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  • Nilsson, K. Peter R., et al. (författare)
  • Imaging distinct conformational states of amyloid-β fibrils in Alzheimer's disease using novel luminescent probes
  • 2007
  • Ingår i: ACS Chemical Biology. - 1554-8929. ; 2:8, s. 553-560
  • Tidskriftsartikel (refereegranskat)abstract
    • Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimer's disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.
  • Röder, Marko, et al. (författare)
  • Coulomb dissociation of N 20,21
  • 2016
  • Ingår i: Physical Review C - Nuclear Physics. - American Physical Society. - 0556-2813. ; 93:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutron-rich light nuclei and their reactions play an important role in the creation of chemical elements. Here, data from a Coulomb dissociation experiment on N20,21 are reported. Relativistic N20,21 ions impinged on a lead target and the Coulomb dissociation cross section was determined in a kinematically complete experiment. Using the detailed balance theorem, the N19(n,γ)N20 and N20(n,γ)N21 excitation functions and thermonuclear reaction rates have been determined. The N19(n,γ)N20 rate is up to a factor of 5 higher at T<1GK with respect to previous theoretical calculations, leading to a 10% decrease in the predicted fluorine abundance.
  • Tesi, Bianca, et al. (författare)
  • Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS and neurological symptoms
  • 2017
  • Ingår i: Blood. - American Society of Hematology. - 1528-0020. ; 129:16, s. 2266-2279
  • Tidskriftsartikel (refereegranskat)abstract
    • Several monogenic causes of familial myelodysplastic syndrome (MDS) have recently been identified. We studied two families with cytopenia, predisposition to MDS with chromosome 7 aberrations, immunodeficiency, and progressive cerebellar dysfunction. Genetic studies uncovered heterozygous missense mutations in SAMD9L, a tumor suppressor gene located on chromosome arm 7q. Consistent with a gain-of-function effect, ectopic expression of the two identified SAMD9L mutants decreased cell proliferation relative to wild-type protein. Of the ten individuals identified heterozygous for either SAMD9L mutation, three developed MDS upon loss of the mutated SAMD9L allele following intracellular infections associated with myeloid, B and NK cell deficiency. Five other individuals, three with spontaneously resolved cytopenic episodes in infancy, harbored hematopoietic revertant mosaicism by uniparental disomy of 7q with loss of the mutated allele or additional in cis SAMD9L truncating mutations. Examination of one individual indicated that somatic reversions were postnatally selected. Somatic mutations were tracked to CD34(+) hematopoietic progenitor cell populations, being further enriched in B and NK cells. Stimulation of these cell types with interferon (IFN)-α or -γ induced SAMD9L expression. Clinically, revertant mosaicism was associated with milder disease, yet neurological manifestations persisted in three individuals. Two carriers also harbored a rare, in trans germline SAMD9L missense loss-of-function variant, potentially counteracting the SAMD9L mutation. Our results demonstrate that gain-of-function mutations in the tumor suppressor SAMD9L cause cytopenia, immunodeficiency, variable neurological presentation, and predisposition to MDS with -7/del(7q), where hematopoietic revertant mosaicism commonly ameliorated clinical manifestations. The findings suggest a role for SAMD9L in regulating IFN-driven, demand-adapted hematopoiesis.
  • Ameur, Adam, et al. (författare)
  • SweGen a whole-genome data resource of genetic variability in a cross-section of the Swedish population
  • 2017
  • Ingår i: European Journal of Human Genetics. - NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
  • Angerås, Oskar, 1976-, et al. (författare)
  • Impact of Thrombus Aspiration on Mortality, Stent Thrombosis, and Stroke in Patients with ST-Segment-Elevation Myocardial Infarction: A Report From the Swedish Coronary Angiography and Angioplasty Registry
  • 2018
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background--Thrombus aspiration is still being used in a substantial number of patients despite 2 large randomized clinical trials showing no favorable effect of routine thrombus aspiration during primary percutaneous coronary intervention in patients with STsegment- elevation myocardial infarction. The aim of this observational study was to evaluate the impact of thrombus aspiration on mortality, stent thrombosis, and stroke using all available data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Methods and Results--We identified 42 829 consecutive patients registered in SCAAR between January 2005 and September 2014 who underwent percutaneous coronary intervention for ST-segment-elevation myocardial infarction. Thrombus aspiration was used in 25% of the procedures. We used instrumental variable analysis with administrative healthcare region as the treatmentpreference instrumental variable to evaluate the effect of thrombus aspiration on mortality, stent thrombosis, and stroke. Thrombus aspiration was not associated with mortality at 30 days (risk reduction: -1.2; 95% confidence interval [CI], -5.4 to 3.0; P=0.57) and 1 year (risk reduction: -2.4; 95% CI, -7.6 to 3.0; P=0.37). Thrombus aspiration was associated with a lower risk of stent thrombosis both at 30 days (risk reduction: -2.7; 95% CI, -4.1 to -1.4; P < 0.001) and 1 year (risk reduction: -3.5; 95% CI, -5.3 to -1.7; P < 0.001). In-hospital stroke and neurologic complications did not differ between groups (risk reduction: 0.1; 95% CI, -0.8 to 1.1; P=0.76). Conclusions--Mortality was not different between the groups. Thrombus aspiration was associated with decreased risk of stent thrombosis. Our study provides important evidence for the external validity of previous randomized studies regarding mortality.
  • Asciutto, Giuseppe, et al. (författare)
  • Low elastin content of carotid plaques is associated with increased risk of ipsilateral stroke.
  • 2015
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 10:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Atherosclerotic plaques with a low content of connective tissue proteins are believed to have an increased risk of rupture and to give rise to clinical events. The aim of the present study was to investigate if the content of elastin, collagen and of the matrix metalloproteinase (MMP) -1, -3, -9 and -12 in plaques removed at surgery can be associated with the occurrence of ipsilateral symptoms.
  • Berglund, Andreas, et al. (författare)
  • 15 koncept för bättre ergonomi Inom äldreomsorg, fysioterapi, däckmontering och varuhantering
  • 2015
  • Rapport (populärvet., debatt m.m.)abstract
    • Den här boken är resultatet av en kurs i ergonomi vid Teknisk design, Luleå tekniska universitet, våren 2015. 15 kursdeltagare har under 10 veckor använt designmetodik och ergonomiska teorier och metoder för att utveckla 15 konceptuella förbättringsförslag baserade på de 4 undersökta kontexterna äldreomsorg, fysioterapi, däckmontering och varuhantering. Fokus för ergonomi inom området teknisk design är att se till att all design, oavsett vilket system det avser, kompletterar människans styrkor och förmågor. Vi ska kort och gott se till att arbetsuppgifter, utrustning, apparater, processer, miljöer och organisationer utformas med människan som utgångspunkt, istället för att tvinga människan att anpassa sig med olika former av överbelastning som möjlig påföljd. För att uppnå detta behöver vi förstå och designa för den variabilitet som är representerad bland oss människor: vi är olika, har olika åldrar, storlek, styrka, kognitiv förmåga, erfarenheter, förväntningar och mål. Att tillämpa ergonomi betyder att studera hur människor interagerar med produkter, processer, miljöer och system för att förbättra dem, dvs. göra dem enklare, säkrare, bekvämare och effektivare att använda. För att kunna göra det behöver vi kunskap om människans förutsättningar och behov. Teknisk design med utgångspunkt och mål i god ergonomi innebär att exempelvis: Att designa produkter och utrustning som är enkla och tillförlitliga att använda med utgångspunkt i kunskap om kognitiv ergonomi, antropometri och belastningsergonomiska och biomekaniska analyserAtt designa säkra och effektiva tillverkningsprocesser med utgångspunkt i kunskap om kognitiv ergonomi och belastningsergonomiska analyserAtt designa organisationer utifrån kunskap om arbetslivsfysiologi och organisationsergonomiAtt designa arbetsuppgifter utifrån kunskap om kognitiv ergonomi, biomekanik och belastningsergonomiska analyserAtt designa enkla och användarvänliga gränssnitt med utgångspunkt i kognitiv ergonomiErgonomisk anpassning av en produkt eller en arbetsmiljö kan exempelvis handla om att se till att människan inte använder kroppen felaktigt. Det kan handla om fysisk belastning när en uppgift utförs, såväl som sensorisk input från olika system eller psykosocial belastning i form av stress. Det handlar om att utveckla kunskaper om människans begränsningar och förmågor, vilket ger bättre förutsättningar att bidra till användarvänliga lösningar. Det i sin tur bidrar till säkerhet och användarvänlighet och i slutändan att alla produkter, system och miljöer i vår omvärld fungerar väl för människan – det är hållbar utveckling om något. I kursen Ergonomi 2 vid civilingenjörsutbildningen Teknisk design, Luleå tekniska universitet, ingår en projektuppgift. Den syftar till att få fördjupad förståelse inom ergonomi genom att tillämpa kunskap och metoder i ett designprojekt för en verklig situation. Våren 2015 omfattade projektuppgiften att enanalys av valfri kontext, med syfte att förstå problem och utmaningar i den miljö, det sammanhang, den situation och för de personer som var berörda. Inledningsvis arbetade kursdeltagarna i grupper bestående av 3-4 personer, för att sedan gå in i en konceptutvecklingsfas individuellt. Det innebar att kursdeltagarna kunde genomföra ergonomiska analyser gemensamt och sedan utveckla konceptuella lösningar på egen hand. Det resulterade i att kursdeltagarna utvecklade tämligen olika lösningar, även om de haft en gemensam utgångspunkt. Bokens kapitel omfattar en beskrivning av respektive kontext följt av de konceptförslag som kursdeltagarna utvecklade. Som lärare är det alltid extra roligt när kursdeltagare är motiverade och engagerade inför projektuppgifter. Vår förhoppning är att det engagemanget ska framgå på följande sidor och att koncepten ska ge inspiration till att förbättra ergonomin i våra vardagsliv. Åsa Wikberg Nilsson, Therese Öhrling, Lars Sundström, Agneta Larsson och Ulrik RöijezonTeknisk design Luleå tekniska universitet, Augusti 2015
  • Björgvinsson, Erling, et al. (författare)
  • Prototyping Futures
  • 2012
  • Rapport (övrigt vetenskapligt)abstract
    • Prototyping Futures gives you a glimpse of what collaborating with academia might look like. Medea and its co-partners share their stories about activities happening at the research centre – projects, methods, tools, and approaches – what challenges lie ahead, and how these can be tackled. Examples of highlighted topics include: What is a living lab and how does it work? What are the visions behind the Connectivity Lab at Medea? And, how can prototyping-methods be used when sketching scenarios for sustainable futures? Other topics are: What is the role of the body when designing technology? What is collaborative media and how can this concept help us understand contemporary media practices? Prototyping Futures also discusses the open-hardware platform Arduino, and the concepts of open data and the Internet of Things, raising questions on how digital media and connected devices can contribute to more sustainable lifestyles, and a better world.
  • Björkelund, Anders, et al. (författare)
  • On the Integration of Skilled Robot Motions for Productivity in Manufacturing
  • 2011
  • Ingår i: IEEE International Symposium on Assembly and Manufacturing (ISAM), 2011. - IEEE - Institute of Electrical and Electronics Engineers Inc.. - 978-1-61284-343-8 - 978-1-61284-342-1 ; s. 1-9
  • Konferensbidrag (refereegranskat)abstract
    • Robots used in manufacturing today are tailored to their tasks by system integration based on expert knowledge concerning both production and machine control. For upcoming new generations of even more flexible robot solutions, in applications such as dexterous assembly, the robot setup and programming gets even more challenging. Reuse of solutions in terms of parameters, controls, process tuning, and of software modules in general then gets increasingly important. There has been valuable progress within reuse of automation solutions when machines comply with standards and behave according to nominal models. However, more flexible robots with sensor-based manipulation skills and congnitive functions for human inteaction are far too complex to manage, and solutions are rarely reusable since knowledge is either implicit in imperative software or not captured in machine readable form. We propose techniques that build on existing knowledge by converting structured data into an RDF-based knowledge base. By enhancements of industrial control systems and available engineering tools, such knowledge can be gradually extended as part of the interaction during the definition of the robot task.
  • Brunk, Elizabeth, et al. (författare)
  • Recon3D enables a three-dimensional view of gene variation in human metabolism
  • 2018
  • Ingår i: Nature Biotechnology. - 1087-0156. ; 36:3, s. 272-281
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-scale network reconstructions have helped uncover the molecular basis of metabolism. Here we present Recon3D, a computational resource that includes three-dimensional (3D) metabolite and protein structure data and enables integrated analyses of metabolic functions in humans. We use Recon3D to functionally characterize mutations associated with disease, and identify metabolic response signatures that are caused by exposure to certain drugs. Recon3D represents the most comprehensive human metabolic network model to date, accounting for 3,288 open reading frames (representing 17% of functionally annotated human genes), 13,543 metabolic reactions involving 4,140 unique metabolites, and 12,890 protein structures. These data provide a unique resource for investigating molecular mechanisms of human metabolism. Recon3D is available at http://vmh.life.
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