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1.	Gaulton, Kyle J, et al. (author) Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. 2015 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415 Journal article (peer-reviewed)abstract We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
2.	Scott, Robert A, et al. (author) No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels 2012 In: Diabetes. - Alexandria, VA : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:5, s. 1291-1296 Journal article (peer-reviewed)abstract Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.
3.	Feng, Shaohong, et al. (author) Dense sampling of bird diversity increases power of comparative genomics 2020 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833 Journal article (peer-reviewed)abstract Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
4.	Almgren, Peter, et al. (author) Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes 2012 In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:9, s. 981- Journal article (peer-reviewed)
5.	Escott-Price, Valentina, et al. (author) Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease 2014 In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661- Journal article (peer-reviewed)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.
6.	Jarvis, Erich D., et al. (author) Whole-genome analyses resolve early branches in the tree of life of modern birds 2014 In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331 Journal article (peer-reviewed)abstract To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
7.	Jones, Lesley, et al. (author) Convergent genetic and expression data implicate immunity in Alzheimer's disease 2015 In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671 Journal article (peer-reviewed)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.
8.	Mahajan, A, et al. (author) Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility 2014 In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:3, s. 234- Journal article (peer-reviewed)
9.	Wain, Louise V, et al. (author) Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets. 2017 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425 Journal article (peer-reviewed)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.
10.	Williamson, Alice, et al. (author) Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake 2023 In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983 Journal article (peer-reviewed)abstract Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
11.	Arrskog, Tobias, et al. (author) Hyperlocal event extraction of future events 2012 In: DeRiVE 2012: Detection, Representation, and Exploitation of Events in the Semantic Web (CEUR Workshop Proceedings). - 1613-0073. ; 902, s. 11-21 Conference paper (peer-reviewed)abstract From metropolitan areas to tiny villages, there is a wide variety of organizers of cultural, business, entertainment, and social events. These organizers publish such information to an equally wide variety of sources. Every source of published events uses its own document structure and provides dierent sets of information. This raises signicant customization issues. This paper explores the possibilities of extracting future events from a wide range of web sources, to determine if the document structure and content can be exploited for time-ecient hyperlocal event scraping. We report on two experimental knowledge-driven, pattern-based programs that scrape events from web pages using both their content and structure.
12.	Bakke, August, et al. (author) The rationale behind recommendations for follow-up after urinary diversion: An evidence-based approach 2007 In: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 41:4, s. 261-9 Research review (peer-reviewed)
13.	Beal, Jacob, et al. (author) Robust estimation of bacterial cell count from optical density 2020 In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1 Journal article (peer-reviewed)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.
14.	Berglund, Lisa, et al. (author) Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB. 2016 In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 65:1, s. 239-254 Journal article (peer-reviewed)abstract Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation is observed in endothelial and smooth muscle cells upon culture conditions yielding a "vascular disease-like" phenotype. Moreover, a common variant rs10423928 in the GIPR gene associated with increased risk of stroke in type 2 diabetes patients.
15.	Birkhofer, Klaus, et al. (author) Methods to identify the prey of invertebrate predators in terrestrial field studies 2017 In: Ecology and Evolution. - : Wiley. - 2045-7758. ; 7:6, s. 1942-1953 Journal article (peer-reviewed)abstract Predation is an interaction during which an organism kills and feeds on another organism. Past and current interest in studying predation in terrestrial habitats has yielded a number of methods to assess invertebrate predation events in terrestrial ecosystems. We provide a decision tree to select appropriate methods for individual studies. For each method, we then present a short introduction, key examples for applications, advantages and disadvantages, and an outlook to future refinements. Video and, to a lesser extent, live observations are recommended in studies that address behavioral aspects of predator-prey interactions or focus on per capita predation rates. Cage studies are only appropriate for small predator species, but often suffer from a bias via cage effects. The use of prey baits or analyses of prey remains are cheaper than other methods and have the potential to provide per capita predation estimates. These advantages often come at the cost of low taxonomic specificity. Molecular methods provide reliable estimates at a fine level of taxonomic resolution and are free of observer bias for predator species of any size. However, the current PCR-based methods lack the ability to estimate predation rates for individual predators and are more expensive than other methods. Molecular and stable isotope analyses are best suited to address systems that include a range of predator and prey species. Our review of methods strongly suggests that while in many cases individual methods are sufficient to study specific questions, combinations of methods hold a high potential to provide more holistic insights into predation events. This review presents an overview of methods to researchers that are new to the field or to particular aspects of predation ecology and provides recommendations toward the subset of suitable methods to identify the prey of invertebrate predators in terrestrial field research.
16.	Bäckström, Christer, et al. (author) Automaton Plans 2014 In: The journal of artificial intelligence research. - : AI ACCESS FOUNDATION. - 1076-9757 .- 1943-5037. ; 51, s. 255-291 Journal article (peer-reviewed)abstract Macros have long been used in planning to represent subsequences of operators. Macros can be used in place of individual operators during search, sometimes reducing the effort required to find a plan to the goal. Another use of macros is to compactly represent long plans. In this paper we introduce a novel solution concept called automaton plans in which plans are represented using hierarchies of automata. Automaton plans can be viewed as an extension of macros that enables parameterization and branching. We provide several examples that illustrate how automaton plans can be useful, both as a compact representation of exponentially long plans and as an alternative to sequential solutions in benchmark domains such as LOGISTICS and GRID. We also compare automaton plans to other compact plan representations from the literature, and find that automaton plans are strictly more expressive than macros, but strictly less expressive than HTNs and certain representations allowing efficient sequential access to the operators of the plan.
17.	Bäckström, Christer, et al. (author) From Macro Plans to Automata Plans 2012 In: ECAI 2012. 20th European Conference on Artificial Intelligence, 27-31 2012, August, Montpellier, France. - 9781614990970 - 9781614990987 ; , s. 91-96 Conference paper (peer-reviewed)abstract Macros have a long-standing role in planning as a tool for representing repeating subsequences of operators. Macros are useful both for guiding search towards a solution and for representing plans compactly. In this paper we introduce automata plans which consist of hierarchies of finite state automata. Automata plans can be viewed as an extension of macros that enables parametrization and branching. We provide several examples of the utility of automata plans, and prove that automata plans are strictly more expressive than macro plans. We also prove that automata plans admit polynomialtime sequential access of the operators in the underlying “flat” plan, and identify a subset of automata plans that admit polynomial-time random access. Finally, we compare automata plans with other representations allowing polynomial-time sequential access.
18.	Bäckström, Christer, et al. (author) Macros, Reactive Plans and Compact Representations 2012 In: ECAI 2012. 20th European Conference on Artificial Intelligence 27-31 August 2+12, Montpellier, France. - 9781614990970 - 9781614990987 ; , s. 85-90 Conference paper (peer-reviewed)abstract The use and study of compact representations of objects is widespread in computer science. AI planning can be viewed as the problem of finding a path in a graph that is implicitly described by a compact representation in a planning language. However, compact representations of the path itself (the plan) have not received much attention in the literature. Although both macro plans and reactive plans can be considered as such compact representations, little emphasis has been placed on this aspect in earlier work. There are also compact plan representations that are defined by their access properties, for instance, that they have efficient random access or efficient sequential access. We formally compare two such concepts with macro plans and reactive plans, viewed as compact representations, and provide a complete map of the relationships between them.
19.	Docherty, Anna R, et al. (author) GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors. 2023 In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738 Journal article (peer-reviewed)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.
20.	Glimelius, Bengt, et al. (author) U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden. 2018 In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194 Journal article (peer-reviewed)abstract Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
21.	Guey, Lin T., et al. (author) Power in the Phenotypic Extremes: A Simulation Study of Power in Discovery and Replication of Rare Variants 2011 In: Genetic Epidemiology. - : Wiley. - 0741-0395. ; 35:4, s. 236-246 Journal article (peer-reviewed)abstract Next-generation sequencing technologies are making it possible to study the role of rare variants in human disease. Many studies balance statistical power with cost-effectiveness by (a) sampling from phenotypic extremes and (b) utilizing a two-stage design. Two-stage designs include a broad-based discovery phase and selection of a subset of potential causal genes/variants to be further examined in independent samples. We evaluate three parameters: first, the gain in statistical power due to extreme sampling to discover causal variants; second, the informativeness of initial (Phase I) association statistics to select genes/variants for follow-up; third, the impact of extreme and random sampling in (Phase 2) replication. We present a quantitative method to select individuals from the phenotypic extremes of a binary trait, and simulate disease association studies under a variety of sample sizes and sampling schemes. First, we find that while studies sampling from extremes have excellent power to discover rare variants, they have limited power to associate them to phenotype-suggesting high false-negative rates for upcoming studies. Second, consistent with previous studies, we find that the effect sizes estimated in these studies are expected to be systematically larger compared with the overall population effect size; in a well-cited lipids study, we estimate the reported effect to be twofold larger. Third, replication studies require large samples from the general population to have sufficient power; extreme sampling could reduce the required sample size as much as fourfold. Our observations offer practical guidance for the design and interpretation of studies that utilize extreme sampling. Genet. Epidemiol. 35: 236-246, 2011. (c) 2011 Wiley-Liss, Inc.
22.	Gustavsson, Anders, et al. (author) Corrigendum to “Cost of disorders of the brain in Europe 2010” [Eur. Neuropsychopharmacol. 21 (2011) 718–779] 2012 In: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 22:3, s. 237-238 Journal article (peer-reviewed)abstract The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.
23.	Jonsson, Anders, et al. (author) Limitations of acyclic causal graphs for planning 2014 In: Artificial Intelligence. - : Elsevier. - 0004-3702 .- 1872-7921. ; 210, s. 36-55 Journal article (peer-reviewed)abstract Causal graphs are widely used in planning to capture the internal structure of planning instances. Researchers have paid special attention to the subclass of planning instances with acyclic causal graphs, which in the past have been exploited to generate hierarchical plans, to compute heuristics, and to identify classes of planning instances that are easy to solve. This naturally raises the question of whether planning is easier when the causal graph is acyclic. In this article we show that the answer to this question is no, proving that in the worst case, the problem of plan existence is PSPACE-complete even when the causal graph is acyclic. Since the variables of the planning instances in our reduction are propositional, this result applies to STRIPS planning with negative preconditions. We show that the reduction still holds if we restrict actions to have at most two preconditions. Having established that planning is hard for acyclic causal graphs, we study two subclasses of planning instances with acyclic causal graphs. One such subclass is described by propositional variables that are either irreversible or symmetrically reversible. Another subclass is described by variables with strongly connected domain transition graphs. In both cases, plan existence is bounded away from PSPACE, but in the latter case, the problem of bounded plan existence is hard, implying that optimal planning is significantly harder than satisficing planning for this class.
24.	Jonsson, Andreas P., et al. (author) Minute quantities of misfolded mutant superoxide dismutase-1 cause amyotrophic lateral sclerosis 2004 In: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 127:Pt 1, s. 73-88 Journal article (peer-reviewed)abstract Mutant forms of superoxide dismutase-1 (SOD1) cause amyotrophic lateral sclerosis (ALS) by an unknown noxious mechanism. Using an antibody against a novel epitope in the G127insTGGG mutation, mutant SOD1 was studied for the first time in spinal cord and brain of an ALS patient. The level was below 0.5% of the SOD1 level in controls. In corresponding transgenic mice the content of mutant SOD1 was also low, although it was enriched in spinal cord and brain compared with other tissues. In the mice the misfolded mutant SOD1 aggregated rapidly and 20% occurred in steady state as detergent-soluble protoaggregates. The misfolded SOD1 and the protoaggregates form, from birth until death, a potentially noxious burden that may induce the motor neuron injury. Detergent-resistant aggregates, as well as inclusions of mutant SOD1 in motor neurons and astrocytes, accumulated in spinal cord ventral horns of the patient and mice with terminal disease. The inclusions and aggregates may serve as terminal markers of long-term assault by misfolded SOD1 and protoaggregates.
25.	Jonsson, Andreas P., et al. (author) Motor neuron disease in mice expressing the wild type-like D90A mutant superoxide dismutase-1 2006 In: Journal of Neuropathology and Experimental Neurology. - : Oxford University Press (OUP). - 0022-3069 .- 1554-6578. ; 65:12, s. 1126-1136 Journal article (peer-reviewed)abstract Mutant human CuZn-superoxide dismutases (hSOD1s) cause amyotrophic lateral sclerosis (ALS). The most common mutation is the wild type-like D90A and to explore its properties, transgenic mice were generated and compared with mice expressing wild-type hSOD1. D90A hSOD1 was both in vivo in mice and in vitro under denaturing conditions nearly as stable as the wild-type human enzyme. It appeared less toxic than other tested mutants, but mice homozygous for the transgene insertion developed a fatal motor neuron disease. In these mice, the disease progression was slow and there were bladder disturbances similar to what is found in human ALS cases homozygous for the D90A mutation. The homozygous D90A mice accumulated detergent-resistant hSOD1 aggregates in spinal cords, and abundant hSOD1 inclusions and vacuoles were seen in the ventral horns. Mice expressing wild-type hSOD1 at a comparable rate showed similar pathologic changes but less and later. Hemizygous D90A mice showed even milder alterations. At 600 days, the wild-type hSOD1 transgenic mice had lost more ventral horn neurons than hemizygous D90A mice (38% vs 31% p < 0.01). Thus, wild-type hSOD1 shows a significant neurotoxicity in the spinal cord, that is less than equal but more than half as large as that of D90A mutant enzyme.
26.	Jonsson, Anders, et al. (author) When Acyclicity is not Enough: Limitations of the Causal Graph 2013 In: Proceedings of the Twenty-Third International Conference on Automated Planning and Scheduling. - : AAAI Press. - 9781577356097 ; , s. 117-125 Conference paper (peer-reviewed)abstract Causal graphs are widely used in planning to capture the internal structure of planning instances. In the past, causal graphs have been exploited to generate hierarchical plans, to compute heuristics, and to identify classes of planning instances that are easy to solve. It is generally believed that planning is easier when the causal graph is acyclic. In this paper we show that this is not true in the worst case, proving that the problem of plan existence is PSPACE-complete even when the causal graph is acyclic. Since the variables of the planning instances in our reduction are propositional, this result applies to STRIPS planning with negative pre-conditions. Having established that planning is hard for acyclic causal graphs, we study a subclass of planning instances with acyclic causal graphs whose variables have strongly connected domain transition graphs. For this class, we show that plan existence is easy, but that bounded plan existence is hard, implying that optimal planning is significantly harder than satisficing planning for this class.
27.	Jonsson, Elin, et al. (author) Differential activity of topotecan, irinotecan and SN-38 in primary cultures of human tumor cells but not in cell lines. 2000 In: Eur J Cancer. ; 36, s. 2120- Journal article (peer-reviewed)
28.	Jonsson, Leif, 1945-, et al. (author) Kommunchefers chefskap : ett lokalt präglat chefskap i politisk miljö 2002 Book (other academic/artistic)abstract Att vara kommunchef (eller kommundirektör, kanslichef) kan vara ett ensamt arbete vanligen finns det bara en i varje kommun. Till vem vänder man sig för råd och hjälp? Hur disponerar man sin tid? Vad innehåller egentligen denna specifika chefsposition? I Kommunchefers chefskap har erfarenheter och tankar från kommunchefer i Östergötland, Småland och Södermanland samlats. Under tre år har de tillsammans med forskare samarbetat kring teori och praktik för att utveckla kunskap kring vad kommunchefskapet innebär. I forskarnas analyser av kommunchefernas empiriska erfarenheter blottläggs bland annat påverkan från rådande företagsledarideal, och hur lokala förhållanden och politisk miljö inverkar. Boken kan till exempel användas vid ledarskapsutbildning i politiskt styrda organisationer, vid rekrytering av kommunchefer, eller vid utformning av kommunchefsfunktioner. Den vänder sig till personer som är praktiskt verksamma i kommuner och andra offentliga organisationer, samt till de som är allmänt intresserade av ledningsfrågor i offentliga organisationer
29.	Jonsson, Magnus P., et al. (author) Simultaneous Nanoplasmonic and Quartz Crystal Microbalance Sensing: Analysis of Biomolecular Conformational Changes and Quantification of the Bound Molecular Mass 2008 In: Analytical Chemistry. - : American Chemical Society. - 0003-2700 .- 1520-6882. ; 80:21, s. 7988-7995 Journal article (peer-reviewed)abstract This paper presents a study of supported lipid bilayer (SIB) formation and subsequent protein binding using a sensor that combines localized surface plasmon resonance (LSPR) and quartz crystal microbalance with dissipation (QCM-D) monitoring. The LSPR activity arises from silicon oxide (SiOx) coated nanometric apertures in a thin gold film, which also serves as the active electrode of a QCM-D crystal. Both transducer principles provide signatures for the formation of a SLB upon adsorption and subsequent rupture of adsorbed lipid vesicles. However, the two techniques are sensitive over different regions of the sample: LSPR primarily inside and on the rim of the holes and QCM-D primarily on the planar areas between the holes. Although the dimension of the lipid vesicles is on the same order as the dimension of the nanoholes, it is concluded from the response of the combined system that vesicle rupture in the nanoholes and on the planar region between the holes is synchronized. Furthermore, by determining the thickness of the SLB from the QCM-D response, the characteristic decay length of the LSPR field intensity could be determined. This made it possible not only to determine the mass and refractive index of the homogeneous SLB but also to postulate a generic means to quantify the LSPR response in terms of mass-uptake also for nonhomogeneous films. This is exemplified by measuring the adsorbed lipid mass during vesicle adsorption, yielding the critical lipid vesicle coverage at which spontaneous rupture into a planar bilayer occurs. The generic applicability and versatility of the method is demonstrated from specific protein binding to a functionalized SLB. From the absolute refractive index of the protein, provided from the LSPR data alone, it was possible to determine both the effective thickness of the protein film and the molecular mass (or number) of bound protein.
30.	Jonsson, P. Andreas, et al. (author) Motor neruon disase in mice expressing the wild-type like D90A mutant superoxide dismutase-1 Other publication (other academic/artistic)
31.	Kaufmann, Tobias, et al. (author) Common brain disorders are associated with heritable patterns of apparent aging of the brain 2019 In: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617- Journal article (peer-reviewed)abstract Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
32.	Kopsch, Fredrik, et al. (author) Höghastighetståg och markvärden : Delrapport 3 i forskningsprojektet “Höghastighetståg: Markvärden och finansiering” 2017 Other publication (other academic/artistic)
33.	Krokhin, Andrei, et al. (author) Constraint satisfaction problems on intervals and lengths 2004 In: SIAM Journal on Discrete Mathematics. - 0895-4801 .- 1095-7146. ; 17:3, s. 453-477 Journal article (peer-reviewed)abstract We study interval-valued constraint satisfaction problems (CSPs), in which the aim is to find an assignment of intervals to a given set of variables subject to constraints on the relative positions of intervals. Many well-known problems such as INTERVAL GRAPH RECOGNITION and INTERVAL SATISFIABILITY can be considered as examples of such CSPs. One interesting question concerning such problems is to determine exactly how the complexity of an interval-valued CSP depends on the set of constraints allowed in instances. For the framework known as Allen's interval algebra this question was completely answered earlier by the authors, by giving a complete description of the tractable cases and showing that all remaining cases are NP-complete. Here we extend the qualitative framework of Allen's algebra with additional constraints on the lengths of intervals. We allow these length constraints to be expressed as Horn disjunctive linear relations, a well-known tractable and sufficiently expressive form of constraints. The class of problems we consider contains, in particular, problems that are very closely related to the previously studied UNIT INTERVAL GRAPH SANDWICH problem. We completely characterize sets of qualitative relations for which the CSP augmented with arbitrary length constraints of the above form is tractable. We also show that, again, all the remaining cases are NP-complete.
34.	Kuivinen, Fredrik, 1981- (author) Algorithms and Hardness Results for Some Valued CSPs 2009 Doctoral thesis (other academic/artistic)abstract In the Constraint Satisfaction Problem (CSP) one is supposed to find an assignment to a set of variables so that a set of given constraints are satisfied. Many problems, both practical and theoretical, can be modelled as CSPs. As these problems are computationally hard it is interesting to investigate what kind of restrictions of the problems implies computational tractability. In this thesis the computational complexity of restrictions of two optimisation problems which are related to the CSP is studied. In optimisation problems one can also relax the requirements and ask for an approximatively good solution, instead of requiring the optimal one.The first problem we investigate is Maximum Solution (Max Sol) where one is looking for a solution which satisfies all constraints and also maximises a linear bjective function. The Maximum Solution problem is a generalisation of the well-known integer linear programming problem. In the case when the constraints are equations over an abelian group we obtain tight inapproximability results. We also study Max Sol for so-called maximal constraint languages and a partial classification theorem is obtained in this case. Finally, Max Sol over the boolean domain is studied in a setting where each variable only occurs a bounded number of times.The second problem is the Maximum Constraint Satisfaction Problem (Max CSP). In this problem one is looking for an assignment which maximises the number of satisfied constraints. We first show that if the constraints are known to give rise to an NP-hard CSP, then one cannot get arbitrarily good approximate solutions in polynomial time, unless P = NP. We use this result to show a similar hardness result for the case when only one constraint relation is used. We also study the submodular function minimisation problem (SFM) on certain finite lattices. There is a strong link between Max CSP and SFM; new tractability results for SFM implies new tractability results for Max CSP. It is conjectured that SFM is the only reason for Max CSP to be tractable, but no one has yet managed to prove this. We obtain new tractability results for SFM on diamonds and evidence which supports the hypothesis that all modular lattices are tractable.
35.	Lyssenko, Valeriya, et al. (author) Clinical risk factors, DNA variants, and the development of type 2 diabetes. 2008 In: New England Journal of Medicine. - 0028-4793. ; 359:21, s. 2220-2232 Journal article (peer-reviewed)abstract BACKGROUND: Type 2 diabetes mellitus is thought to develop from an interaction between environmental and genetic factors. We examined whether clinical or genetic factors or both could predict progression to diabetes in two prospective cohorts. METHODS: We genotyped 16 single-nucleotide polymorphisms (SNPs) and examined clinical factors in 16,061 Swedish and 2770 Finnish subjects. Type 2 diabetes developed in 2201 (11.7%) of these subjects during a median follow-up period of 23.5 years. We also studied the effect of genetic variants on changes in insulin secretion and action over time. RESULTS: Strong predictors of diabetes were a family history of the disease, an increased body-mass index, elevated liver-enzyme levels, current smoking status, and reduced measures of insulin secretion and action. Variants in 11 genes (TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX) were significantly associated with the risk of type 2 diabetes independently of clinical risk factors; variants in 8 of these genes were associated with impaired beta-cell function. The addition of specific genetic information to clinical factors slightly improved the prediction of future diabetes, with a slight increase in the area under the receiver-operating-characteristic curve from 0.74 to 0.75; however, the magnitude of the increase was significant (P=1.0x10(-4)). The discriminative power of genetic risk factors improved with an increasing duration of follow-up, whereas that of clinical risk factors decreased. CONCLUSIONS: As compared with clinical risk factors alone, common genetic variants associated with the risk of diabetes had a small effect on the ability to predict the future development of type 2 diabetes. The value of genetic factors increased with an increasing duration of follow-up.
36.	Lyssenko, Valeriya, et al. (author) Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. 2009 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 82-88 Journal article (peer-reviewed)abstract Genome-wide association studies have shown that variation in MTNR1B (melatonin receptor 1B) is associated with insulin and glucose concentrations. Here we show that the risk genotype of this SNP predicts future type 2 diabetes (T2D) in two large prospective studies. Specifically, the risk genotype was associated with impairment of early insulin response to both oral and intravenous glucose and with faster deterioration of insulin secretion over time. We also show that the MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets. Nondiabetic individuals carrying the risk allele and individuals with T2D showed increased expression of the receptor in islets. Insulin release from clonal beta cells in response to glucose was inhibited in the presence of melatonin. These data suggest that the circulating hormone melatonin, which is predominantly released from the pineal gland in the brain, is involved in the pathogenesis of T2D. Given the increased expression of MTNR1B in individuals at risk of T2D, the pathogenic effects are likely exerted via a direct inhibitory effect on beta cells. In view of these results, blocking the melatonin ligand-receptor system could be a therapeutic avenue in T2D.
37.	Lyssenko, Valeriya, et al. (author) Pleiotropic Effects of GIP on Islet Function Involve Osteopontin 2011 In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 60:9, s. 2424-2433 Journal article (peer-reviewed)abstract OBJECTIVE-The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) promotes pancreatic beta-cell function by potentiating insulin secretion and beta-cell proliferation. Recently, a combined analysis of several genome-wide association studies (Meta-analysis of Glucose and Insulin-Related Traits Consortium [MAGIC]) showed association to postprandial insulin at the GIP receptor (GIPR) locus. Here we explored mechanisms that could explain the protective effects of GIP on islet function. RESEARCH DESIGN AND METHODS-Associations of GIPR rs10423928 with metabolic and anthropometric phenotypes in both nondiabetic (N = 53,730) and type 2 diabetic individuals (N = 2,731) were explored by combining data from 11 studies.Insulin secretion was measured both in vivo in nondiabetic subjects and in vitro in islets from cadaver donors. Insulin secretion was also measured in response to exogenous GIP. The in vitro measurements included protein and gene expression as well as measurements of beta-cell viability and proliferation. RESULTS-The A allele of GIPR rs10423928 was associated with impaired glucose- and GIP-stimulated insulin secretion and a decrease in BMI, lean body mass, and waist circumference. The decrease in BMI almost completely neutralized the effect of impaired insulin secretion on risk of type 2 diabetes. Expression of GIPR mRNA was decreased in human islets from carriers of the A allele or patients with type 2 diabetes. GIP stimulated osteopontin (OPN) mRNA and protein expression. OPN expression was lower in carriers of the A allele. Both GIP and OPN prevented cytokine-induced reduction in cell viability (apoptosis). In addition, OPN stimulated cell proliferation in insulin-secreting cells. CONCLUSIONS-These findings support beta-cell proliferative and antiapoptotic roles for GIP in addition to its action as an incretin hormone. Identification of a link between GIP and OPN may shed new light on the role of GIP in preservation of functional beta-cell mass in humans. Diabetes 60:2424-2433, 2011
38.	McKinlay, Audrey, et al. (author) Service provision for children and young people with acquired brain injury : Practice recommendations 2016 In: Brain Injury. - : Informa UK Limited. - 0269-9052 .- 1362-301X. ; 30:13-14, s. 1656-1664 Journal article (peer-reviewed)abstract Background: Providing appropriate rehabilitation services for Acquired Brain Injury (ABI) in childhood presents a number of challenges for caregivers, health and education professionals and the young person as they develop. Primary objective: To record the challenges and possible creative solutions generated by an international group of professionals to address the needs of children with ABI. Review of information: Recommendations were generated from children's special interest group meetings of the International Brain Injury Association (Turin, Italy, 2001; Stockholm, Sweden, 2003; Melbourne, Australia, 2005; Lisbon, Portugal, 2008) and through meetings of the International Paediatric Brain Injury Society (IPBIS), formed in 2009. Delegates participating in the workshops were representative of nations from around the world and included The Netherlands, New Zealand, Australia, the UK, Finland, Germany, South Africa, the US, Canada, Sweden, Brazil and Italy. Outcomes: The information presented is based on a retrospective review of those meetings and the summaries of the topics considered.
39.	Mitra, M. Tanya, et al. (author) Social, educational and vocational outcomes in patients with childhood-onset and young-adult-onset growth hormone deficiency 2017 In: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 86:4, s. 526-533 Journal article (peer-reviewed)abstract Objective Hypopituitarism diagnosed in childhood, adolescence and young adulthood has the potential to affect growth and somatic development. Less is known about the impact of such a diagnosis on other aspects of development. Design An analysis of the KIMS database (Pfizer International Metabolic Database) was performed to explore social, educational and vocational outcomes of adult patients diagnosed in childhood, adolescence and young adulthood compared with adult-onset controls. Patients A total of 2952 adult patients diagnosed with hypothalamic pituitary conditions before the age of 25 were divided into two groups: childhood-onset [<16 years (CO)] (n = 1782) and young-adult-onset [16 to <25 years (YAO)] (n = 1170). A total of 1617 adult patients diagnosed with a nonfunctioning pituitary adenoma at the age of 25 or older formed the adult-onset control group (AO). Measurements KIMS Patient Life Situation Form which provided information on social, educational and vocational outcomes. Results Compared with the AO control group, CO and YAO patients were between 45 and 80 times more likely to live with their parents in adulthood; CO and YAO patients were also less likely to live in partnership and to have children. The impact on educational and vocational outcomes was less marked than on social outcomes with no significant differences compared with the AO control group. Educational and vocational outcomes showed the lowest level in male and female CO and YAO patients who had been previously diagnosed with a brain tumour. ConclusionsSocial outcomes were more affected than educational and vocational outcomes. Although CO patients are more adversely affected, YAO patients were also failing to achieve social milestones. This has consequences for the delivery of endocrine care in both paediatric and adult services.
40.	Moberg, Christina, et al. (author) De unga gör helt rätt när de stämmer staten 2022 In: Aftonbladet. - 1103-9000. Journal article (pop. science, debate, etc.)abstract 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
41.	Mullins, Niamh, et al. (author) Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors 2022 In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327 Journal article (peer-reviewed)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.
42.	Nordmark, Gunnel, et al. (author) Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome 2011 In: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 12:2, s. 100-109 Journal article (peer-reviewed)abstract We performed a candidate gene association study in 540 patients with primary Sjögren's Syndrome (SS) from Sweden (n=344) and Norway (n=196) and 532 controls (n=319 Swedish, n=213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P=9.9 × 10−5, OR 1.68, the family with sequence similarity 167 member A–B-lymphoid tyrosine kinase (FAM167A–BLK) locus, P=4.7 × 10−4, OR 1.37 and the tumor necrosis factor superfamily (TNFSF4=Ox40L) gene, P=7.4 × 10−4, OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.
43.	Paananen, Ilkka, et al. (author) Functional results after orthotopic bladder substitution : a prospective multicentre study comparing four types of neobladder 2014 In: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1813 .- 2168-1805. ; 48:1, s. 90-98 Journal article (peer-reviewed)abstract Objective: The aim of this study was to evaluate enterocystometry, voiding pattern and urine leakage of four types of orthotopic bladder substitute. Material and methods: At eight urological departments, 78 consecutive men were studied: 66 with an ileal neobladder [30 Studer pouches (S), 24 Hautmann pouches (H) and 12 T-pouches (T)] and 12 with a right colonic [Goldwasser type (G)] neobladder. Enterocystometry, determination of residual urine, micturition protocol and 24 h pad weight test were performed 6 and 12 months postoperatively. Results: Colonic neobladders had higher pouch pressure at first desire, normal desire and strong desire than ileal neobladders (except at first and normal desire at 12 months) (p < 0.02) and contraction was present more often at both 6 and 12 months (p < 0.01 and p < 0.01). Compliance was good in all types of pouch. Intermittent self-catheterization was more common in H patients at 6 months (p = 0.033). All patients with colonic neobladders used pads during the day and night. In patients with ileal pouches 32% used pads during the day and 70% during the night at 12 months. Urine leakage was higher in patients with colonic bladders at 6 and 12 months during the day (mean/median of 98/31 ml and 82/16 ml versus 10/0 ml and 4/0 ml, p < 0.001). T-pouches had excellent day-time continence, but nocturnal leakage was high. Conclusions: The Hautmann pouch and the Studer pouch behaved similarly at enterocystometry and clinically, and continence was good in the majority of patients. The low number of patients with the other two types of pouch precludes definitive statements.
44.	Stacey, Simon N, et al. (author) A germline variant in the TP53 polyadenylation signal confers cancer susceptibility. 2011 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103 Journal article (peer-reviewed)abstract To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
45.	Thapper, Johan, 1977- (author) Combinatorial Considerations on Two Models from Statistical Mechanics 2007 Licentiate thesis (other academic/artistic)abstract Interactions between combinatorics and statistical mechanics have provided many fruitful insights in both fields. A compelling example is Kuperberg’s solution to the alternating sign matrix conjecture, and its following generalisations. In this thesis we investigate two models from statistical mechanics which have received attention in recent years.The first is the fully packed loop model. A conjecture from 2001 by Razumov and Stroganov opened the field for a large ongoing investigation of the O(1) loop model and its connections to a refinement of the fully packed loop model. We apply a combinatorial bijection originally found by de Gier to an older conjecture made by Propp.The second model is the hard particle model. Recent discoveries by Fendley et al. and results by Jonsson suggests that the hard square model with cylindrical boundary conditions possess some beautiful combinatorial properties. We apply both topological and purely combinatorial methods to related independence complexes to try and gain a better understanding of this model.
46.	Thorgeirsson, Thorgeir E, et al. (author) A variant associated with nicotine dependence, lung cancer and peripheral arterial disease 2008 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 452:7187, s. 9-638 Journal article (peer-reviewed)abstract Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year(1,2). Evidence for genetic influence on smoking behaviour and nicotine dependence (ND)(3-8) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health(9,10). Smoking is the major risk factor for lung cancer (LC)(11-14) and is one of the main risk factors for peripheral arterial disease (PAD)(15-17). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking- related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genomewide association study that used low- quantity smokers as controls(18,19), and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene - environment interaction(20), highlighting the role of nicotine addiction in the pathology of other serious diseases.
47.	Tomkowski, Robert (author) The Barkhasuen Noise Measurements : Good Practice Guide 2022. - 2 Book (peer-reviewed)abstract The KTH Royal Institute of Technology (Stockholm, Sweden) as a project leader allowed strengthening collaboration between academic and industrial experts in the field of non-destructive testing (NDT), machining and metrology. This scientific consortium had found an efficient way for scientific collaboration, in which we conducted many experiments, meetings, and talks on the project’s research subject. This book is a result of all the mentioned activities and more. Many experts from both sides actively participated in the creation of this guide and are listed in the list of contributors.The authors hope that after reading this guide, BN measurements can be carried out more systematically, with higher accuracy, traceability and lower uncertainty. The authors do not aim to replace a whole raft of good textbooks, operator’s manuals, specifications, and standards (if they exist); rather, they want to present an overview of good practices and techniques. These recommendations are also a result of many discussions conducted by the project team members during the project’s duration.The book is divided into two parts. The first part of the book, “Measurement Good Practice Guide”, presents a comprehensive overview of the Barkhausen noise (BN) measurement method used to describe and analyze different features of ferromagnetic materials, such as residual stress level, hardening depth, among others. The primary focus is on mechanical parts for the automotive industry, in particular, the camshaft and crankshaft. The good practice guide is intended for those who need to make BN measurements but are not necessarily trained to use this method or are still not comfortable about measurement itself. By reading this guide, one can gain basic knowledge regarding good practices for making magnetic measurements with the BN method. Based on a few principles and tips from good practices, the reader will be able to create a Standard Operating Procedure (SOP) for their purpose. SOPs for BN are presented in the appendices.The second part of the book “Qualification and Certification of Personnel” presents requirements of the personal certification for Barkhausen testing and is aligned with applicable standards. The authors recommend performing internal and external certification of personnel to do achieve more conscious and reliable measurements.This book has been prepared by the scientific consortium under the research project FFI OFP4p – Non-Destructive Characterization Concepts for Production, 2015–2018 co-founded in 50% by VINNOVA, Sweden’s innovation agency. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights.
48.	Yasinska, Valentyna, et al. (author) Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids 2023 In: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 9:5 Journal article (peer-reviewed)abstract Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study.Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12–18 months.Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.
49.	Åslund, Andreas, et al. (author) Studies of luminescent conjugated polythiophene derivatives-Enhanced spectral discrimination of protein conformational states 2007 In: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 18:6, s. 1860-1868 Journal article (peer-reviewed)abstract Improved probes for amyloid fibril formation are advantageous for the early detection and better understanding of this disease-associated process. Here, we report a comparative study of eight luminescent conjugated polythiophene derivates (LCPs) and their discrimination of a protein (insulin) in the native or amyloid-like fibrillar state. For two of the LCPs, the synthesis is reported. Compared to their monomer-based analogues, trimer-based LCPs showed significantly better optical signal specificity for amyloid-like fibrils, seen from increased quantum yield and spectral shift. The trimer-based LCPs alone were highly quenched and showed little interaction with native insulin, as seen from analytical ultracentrifugation and insignificant spectral differences from the trimer-based LCP in buffered and native protein solution. Hence, the trimer-based LCPs showed enhanced discrimination between the amyloid-like fibrillar state and the corresponding native protein.
50.	Aaltonen, T., et al. (author) Tevatron Combination of Single-Top-Quark Cross Sections and Determination of the Magnitude of the Cabibbo-Kobayashi-Maskawa Matrix Element V-tb 2015 In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 115:15 Journal article (peer-reviewed)abstract We present the final combination of CDF and D0 measurements of cross sections for single-top-quark production in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb(-1) per experiment. The t-channel cross section is measured to be sigma(t) = 2.25(-0.31)(+0.29) pb. We also present the combinations of the two-dimensional measurements of the s- vs t-channel cross section. In addition, we give the combination of the s + t channel cross section measurement resulting in sigma(s+t) = 3.30(-0.40)(+0.52) pb, without assuming the standard model value for the ratio sigma(s)/sigma(t). The resulting value of the magnitude of the top-to-bottom quark coupling is vertical bar V-tb vertical bar = 1.02(-0.05)(+0.06), corresponding to vertical bar V-tb vertical bar > 0.92 at the 95% C. L.

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