can result in enzymatic synthesis of novel glycoconjugates. Using alcohols as glycosyl acceptors (alcoholysis), β-mannanases can potentially be used to synthesize alkyl glycosides, biodegradable surfactants, from renewable β-mannans. In this paper, we investigate the synthesis of alkyl mannooligosides using glycoside hydrolase family 5 β-mannanases from the fungi Trichoderma reesei (TrMan5A and TrMan5A-R171K) and Aspergillus nidulans (AnMan5C). To evaluate β-mannanase alcoholysis capacity, a novel mass spectrometry-based method was developed that allows for relative comparison of the formation of alcoholysis products using different enzymes or reaction conditions. Differences in alcoholysis capacity and potential secondary hydrolysis of alkyl mannooligosides were observed when comparing alcoholysis catalyzed by the three β-mannanases using methanol or 1-hexanol as acceptor. Among the three β-mannanases studied, TrMan5A was the most efficient in producing hexyl mannooligosides with 1-hexanol as acceptor. Hexyl mannooligosides were synthesized using TrMan5A and purified using high-performance liquid chromatography. The data suggests a high selectivity of TrMan5A for 1-hexanol as acceptor over water. The synthesized hexyl mannooligosides were structurally characterized using nuclear magnetic resonance, with results in agreement with their predicted β-conformation. The surfactant properties of the synthesized hexyl mannooligosides were evaluated using tensiometry, showing that they have similar micelle-forming properties as commercially available hexyl glucosides. The present paper demonstrates the possibility of using β-mannanases for alkyl glycoside synthesis and increases the potential utilization of renewable β-mannans.
38.	Nordberg Karlsson, Eva, et al. (författare) Endo-xylanases as tools for production of substituted xylooligosaccharides with prebiotic properties 2018 Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 0175-7598 .- 1432-0614. ; 102:21, s. 9081-9088 Forskningsöversikt (refereegranskat)abstract Xylan has a main chain consisting of β-1,4-linked xylose residues with diverse substituents. Endoxylanases cleave the xylan chain at cleavage sites determined by the substitution pattern and thus give different oligosaccharide product patterns. Most known endoxylanases belong to glycoside hydrolase (GH) families 10 and 11. These enzymes work well on unsubstituted xylan but accept substituents in certain subsites. The GH11 enzymes are more restricted by substituents, but on the other hand, they are normally more active than the GH10 enzymes on insoluble substrates, because of their smaller size. GH5 endoxylanases accept arabinose substituents in several subsites and require it in the − 1 subsite. This specificity makes the GH5 endoxylanases very useful for degradation of highly arabinose-substituted xylans and for the selective production of arabinoxylooligosaccharides, without formation of unsubstituted xylooligosaccharides. The GH30 endoxylanases have a related type of specificity in that they require a uronic acid substituent in the − 2 subsite, which makes them very useful for the production of uronic acid substituted oligosaccharides. The ability of dietary xylooligosaccharides to function as prebiotics in humans is governed by their substitution patterns. Endoxylanases are thus excellent tools to tailor prebiotic oligosaccharides to stimulate various types of intestinal bacteria and to cause fermentation in different parts of the gastrointestinal tract. Continuously increasing knowledge on the function of the gut microbiota and discoveries of novel endoxylanases increase the possibilities to achieve health-promoting effects.
39.	Rather, Younus, et al. (författare) Characterization of cyclodextrin glycosyltransferases (CGTases) and their application for synthesis of alkyl glycosides with oligomeric head group 2015 Ingår i: Process Biochemistry. - : Elsevier BV. - 1873-3298 .- 1359-5113. ; 50:5, s. 722-728 Tidskriftsartikel (refereegranskat)abstract Cyclodextrin glycosyltransferases (CGTases) from Paenibacillus macerans, Thermoanaerobacter sp. ATCC 53627, Bacillus stearothermophilus and a Carboxydocella sp. (phylogenetically identified from genomic DNA) were characterized with respect to their catalytic activity in different reactions, with emphasis on reactions useful for the elongation of the carbohydrate group of alkyl glycosides. All CGTases had activities between 95 and 115 U/mg in the coupling reaction between a-cyclodextrin (alpha-CD) as glucosyl donor and beta-dodecyl maltoside as glucosyl acceptor, but differed very much in the competing hydrolysis of a-CD. The alpha-CD hydrolysis activity ranged from 0.13 U/mg for P. macerans CGTase to 10.5 U/mg for the Carboxydocella sp. (CspCGT13). Furthermore, the disproportionation activity was much lower for the Paenibacillus CGTase compared to the other CGTases, and consequently this enzyme produced the highest yield of the primary coupling product beta-dodecyl maltooctaoside, which is a valuable surfactant. For production of a polydisperse alkyl glycoside product, disproportionation reactions are useful and the other three CGTases of the current study are efficient catalysts. The newly discovered Carboxydocella sp. (CspCGT13) CGTase has the special feature to produce more of products with even longer carbohydrate groups than the primary coupling product. (C) 2015 Elsevier Ltd. All rights reserved.
40.	Rather, Younus, et al. (författare) Complexation of alkyl glycosides with α-cyclodextrin can have drastically different effects on their conversion by glycoside hydrolases. 2015 Ingår i: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 200, s. 52-58 Tidskriftsartikel (refereegranskat)abstract Substrates present in aggregated forms, such as micelles, are often poorly converted by enzymes. Alkyl glycosides constitute typical examples and the critical micelle concentration (CMC) decreases with increasing length of the alkyl group. In this study, possibilities to hydrolyse alkyl glycosides by glycoside hydrolases were explored, and α-cyclodextrin was used as an agent to form inclusion complexes with the alkyl glycosides, thereby preventing micelle formation. The cyclodextrin complexes were accepted as substrates by the enzymes to variable extent. The β-glucosidases originating from Thermotoga neapolitana (Tn Bgl3B) and from almond were not at all able to hydrolyse alkyl β-glucosides in the presence of 100mM α-cyclodextrin. However, Aspergillus niger amyloglucosidase readily accepted the complexes as substrates. In reactions involving decyl and dodecyl maltosides, the presence of 100mM α-cyclodextrin caused an increase in reaction rate in most cases, especially at high substrate concentrations. Surprisingly, the amyloglucosidase-catalyzed hydrolysis of octyl-β-maltoside to glucose and β-octylglucoside was faster in the presence of α-cyclodextrin than without, even at substrate concentrations below CMC. A possible explanation of the observed rate enhancement is that binding sites on the carbohydrate binding domain of amyloglucosidase, known to bind cyclodextrins, help to guide the alkyl glycoside-cyclodextrin complex to the active site, and thereby promote its conversion.
41.	Ribi, Karin, et al. (författare) Adjuvant Tamoxifen Plus Ovarian Function Suppression Versus Tamoxifen Alone in Premenopausal Women With Early Breast Cancer: Patient-Reported Outcomes in the Suppression of Ovarian Function Trial. 2016 Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 34:14, s. 1601-1610 Tidskriftsartikel (refereegranskat)abstract The Suppression of Ovarian Function trial showed improved disease control for tamoxifen plus ovarian function suppression (OFS) compared with tamoxifen alone for the cohort of premenopausal patients who received prior chemotherapy. We present the patient-reported outcomes.
42.	Ribi, Karin, et al. (författare) Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial. 2019 Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 120, s. 959-967 Tidskriftsartikel (refereegranskat)abstract In the phase III SOLE trial, the extended use of intermittent versus continuous letrozole for 5 years did not improve disease-free survival in postmenopausal women with hormone receptor-positive breast cancer. Intermittent therapy with 3-month breaks may be beneficial for patients' quality of life (QoL).In the SOLE QoL sub-study, 956 patients completed the Breast Cancer Prevention Trial (BCPT) symptom and further QoL scales up to 24 months after randomisation. Differences in change of QoL from baseline between the two administration schedules were tested at 12 and 24 months using repeated measures mixed-models. The primary outcome was change in hot flushes at 12 months.There was no difference in hot flushes at 12 months between the two schedules, but patients receiving intermittent letrozole reported significantly more improvement at 24 months. They also indicated less worsening in vaginal problems, musculoskeletal pain, sleep disturbance, physical well-being and mood at 12 months. Overall, 25-30% of patients reported a clinically relevant worsening in key symptoms and global QoL.Less symptom worsening was observed during the first year of extended treatment with the intermittent administration. For women experiencing an increased symptom burden of extended adjuvant endocrine therapy, an intermittent administration is a safe alternative.Clinical trial information: NCT00651456.
43.	Ruilope, LM, et al. (författare) Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial 2019 Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356 Tidskriftsartikel (refereegranskat)abstract <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
44.	Sajib, Mursalin, 1987, et al. (författare) Valorization of Brewer's spent grain to prebiotic oligosaccharide: Production, xylanase catalyzed hydrolysis, in-vitro evaluation with probiotic strains and in a batch human fecal fermentation model 2018 Ingår i: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 268, s. 61-70 Tidskriftsartikel (refereegranskat)abstract Brewer's spent grain (BSG) accounts for around 85% of the solid by-products from beer production. BSG was first extracted to obtain water-soluble arabinoxylan (AX). Using subsequent alkali extraction (0.5 M KOH) it was possible to dissolve additional AX. In total, about 57% of the AX in BSG was extracted with the purity of 45–55%. After comparison of nine xylanases, Pentopan mono BG, a GH11 enzyme, was selected for hydrolysis of the extracts to oligosaccharides with minimal formation of monosaccharides. Growth of Bifidobacterium adolescentis (ATCC 15703) was promoted by the enzymatic hydrolysis to arabinoxylooligosaccharides, while Lactobacillus brevis (DSMZ 1264) utilized only unsubstituted xylooligosaccharides. Furthermore, utilization of the hydrolysates by human gut microbiota was also assessed in a batch human fecal fermentation model. Results revealed that the rates of fermentation of the BSG hydrolysates by human gut microbiota were similar to that of commercial prebiotic fructooligosaccharides, while inulin was fermented at a slower rate. In summary, a sustainable process to valorize BSG to functional food ingredients has been proposed.
45.	Salas Veizaga, Daniel, et al. (författare) Extraction of Glucuronoarabinoxylan from Quinoa Stalks (Chenopodium quinoa Willd.) and Evaluation of Xylooligosaccharides Produced by GH10 and GH11 Xylanases 2017 Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 65:39, s. 8663-8673 Tidskriftsartikel (refereegranskat)abstract Byproducts from quinoa are not yet well explored sources of hemicellulose or products thereof. In this work, xylan from milled quinoa stalks was retrieved to 66% recovery by akaline extraction using 0.5 M NaOH at 80 °C, followed by ethanol precipitation. The isolated polymer eluted as a single peak in size-exclusion chromatography with a molecular weight of >700 kDa. Analysis by Fourier transform infrared spectroscopy and nuclear magnetic resonance (NMR) combined with acid hydrolysis to monomers showed that the polymer was built of a backbone of β(1 → 4)-linked xylose residues that were substituted by 4-O-methylglucuronic acids, arabinose, and galactose in an approximate molar ratio of 114:23:5:1. NMR analysis also indicated the presence of α(1 → 5)-linked arabinose substituents in dimeric or oligomeric forms. The main xylooligosaccharides (XOs) produced after hydrolysis of the extracted glucuronoarabinoxylan polymer by thermostable glycoside hydrolases (GHs) from families 10 and 11 were xylobiose and xylotriose, followed by peaks of putative substituted XOs. Quantification of the unsubstituted XOs using standards showed that the highest yield from the soluble glucuronoarabinoxylan fraction was 1.26 g/100 g of xylan fraction, only slightly higher than the yield (1.00 g/100 g of xylan fraction) from the insoluble fraction (p < 0.05). No difference in yield was found between reactions in buffer or water (p > 0.05). This study shows that quinoa stalks represent a novel source of glucuronoarabinoxylan, with a substituent structure that allowed for limited production of XOs by GH10 or GH11 enzymes.
46.	Surowiec, Izabella, et al. (författare) Metabolic signature profiling as a diagnostic and prognostic tool in paediatric Plasmodium falciparum malaria 2015 Ingår i: Open Forum Infectious Diseases. - : Oxford University Press. - 2328-8957. ; 2:2 Tidskriftsartikel (refereegranskat)abstract Background: Accuracy in malaria diagnosis and staging is vital in order to reduce mortality and post infectious sequelae. Herein we present a metabolomics approach to diagnostic staging of malaria infection, specifically Plasmodium falciparum infection in children. Methods: A group of 421 patients between six months and six years of age with mild and severe states of malaria with age-matched controls were included in the study, 107, 192 and 122 individuals respectively. A multivariate design was used as basis for representative selection of twenty patients in each category. Patient plasma was subjected to Gas Chromatography-Mass Spectrometry analysis and a full metabolite profile was produced from each patient. In addition, a proof-of-concept model was tested in a Plasmodium berghei in-vivo model where metabolic profiles were discernible over time of infection. Results: A two-component principal component analysis (PCA) revealed that the patients could be separated into disease categories according to metabolite profiles, independently of any clinical information. Furthermore, two sub-groups could be identified in the mild malaria cohort who we believe represent patients with divergent prognoses. Conclusion: Metabolite signature profiling could be used both for decision support in disease staging and prognostication.
47.	Tucker, S., et al. (författare) Improving the mix of institutional and community care for older people with dementia : an application of the balance of care approach in eight European countries 2016 Ingår i: Aging and Mental Health. - Abingdon : Informa UK Limited. - 1360-7863 .- 1364-6915. ; 20:12, s. 1327-1338 Tidskriftsartikel (refereegranskat)abstract Objectives: To examine whether the mix of community and institutional long-term care (ILTC) for people with dementia (PwD) in Europe could be improved; assess the economic consequences of providing alternative services for particular groups of ILTC entrants and explore the transnational application of the ‘Balance of Care’ (BoC) approach. Method: A BoC study was undertaken in Estonia, Finland, France, Germany, the Netherlands, Spain, Sweden, and the UK as part of the RightTimePlaceCare project. Drawing on information about 2014 PwD on the margins of ILTC admission, this strategic planning framework identified people whose needs could be met in more than one setting, and compared the relative costs of the possible alternatives. Results: The findings suggest a noteworthy minority of ILTC entrants could be more appropriately supported in the community if enhanced services were available. This would not necessarily require innovative services, but more standard care (including personal and day care), assuming quality was ensured. Potential cost savings were identified in all countries, but community care was not always cheaper than ILTC and the ability to release resources varied between nations. Conclusions: This is believed to be the first transnational application of the BoC approach, and demonstrates its potential to provide a consistent approach to planning across different health and social care systems. Better comparative information is needed on the number of ILTC entrants with dementia, unit costs and outcomes. Nevertheless, the findings offer important evidence on the appropriateness of current provision, and the opportunity to learn from different countries' experience.
48.	van Beest, Floris M, et al. (författare) Classifying grey seal behaviour in relation to environmental variability and commercial fishing activity -a multivariate hidden Markov model 2019 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1 Tidskriftsartikel (refereegranskat)abstract Classifying movement behaviour of marine predators in relation to anthropogenic activity and environmental conditions is important to guide marine conservation. We studied the relationship between grey seal (Halichoerus grypus) behaviour and environmental variability in the southwestern Baltic Sea where seal-fishery conflicts are increasing. We used multiple environmental covariates and proximity to active fishing nets within a multivariate hidden Markov model (HMM) to quantify changes in movement behaviour of grey seals while at sea. Dive depth, dive duration, surface duration, horizontal displacement, and turning angle were used to identify travelling, resting and foraging states. The likelihood of seals foraging increased in deeper, colder, more saline waters, which are sites with increased primary productivity and possibly prey densities. Proximity to active fishing net also had a pronounced effect on state occupancy. The probability of seals foraging was highest <5 km from active fishing nets (51%) and decreased as distance to nets increased. However, seals used sites <5 km from active fishing nets only 3% of their time at sea highlighting an important temporal dimension in seal-fishery interactions. By coupling high-resolution oceanographic, fisheries, and grey seal movement data, our study provides a scientific basis for designing management strategies that satisfy ecological and socioeconomic demands on marine ecosystems.
49.	Vigren, Patrick, 1977- (författare) On the Kleine-Levin Syndrome 2017 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Populärvetenskaplig sammanfattning på svenska Kleine-Levins syndrom är en sömnsjukdom som beskrevs av Willi Kleine 1925 och därefter utvecklades i fallbeskrivningar av Max Levin och McDonald Chritchley. De symptom som beskrevs var återkommande sömnperioder (periodisk hypersomnia), en tendens att äta mycket i samband med dessa perioder (hyperfagi) och ökad sexdrift i samband med perioderna (hypersexualitet) och, i senare beskrivningar, kognitiva och beteendemässiga störningar. Enligt tidigare beskrivningar var patienterna återställda mellan sömnperioderna. Dessa varade i dagar-veckor och återkom flera gånger årligen. Sjukdomen debuterade vanligtvis i tonåren och beskrevs gå över efter åtta år.d avhandling beskriver diagnosens utveckling över tid och sätter forskningen i sitt teoretiska sammanhang. Med det senare menas att det diskuteras hur forskningen förhåller sig till en diagnos som förändras över tid och där olika läkare kan ha olika kunskap kring och förhållningssätt till diagnosen.De studier som ingår i avhandlingen har undersökt flera olika aspekter av Kleine-Levins syndrom. Den första studien undersökte arbetsminnet hos patienterna och kunde påvisa att det var nedsatt jämfört med friska försökspersoner, även mellan sömnperioderna, något som inte var visat systematiskt tidigare. Dessutom sågsandra aktiveringsmönster i hjärnan när patienterna försökte klara arbetsminnesuppgiften, jämfört med aktiveringsmönstren hos friska försökspersoner. Hos hälften av patienterna sågs dessutom avvikande blodflöde i delar av hjärnan även när ingen särskild arbetsuppgift utfördes. Detta sågs även hos patienter som tillfrisknat.Då det funnits hypoteser i annan forsking att sjukdomen kan ha ett genetiskt/ärftligt inslag undersöktes huruvida patienterna hade en gen som tidigare har kopplats till sjukdomen. I den grupp av patienter som undersöktes i avhandlingens sista artikel kunde dock ingen sådan koppling ses.Slutsatsen av forskningsresultaten är att (1) patienter med Kleine-Levins syndrom har en störning av arbetsminnet som verkar konstant. (2) De uppvisar andra hjärnaktiveringsmönster än friska personer som gör samma arbetsminnesuppgift. (3) Hälften av patienterna har ett avvikande blodflödesmönster även i vila och efter tillfrisknande. (4) En eventuell ärftlig komponent kan inte påvisas avseende de undersökta generna.

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