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  • Public defence: 2019-09-11 13:15 B42 BMC, Uppsala
    Omar-Hmeadi, Muhmmad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Regulation of docking and priming in pancreatic α- and β-cells2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The secretion of islet hormones from endocrine cells of the pancreas plays vital roles in maintaining glucose homeostasis. Dysfunction of these cells leads to diabetes, a devastating metabolic disorder affecting millions worldwide, but underlying mechanisms remain poorly understood. In hyperglycemic conditions, β-cells secrete insulin, whereas α-cells secrete an increased amount of glucagon in hypoglycemic conditions. Both insulin and glucagon are stored in secretory granules preceding their release by regulated exocytosis. This process involves several steps, including tethering, docking, priming, and finally, a fusion of the granules with the plasma membrane. Soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) proteins and phosphoinositides (PIs) drive pancreatic hormone exocytosis and secretion, which follows a biphasic time course. Biphasic secretion is thought to reflect the vastly different release probabilities of individual granules, but direct evidence for this is still lacking.  Therefore, this thesis investigates exocytosis in the two main pancreatic cell types with a particular focus on preceding steps docking and priming, to identify rate-limiting steps in health and type-2 diabetes (T2D). Our data indicated that granule docking is critical for sustained secretion in α- and β-cells. Glucagon granule exocytosis had a U-shaped sensitivity to glucose in both healthy and T2D α-cells. However, T2D α-cells exhibited a marginal decrease in exocytosis, as well as docking, and they were markedly insensitive to somatostatin and insulin. T2D β-cells reduced exocytosis dramatically, and docking was compromised and no longer responsive to glucose, which correlated with reduced insulin secretion and elevated donor HbA1c. These results were further strengthened by the finding that expression of a group of genes that are involved explicitly in granule docking was reduced (by RNAseq of islets from over 200 human donors), and overexpression of the corresponding proteins increased granule docking in human β-cells.

    We further aimed to study the basis for the recruitment of these proteins to the docking site. Here we tested the hypothesis that highly charged lipids mainly PIs act as a hotspot to interact with SNARE proteins that initiate docking. We showed the homogenous distribution of all PIs markers in the plasma membrane, with no PIs microdomains at the exocytotic site during granule docking. However, rapid and local PI(4,5)P2 signaling at fusion sites was crucial for stabilizing fusion pore by binding to proteins related to the release site. These results suggested a role of PI(4,5)P2 in priming and fusion regulation rather than docking. Overall, this work gives new insights into the mechanisms underlying pancreatic hormone secretion in both healthy and diabetic conditions.

    List of papers
    1. Glucose-Dependent Granule Docking Limits Insulin Secretion and Is Decreased in Human Type 2 Diabetes
    Open this publication in new window or tab >>Glucose-Dependent Granule Docking Limits Insulin Secretion and Is Decreased in Human Type 2 Diabetes
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    2018 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 27, no 2, p. 470-478Article in journal (Refereed) Published
    Abstract [en]

    Glucose-stimulated insulin secretion is biphasic, with a rapid first phase and a slowly developing sustained second phase; both are disturbed in type 2 diabetes (T2D). Biphasic secretion results from vastly different release probabilities of individual insulin granules, but the morphological and molecular basis for this is unclear. Here, we show that human insulin secretion and exocytosis critically depend on the availability of membrane-docked granules and that T2D is associated with a strong reduction in granule docking. Glucose accelerated granule docking, and this effect was absent in T2D. Newly docked granules only slowly acquired release competence; this was regulated by major signaling pathways, but not glucose. Gene expression analysis indicated that key proteins involved in granule docking are downregulated in T2D, and overexpression of these proteins increased granule docking. The findings establish granule docking as an important glucose-dependent step in human insulin secretion that is dysregulated in T2D.

    Keywords
    GLP-1, biphasic secretion, dense core vesicle, docking, exocytosis, genome-wide association, insulin secretion, priming, somatostatin, type 2 diabetes
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-341518 (URN)10.1016/j.cmet.2017.12.017 (DOI)000424465200021 ()29414688 (PubMedID)
    Funder
    Swedish Research CouncilSwedish Diabetes AssociationSwedish Society for Medical Research (SSMF)The Swedish Brain FoundationNovo NordiskErnfors Foundation
    Available from: 2018-02-09 Created: 2018-02-09 Last updated: 2019-08-02Bibliographically approved
    2. Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes
    Open this publication in new window or tab >>Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-389793 (URN)
    Available from: 2019-07-27 Created: 2019-07-27 Last updated: 2019-08-02
    3. PtdIns(4,5)P2 is not required for secretory granule docking
    Open this publication in new window or tab >>PtdIns(4,5)P2 is not required for secretory granule docking
    2018 (English)In: Traffic: the International Journal of Intracellular Transport, ISSN 1398-9219, E-ISSN 1600-0854, Vol. 19, no 6, p. 436-445Article in journal (Refereed) Published
    Abstract [en]

    Phosphoinositides (PtdIns) play important roles in exocytosis and are thought to regulate secretory granule docking by co-clustering with the SNARE protein syntaxin to form a docking receptor in the plasma membrane. Here we tested this idea by high-resolution total internal reflection imaging of EGFP-labeled PtdIns markers or syntaxin-1 at secretory granule release sites in live insulin-secreting cells. In intact cells, PtdIns markers distributed evenly across the plasma membrane with no preference for granule docking sites. In contrast, syntaxin-1 was found clustered in the plasma membrane, mostly beneath docked granules. We also observed rapid accumulation of syntaxin-1 at sites where granules arrived to dock. Acute depletion of plasma membrane phosphatidylinositol (4,5) bisphosphate (PtdIns(4,5)P-2) by recruitment of a 5-phosphatase strongly inhibited Ca2+-dependent exocytosis, but had no effect on docked granules or the distribution and clustering of syntaxin-1. Cell permeabilization by -toxin or formaldehyde-fixation caused PtdIns marker to slowly cluster, in part near docked granules. In summary, our data indicate that PtdIns(4,5)P-2 accelerates granule priming, but challenge a role of PtdIns in secretory granule docking or clustering of syntaxin-1 at the release site.

    Keywords
    exocytosis, insulin, live cell imaging, phosphoinositides, PtdIns(4, 5)P-2, syntaxin clustering, vesicle docking
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-356858 (URN)10.1111/tra.12562 (DOI)000432037000005 ()29542271 (PubMedID)
    Funder
    Swedish Research CouncilSwedish Child Diabetes FoundationSwedish Society for Medical Research (SSMF)Novo NordiskThe Swedish Brain FoundationErnfors Foundation
    Available from: 2018-08-15 Created: 2018-08-15 Last updated: 2019-08-02Bibliographically approved
    4. Fusion pore regulation by transient local generation of PI(4,5)P2 in pancreatic in β-cells
    Open this publication in new window or tab >>Fusion pore regulation by transient local generation of PI(4,5)P2 in pancreatic in β-cells
    (English)Manuscript (preprint) (Other academic)
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-389794 (URN)
    Available from: 2019-07-27 Created: 2019-07-27 Last updated: 2019-08-02
  • Andersdotter, Karolina
    Uppsala University, University Library.
    Public Art and Policy: Educating Library Users and Accidental Recidivists in Copyright Literacy2019In: Icepops Annual 2019: Proceedings of the International Copyright-literacy Event with Playful Opportunities for Practitioners and Scholars. Held at the University of Liverpool 3rd April 2018. / [ed] Secker, Jane; Morrison, Chris, London: UK Copyright Literacy , 2019, p. 44-45Conference paper (Other academic)
    Abstract [en]

    The paper describes a copyright literacy/art map project which had the initial purpose to educate library users and accidental recidivists in copyright literacy. While library users were the first target group (due to the public library event for which I created the map proto-types), the target group could most certainly be extended to the general public.

    The project takes the form of art maps published online with clear markings on whether the art object (statue, sculpture etc.) is selfie safe; i.e. whether it is possible to take a photograph which depicts the public art piece and then publish it in a database online (e.g. through social media).

  • Sigfridson, Marcus
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Skyddsinfiltrationens influensområde för en fallstudie: - modellering och osäkerheter2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    To evaluate the area of influence due to artificial infiltration several analytical models are available. Some of the parameters taken into account by these models are the hydraulic conductivity and storage coefficient, but with these models some assumptions, which in reality cannot be fulfilled, are made. An alternative approach to evaluate the area of influence is therefore with numerical models, which in a greater extent account for the site-specific conditions. Due to this, numerical models are more time consuming and require more input data.

    This project aims to investigate the most effective approaches to evaluate the area of influence due to artificial infiltration for a case study in Bromsten, located 15 kilometers northwest of Stockholm. Two numerical models, with different background data due to the extent of site knowledge, were developed to represent the site's geological settings and groundwater properties to simulate the groundwaterlevels with and without infiltration. Moreover the area of influence were calculated with four analytical models. All of the models were then applied on four different scenarios, in which the data resolution and the site knowledge increased. Site-specific data was added as a result of geological surveys and hydrogeological tests. The study also aims to answer which data is most important in order to determine the area of influence with analytical and numerical models and what differences there are between the analytical solutions compared with the numerical solutions.

    Among the methods investigated, constructing a more complex model with data from scenario 4, the scenario with the greatest data supply, resulted in the most reliable results and was therefore the best method and the method to choose for this case-study. Other results indicated that the numerical models first of all are sensitive to the conductivity and that the more simpel numerical model is sensitive to the storage coefficient as well. The last result shows that this model does not reach the steady state conditions as observed in field, which highlights the importance of goetechnical investigation for the numerical models. Moreover none of the numerical models were sensitive to the specific yield. Among the analytical models the storage coefficient was the most important followed by the conductivity. For one of the analytical models (Sichardts formula) the conductivity was the most sensitive parameter. The thickness of the aquifer had no significant impact on the analytical models.

  • Daud, Taufik
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Jassem, Andam
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Anpassningar för grundskoleelever med funktionsnedsättningen ADHD2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • Lindqvist, Sandra
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Vilken effekt har framtida klimat på strömningsmönster i Ekoln - en modelleringsstudie baserad på MIKE 3 FM2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    For centuries in the future, the climate on Earth will be affected by the global warming.Effects as melting ices, increasing sea levels and extreme weather, are all consequencesof the high amount of carbon dioxide (CO2), that we humans have caused. In Sweden,can climate effects like higher temperatures, longer vegetation periods and greaterseasonal variations in water fluxes, be expected. Due to climate changes and anincreasing population, the drinking water production in Uppsala will be affected. Interms of securing the drinking water production in the future, Uppsala Vatten och Avfall AB are investigating the possibility to use the Ekoln basin in lake Mälaren, as acomplementary raw water catchment area.

    In order to keep a secure drinking water production, in regard to quantity and quality, itis of interest to investigate how fluxes and water quality will be affected in the future.The annual pattern of water mixing, with summer- and winter stratification, and overturnduring spring and autumn, is something that significantly affects the water quality in theSwedish lakes. With the aim to study how the annual pattern of water mixing in theEkoln basin, might change due to future climate changes, hydrodynamic modelling wasperformed on a model area consisting of the Ekoln basin with adjacently bays.

    A hydrodynamic (3D) transport model of type MIKE 3 Flow Model FM, created byTyréns AB for simulating transport of pollutions, was calibrated and adapted to simulatetemperature profiles in the model area. To be able to study the annual pattern of watermixing, the model was also adapted to simulate a period of a year. Three scenarios weresimulated, one reference year and two future scenarios, where the future scenarios werebased on the climate scenarios RCP4.5 and RCP8.5 in year 2050.

    The calibration of the model was successful, and the calculation time was reduced byadapting the mesh. Results from the three scenarios, showed that the period with summerstratification might become nine days longer by RCP4.5 in year 2050, compared to thereference scenario. Simulation of RCP8.5 during the same time period, did not showany changes. By RCP8.5 it is possible that water temperatures in the epilimnion, areincreasing and that there will be no winter stratification. The temperature in the surfacewater are affected by the air temperature, in future studies it is in interest to investigatehow stratification and cirkulation will be affected by changes in wind speed and winddirection, how different types of wind data effect the results, it is also in interest to studychanges during a time period longer than one year.

  • Dufbäck, Emma
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences.
    Nitrogen Uptake by Vegetation in the Wakkerstroom Wetland, South Africa2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The lack of proper wastewater treatment inhibits the social and economic development in many communities. The South African town Wakkerstroom is an example where wastewater is first treated before it is released. Due to the lack of technical expertise and funding to manage the sewage disposal system, a large part of the wastewater goes directly, without any treatment, into a stream feeding the Wakkerstroom wetland. The wetland purifies the wastewater and provides clean water downstream, thus is indispensable for its detoxification capacity.

    One relatively cheap method to determine the absorption capacity of a wetland with respect to nitrogen loading is to investigate the nitrogen uptake by the wetland vegetation. In this study, the nitrogen uptake of the vegetation in the Wakkerstroom wetland during the growing seasons between the years 2000-2018 was investigated by using harvested biomass and its nitrogen content as a proxy. The interannual variability of Net Primary Production (NPP) was calculated using a Light Use Efficiency (LUE) model for the period 2000-2018. The NPP derived with LUE-modelling was compared to NPP based on an end-of season harvest of biomass in March 2019. The nitrogen content and carbon and nitrogen (C:N) ratio were determined in the harvested biomass by carbon and nitrogen content analysis. The annual nitrogen uptake of the growing seasons between the years 2000-2018 was subsequently determined by multiplying the calculated NPP by the fraction of nitrogen found in the harvested material.

    The NPPtot based on harvested biomass (NPPharvest) towards the end of the growing season 2018/2019 was estimated to be 2.01 kg‧m-2‧season-1. The NPPtot calculated from LUE modelling (NPPLUE) varied between 0.49-1.64 kg‧m-2 for the growing seasons between 2000-2018. NPPharvest was between 1.2-4 times higher compared to NPPLUE, probably due to overestimation of NPPharvest because of biomass sampling of more than one-year production, or underestimation of NPPLUE due to a low maximum radiation conversion efficiency factor, εmax. The community mean nitrogen (N) content found in the biomass harvested aboveground was 1.29 % for the Phragmites community and 1.00 % for the Typha community. The nitrogen uptake of the vegetation was estimated to vary between 6.10-20.5 g N∙m-2 per growing season between the years 2000-2018.

  • Hane, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Computing Science.
    Angergård, Madeleine
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Computing Science.
    Do people actually listen to ads in podcasts?: A study about how machine learning can be used to gain insight in listening behaviour2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Today, listening to podcasts is a common way of consuming media and it has been proven that listeners are much more recipient to advertisement when being addressed in a podcast, rather than through radio. This study has been performed at Acast, an audio-on-demand and podcast platform that hosts, monetizes, and distributes podcasts globally. With the use of machine learning, the goal of this study has been to obtain a credible estimate of how listeners outside the application tend to respond when exposed to ads in podcasts. The study includes a number of different machine learning models, such as Random Forest, Logistic Regression, Neural Networks and kNN. It was shown that machine learning could be applied to obtain a credible estimate of how ads are received outside the Acast application, based on data collected from the application. Additionally, out of the models included in the study, Random Forest was proven being the best performing model for this problem. Please note that the results presented in the report are based on a mix of real and simulated data.

  • Andersson, Oliver
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Government.
    Democratic Consolidation: Thailand’s attempt at democracy2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The purpose of this dissertation was to examine the process of democratic consolidation in Thailand between 1997-2006.  The country’s consolidation of democracy has been hampered by continuous cycle of coup d’états which throughout history have halted the overall process of democratization. The coup of 2006 is one example of those instances where the democratic consolidation process was interrupted.

     

    The method used to examine the years of 1997-2006 was theory consuming by qualitative text analysis where the data used to assess the situation was qualitative. The theory of democratic consolidation was offered by Juan J. Linz and Alfred Stepan. The theory’s prerequisites were applied to examine the case study of Thailand. The theory chosen were hoped to give a plausible explanation for the failure of democratic consolidation in the case of Thailand. It was also hoped that it could assess the overall quality of Thai democracy and possibly give a better insight in why military coups seem to be a reoccurring phenomenon in the case of Thailand.

  • Winbergh, Göran
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Archaeology and Ancient History.
    Elit och tvång, eller släkt och rådslag?: Två tolkningar av makten på Gotland under romersk järnålder2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    In the archaeological research about the Baltic Sea island of Gotland during Roman Iron Age, 0–400 AD, two different approaches are visible: One that sees the community life on Gotland as different from the one on the main land with a relative stabile development, based on the family and kin, where no higher elite separate itself. The other perception emanates from the changes in southern Scandinavia, where an elite steadily grows and finally isolate itself as an aristocracy with unlimited power over others, the development on Gotland is no exception.

    This paper is about describing, investigating and explaining these two points of view. By using a selection of written sources the paper tries to answer three questions: What archaeological argumentations are there for that Gotland should be particular? What support the views that the island was a part of an over-regional development when it comes to struggle for power? What lies behind these very diverse positions among archaeological scholars?

    Two scholars, Kerstin Cassel and Frands Herschend, represents the two opposite standpoints and the three questions are to be answered by a comparison with two of their main archaeological works. This comparison, based on the other written sources and my own understanding, will show that the two different views on the gotlandish development can be traced to, more than anything, the two writers pre-understanding of their own scientific argumentations.

  • Svensson, Helena
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History.
    Hillefors grynkvarn: En studie i industriell arkitektur2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Den här uppsatsen är en studie i industriell arkitektur och då specifikt Hillefors grynkvarn. Mitt syfte är ta reda på hur den exteriöra arkitekturen har anpassats och formats efter kvarnens inre verksamhet och geografiska läge. Den industrianläggning jag fokuserar på är kvarnen byggd i tegel 1913, tillbyggd 1929 och 1940, fram till dess att den industriella verksamheten avslutades 1987. Anledningen till mitt val av ämne är att industribyggnader icke placerade i storstadsområde ofta inte är dokumenterade i samma utsträckning. Den metod som använts är empirisk forskning på plats för att undersöka kvarnens placering i terrängen, exteriöra respektive interiöra utformning samt dess maskinpark. Arkiv-och litteraturstudier har genomförts. Resultatet och analysen av mitt arbete visar på att Hillefors grynkvarns placering i terrängen samt exteriöra arkitektur har formats efter dess inre verksamhet. Havregrynstillverkningen kräver ett uppfordringsverk som innebär att utrymme uppåt måste finnas. Kvarnens placering vid ett stup ner mot Säveån har gjort det möjligt att bygga sutteräng i fyra våningar vilket verksamheten var i behov av. Havren levererades av bönder vid våning fyra och föll succesivt via magasin ner i byggnaden för att sedan genom uppfodringsverket transporteras uppåt via remtransmisson. Kraften att driva kvarnens turbiner kom från Säveån via en vattenränna.

  • Samuelsson, Charlotte
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History.
    "Viktigast ändå är drivkraften": Kvinnliga bild- och formkonstnärer om betydelsen av olika kapital2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Syftet med uppsatsen är att beskriva vilken betydelse kvinnliga konstnärer upplever att eget kapital i form av framför allt utbildning, ekonomi och sociala relationer har haft för deras konstnärskap. Det empiriska materialet är av kvalitativ karaktär och består av enkätsvar från 256 kvinnliga bild- och formkonstnärer. Svaren skrivna med egna ord har analyserats med kvalitativ innehållsanalys. Pierre Bourdieus begrepp kapital utgör uppsatsens teoretiska ram.

  • Frick, Urszula
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History.
    Culture in motion: Material culture in the inventory of Catherine Jagiellon’s dowry from 1562 and its analysis from culture transfer perspective2019Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    On the 4th of October 1562, the Polish princess Catherine Jagiellon married the Swedish prince and duke of Finland Johan Vasa. Leaving Poland, Catherine Jagiellon was equipped with a very rich dowry and followed by an entourage of nearly 50 people. The objective of this study is to investigate the objects and people surrounding the newly wedded 16th century princess and asses if the document mirrors the complex cultural interactions of the early modern world. The analysis of the inventory is carried out using two theoretical approaches: material culture and culture transfer. The study is constructed in two parts. The first part focuses on the analysis of the sections of the inventory following the order of the document. If possible, the objects are mapped, their history is traced through the sources, their appearance and function are discussed. The examination of the members of the court is also carried out. With the deepened analysis of the inventory as a basis, the second part of the study is dedicated to the search of culture hybridization markers in described artefacts, people, practices as well as the language of the document itself. With the result of this investigation, the author is able to pinpoint the complex international cultural processes that were occurring in an early modern world.

  • Axelsson Blomqvist, Erik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History.
    Hembygd och museer: En undersökning om den svenska hembygdsrörelsens förhållande till länsmuseerna2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Syftet med denna studie har varit att undersöka förhållandet mellan den svenska hembygdsrörelsen och länsmuseerna, för att ta reda på om det finns ett fungerande samarbete mellan dem, vad samarbetet innefattar, hur attityderna gentemot samarbete är och om länsmuseerna har något formellt ansvar för att bedriva samarbete med hembygdsrörelsen. Studien har genomförts huvudsakligen genom litteraturstudier samt två enkätundersökningar och presenterar resultat för varje län i Sverige. De genomförda undersökningarna har visat på att det i varje län generellt finns välfungerande samarbeten av någon omfattning mellan de båda parterna. Samarbetena kretsar kring ett antal olika områden såsom vanligtvis rådgivning, kursverksamhet, projekt, administration med mera. Attityderna till samarbete uppfattas från båda parter generellt vara goda, de anser att de kan komplettera varandra och gemensamt kan dra nytta av välfungerande samarbeten. Länsmuseerna har inget formellt ansvar för att samverka med hembygdsrörelsen men det finns ett antal dokument som uttrycker att samarbete är önskvärt och bör eftersträvas.

  • Dahl, Humla
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History, Conservation.
    Solcellspaneler på kulturhistoriska tak – En skänk från ovan?: En komparativ fallstudie om Fläckebo kyrka och Stuguns nya kyrka2019Independent thesis Basic level (degree of Bachelor), 180 HE creditsStudent thesis
    Abstract [sv]

    Följande undersökning är en komparativ fallstudie av två tillståndsansökningar, genomförda i enlighet med Kulturmiljölag 1988:950, gällande solcellspaneler på kyrkligt kulturminne. Undersökningar belyser Fläckebo kyrka i Västmanlands län och Stuguns nya kyrka i Jämtlands län och studerar hur dessa fått avslag, respektive bifall till montering av solcellspaneler på kyrkobyggnadernas tak. Syftet med undersökningen är att studera om KML-relaterade ärenden bedöms olika i tid och rum.För att förklara skillnaderna mellan fallen används analysmetoden ”Most Similar Systems Design”. Undersökningen visar att rättspraxis är oförändrat men att praxis vid handläggning av dessa ärenden skiljer sig åt.

  • Martijn, Joran
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Anders E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Schön, Max E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Spiertz, Ian
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Juzokaite, Lina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bunikis, Ignas
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pettersson, Olga V.
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ettema, Thijs J. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab. Wageningen Univ, Dept Agrotechnol & Food Sci, Lab Microbiol, NL-6708 WE Wageningen, Netherlands.
    Confident phylogenetic identification of uncultured prokaryotes through long read amplicon sequencing of the 16S-ITS-23S rRNA operon2019In: Environmental Microbiology, ISSN 1462-2912, E-ISSN 1462-2920, Vol. 21, no 7, p. 2485-2498Article in journal (Refereed)
    Abstract [en]

    Amplicon sequencing of the 16S rRNA gene is the predominant method to quantify microbial compositions and to discover novel lineages. However, traditional short amplicons often do not contain enough information to confidently resolve their phylogeny. Here we present a cost-effective protocol that amplifies a large part of the rRNA operon and sequences the amplicons with PacBio technology. We tested our method on a mock community and developed a read-curation pipeline that reduces the overall read error rate to 0.18%. Applying our method on four environmental samples, we captured near full-length rRNA operon amplicons from a large diversity of prokaryotes. The method operated at moderately high-throughput (22286-37,850 raw ccs reads) and generated a large amount of putative novel archaeal 23S rRNA gene sequences compared to the archaeal SILVA database. These long amplicons allowed for higher resolution during taxonomic classification by means of long (similar to 1000 bp) 16S rRNA gene fragments and for substantially more confident phylogenies by means of combined near full-length 16S and 23S rRNA gene sequences, compared to shorter traditional amplicons (250 bp of the 16S rRNA gene). We recommend our method to those who wish to cost-effectively and confidently estimate the phylogenetic diversity of prokaryotes in environmental samples at high throughput.

  • Middlemiss Lé Mon, Martha
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Uppsala Religion and Society Research Centre.
    Exhausted Women, Exhausted Welfare and the Role of Religion2019In: Social Inclusion, ISSN 2183-2803, E-ISSN 2183-2803, Vol. 7, no 2, p. 1-3Article in journal (Other academic)
    Abstract [en]

    This themed collection is bound together by some foundational observations which have been well documented in earlier research. European post-war welfare systems face challenges related to aging populations, globalization, migration, changing patterns of family and gender roles. The post-war model of welfare dependent on the idea of stable heterosexual families, with male breadwinners and women carers is giving way to more individualized and mobile systems. The four articles and commentary in this issue provide glimpses of the issues within this field that unite contexts as diverse as the Nordic countries, Brazil and the United States. They explore the intersection of welfare, religion and gender charting gendered problems in welfare provision in relation to religious organisation, affiliation and identity. This issue provides examples of how the exhaustion of women and welfare systems is interconnected and the understanding of this crucial to any attempts to reform welfare systems to enhance social inclusion or reduce exclusion.

  • Blachucki, Wojciech
    et al.
    Polish Acad Sci, Inst Phys Chem, 44-52 Kasprzaka St, PL-01224 Warsaw, Poland.
    Czapla-Masztafiak, Joanna
    Polish Acad Sci, Inst Nucl Phys, 152 Radzikowskiego St, PL-31342 Krakow, Poland.
    Sá, Jacinto
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry. Polish Acad Sci, Inst Phys Chem, 44-52 Kasprzaka St, PL-01224 Warsaw, Poland.
    Szlachetko, Jakub
    Polish Acad Sci, Inst Nucl Phys, 152 Radzikowskiego St, PL-31342 Krakow, Poland.
    A laboratory-based double X-ray spectrometer for simultaneous X-ray emission and X-ray absorption studies2019In: Journal of Analytical Atomic Spectrometry, ISSN 0267-9477, E-ISSN 1364-5544, Vol. 34, no 7, p. 1409-1415Article in journal (Refereed)
    Abstract [en]

    X-ray spectroscopy studies are usually performed using synchrotron radiation sources, which offer bright, coherent, energy-tuneable and monochromatic light. However, the application of synchrotron-based Xray emission spectroscopy (XES) and X-ray absorption spectroscopy (XAS) is directly constrained by the limited, infrequent access to central facilities. With the advent of new technological solutions in the field of X-ray sources, optics and detectors, the development of efficient and compact laboratory X-ray spectroscopy systems is possible. A permanent laboratory-based setup offers the advantages of low cost and easy accessibility and, therefore, more flexibility in the preparation and scheduling of measurements. Herein, we report a laboratory X-ray setup allowing simultaneous XES and XAS measurements. The double von Hamos spectrometer performances are demonstrated by concurrent K beta XES and K-edge XAS measurements done for 3d elements.

  • Lokken, Jorn Olav
    et al.
    Norwegian Inst Nat Res, POB 5685, NO-7485 Trondheim, Norway;Norwegian Univ Sci & Technol, Dept Biol, Trondheim, Norway.
    Hofgaard, Annika
    Norwegian Inst Nat Res, POB 5685, NO-7485 Trondheim, Norway.
    Dalen, Linda
    Norwegian Environm Agcy, Trondheim, Norway.
    Hytteborn, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Grazing and warming effects on shrub growth and plant species composition in subalpine dry tundra: An experimental approach2019In: Journal of Vegetation Science, ISSN 1100-9233, E-ISSN 1654-1103, Vol. 30, no 4, p. 698-708Article in journal (Refereed)
    Abstract [en]

    Questions

    Vegetation in the forest–tundra ecotone faces changes in both climate and land‐use. While climate warming is an important driver of vegetation growth and composition, herbivory may have opposing effects. In the present study, we experimentally test how removal of sheep herbivory affects the vegetation in an alpine forest–tundra ecotone, and how responses are manifested at higher temperatures.

    Location

    Dovre Mountains, Central Norway.

    Methods

    Shrub growth (height and cover) and ground layer composition were analysed each third year over an 18‐year period in a nested, three‐factorial experiment (ambient temperature and herbivory; ambient temperature and no herbivory; increased temperature and no herbivory). Fencing and open‐top‐chambers were used as expedients. Treatment effects and interactions over time were analysed using linear mixed effects models and ordination.

    Results

    Shrub height and cover increased over time due to reduced herbivory, but without additional warming effect. Lichen cover declined in all treatments over time, but more rapidly and earlier under warming treatment (significant after three years). Contrary to expectations, there was no statistically significant increase in woody species due to warming, although evergreen woody species displayed a trend shift after six years, comprising a sharp decline towards year twelve. Litter accumulated in all treatments, but at higher rates under warming (significant after nine years).

    Conclusions

    Our results disclose removal of sheep herbivory as a prominent driver of shrub growth, with warming as a subordinate driver in the studied alpine vegetation. The warming‐driven increased litter abundance may, however, be caused by the decrease of wind inside chambers and the subsequent absence of wind‐driven removal of litter. This chamber effect and the displayed timing differences in vegetation responses call for the critical use of short‐term experimental data in predictions of long‐term consequences of environmental change.

  • Herner, William
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Game Design.
    Leiman, Edward
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Game Design.
    How does toxicity change depending on rank in League of Legends?2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This thesis aims to investigate toxic remarks in three different ranks in League of Legends, Bronze, Gold, and Diamond. The purpose is to understand how toxic communication between players would change depending on rank. A framework from Neto, Alvino and Becker (2018) was adopted to define and count toxic remarks. The method relied on participant observation to gather data; three different ranks were specified for data collection. Fifteen games were played in each of the ranks; Bronze, Gold, and Diamond. Each game was recorded, transcribed and analyzed by dividing each toxic remark registered into Neto, Alvino and Becker’s predetermined categories. The study concluded that domain language is more often used by players with a higher rank, meaning that high ranked players tend to use toxicity that requires previous game knowledge to understand. On the contrary, low ranked players tend to stick to basic complaints and insults when using toxicity to remark teammates while playing. 

  • Ansgariusson, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Game Design.
    Selleby, Patrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Game Design.
    Game or watch: The effect of interactivity on arousal and immersion in horror game media2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of the study was to determine if interactivity would affect how immersed and aroused the participants would become when exposed to horror media with different levels of interactivity. Two groups of participants were asked to either play or watch a virtual scenario. The participants had their heart rate measured using an activity bracelet and eyes tracked using a Tobii 4C eye tracker. The study found that as interactivity increased, so did arousal, whilst immersion did not. The results indicated that cutscenes may result in significantly lower levels of arousal, compared to interactive gameplay.

  • Lemkhül, Niklas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Game Design.
    Man, Raoul
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Game Design.
    How Do Different DLC Delivery Methods Impact Appeal and Effectiveness2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Downloadable content (DLC) distribution models employ various methods to keep consumers interested. Some methods encourage consumers to purchase and engage with a DLC model and some methods discourage consumers from engaging with the model. This study seeks to determine which models keep consumers interested and which discourage consumers from purchasing DLC. We do this by reaching out to multiplayer communities of four different games that are affected by different models and have them fill out a survey regarding their purchasing behaviour. After analysing the results, we concluded that models that require players to own the same DLC in order to play together or that utilize watermarks for DLC that are not owned, are less effective at incentivizing players to purchase when compared to models that either allow players to share DLC, or acquire it through in-game means.

  • Dvizac, Nino
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Turismens utsläpp på Gotland2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The tourism industry is accounted for high monetary revenues but is also responsible for a high amount of emissions globally. In this study the emissions from the tourism sector are discussed with a special focus on the Swedish island, Gotland. Because Gotland is an island there are limited ways to travel to the island. There are generally three ways to get to the island, by ferry, airplane or by a cruise ship. Approximately 70% of the tourists travel by ferry and it is therefore the focus of this study. In this study emissions from tourism were calculated by the travel to and from the island, and during the stay. Emissions from transport on the island to various destinations were calculated as well as emissions from accommodations. The result from the study shows that the tourism on Gotland has far lower emissions than the general global tourism. This is mostly due to the low emissions from the electric production in Sweden.

  • Barkino, Iliam
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Scientific Computing.
    Summary Statistic Selection with Reinforcement Learning2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Multi-armed bandit (MAB) algorithms could be used to select a subset of the k most informative summary statistics, from a pool of m possible summary statistics, by reformulating the subset selection problem as a MAB problem. This is suggested by experiments that tested five MAB algorithms (Direct, Halving, SAR, OCBA-m, and Racing) on the reformulated problem and comparing the results to two established subset selection algorithms (Minimizing Entropy and Approximate Sufficiency). The MAB algorithms yielded errors at par with the established methods, but in only a fraction of the time. Establishing MAB algorithms as a new standard for summary statistics subset selection could therefore save numerous scientists substantial amounts of time when selecting summary statistics for approximate bayesian computation.

  • Public defence: 2019-09-13 10:30 Zootissalen, Uppsala
    Campbell, Charles
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Sphagnum limits: Physiology, morphology and climate2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Sphagnum is the most important plant genus in terms of terrestrial carbon cycling. It and the habitats it creates store an equivalent of ~68% of the CO2 in the atmosphere. The genus has little dispersal limitation and the mire habitats are functionally similar at global scales. Sphagnum species are limited by water deficit at local and biogeographic scales, but this alone is not sufficient to explain local and global scale species patterns. As Sphagnum shoots are long-lived they may be limited by stochastic periods of cold temperature. Within Europe, species are associated with climate gradients along north-south (cold-warm) and oceanic-continental (wet-dry) clines. Within mires, species are sorted along a moisture (hummock-hollow) gradient.

    In this thesis I examined species responses to and recovery from freezing (I). I compared species with different water level niches in traits related to water management of individual shoots and colonies (II). Using distribution modelling of GBIF data, I estimated how different aspects of climate contributed to Sphagnum species distributions in Europe (III). Combining the approaches in papers II and III, I modelled the climatic distributions of the parapatric species S. cuspidatum and S. lindbergii and assessed how traits of water economy varied across the distribution boundary (IV).

    Species responses to winter stress were largely allied to both their hydrological niche and geographic range. Generally, hollow species managed better than hummock species, but species from intermediate positions were less consistent in their response. Species associated with boreal regions were generally less affected than those from temperate regions. Hardening against low temperature was triggered by shorter days and cold nights. Cold temperatures during late autumn may be more important for Sphagnum limits than the minimum temperature during winter.

    Water-related traits split the species into two groups; hollows species with large capitula and hummock species with small capitula. However, inter- and intra-specific trait variation and trait trends along the hydrological gradient were not necessarily the same at the shoot and canopy scale. Some trait correlations were common to all species. Canopy traits, which were emergent traits of colonies of shoots, had the strongest trait associations with the species position along the hummock-hollow gradient.

    At the continental scale the distribution of most Sphagnum species could be successfully modelled by a combination of annual degree days and water balance and the degree of seasonality in these two variables. Individual species distributions were shaped more by the seasonality in degree days than in water balance.

    Across the distributional border of S. cuspidatum and S. lindbergii divergence in the measured traits was mostly seen in the capitula indicating that limits to Sphagnum species are strongly linked to the functioning of the capitulum. Capitulum mass of both species was lower in sympatry than in allopatry, even though the measured values were similar. Canopy traits most strongly separated the species though did not change across the species boundaries.

    In summary, Sphagnum species in general are limited by the availability of water. Low temperature, particularly during late autumn are probably decisive for the biogeographic limits and for the distribution of species along the hydrological gradient.

    List of papers
    1. The effects of winter stress on Sphagnum specieswith contrasting macro- and microdistributions
    Open this publication in new window or tab >>The effects of winter stress on Sphagnum specieswith contrasting macro- and microdistributions
    2019 (English)In: Journal of Bryology, ISSN 0373-6687, E-ISSN 1743-2820Article in journal (Refereed) Published
    Place, publisher, year, edition, pages
    Taylor & Francis, 2019
    National Category
    Ecology
    Identifiers
    urn:nbn:se:uu:diva-387429 (URN)10.1080/03736687.2019.1626167 (DOI)
    Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-07-29
    2. Structural traits of Sphagnum: Interrelationships and implications on water economy
    Open this publication in new window or tab >>Structural traits of Sphagnum: Interrelationships and implications on water economy
    (English)Manuscript (preprint) (Other academic)
    National Category
    Ecology
    Identifiers
    urn:nbn:se:uu:diva-387441 (URN)
    Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-06-24
    3. Climatic drivers of Sphagnum species distributions
    Open this publication in new window or tab >>Climatic drivers of Sphagnum species distributions
    (English)Manuscript (preprint) (Other academic)
    National Category
    Ecology
    Identifiers
    urn:nbn:se:uu:diva-387440 (URN)
    Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-06-24
    4. Trait variation across species distribution boundaries in Sphagnum
    Open this publication in new window or tab >>Trait variation across species distribution boundaries in Sphagnum
    (English)Manuscript (preprint) (Other academic)
    National Category
    Ecology
    Identifiers
    urn:nbn:se:uu:diva-387436 (URN)
    Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-06-24
  • Bergqvist, Louise
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Ridsportens miljö- och klimatpåverkan: Miljöarbete bland Sveriges ridklubbar2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Our society is facing challenges from a changing climate and environmental issues, which makes it important for everyone to take action for a better future. Equestrian sports, one of Sweden’s biggest sports, also have a part to play. The Swedish Equestrian Federation has a sustainability and environmental strategy since 2016, and seeks to continuously improve their environmental work. The present study aims to investigate how riding clubs work with two out of five sections presented in the strategy: Education and Operational management of stables. Impact from equestrian activities includes the six categories fodder, manure handling, electricity comsumption, transportation, horse and rider equipment. and chemicals, which, in this study are linked to Sweden’s environmental objective. It is clear that horses and stabling have significant impact on both the nearby environment and is a contributing factor to global warming, though the level of impact ranges depending on the type of actions taken to reduce the ecological footprint. A survey was conducted to find out how the Swedish riding associations works with environmental and climate issues, including education and the operational management of the categories listed above. The main finding in the survey is a communication gap between the Swedish Equestrian Federation and the riding associations, as well as a lack of knowledge of the environmental and climate impact from equestrian activities.

  • Mao, Robin
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economics.
    Jonsson, Arvid
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economics.
    Spellagens påverkan på aktiekurser: En eventstudie om huruvida beviljandet av spellicens har en positiv påverkan på spelbolagens aktier2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Den svenska riksdagen röstade 2018-06-07 ja till regeringens förslag om en ny spellag. Den nya spellagen innebär bland annat införandet av ett licenssystem för spelbolag verksamma på den svenska spelmarknaden. Denna studie undersöker huruvida nyheter om beviljade licenser leder till positiv avkastning hos spelbolagens aktier. För att undersöka effekten av nyheterna utförs en eventstudie med licensierade spelbolag på den svenska och norska aktiemarknaden. Eventstudien undersöker eventfönster som består av en, fem, tio och tjugo dagar där signifikansen testas genom ett t-test. Resultaten visar att den kumulativa genomsnittliga abnormala avkastningen är signifikant för eventfönster med längd av en dag, men icke-signifikant för eventfönster med längd av fem, tio och tjugo dagar.

  • Magnusson, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Karolinska Inst, Dept Med, Cardiol Res Unit, Stockholm, Sweden.
    Kihlstrom, Gabriella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Wallhagen, Marita
    Univ Gavle, Dept Bldg Energy & Environm Engn, Gavle, Sweden.
    Rambaree, Komalsingh
    Univ Gavle, Dept Social Work & Psychol, Gavle, Sweden.
    Life-threatening peripartum cardiomyopathy-Not expected when expecting2019In: Clinical Case Reports, E-ISSN 2050-0904, Vol. 7, no 6, p. 1127-1132Article in journal (Refereed)
    Abstract [en]

    Key Clinical Message Peripartum cardiomyopathy is challenging to diagnose as it mimics symptoms present in normal pregnancy. The clinical course and prognosis are various. In selected cases, a cardioverter implantable defibrillator with/without cardiac resynchronization therapy, mechanical ventricular assist device treatment, and transplantation is indicated.

  • Hitte, Christophe
    et al.
    Univ Rennes, CNRS, IGDR, UMR 6290, F-35000 Rennes, France.
    Le Beguec, Celine
    Univ Rennes, CNRS, IGDR, UMR 6290, F-35000 Rennes, France.
    Cadieu, Edouard
    Univ Rennes, CNRS, IGDR, UMR 6290, F-35000 Rennes, France.
    Wucher, Valentin
    Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain.
    Primot, Aline
    Univ Rennes, CNRS, IGDR, UMR 6290, F-35000 Rennes, France.
    Prouteau, Pings
    Univ Rennes, CNRS, IGDR, UMR 6290, F-35000 Rennes, France.
    Botherel, Nadine
    Univ Rennes, CNRS, IGDR, UMR 6290, F-35000 Rennes, France.
    Hedan, Benoit
    Univ Rennes, CNRS, IGDR, UMR 6290, F-35000 Rennes, France.
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Andre, Catherine
    Univ Rennes, CNRS, IGDR, UMR 6290, F-35000 Rennes, France.
    Derrien, Thomas
    Univ Rennes, CNRS, IGDR, UMR 6290, F-35000 Rennes, France.
    Genome-Wide Analysis of Long Non-Coding RNA Profiles in Canine Oral Melanomas2019In: Genes, ISSN 2073-4425, E-ISSN 2073-4425, Vol. 10, no 6, article id 477Article in journal (Refereed)
    Abstract [en]

    Mucosal melanomas (MM) are rare aggressive cancers in humans, and one of the most common forms of oral cancers in dogs. Similar biological and histological features are shared between MM in both species, making dogs a powerful model for comparative oncology studies of melanomas. Although exome sequencing recently identified recurrent coding mutations in canine MM, little is known about changes in non-coding gene expression, and more particularly, in canine long non-coding RNAs (lncRNAs), which are commonly dysregulated in human cancers. Here, we sampled a large cohort (n = 52) of canine normal/tumor oral MM from three predisposed breeds (poodles, Labrador retrievers, and golden retrievers), and used deep transcriptome sequencing to identify more than 400 differentially expressed (DE) lncRNAs. We further prioritized candidate lncRNAs by comparative genomic analysis to pinpoint 26 dog-human conserved DE lncRNAs, including SOX21-AS, ZEB2-AS, and CASC15 lncRNAs. Using unsupervised co-expression network analysis with coding genes, we inferred the potential functions of the DE lncRNAs, suggesting associations with cancer-related genes, cell cycle, and carbohydrate metabolism Gene Ontology (GO) terms. Finally, we exploited our multi-breed design to identify DE lncRNAs within breeds. This study provides a unique transcriptomic resource for studying oral melanoma in dogs, and highlights lncRNAs that may potentially be diagnostic or therapeutic targets for human and veterinary medicine.

  • Megquier, Kate
    et al.
    Broad Inst MIT & Harvard, Vertebrate Genom, Cambridge, MA 02142 USA.
    Genereux, Diane P.
    Broad Inst MIT & Harvard, Vertebrate Genom, Cambridge, MA 02142 USA.
    Hekman, Jessica
    Broad Inst MIT & Harvard, Vertebrate Genom, Cambridge, MA 02142 USA.
    Swofford, Ross
    Broad Inst MIT & Harvard, Vertebrate Genom, Cambridge, MA 02142 USA.
    Turner-Maier, Jason
    Broad Inst MIT & Harvard, Vertebrate Genom, Cambridge, MA 02142 USA.
    Johnson, Jeremy
    Broad Inst MIT & Harvard, Vertebrate Genom, Cambridge, MA 02142 USA.
    Alonso, Jacob
    Broad Inst MIT & Harvard, Vertebrate Genom, Cambridge, MA 02142 USA.
    Li, Xue
    Broad Inst MIT & Harvard, Vertebrate Genom, Cambridge, MA 02142 USA;Univ Massachusetts, Bioinformat & Integrat Biol, Med Sch, Worcester, MA 01655 USA.
    Morrill, Kathleen
    Broad Inst MIT & Harvard, Vertebrate Genom, Cambridge, MA 02142 USA;Univ Massachusetts, Bioinformat & Integrat Biol, Med Sch, Worcester, MA 01655 USA.
    Anguish, Lynne J.
    Cornell Univ, Coll Vet Med, Baker Inst Anim Hlth, Ithaca, NY 14853 USA.
    Koltookian, Michele
    Broad Inst MIT & Harvard, Vertebrate Genom, Cambridge, MA 02142 USA.
    Logan, Brittney
    Univ Massachusetts, Bioinformat & Integrat Biol, Med Sch, Worcester, MA 01655 USA.
    Sharp, Claire R.
    Murdoch Univ, Coll Vet Med, Sch Vet & Life Sci, Murdoch, WA 6150, Australia.
    Ferrer, Lluis
    Univ Autonoma Barcelona, Dept Med & Cirurgia Anim, Vet Sch, E-08193 Barcelona, Spain.
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Broad Inst MIT & Harvard, Vertebrate Genom, Cambridge, MA 02142 USA.
    Meyers-Wallen, Vicki N.
    Cornell Univ, Coll Vet Med, Baker Inst Anim Hlth, Ithaca, NY 14850 USA;Cornell Univ, Coll Vet Med, Dept Biomed Sci, Ithaca, NY 14850 USA.
    Hoffman, Andrew
    Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA;Tufts Univ, Cummings Sch Vet Med, Grafton, MA 01536 USA.
    Karlsson, Elinor K.
    Broad Inst MIT & Harvard, Vertebrate Genom, Cambridge, MA 02142 USA;Univ Massachusetts, Bioinformat & Integrat Biol, Med Sch, Worcester, MA 01655 USA;Univ Massachusetts, Med Sch, Program Mol Med, Worcester, MA 01655 USA.
    BarkBase: Epigenomic Annotation of Canine Genomes2019In: Genes, ISSN 2073-4425, E-ISSN 2073-4425, Vol. 10, no 6, article id 433Article in journal (Refereed)
    Abstract [en]

    Dogs are an unparalleled natural model for investigating the genetics of health and disease, particularly for complex diseases like cancer. Comprehensive genomic annotation of regulatory elements active in healthy canine tissues is crucial both for identifying candidate causal variants and for designing functional studies needed to translate genetic associations into disease insight. Currently, canine geneticists rely primarily on annotations of the human or mouse genome that have been remapped to dog, an approach that misses dog-specific features. Here, we describe BarkBase, a canine epigenomic resource available at barkbase.org. BarkBase hosts data for 27 adult tissue types, with biological replicates, and for one sample of up to five tissues sampled at each of four carefully staged embryonic time points. RNA sequencing is complemented with whole genome sequencing and with assay for transposase-accessible chromatin using sequencing (ATAC-seq), which identifies open chromatin regions. By including replicates, we can more confidently discern tissue-specific transcripts and assess differential gene expression between tissues and timepoints. By offering data in easy-to-use file formats, through a visual browser modeled on similar genomic resources for human, BarkBase introduces a powerful new resource to support comparative studies in dogs and humans.

  • Fürsten Maxe, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Tallberg, Lukas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Instagram, Youtube och Fortnite: Den digitaliserade världens inverkan på barns motivation och attityd till det engelska språket2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • Hill, Jason
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Stockholm Univ, Dept Zool, Populat Genet, Stockholm, Sweden.
    Rastas, Pasi
    Univ Helsinki, Inst Biotechnol, Helsinki, Finland.
    Hornett, Emily A.
    Univ Cambridge, Dept Zool, Cambridge, England;Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England;Univ Liverpool Liverpool Sch Trop Med, Dept Vector Biol, Liverpool, Merseyside, England.
    Neethiraj, Ramprasad
    Stockholm Univ, Dept Zool, Populat Genet, Stockholm, Sweden.
    Clark, Nathan
    Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA.
    Morehouse, Nathan
    Univ Cincinnati, Dept Biol Sci, Cincinnati, OH 45221 USA.
    Celorio-Mancera, Maria de la Paz
    Stockholm Univ, Dept Zool, Populat Genet, Stockholm, Sweden.
    Cols, Jofre Carnicer
    Univ Barcelona, Dept Evolutionary Biol Ecol & Environm Sci, E-08028 Barcelona, Spain;Autonomous Univ Barcelona, Global Ecol Unit, CREAF, Cerdanyola Dell Valles 08193, Spain.
    Dircksen, Heinrich
    Stockholm Univ, Dept Zool, Funct Morphol, Stockholm, Sweden.
    Meslin, Camille
    Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA;INRA, Inst Ecol & Environm Sci Paris, Dept Sensory Ecol, Route St Cyr, F-78026 Versailles, France.
    Keehnen, Naomi
    Stockholm Univ, Dept Zool, Populat Genet, Stockholm, Sweden.
    Pruisscher, Peter
    Stockholm Univ, Dept Zool, Populat Genet, Stockholm, Sweden.
    Sikkink, Kristin
    Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA;Univ Mississippi, Dept Biol, University, MS 38677 USA.
    Vives, Maria
    Univ Barcelona, Dept Evolutionary Biol Ecol & Environm Sci, E-08028 Barcelona, Spain;Autonomous Univ Barcelona, Global Ecol Unit, CREAF, Cerdanyola Dell Valles 08193, Spain.
    Vogel, Heiko
    Max Planck Inst Chem Ecol, Dept Entomol, D-07745 Jena, Germany.
    Wiklund, Christer
    Stockholm Univ, Dept Zool, Populat Genet, Stockholm, Sweden.
    Woronik, Alyssa
    Stockholm Univ, Dept Zool, Populat Genet, Stockholm, Sweden;NYU, Ctr Dev Genet, Dept Biol, 100 Washington Sq East, New York, NY 10003 USA.
    Boggs, Carol L.
    Univ South Carolina, Dept Biol Sci, Columbia, SC 29208 USA.
    Nylin, Soren
    Stockholm Univ, Dept Zool, Populat Genet, Stockholm, Sweden.
    Wheat, Christopher W.
    Stockholm Univ, Dept Zool, Populat Genet, Stockholm, Sweden.
    Unprecedented reorganization of holocentric chromosomes provides insights into the enigma of lepidopteran chromosome evolution2019In: Science Advances, E-ISSN 2375-2548, Vol. 5, no 6, article id eaau3648Article in journal (Refereed)
    Abstract [en]

    Chromosome evolution presents an enigma in the mega-diverse Lepidoptera. Most species exhibit constrained chromosome evolution with nearly identical haploid chromosome counts and chromosome-level gene collinearity among species more than 140 million years divergent. However, a few species possess radically inflated chromosomal counts due to extensive fission and fusion events. To address this enigma of constraint in the face of an exceptional ability to change, we investigated an unprecedented reorganization of the standard lepidopteran chromosome structure in the green-veined white butterfly (Pieris napi). We find that gene content in P. napi has been extensively rearranged in large collinear blocks, which until now have been masked by a haploid chromosome number close to the lepidopteran average. We observe that ancient chromosome ends have been maintained and collinear blocks are enriched for functionally related genes suggesting both a mechanism and a possible role for selection in determining the boundaries of these genome-wide rearrangements.

  • Andersson, Emma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Industrial Engineering & Management.
    Uppdraget och ansvaret: En fallstudie hur några lärare uppfattar sitt uppdrag och dess ansvar på en grundskola2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    During the last couple of years, an increasing number of teachers have chosen to leave their profession in the world of teaching. There a number of reasons as to why teachers are leaving their current employment; some teachers describe their administrative workload being overwhelming whilst others state that the general responsibility at the workplace has increased. In addition, some teachers declare that the general workload also has increased. Nowadays there is a lack of educated teachers, approximately around 60 000 vacant posts need to be filled in the Swedish school-system. In a school, located in the south of Sweden, there has been a large shift of employees. There has been a large number of teachers, who have been on sick leave or left their employment voluntarily. In a pre-study, made in the spring of 2019, which this essay is based on, ambiguities were identified in regard to the job description and the division of responsibility, in the teaching profession. In order to carry out the study of this essay, a case study with an abductive approach was chosen to investigate the factors behind the problems previously mentioned, in the previously mentioned a south-Swedish school. The premise of the study was to present different factors which influence and support the teachers’ mission. The intention of the essay was to identify and map factors which can promote mission- and responsibility-comprehension in the school.  To enable the essay and the study, the following questions were used: Which factors are hindering the teachers’ mission- and responsibility comprehension? and Which factors create mission- and responsibility comprehension?. To understand the teachers’ challenges in everyday tasks and discover possible factors that are influencing the teachers’ mission, the author of the essay has studied results which previous research has produced. The collection of data is a qualitative data collection method consisting of observations of teachers as well as individual with the teachers. In chapter 4, results, the results of the observation-schedule and the teachers’ dictums are presented. The factors which obstructed the teachers in their daily work were (1) Digitalized communication, (2) Confidence and honesty between staff, (3) Lack of cooperation between colleagues, (4) The meeting’s agenda, which took time from the teachers’ work, (5) The lack of leadership and (6) The teachers’ working methods. The factors which promoted mission- and responsibility comprehension were (1) The teachers’ comprehension of their mission, (2) The structure of the meetings, in the shape of a scheduled day and time for the meeting, (3) The motivation and dedication the teachers feel for their job as well as (4) The willingness to cooperate between teachers. To create better opportunities for mission- and responsibility comprehension, a PDSA-cycle was presented for the continuation of the work improvement for the school.

  • Al-Jebari, Yahia
    et al.
    Lund Univ, Mol Reprod Med, Dept Translat Med, Malmo, Sweden.
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Div Clin Epidemiol, Dept Med, Stockholm, Sweden.
    Nord, Carina Berglund
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Cohn-Cedermark, Gabriella
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Stahl, Olof
    Skane Univ Hosp, Dept Oncol, Lund, Sweden.
    Tandstad, Torgrim
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Fac Med & Hlth Sci, Trondheim, Norway;St Olavs Univ Hosp, Canc Clin, Trondheim, Norway.
    Jensen, Allan
    Danish Canc Soc Res Ctr, Virus Lifestyle & Genes, Copenhagen, Denmark.
    Haugnes, Hege Sagstuen
    Univ Hosp North Norway, Dept Oncol, Tromso, Norway;UiT Arctic Univ Norway, Inst Clin Med, Tromso, Norway.
    Daugaard, Gedske
    Rigshosp, Dept Oncol, Copenhagen Univ Hosp, Copenhagen, Denmark.
    Rylander, Lars
    Lund Univ, Div Occupat & Environm Med, Lund, Sweden.
    Giwercman, Aleksander
    Lund Univ, Mol Reprod Med, Dept Translat Med, Malmo, Sweden.
    Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer: A nationwide register study2019In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 16, no 6, article id e1002816Article in journal (Refereed)
    Abstract [en]

    Background Because of the potential mutagenic effects of chemo- and radiotherapy, there is concern regarding increased risk of congenital malformations (CMs) among children of fathers with cancer. Previous register studies indicate increased CM risk among children conceived after paternal cancer but lack data on oncological treatment. Increased CM risk was recently reported in children born before paternal cancer. This study aims to investigate whether anti-neoplastic treatment for testicular germ-cell cancer (TGCC) implies additional CM risk. Methods and findings In this nationwide register study, all singletons born in Sweden 1994-2014 (n = 2,027,997) were included. Paternal TGCC diagnoses (n = 2,380), anti-neoplastic treatment, and offspring CMs were gathered from the Swedish Norwegian Testicular Cancer Group (SWENOTECA) and the Swedish Medical Birth Register. Children were grouped based on +/- paternal TGCC; treatment regimen: surveillance (n = 1,340), chemotherapy (n = 2,533), or radiotherapy (n = 360); and according to time of conception: pre- (n = 2,770) or post-treatment (n = 1,437). Odds ratios (ORs) for CMs were calculated using logistic regression with adjustment for parental ages, maternal body mass index (BMI), and maternal smoking. Children conceived before a specific treatment acted as reference for children conceived after the same treatment. Among children fathered by men with TGCC (n = 4,207), 184 had a CM. The risk of malformations was higher among children of fathers with TGCC compared with children fathered by men without TGCC (OR 1.28, 95% confidence interval [CI] 1.19-1.38, p = 0.001, 4.4% versus 3.5%). However, no additional risk increase was associated with oncological treatment when comparing post-treatment-to pretreatment-conceived children (chemotherapy, OR = 0.82, 95% CI 0.54-1.25, p = 0.37, 4.1% versus 4.6%; radiotherapy, OR = 1.01, 95% CI 0.25-4.12, p = 0.98, 3.2% versus 3.0%). Study limitations include lack of data on use of cryopreserved or donor sperm and on seminoma patients for the period 1995-2000-both tending to decrease the difference between the groups with TGCC and without TGCC. Furthermore, the power of analyses on chemotherapy intensity and radiotherapy was limited. Conclusions No additional increased risk of CMs was observed in children of men with TGCC treated with radio- or chemotherapy. However, paternal TGCC per se was associated with modestly increased risk for offspring malformations. Clinically, this information can reassure concerned patients.

  • Shanahan, Danielle F.
    et al.
    Zealandia Ctr People & Nat, Wellington 6012, New Zealand.
    Astell-Burt, Thomas
    Univ Wollongong, Sch Hlth & Soc, Populat Wellbeing & Environm Res Lab PowerLab, Wollongong, NSW 2522, Australia.
    Barber, Elizabeth A.
    Univ Queensland, Sch Publ Hlth, Brisbane, Qld 4006, Australia.
    Brymer, Eric
    Australian Coll Appl Psychol, Discipline Psychol, Brisbane, Qld 4000, Australia.
    C., Daniel T.
    Univ Exeter, Environm & Sustainabil Inst, Penryn TR10 9EZ, Cornwall, England.
    Dean, Julie
    Univ Queensland, Sch Publ Hlth, Brisbane, Qld 4006, Australia.
    Depledge, Michael
    Univ Exeter, Sch Med, European Ctr Environm & Human Hlth, Exeter EX1 2LU, Devon, England.
    Fuller, Richard A.
    Univ Queensland, Sch Biol Sci, Brisbane, Qld 4072, Australia.
    Hartig, Terry
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Institute for Housing and Urban Research.
    Irvine, Katherine N.
    James Hutton Inst, Social Econ & Geog Sci, Aberdeen AB15 8QH, Scotland.
    Jones, Andy
    Univ East Anglia, Norwich Med Sch, Norwich NR15 1LT, Norfolk, England.
    Kikillus, Heidy
    Victoria Univ Wellington, Ctr Biodivers & Restorat Ecol, Wellington 6012, New Zealand.
    Lovell, Rebecca
    Univ Exeter, Sch Med, European Ctr Environm & Human Hlth, Truro TR1 3HD, England.
    Mitchell, Richard
    Univ Glasgow, Ctr Res Environm Soc & Hlth, Glasgow G12 8QQ, Lanark, Scotland.
    Niemelae, Jari
    Univ Helsinki, Dept Environm Sci, Helsinki 00014, Finland.
    Nieuwenhuijsen, Mark
    Barcelona Inst Global Hlth, ISGlobal, Barcelona Biomed Res Pk PRBB, Barcelona 08003, Spain.
    Pretty, Jules
    Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England.
    Townsend, Mardie
    Deakin Univ, Sch Hlth & Social Dev, Geelong, Vic 3217, Australia.
    van Heezik, Yolanda
    Univ Otago, Dept Zool, Dunedin 9016, New Zealand.
    Warber, Sara
    Univ Michigan, Integrat Med, Ann Arbor, MI 48710 USA.
    Gaston, Kevin J.
    Univ Exeter, Environm & Sustainabil Inst, Penryn TR10 9EZ, Cornwall, England.
    Nature-Based Interventions for Improving Health and Wellbeing: The Purpose, the People and the Outcomes2019In: SPORTS, ISSN 2075-4663, Vol. 7, no 6, article id 141Article in journal (Refereed)
    Abstract [en]

    Engagement with nature is an important part of many people's lives, and the health and wellbeing benefits of nature-based activities are becoming increasingly recognised across disciplines from city planning to medicine. Despite this, urbanisation, challenges of modern life and environmental degradation are leading to a reduction in both the quantity and the quality of nature experiences. Nature-based health interventions (NBIs) can facilitate behavioural change through a somewhat structured promotion of nature-based experiences and, in doing so, promote improved physical, mental and social health and wellbeing. We conducted a Delphi expert elicitation process with 19 experts from seven countries (all named authors on this paper) to identify the different forms that such interventions take, the potential health outcomes and the target beneficiaries. In total, 27 NBIs were identified, aiming to prevent illness, promote wellbeing and treat specific physical, mental or social health and wellbeing conditions. These interventions were broadly categorized into those that change the environment in which people live, work, learn, recreate or heal (for example, the provision of gardens in hospitals or parks in cities) and those that change behaviour (for example, engaging people through organized programmes or other activities). We also noted the range of factors (such as socioeconomic variation) that will inevitably influence the extent to which these interventions succeed. We conclude with a call for research to identify the drivers influencing the effectiveness of NBIs in enhancing health and wellbeing.

  • Hermann, Robert
    et al.
    Cr Appliance, Heinrich Vingerhut Weg 3, D-63571 Gelnhausen, Germany.
    Litwin, Jeffrey S.
    WCG Clin, Princeton, NJ USA.
    Friberg, Lena E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Dangond, Fernando
    EMD Serono Inc, Billerica, MA USA.
    Munafo, Alain
    Merck Inst Pharmacometr, Quantitat Pharmacol, Lausanne, Switzerland.
    Effects of cladribine tablets on heart rate, atrio-ventricular conduction and cardiac repolarization in patients with relapsing multiple sclerosis2019In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 85, no 7, p. 1484-1494Article in journal (Refereed)
    Abstract [en]

    Aims Cladribine tablets have shown significant efficacy for the treatment of relapsing multiple sclerosis, a chronic and debilitating immune-mediated disorder. This study was conducted to examine acute and/or cumulative effects of cladribine tablets 10 mg (3.5 or 5.25 mg/kg cumulative dose over 2 years) on heart rate, AV conduction and cardiac repolarization in patients with relapsing-remitting multiple sclerosis (RRMS). Methods CLARITY was a 96-week, double-blind, placebo-controlled, multicentre trial which evaluated the safety and efficacy of cladribine tablets 3.5 and 5.25 mg/kg body weight in patients with RRMS. A total of 135 patients were included in the ECG substudy, providing a total of 1534 post-dose ECGs. ECG data were collected 15 minutes pre-dose and between 0.5 and 3 hours post-dose at pre-study evaluation, study Day 1 and Weeks 5, 9, 13, 48 and 52. Results For cladribine tablets 3.5 mg/kg, the maximum change in placebo-adjusted post-dose QTcF vs. visit-baseline (BL) was -0.42 ms (90% CI: -3.61-4.44) at Week 1 (acute effects), and 3.20 ms (90% CI: -0.08-6.33) for cladribine tablets 5.25 mg/kg. The greatest observed differences in post-dose QTcF vs. study BL occurred at Week 48 for both the 3.5 and 5.25 mg/kg doses of cladribine tablets with 5.99 ms (90% CI: 0.53-11.44) and 8.74 ms (90% CI: 3.18-14.31), respectively. No significant changes were observed in T-wave morphology in either treatment group. Conclusions Cladribine tablets 3.5 mg/kg (approved dose in Europe/other regions) did not confer clinically meaningful effects on heart rate, AV conduction and ventricular repolarization.

  • Högvall, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Vellutini, Bruno C.
    Univ Bergen, Sars Int Ctr Marine Mol Biol, Thormohlensgate 55, N-5006 Bergen, Norway;Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany.
    Martin-Duran, Jose M.
    Univ Bergen, Sars Int Ctr Marine Mol Biol, Thormohlensgate 55, N-5006 Bergen, Norway;Queen Mary Univ London, Sch Biol & Chem Sci, Mile End Rd, London E1 4NS, England.
    Hejnol, Andreas
    Univ Bergen, Sars Int Ctr Marine Mol Biol, Thormohlensgate 55, N-5006 Bergen, Norway.
    Budd, Graham
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Janssen, Ralf
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Embryonic expression of priapulid Wnt genes2019In: Development, Genes and Evolution, ISSN 0949-944X, E-ISSN 1432-041X, Vol. 229, no 4, p. 125-135Article in journal (Refereed)
    Abstract [en]

    Posterior elongation of the developing embryo is a common feature of animal development. One group of genes that is involved in posterior elongation is represented by the Wnt genes, secreted glycoprotein ligands that signal to specific receptors on neighbouring cells and thereby establish cell-to-cell communication. In segmented animals such as annelids and arthropods, Wnt signalling is also likely involved in segment border formation and regionalisation of the segments. Priapulids represent unsegmented worms that are distantly related to arthropods. Despite their interesting phylogenetic position and their importance for the understanding of ecdysozoan evolution, priapulids still represent a highly underinvestigated group of animals. Here, we study the embryonic expression patterns of the complete sets of Wnt genes in the priapulids Priapulus caudatus and Halicryptus spinulosus. We find that both priapulids possess a complete set of 12 Wnt genes. At least in Priapulus, most of these genes are expressed in and around the posterior-located blastopore and thus likely play a role in posterior elongation. Together with previous work on the expression of other genetic factors such as caudal and even-skipped, this suggests that posterior elongation in priapulids is under control of the same (or very similar) conserved gene regulatory network as in arthropods.

  • Song, Tianyi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Spillmann, Dorothe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Transcriptomic analysis reveals cell apoptotic signature modified by heparanase in melanoma cells2019In: Journal of Cellular and Molecular Medicine (Print), ISSN 1582-1838, E-ISSN 1582-4934, Vol. 23, no 7, p. 4559-4568Article in journal (Refereed)
    Abstract [en]

    Heparanase has been implicated in many pathological conditions, especially inflammation and cancer, attributed to its degradation of heparan sulfate, a crucial component maintaining the integrity of the extracellular matrix. By silencing the heparanase gene (HPSE) in MDA-MB-435s melanoma cells, we investigated the impact of this protein on gene transcription. Transcriptome sequencing yielded a list of 279 differentially expressed genes, of which 140 were up-regulated and 239 down-regulated. The 140 up-regulated genes were classified into a substantial set of gene ontology defined functions, for example, positive regulation of cell death, apoptotic process, response to cytokine, while 239 down-regulated genes classify only into the two categories: nucleosome and nucleosome assembly. Our focus was drawn to an array of 28 pro-apoptotic genes regulated by heparanase: real-time PCR experiments further validated up-regulation of EGR1, TXNIP, AXL, CYR61, LIMS2 and TNFRSF12A by at least 1.5-fold, among which EGR1, CYR61, and TNFRSF12A were confirmed on protein level. We demonstrated significantly increased apoptotic cells by TUNEL staining upon HPSE silencing, mediated by activation of caspase 3/PARP1 pathway. The pro-apoptotic gene expression and observation of apoptosis were extended to another melanoma cell line, MV3 cells, thus consolidating the anti-apoptosis effect of heparanase in melanoma cells.

  • Buvailo, Halyna I.
    et al.
    Taras Shevchenko Natl Univ Kyiv, Dept Chem, Volodymyrska 64-13, UA-01601 Kiev, Ukraine.
    Makhankova, Valeriya G.
    Taras Shevchenko Natl Univ Kyiv, Dept Chem, Volodymyrska 64-13, UA-01601 Kiev, Ukraine.
    Kokozay, Vladimir N.
    Taras Shevchenko Natl Univ Kyiv, Dept Chem, Volodymyrska 64-13, UA-01601 Kiev, Ukraine.
    Omelchenko, Irina V.
    Natl Acad Sci Ukraine, Inst Single Crystals, Nauky Ave 60, UA-61001 Kharkov, Ukraine.
    Shishkina, Svitlana V.
    Natl Acad Sci Ukraine, Inst Single Crystals, Nauky Ave 60, UA-61001 Kharkov, Ukraine.
    Jezierska, Julia
    Univ Wroclaw, Inst Chem, F Joliot Curie 14, PL-50383 Wroclaw, Poland.
    Pavliuk, Mariia V.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Shylin, Sergii I.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Copper-containing hybrid compounds based on extremely rare [V2Mo6O26]6- POM as water oxidation catalysts2019In: INORGANIC CHEMISTRY FRONTIERS, ISSN 2052-1553, Vol. 6, no 7, p. 1813-1823Article in journal (Refereed)
    Abstract [en]

    Herein, we report two approaches to the synthesis of heterometallic complexes (NH4)(2n)(H(2)en)(n){[Cu(en)(2)][alpha-V2Mo6O26]}center dot 4nH(2)O (1), (NH4)(2){[Cu(dien)(H2O)](2)[alpha-V2Mo6O26]}center dot 5H(2)O (2) and (NH4)(2){[Cu(dien)(H2O)](2)[alpha-V2Mo6O26]}center dot 8H(2)O (3) that have been employed in homogeneous photochemical oxidation of water to dioxygen. In these hybrid metalorganic-inorganic compounds, copper-containing complex fragments are covalently bound to the rare vanadium-disubstituted alpha-octamolybdate cluster. They exhibit variable catalytic activity controlled by the local coordination environment of copper reaching a notably high turnover frequency of 0.24 s(-1) for 3 in combination with a relatively low water oxidation overpotential. The complexes have been also used as precursors for the preparation of mixed oxide phases that have proven to be active heterogeneous water oxidation catalysts.

  • Di Gravio, Chiara
    et al.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton Gen Hosp, Tremona Rd, Southampton SO16 6YD, Hants, England.
    Lawande, Ashwin
    Dr Joshi Imaging Clin, Mumbai, Maharashtra, India.
    Potdar, Ramesh D.
    Ctr Study Social Change, Mumbai, Maharashtra, India.
    Sahariah, Sirazul A.
    Ctr Study Social Change, Mumbai, Maharashtra, India.
    Gandhi, Meera
    Ctr Study Social Change, Mumbai, Maharashtra, India.
    Brown, Nick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Chopra, Harsha
    Ctr Study Social Change, Mumbai, Maharashtra, India.
    Sane, Harshad
    Ctr Study Social Change, Mumbai, Maharashtra, India.
    Kehoe, Sarah H.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton Gen Hosp, Tremona Rd, Southampton SO16 6YD, Hants, England.
    Marley-Zagar, Ella
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton Gen Hosp, Tremona Rd, Southampton SO16 6YD, Hants, England.
    Margetts, Barrie M.
    Univ Southampton, Publ Hlth Nutr, Southampton, Hants, England.
    Jackson, Alan A.
    NIHR Southampton Biomed Res Ctr, Southampton, Hants, England.
    Fall, Caroline H. D.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton Gen Hosp, Tremona Rd, Southampton SO16 6YD, Hants, England.
    The Association of Maternal Age With Fetal Growth and Newborn Measures: The Mumbai Maternal Nutrition Project (MMNP)2019In: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 26, no 7, p. 918-927Article in journal (Refereed)
    Abstract [en]

    Background: Young maternal age is associated with poorer birth outcomes, but the mechanisms are incompletely understood. Using data from a prospective cohort of pregnant women living in Mumbai slums, India, we tested whether lower maternal age was associated with adverse fetal growth.

    Methods: Fetal crown-rump length (CRL) was recorded at a median (interquartile range, IQR) of 10 weeks' gestation (9-10 weeks). Head circumference (HC), biparietal diameter (BPD), femur length (FL), and abdominal circumference (AC) were recorded at 19 (19-20) and 29 (28-30) weeks. Newborns were measured at a median (IQR) of 2 days (1-3 days) from delivery. Gestation was assessed using prospectively collected menstrual period dates.

    Results: The sample comprised 1653 singleton fetuses without major congenital abnormalities, of whom 1360 had newborn measurements. Fetuses of younger mothers had smaller CRL (0.01 standard deviation [SD] per year of maternal age; 95% confidence interval CI: 0.00-0.02(1); P = .04), and smaller HC, FL, and AC at subsequent visits. Fetal growth of HC (0.04 cm; 95% CI: 0.02-0.05; P < .001), BPD (0.01 cm; 95% CI: 0.00-0.01; P = .009), FL (0.04 cm; 95% CI: 0.02-0.06; P < .001), and AC (0.01 cm; 95% CI: 0.00-0.01; P = .003) up to the third trimester increased with maternal age. Skinfolds, head, and mid-upper arm circumferences were smaller in newborns of younger mothers. Adjusting for maternal prepregnancy socioeconomic status, body mass index, height, and parity attenuated the associations between maternal age and newborn size but did not change those with fetal biometry.

    Conclusion: Fetuses of younger mothers were smaller from the first trimester onward and grew slower, independently of known confounding factors.

  • Axelsson Olsson, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Förbättringsarbete inom den offentliga sektorn: Rekryteringsprocessen och dess ansvarsfördelning2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The study aims to gain an understanding of how the seasonal recruitment and division of responsibilities within the Resource Team at Region Gotland currently established in order to find opportunities for improvement in the process. The study is based on two questions of aim, "How do the seasonal recruitment and the division of responsibilities currently look like?" And "How can the seasonal recruitment process be developed?". The data material has been collected through qualitative methods in the form of interviews, observations of the daily operations and provision of internal documents. The material shows that there are certain ambiguities when it comes to seasonal recruitment in its entirety, and also when it comes to the distribution of responsibility among the employees, whereas there is uncertainty who is responsible for the different activities in the process. The problem that can arise in the case of an ambiguous division of responsibility is that employees do not know what is expected of them in their work roles, which can result in tasks not being performed. To develop and hopefully improve the seasonal recruitment process, a visualization of the process is inspired by the model for process charts, blueprinting. The Resource Team should clarify the division of responsibilities associated with the seasonal recruitment as some activities currently have no one in charge. It is advised and proposed that the Resource Team should create a work role in order to delegate the responsibilities in case of absence.

  • Björck, Lovisa
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Arbetsplatslärande: En fallstudie om ledningsarbete inom upplärningsprocessen.2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The concept of competence summarizes requirements for knowledge and skills that are required for individuals, companies, organisations and nations to function effectively and in a timely manner. The growth of the service society in parallel with today’s rapid knowledge and technology development and increased processional competition has resulted in competence becoming a central concept in education and management. The development has meant a greater focus on external efficiency (to do the right things), which means that human performance, competence, nowadays are a prerequisite for delivering value to the customer.

    The improvement has been carried out at Liseberg which is one of Sweden’s most visited tourist destinations. The work has been delimited to the housing department and the working group reception. The reception is one of three working groups that are active in the department and is responsible for the guest’s stay at Liseberg’s residential facilities, Lisebergsbyn and Askim Stand. Before the improvement, a preliminary study was carried out that identified improvement possibilities in the training process of new employees to the reception. The preliminary study showed a great variation in the result and the experience of the execution of the training, which was considered an urgent improvement as the department is driven by human performance.

    Therefore, the aim of the improvement has been to improve the training process within the workgroup reception by clarifying working techniques and ensuring competence. Investigations of the present education process, how the work techniques can be clarified and how the competence can be ensured have been used to achieve the aim of the study.

    The result indicates that the working group has a common understanding of what needs to be taught and why it is important, however when and how a work task should be taught. The training process is currently not process-focused or defined, among other things, lacking management processes completely, which explains the employees’ experience of lack of structure and focus. The process function in such a way, as allowing the responsible managers to plan the work process themselves. The results also show that the managers’ motivation and self-confidence to their own competence to carry out the work with the process are varied.

    The study concludes that the training process needs to be process-focused, have management processes and add a supervisor course to the existing support process to ensure the necessary competence needed, as well as unifying and clarifying the working techniques. The working group also needs to clarify roles and expectations linked to the process’s activities and apply situational based management to the operative part of the process.

  • Laskar, Tasnim
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Determining shallow P-wave velocity and its engineering implication in Adama City, Ethiopia2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    A great number of the urban areas in Ethiopia are situated within the Great Rift Valley of Ethiopia, a system consisting of depressions and large faults. As a region with significant seismic activities, it is vital that careful planning is implemented to avoid constructing buildings on flat surfaces as they can amplify ground motion in the case of an earthquake.

     

    This study was conducted in Adama, a city located within the rift system, to map and characterize the subsurface of a construction site with seismic refraction and investigate whether this is an optimal area to construct a building should an earthquake occur. Seismic refraction is based on Snell’s law, specifically the case of the critical angle, which is when the refracted angle is at 90 degrees and a number of the energy from the wave is rebounded back to the surface in accordance with Huygen’s Principle.    

     

    Seismic waves were generated with a sledgehammer and recorded with 24 vertical geophones. The acquired data was then analysed with SeisImager and produced a 2D-tomography of the site with the corresponding velocity layers for a P-wave. Comparing the P-wave velocities to a table of Seismic Velocities of Rocks and Various Materials, one could determine that the subsurface layers consisted of rock soils, sand and silt. These are incredibly loose materials that will amplify ground motion during earthquake crisis and are therefore not optimal or ideal for constructing buildings.

  • Jansson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics, Byggteknik.
    Jumlin, Kenny
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics, Byggteknik.
    Nyckeltal inom projektering: En undersökning av uppdelade kostnader förprojektering av förskolor och skolor2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The objective of this report is to examine the estimated cost in thedesign phase when building schools or preschools in Sweden. The contentcan be used in early stages of a project to get a better picture ofwhat the cost might be of each profession. Furthermore the reportexamines current key figures used in the industry as of today. The workhas been done in collaboration with ÅF-Pöyry AB. The backgroundgenerating this report is the uncertainty around the design phase costsand how it is divided between the professions.The key figures are presented as a percentage of the total productioncost and the result in design phase is 11,2 % for preschools and6,9 % for schools.Additionally the report present how the total production cost varieswith increasing amount of children or size (BTA). Finally the reportsuggest how the new key figures and results should be used.

  • Moberg, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Development of measurement algorithm in an industrial PLC: An evaluation of DSOGI-PLL for real time measurements2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The aim of this project was to devise an algorithm for three phase AC power grid measurements that could be utilized in an excitation system for controlling generators. This application requires fast and accurate measurements even when the voltages in the power grid are characterized by unbalanced three-phase, frequency variations and harmonic distortions. Phase locked loop algorithms are used in grid synchronization techniques and are developed to withstand disturbances in the power grid. A DSOGI-PLL was implemented on a PLC and then evaluated. The DSOGI-PLL was tested with input voltages generated by a relay testing system. The result showed that the DSOGI-PLL could measure positive sequence component RMS and grid frequency of unbalanced three-phase voltages and voltages characterized by frequency variations and harmonic distortions. However, the measurements response time and accuracy did not meet the requirements for application in excitation systems. 

  • Raaby, Erika
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences.
    Investigating Reflections on Social Sustainability: The Case of EU-Funded Projects in Remote Northern Communities2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    There has been a general population decline in the European Arctic and northern periphery, with out-migration being one of the main drivers. The population is ageing and less able to contribute to the economic welfare. The EU has implemented a series of projects in the region in an attempt to remedy the out-migration and make the regions attractive for further investments and development. The study investigates how actors within a number of EU-funded projects perceived local social sustainability, in their communities and within their projects. It aims to gain a better understanding of what social sustainability means in northern contexts, and how EU-funded projects could improve social sustainability. Using coding inspired by the Arctic Social Indicators, the study mapped perceptions and reflections through conducting a series of interviews with actors attached to EU projects. The results show that a majority of projects potentially have had a higher impact on social sustainability than the actors reflected upon, such as the impact on cultural wellbeing that comes from improving local slow tourism, focussing on local traditions and heritage. The study also finds that transnational cooperation is perceived to be beneficial for socially sustainable outcomes with benefits including knowledge transfer and business cooperation. Transnational cooperation, however, comes with challenges such as communication issues due to language barriers, and policy difficulties when working across borders. Overall the study concludes that the EU projects are perceived to have positive outcomes on the social sustainability in northern communities. Not only did the actors perceive these EU-funded projects to be important for monetary development, but also in creating invaluable bonds between partners.

  • Stenberg, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Melin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Lindberg, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Gavle, Dept Hlth & Caring Sci, Gavle, Sweden.
    Furuland, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Brain natriuretic peptide reflects individual variation in hydration status in hemodialysis patients2019In: Hemodialysis International, ISSN 1492-7535, E-ISSN 1542-4758, Vol. 23, no 3, p. 402-413Article in journal (Refereed)
    Abstract [en]

    Introduction: Fluid management in hemodialysis patients is a controversial topic. Brain natriuretic peptide (BNP) is secreted from the heart in response to volume overload, and may be a marker of overhydration in hemodialysis patients. Our aim was to investigate the correlation between BNP and overhydration in a cohort of hemodialysis patients, and to find out whether BNP and overhydration correlate in repeated measurements within individuals with elevated BNP.

    Methods: The study was prospective, observational, and had a cross-sectional part and a longitudinal follow-up. The distribution of BNP was investigated in a cohort of 64 hemodialysis patients. Blood samples and bioimpedance spectroscopy measurements were performed before midweek dialysis. Subsequently, 11 study participants with elevated BNP concentrations (>500 pg/mL) were assessed in another nine dialysis sessions each. These individuals also had their cardiac function and heart rate variability (HRV) examined.

    Findings: BNP was above 500 pg/mL in 38% of the participants, and correlated positively with overhydration (r(s) = 0.381), inflammation and malnutrition, but not with systolic blood pressure. In comparison to participants with BNP below 500 pg/mL, participants with elevated BNP were older, had lower muscle strength, lower bodyweight and lower levels of hemoglobin and albumin. Echocardiography revealed cardiac anomalies in all 11 participants in the longitudinal follow-up, and HRV, as measured by SDNN, was pathologically low. In repeated measurements, the between-individuals variation of BNP in relation to overhydration was greater (SD = 0.581) than the within-person variation (SD = 0.285).

    Discussion: BNP correlates positively to overhydration, malnutrition, and inflammation. In a subgroup of patients with elevated BNP, who are mainly elderly and frail, BNP reflects individual variation in hydration status, and hence seems to be a modifiable marker of overhydration. These data suggest that BNP is best applied for measuring changes in hydration status within an individual over time.

  • Vorobyeva, Anzhelika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Schulga, Alexey
    Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow, Russia.
    Konovalova, Elena
    Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow, Russia.
    Guler, Rezan
    KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
    Lofblom, John
    KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Garousi, Javad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Chernov, Vladimir
    Russian Acad Sci, Tomsk Natl Res Med Ctr, Canc Res Inst, Nucl Med Dept, Tomsk, Russia.
    Bragina, Olga
    Russian Acad Sci, Tomsk Natl Res Med Ctr, Canc Res Inst, Nucl Med Dept, Tomsk, Russia.
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Deyev, Sergey M.
    Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow, Russia;Natl Res Tomsk Polytech Univ, Tomsk, Russia;Natl Res Nucl Univ MEPhI, Inst Engn Phys Biomed PhysBio, Bionanophoton Lab, Moscow, Russia.
    Optimal composition and position of histidine-containing tags improves biodistribution of Tc-99m-labeled DARP in G32019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 9405Article in journal (Refereed)
    Abstract [en]

    Radionuclide molecular imaging of HER2 expression in disseminated cancer enables stratification of patients for HER2-targeted therapies. DARP in G3, a small (14 kDa) engineered scaffold protein, is a promising probe for imaging of HER2. We hypothesized that position (C- or N-terminus) and composition (hexahistidine or (HE)(3)) of histidine-containing tags would influence the biodistribution of [Tc-99m]Tc(CO)(3)-labeled DARP in G3. To test the hypothesis, G3 variants containing tags at N-terminus (H-6-G3 and (HE)(3)-G3) or at C-terminus (G3-H-6 and G3-(HE)(3)) were labeled with [Tc-99m]Tc(CO)(3). Labeling yield, label stability, specificity and affinity of the binding to HER2, biodistribution and tumor targeting properties of these variants were compared side-by-side. There was no substantial influence of position and composition of the tags on binding of [Tc-99m]Tc(CO)(3)-labeled variants to HER2. The specificity of HER2 targeting in vivo was confirmed. The tumor uptake in BALB/c nu/nu mice bearing SKOV3 xenografts was similar for all variants. On the opposite, there was a strong influence of the tags on uptake in normal tissues. The tumor-to-liver ratio for [Tc-99m]Tc(CO)(3)-(HE)(3)-G3 was three-fold higher compared to the hexahistidine-tag containing variants. Overall, [Tc-99m]Tc(CO)(3)-(HE)(3)-G3 variant provided the highest tumor-to-lung, tumor-to-liver, tumor-to-bone and tumor-to-muscle ratios, which should improve sensitivity of HER2 imaging in these common metastatic sites.

  • Lindman, Joel
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics.
    Westerlund, Lina
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics.
    DIMENSIONERING AV KONSTRUKTIONER I ROBOT STRUCTURAL ANALYSIS 2019: Skillnader och likheter med FEM-Design2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The basis of this thesis was that Kåver & Mellin Uppsala wanted todetermine if they should train their employees in the software RobotStructural Analysis. The company had licenses for the program that theydid not use due to lack of experience. The purpose of the project wastherefore to examine how Robot is used for designing structures and tocompare its usefulness to its competitor FEM-Design. The comparison ofusefulness was made by designing an identical structure in bothprograms. The focus of the study was to compare three main areas,workflow, areas of use and calculation results. This was made for themost common construction elements that were limited to concrete slabs,concrete walls, steel columns and steel beams.The study proved the programs to be similar. Designing steel profilesis more efficient in Robot. Another advantage of Robot is that there isan official online help page and a useful online forum, that FEM-Designlacks. One significant disadvantage of Robot is that the calculationsfor concrete are made with outdated national standards for Eurocode.The disadvantage was crucial and led to the conclusion that Kåver &Mellin Uppsala should wait for updated standards before using theprogram fully but they could start using Robot for load calculationsand steel design.

  • Bastani, Spencer
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economics, Uppsala Center for Fiscal Studies. Linnaeus Univ, Dept Econ & Stat, Vaxjo, Sweden;Linnaeus Univ, Ctr Integrat & Discriminat Studies, Vaxjo, Sweden;Uppsala Ctr Labor Studies, Uppsala, Sweden;CESifo, Munich, Germany.
    Blomquist, Sören
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economics, Uppsala Center for Fiscal Studies.
    Micheletto, Luca
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economics, Uppsala Center for Fiscal Studies. CESifo, Munich, Germany;Univ Milan, Dept Law, Milan, Italy;Bocconi Univ, Dondena Ctr Res Social Dynam, Milan, Italy.
    Nonlinear and piecewise linear income taxation, and the subsidization of work-related goods2019In: International Tax and Public Finance, ISSN 0927-5940, E-ISSN 1573-6970, Vol. 26, no 4, p. 806-834Article in journal (Refereed)
    Abstract [en]

    We investigate how the social welfare gain of subsidizing work-related goods depends on whether the underlying income tax system is linear, piecewise linear or fully nonlinear, focusing on child care services as a paradigmatic example of goods/services that are complements with labor supply. Our quantitative analysis employs an empirically relevant labor supply model and shows that the welfare gain of an optimally chosen subsidy is negligible when the optimal income tax is restricted to be linear but about the same as under fully nonlinear taxation when the optimal income tax is restricted to be piecewise linear. Our findings enhance the policy relevance of the optimal tax argument in favor of providing subsidies to work-related goods and also shed light on the relative welfare gains of employing piecewise linear rather than fully nonlinear income taxes.

  • Lindberg, Terese
    et al.
    Blekinge Inst Technol, Karlskrona, Sweden;Blekinge Ctr Competence, Karlskrona, Sweden;Lund Univ, Lund, Sweden.
    Wimo, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Karolinska Inst, Stockholm, Sweden;Stockholm Univ, Stockholm, Sweden.
    Elmstahl, Solve
    Lund Univ, Lund, Sweden.
    Qiu, Chengxuan
    Karolinska Inst, Stockholm, Sweden;Stockholm Univ, Stockholm, Sweden.
    Bohman, Doris M.
    Blekinge Inst Technol, Karlskrona, Sweden.
    Berglund, Johan Sanmartin
    Blekinge Inst Technol, Karlskrona, Sweden;Blekinge Ctr Competence, Karlskrona, Sweden.
    Prevalence and Incidence of Atrial Fibrillation and Other Arrhythmias in the General Older Population: Findings From the Swedish National Study on Aging and Care2019In: Gerontology and geriatric medicine, E-ISSN 2333-7214, Vol. 5, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Aim: To study the prevalence and cumulative incidence of arrhythmias in the general population of adults aged 60 and older over a 6-year period. Study Design and Setting: Data were taken from the Swedish National Study on Aging and Care (SNAC), a national, longitudinal, multidisciplinary study of the general elderly population (defined as 60 years of age or older). A 12-lead resting electrocardiography (ECG) was performed at baseline and 6-year follow-up. Results: The baseline prevalence of atrial fibrillation (AF) was 4.9% (95% confidence interval [CI] = [4.5%, 5.5%]), and other arrhythmias including ventricular premature complexes (VPCs), supraventricular tachycardia (SVT), and supraventricular extrasystole (SVES) were seen in 8.4% (7.7%, 9.0%) of the population. A first- or second-degree atrioventricular (AV) block was found in 7.1% of the population (95% CI = [6.5%, 7.7%]), and there were no significant differences between men and women in baseline arrhythmia prevalence. The 6-year cumulative incidence of AF was 4.1% (95% CI = [3.5%, 4.9%]), or 6.9/1,000 person-years (py; 95% CI = [5.7, 8.0]). The incidence of AF, other arrhythmias, AV block, and pacemaker-induced rhythm was significantly higher in men in all cohorts except for the oldest. Conclusion: Our data highlight the prevalence and incidence of arrhythmias, which rapidly increase with advancing age in the general population.