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  • Public defence: 2017-12-01 13:15 2446, Uppsala
    Peters, Anne-Kathrin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computer Systems.
    Learning Computing at University: Participation and Identity: A Longitudinal Study2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Computing education has struggled with student engagement and diversity in the student population for a long time. Research in science, technology, engineering, and mathematics (STEM) education suggests that taking a social, long-term perspective on learning is a fruitful approach to resolving some of these persistent challenges.

    A longitudinal study has been conducted, following students from two computing study programmes (CS/IT) over a three-year period. The students reflected on their experiences with CS/IT in a series of interviews. Drawing on social identity theory, the analysis has focused on describing participation in CS/IT, doing, thinking, feeling in relation to CS/IT, as negotiated among different people.

    Phenomenographic analysis yields an outcome space that describes increasingly broad ways in which the students experience participation in CS/IT over the years. Two further outcome spaces provide nuanced insights into experiences that are of increasing relevance as the students advance in their studies; participation as problem solving and problem solving for others. Problem solving defined as solving difficult (technical) problems seems predominate in the learning environment. Problem solving for others brings the user into perspective, but first in the human computer interaction (HCI) course in year three. Students react with scepticism to HCI, excluding HCI from computing, some are students who commenced their studies with broader interests in computing.

    Demonstrating (technical) problem solving competence is the most vital indicator competence in the two study programmes and the students adapt their reflections on who they are as computing students and professionals accordingly. People showing broader interests in computing risk being marginalised. I identify a gap between conceptions of computing as interdisciplinary and important for society and constructions of computing as technical. Closing the gap could improve retention and diversity, and result in graduates that are better prepared to contribute to societal development.

    List of papers
    1. Students' experiences and attitudes towards learning Computer Science
    Open this publication in new window or tab >>Students' experiences and attitudes towards learning Computer Science
    2012 (English)In: Proc. 42nd ASEE/IEEE Frontiers in Education Conference, Piscataway, NJ: IEEE , 2012, 88-93 p.Conference paper, Published paper (Refereed)
    Place, publisher, year, edition, pages
    Piscataway, NJ: IEEE, 2012
    National Category
    Computer Science Educational Sciences
    Identifiers
    urn:nbn:se:uu:diva-184605 (URN)10.1109/FIE.2012.6462238 (DOI)000356489200033 ()978-1-4673-1353-7 (ISBN)
    Available from: 2012-10-06 Created: 2012-11-09 Last updated: 2017-10-16Bibliographically approved
    2. Engagement in Computer Science and IT — What!: A matter of identity?
    Open this publication in new window or tab >>Engagement in Computer Science and IT — What!: A matter of identity?
    2013 (English)In: Proc. 1st International Conference on Learning and Teaching in Computing and Engineering, Los Alamitos, CA: IEEE Computer Society, 2013, 114-121 p.Conference paper, Published paper (Refereed)
    Place, publisher, year, edition, pages
    Los Alamitos, CA: IEEE Computer Society, 2013
    National Category
    Computer Science Educational Sciences
    Identifiers
    urn:nbn:se:uu:diva-202686 (URN)10.1109/LaTiCE.2013.42 (DOI)000324484000016 ()978-1-4673-5627-5 (ISBN)
    Conference
    LaTiCE 2013
    Available from: 2013-06-22 Created: 2013-06-25 Last updated: 2017-10-16Bibliographically approved
    3. First year Computer Science and IT students' experience of participation in the discipline
    Open this publication in new window or tab >>First year Computer Science and IT students' experience of participation in the discipline
    2014 (English)In: Proc. 2nd International Conference on Learning and Teaching in Computing and Engineering, Los Alamitos, CA: IEEE Computer Society, 2014, 1-8 p.Conference paper, Published paper (Refereed)
    Place, publisher, year, edition, pages
    Los Alamitos, CA: IEEE Computer Society, 2014
    National Category
    Computer Science Educational Sciences
    Identifiers
    urn:nbn:se:uu:diva-224653 (URN)10.1109/LaTiCE.2014.9 (DOI)000355978500001 ()978-1-4799-3591-8 (ISBN)
    Conference
    LaTiCE 2014
    Available from: 2014-06-10 Created: 2014-05-16 Last updated: 2017-10-16Bibliographically approved
    4. Second year Computer Science and IT students' experience of participation in the discipline
    Open this publication in new window or tab >>Second year Computer Science and IT students' experience of participation in the discipline
    2015 (English)In: Proc. 15th International Conference on Computing Education Research: Koli Calling, New York: ACM Press, 2015, 68-76 p.Conference paper, Published paper (Refereed)
    Place, publisher, year, edition, pages
    New York: ACM Press, 2015
    National Category
    Computer Science Educational Sciences
    Identifiers
    urn:nbn:se:uu:diva-269178 (URN)10.1145/2828959.2828962 (DOI)978-1-4503-4020-5 (ISBN)
    Available from: 2015-11-21 Created: 2015-12-14 Last updated: 2017-10-16Bibliographically approved
    5. Students' experience of participation in a discipline: A longitudinal study of computer science and IT engineering students
    Open this publication in new window or tab >>Students' experience of participation in a discipline: A longitudinal study of computer science and IT engineering students
    2017 (English)In: ACM Transactions on Computing Education, ISSN 1946-6226, E-ISSN 1946-6226Article in journal (Refereed) Accepted
    National Category
    Computer and Information Science Educational Sciences
    Identifiers
    urn:nbn:se:uu:diva-331401 (URN)
    Available from: 2017-10-13 Created: 2017-10-13 Last updated: 2017-10-24Bibliographically approved
  • Poelzl, Gerhard
    et al.
    Univ Klin Innsbruck, Innsbruck, Austria..
    Altenberger, Johann
    Rehabil Zentrum Grossgmain, Salzburg, Austria..
    Baholli, Loant
    Klinikum Dortmund Mitte, Dortmund, Germany..
    Beltran, Paola
    HM Broggi, Barcelona, Spain..
    Borbely, Attila
    Univ Debrecen, Fac Med, Div Clin Physiol, Debrecen, Hungary..
    Comin-Colet, Josep
    Univ Hosp Bellvitge, Barcelona, Spain..
    Delgado, Juan F.
    Hosp 12 Octubre, Madrid, Spain..
    Fedele, Francesco
    Sapienza Univ, Policlin Umberto 1, Rome, Italy..
    Fontana, Antonella
    Orion Pharma Srl, Milan, Italy..
    Fruhwald, Friedrich
    Med Univ Klin, Graz, Austria..
    Giamouzis, Gregory
    Univ Thessaly, Larissa Univ Hosp, Larisa, Greece..
    Giannakoulas, George
    Aristotle Univ Thessaloniki, Thessaloniki, Greece..
    Garcia-Gonzalez, Martin J.
    H La Laguna, Tenerife, Spain..
    Gustafsson, Finn
    Rigshosp, Copenhagen, Denmark..
    Kaikkonen, Kari
    Oulu Univ Hosp, Oulu, Finland..
    Kivikko, Matti
    Orion Pharma, Espoo, Finland..
    Kubica, Jacek
    Nicolaus Copernicus Univ, Coll Med, Bydgoszcz, Poland..
    von Lewinski, Dirk
    Med Univ Klin, Graz, Austria..
    Lofman, Ida
    Karolinska Univ Sjukhus Huddinge, Huddinge, Sweden..
    Malfatto, Gabriella
    Ist Auxol Italiano, Milan, Italy..
    Manito, Nicolas
    Univ Hosp Bellvitge, Barcelona, Spain..
    Martinez-Selles, Martin
    H Gregorio Maranon, Madrid, Spain..
    Masip, Josep
    HM Broggi, Barcelona, Spain..
    Merkely, Bela
    Semmelweis Univ, Heart & Vasc Ctr, Budapest, Hungary..
    Morandi, Fabrizio
    Circolo Hosp & Macchi Fdn, Varese, Italy..
    Molgaard, Henning
    Aarhus Univ Hosp, Skejby, Denmark..
    Oliva, Fabrizio
    Osped Niguarda Ca Granda, Milan, Italy..
    Pantev, Emil
    Helsingborgs Iasarett, Helsingborg, Sweden..
    Papp, Zoltan
    Univ Debrecen, Fac Med, Div Clin Physiol, Debrecen, Hungary..
    Perna, Gian Piero
    Osped Riuniti, Dipartimento Sci Cardiol Med Chirurg, Ancona, Italy..
    Pfister, Roman
    Univ Cologne, Herzzentrum, Klin Innere Med 3, Cologne, Germany..
    Piazza, Vito
    Azienda Osped San Camillo Forlanini, Rome, Italy..
    Bover, Ramon
    H Clin San Carlos, Madrid, Spain..
    Rangel-Sousa, Diego
    H Virgen Rocio, Seville, Spain..
    Recio-Mayoral, Alejandro
    Hosp Univ Virgen Macarena, Seville, Spain..
    Reinecke, Alexander
    Uni Klinikum Schleswig Holstein, Kiel, Germany..
    Rieth, Andreas
    Kerckhoff Klin, Bad Nauheim, Germany..
    Sarapohja, Toni
    Orion Pharma, Espoo, Finland..
    Schmidt, Gunter
    CHARITE Univ Med Berlin, Berlin, Germany..
    Seidel, Mirko
    Unfallkrankenhaus Berlin, Innere Med Klin, Berlin, Germany..
    Stoerk, Stefan
    Univ Wurzburg, Comprehens Heart Failure Ctr, Wurzburg, Germany.;Univ Hosp, Wurzburg, Germany..
    Vrtovec, Bojan
    Univ Clin Ctr, Ljubljana, Slovenia..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Yerly, Patrik
    CHU Vaudois, Lausanne, Switzerland..
    Pollesello, Piero
    Orion Pharma, Espoo, Finland..
    Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 243, 389-395 p.Article in journal (Refereed)
    Abstract [en]

    Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminalprohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.

  • Public defence: 2017-12-01 09:15 Sal IX, Uppsala
    Fängström, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    ‘I don’t even remember anything’: Optimising the choice of method when interviewing preschoolers2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    There is increasing need and demand in various contexts to take children’s perspectives into account, including the views and opinions of the youngest children. However, listening to the voices of children is a challenging and complex task, and the field is normatively loaded. There is thus a growing need for valid and reliable methods and techniques that aid children to verbalise their experiences. The overall aim of this thesis was to examine the ability of the In My Shoes computer assisted interview and a Standard verbal interview to elicit accurate information and evaluative content, when used with preschool-aged children and determine their suitability in relation to situationally shy children.

    Our studies show that the two interview methods, in general, provided equally accurate and complete statements. In addition, the IMS interview can be a more useful and suitable tool during the rapport phase with situationally shy children compared to the Standard verbal method. For non-shy children, the interview methods were equally adequate. In relation to evaluative information, the recommended open-ended questions in the Standard verbal interview were insufficient. Children appeared to need evaluative questions in order to provide evaluative content. Examining the ability of IMS to elicit subjective experiences showed that using IMS aided children to provide detailed and varied descriptions of emotions, somatic experiences, and objects such as toys.  

    Thus, when choosing the optimal child interview method, there are several aspects that need to be considered, including the degree to which children’s statements need to be accurate and complete and/or contain evaluative information and the child’s level of shyness. These studies have increased the number of evaluated methods for interviewing children and contributed to new knowledge about the challenging task of optimising the choice of method for interviewing preschoolers.

    List of papers
    1. In My Shoes - Validation of a computer assisted approach for interviewing children
    Open this publication in new window or tab >>In My Shoes - Validation of a computer assisted approach for interviewing children
    Show others...
    2016 (English)In: Child Abuse & Neglect: The International Journal, ISSN 0145-2134, Vol. 58, 160-172 p.Article in journal (Refereed) Published
    Abstract [en]

    Interviewing young children presents a challenge because they tend to provide incomplete accounts and are easily misled. Therefore there is a need for techniques to improve young children's recall, while maintaining accuracy and increasing completeness. The computer-assisted interview In My Shoes (IMS) is an aid that potentially offers a way for young children to provide accounts of their experiences. This study examined the validity of IMS, by comparing it with a forensic best practice interview approach using a real life clinical situation to ensure high ecological validity. Children were randomly assigned to either method and both accuracy and completeness of statements made by 4- and 5-year-olds (N = 54) regarding a video-documented health check-up were assessed. The In My Shoes interviews were as good as best practice interviews on all accuracy measures for both age groups, except for object accuracy that was better in the forensic interview condition. Events description completeness was similar in both interview conditions; however, IMS interviews generated more complete statements about people present at the visit. The findings suggest that the IMS approach yields comparable results to a best practice interview, and it can be used as an alternative aid in child interviews.

    Keyword
    Interviewing aid, Child, Computer-assisted interview, Validity, In My Shoes
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Research subject
    Social Medicine; Psychology
    Identifiers
    urn:nbn:se:uu:diva-303099 (URN)10.1016/j.chiabu.2016.06.022 (DOI)000381241400016 ()27394051 (PubMedID)
    Funder
    VINNOVA, 259-2012-68Forte, Swedish Research Council for Health, Working Life and Welfare, 259-2012-68
    Note

    Forskningsfinansiär: Allmänna Barnhuset, FB13-0014

    Available from: 2016-09-28 Created: 2016-09-15 Last updated: 2017-10-13
    2. The computer-assisted interview In My Shoes can benefit shy preschool children's communication
    Open this publication in new window or tab >>The computer-assisted interview In My Shoes can benefit shy preschool children's communication
    2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 8, e0182978Article in journal (Refereed) Published
    Abstract [en]

    Interviewing children is a cognitively, socially, and emotionally challenging situation, especially for young and shy children. Thus, finding methods that aid rapport and increase these children's communication is important. The present study investigated whether children's verbal and non-verbal communicative behavior developed differently during the rapport phase, depending on whether children were situationally shy or not, and whether the interview was conducted using the computer-assisted interview In My Shoes (IMS) or a Standard verbal interview. The sample consisted of 60 children aged 4 to 5-years-old. The results showed that for the shy children in the IMS group their talkativeness increased and their answer latency decreased including the amount of encouragement the child needed to talk, while no changes were observed for the shy children in the Standard verbal interview group. There were no significant differences in the non-verbal behavior for the shy children regardless of the interview method used. For the non-shy children, overall, the interview method did not affect either the verbal or the non-verbal outcomes. Our findings indicate that IMS can be a useful tool during the rapport-building phase with shy children as it helps these children to improve their verbal communication.

    Keyword
    child, interview, communication, In My Shoes
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Research subject
    Psychology
    Identifiers
    urn:nbn:se:uu:diva-328584 (URN)10.1371/journal.pone.0182978 (DOI)000407550500034 ()28813534 (PubMedID)
    Funder
    Swedish Research Council, 259-2012-68Swedish Research Council FormasVINNOVA
    Available from: 2017-08-28 Created: 2017-08-28 Last updated: 2017-11-14Bibliographically approved
    3. “And they gave me a shot, it really hurt” – Evaluative content in investigative interviews with young children
    Open this publication in new window or tab >>“And they gave me a shot, it really hurt” – Evaluative content in investigative interviews with young children
    Show others...
    2017 (English)In: Children and youth services review, ISSN 0190-7409, E-ISSN 1873-7765, Vol. 82, 434-443 p.Article in journal (Refereed) Published
    Abstract [en]

    Research is scarce on the suitability of the evidence-based components of child investigative interviews when used in non-forensic contexts such as social work or school, particularly in relation to children’s reports on emotional content.

    This explorative study investigated to what extent a structured forensic interview protocol aids children in verbalizing negative emotional experiences of distress or discomfort. To do this we assessed and compared children’s displayed distress or discomfort during a video-recorded health visit with the verbalized distress or discomfort in interviews 2-4 weeks later about this visit. The children, aged 4 and 5 years (N = 26), were interviewed with a forensic interview protocol. Children’s statements regarding distress and discomfort and the interviewer questions preceding these statements were analyzed qualitatively.

    The results showed that 46% of the 4-year-olds and 39 % of the 5-year-olds displayed discomfort or distress during their health visit. In the interviews, open-ended questions were posed to all children, however, these questions were sufficient to aid only some children (n = 6) to share evaluative content. None of the children who displayed distress or discomfort during the visit verbalized such experiences after an invitation only. Most children who described experiences of distress or discomfort did so in relation to evaluative questions.

    The results suggest that more research is warranted to investigate exactly how and when evaluative questions should be posed and whether this differs depending on severity of experience or the child’s age. The need for protocol development and its suitability when used in other fields of practice is discussed.

    Keyword
    investigative interviews, evaluative, emotion, question, distress
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Research subject
    Psychology
    Identifiers
    urn:nbn:se:uu:diva-328585 (URN)10.1016/j.childyouth.2017.10.017 (DOI)
    Funder
    Swedish Research Council, 259-2012-68
    Note

    Forskningsfinansiär: Allmänna Barnhuset, FB13-0014

    Available from: 2017-10-11 Created: 2017-10-11 Last updated: 2017-10-19
    4. 'I felt a little bubbly in my tummy': Eliciting pre-schoolers' accounts of their health visit using a computer-assisted interview method.
    Open this publication in new window or tab >>'I felt a little bubbly in my tummy': Eliciting pre-schoolers' accounts of their health visit using a computer-assisted interview method.
    Show others...
    2016 (English)In: Child Care Health and Development, ISSN 0305-1862, E-ISSN 1365-2214, Vol. 42, no 1, 87-97 p.Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: In the health care services, children's rights to participate in all matters that concern them are considered important. However, in practice this can be challenging with young children. In My Shoes (IMS) is a computer-assisted interview tool developed to help children talk about their experiences. The aim of the study was to evaluate the IMS' ability to elicit pre-schoolers' subjective experiences and accurate accounts of a routine health visit as well as the children's engagement in the interview process.

    METHODS: Interviews were conducted with 23 children aged 4-5 years, 2-4 weeks after their health visit. The interviews were transcribed verbatim and analysed using a method inspired by Content Analysis to evaluate IMS's ability to elicit accounts about subjective experiences. Accurate accounts were assessed by comparing the transcribed interviews with the filmed visits at the child health centre. The children's engagement was defined by the completion and length of the interviews, and the children's interaction with the software.

    RESULTS: All children gave accounts about their subjective experiences, such as their emotional state during the visit, available toys or rewards they received. All children related to the correct event, they all named at least one person who was present and 87% correctly named at least one examination procedure. The majority of children (91%) completed the interview, which lasted 17-39 min (M = 24), and 96% interacted with the IMS software.

    CONCLUSIONS: IMS was feasible to help children describe their health care experiences, in both detail and depth. The children interacted with the software and maintained their interest for an extended period of time.

    Keyword
    child interview; child public health; children's rights; children's views; computer; qualitative research methods
    National Category
    Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-269207 (URN)10.1111/cch.12293 (DOI)000367930300011 ()26564782 (PubMedID)
    Funder
    VINNOVA, 259-2012-68Swedish Research Council, 259-2012-68Forte, Swedish Research Council for Health, Working Life and Welfare, 259-2012-68
    Note

    Forskningsfinansiär: Allmänna Barnhuset, FB13-0014

    Available from: 2015-12-14 Created: 2015-12-14 Last updated: 2017-10-13
  • Hjelm, Annica
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of ALM.
    Att knyta näven i fickan? : En studie av socialdemokratiska och kommunistiska 1 maj-affischer 1922-1948 utifrån begreppet vredeskultur 2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This study is intended to illustrate how the reformist and revolutionary directions in the labor movement are manifested and visualized in the empirical material with regard to angry culture, thus contributing to an understanding of the informative importance of the image. It is clear that the investigated material in the form of social democratic and communist 1 May posters from the period 1922-1948 reflects its time (the interwar period to the post-war era) with regard to angry culture.  It is not the aesthetic aspect that is central, but the historical and political perspective in terms of information transmission. This study focuses on how to understand a historical period through an image material. The study aims to answer the question of what kind of information is communicated built on an analysis based on a combination of semiotics and hegemony analysis of the empirical material.

    Using the semiotic concepts denotation and connotation, the posters are analyzed in detail in the image analysis in combination with Stuart Hall's three hypothetical positions (codes), Antonio Gramsci’s hegemony concept, primarily in the form of “war of position” and “historic blocs”, is used to understand the historical period investigated. This method triangulation increases the credibility of the results.

    As far as the study and its results are concerned, it can be noted that the social democratic 1 May posters before 1936 (Social Democrats’ power access) with regard to “sublimed wrath” mainly represent consensus across class boundaries. The communist 1 May posters from that period, however, primarily represent “class war” and stand for “open anger”. After the Social Democrats’ access to power, it is clear that they constitute a historic bloc and that the communists are forced to adopt a more defensive approach, pronounced in drained paroles with a vague content.

    The conclusion with regard to the visual transmission of political and historical information and messages regarding social democratic and communistic 1 May posters from 1922-1948, based on socialist angry cultures is that the period between the wars was characterized by class struggle versus consensus, World War ll reduced everything to “hold together” and post-war time represents the starting point for the welfare state, as a successful consequence of the social democratic “dignity project”.

     

  • Johannesson, Elsa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of ALM.
    Klassiker på barn- och ungdomsbiblioteket: Bibliotekariens arbete med barn- och ungdomslitteraturens klassiker2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Introduction. This empirical study investigates the attitudes of Swedish public librarians who work in the children’s and/or young adult departments, towards children’s literary classics. This is achieved by examining work with the Classics shelf, a genre classification located in the children’s or young adult section.

    Method. The empirical material consists of transcripts from interviews with seven children’s and young adult public librarians in four Swedish municipalities, the Classics shelves and the libraries’ policy documents.

    Analysis. The Classics shelves’ genre definition, target group and location were investigated and compared to the libraries’ policy documents. Interview transcripts were examined in regard to the explicit contents of the participants’ statements and divided in themes by perceptions of value, function and use of the literature in a library context. Magnus Persson’s concept of myths describing naturalised perceptions of literature was used to interpret attitudes. A concluding analysis was conducted using the discourse theories of Michel Foucault, Ernesto Laclau and Chantal Mouffe.

    Results. The analysis indicated both shared and conflicting attitudes to children’s and young adult literary classics, with perceptions predominantly taken for granted. Three coexisting discourses were identified: the Reading experience discourse, the Durability discourse and the Fresh discourse. These are mainly tied to different tasks and influenced by the librarians’ preconceived notions, workplace management and external influences such as media debates, with the user perspective as a prerequisite.

    Conclusion. The results show that the librarian accommodates contradictory and ambivalent views of children’s and young adult literary classics in the library. Literature is mediated indirectly and directly, and expresses the librarian’s personal experience rather than a professional identity.

    This is a two years master’s thesis in Library and Information Science.

  • Wiezell, Astrid
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of ALM.
    Äldre användare på Stockholms stadsbibliotek: en nutida kvalitativ intervjustudie2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The aim of this study is to gain deeper understanding of how older patrons (65 years of age and above) experien- ce the Stockholm Public Library: how the older patrons use the library, experience information about events and programs; experiences in contact with librarians; how user-friendly they find the library and what might attract or detract visits. The study consists of qualitative interviews with five older patrons of the Stockholm Public Lib- rary who were approached during a library visit. The study also contains interviews with two librarians from the library. The interviews have been transcribed and the results are organized into six areas: using the library and its services; digital aspects of the library; contact with librarians; the library space in a user-friendly context; the cultural value of the library building; library programmes; events and programs.

    The theoretical framework of the study is that of sociologist and philosopher Zygmunt Bauman and his ide- as about the individualised society and consumerism. Bauman's thoughts on the individualised society where on- ly the desired consumers are welcome even in public spaces have also been included. These theories are combi- ned with research on how society views aging and older people, international studies and studies on older pa- trons and libraries in Sweden.

    This study finds that a main issue in accessing the library's services and material is how they are placed: shelves that are too high or low to reach, and problems with finding material without help. The patrons are drawn to places where books are exposed, whether on purpose or not. The study concludes with the suggestion of crea- ting national guidelines for how libraries can make their spaces more welcoming to older patrons, such as ex- isting guidelines in the U.S. And Australia. Previous research shows the mere existance of guidelines may high- light the issue in itself and create a helpful start for libraries wanting to accommodate older patrons better.

  • Schwager, Evelyn E.
    et al.
    Oxford Brookes Univ, Dept Biol & Med Sci, Gipsy Lane, Oxford OX3 0BP, England.;Univ Massachusetts Lowell, Dept Biol Sci, 198 Riverside St, Lowell, MA 01854 USA..
    Sharma, Prashant P.
    Univ Wisconsin Madison, Dept Zool, 430 Lincoln Dr, Madison, WI 53706 USA..
    Clarke, Thomas
    Washington & Lee Univ, Dept Biol, 204 West Washington St, Lexington, VA 24450 USA.;Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA.;J Craig Venter Inst, 9714 Med Ctr Dr, Rockville, MD 20850 USA..
    Leite, Daniel J.
    Oxford Brookes Univ, Dept Biol & Med Sci, Gipsy Lane, Oxford OX3 0BP, England..
    Wierschin, Torsten
    Ernst Moritz Arndt Univ Greifswald, Inst Math & Comp Sci, Walther Rathenau Str 47, D-17487 Greifswald, Germany..
    Pechmann, Matthias
    Univ Goettingen, Johann Friedrich Blumenbach Inst Zool & Anthropol, Dept Dev Biol, GZMB Ernst Caspari Haus, Justus von Liebig Weg 11, D-37077 Gottingen, Germany.;Univ Cologne, Cologne Bioctr, Inst Zool, Dept Dev Biol, Zuelpicher Str 47b, D-50674 Cologne, Germany..
    Akiyama-Oda, Yasuko
    JT Biohist Res Hall, 1-1 Murasaki Cho, Takatsuki, Osaka 5691125, Japan.;Osaka Med Coll, Takatsuki, Osaka, Japan..
    Esposito, Lauren
    Calif Acad Sci, Inst Biodivers Sci & Sustainabil, 55 Mus Concourse Dr, San Francisco, CA 94118 USA..
    Bechsgaard, Jesper
    Aarhus Univ, Dept Biosci, Ny Munkegade 116,Bldg 1540, DK-8000 Aarhus C, Denmark..
    Bilde, Trine
    Aarhus Univ, Dept Biosci, Ny Munkegade 116,Bldg 1540, DK-8000 Aarhus C, Denmark..
    Buffry, Alexandra D.
    Oxford Brookes Univ, Dept Biol & Med Sci, Gipsy Lane, Oxford OX3 0BP, England..
    Chao, Hsu
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    Dinh, Huyen
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    Doddapaneni, HarshaVardhan
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    Dugan, Shannon
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    Eibner, Cornelius
    Friedrich Schiller Univ Jena, Dept Genet, Philosophenweg 12, D-07743 Jena, Germany..
    Extavour, Cassandra G.
    Harvard Univ, Dept Organism & Evolutionary Biol, 16 Divin Ave, Cambridge, MA 02138 USA..
    Funch, Peter
    Aarhus Univ, Dept Biosci, Ny Munkegade 116,Bldg 1540, DK-8000 Aarhus C, Denmark..
    Garb, Jessica
    Univ Massachusetts Lowell, Dept Biol Sci, 198 Riverside St, Lowell, MA 01854 USA..
    Gonzalez, Luis B.
    Oxford Brookes Univ, Dept Biol & Med Sci, Gipsy Lane, Oxford OX3 0BP, England..
    Gonzalez, Vanessa L.
    Smithsonian Natl Museum Nat Hist, MRC 163,POB 37012, Washington, DC 20013 USA..
    Griffiths-Jones, Sam
    Univ Manchester, Fac Biol Med & Hlth, D1416 Michael Smith Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England..
    Han, Yi
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    Hayashi, Cheryl
    Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA.;Amer Museum Nat Hist, Div Invertebrate Zool, New York, NY 10024 USA..
    Hilbrant, Maarten
    Oxford Brookes Univ, Dept Biol & Med Sci, Gipsy Lane, Oxford OX3 0BP, England.;Univ Cologne, Cologne Bioctr, Inst Zool, Dept Dev Biol, Zuelpicher Str 47b, D-50674 Cologne, Germany..
    Hughes, Daniel S. T.
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    Janssen, Ralf
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Lee, Sandra L.
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    Maeso, Ignacio
    Univ Pablo de Olavide, CABD, CSIC, Seville, Spain..
    Murali, Shwetha C.
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    Muzny, Donna M.
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    da Fonseca, Rodrigo Nunes
    Univ Fed Rio de Janeiro, Nucleo Ecol & Desenvolvimento SocioAmbiental Maca, Campus Macae, BR-27941222 Rio de Janeiro, Brazil..
    Paese, Christian L. B.
    Oxford Brookes Univ, Dept Biol & Med Sci, Gipsy Lane, Oxford OX3 0BP, England..
    Qu, Jiaxin
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    Ronshaugen, Matthew
    Univ Manchester, Fac Biol Med & Hlth, D1416 Michael Smith Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England..
    Schomburg, Christoph
    Univ Goettingen, Johann Friedrich Blumenbach Inst Zool & Anthropol, Dept Dev Biol, GZMB Ernst Caspari Haus, Justus von Liebig Weg 11, D-37077 Gottingen, Germany..
    Schönauer, Anna
    Oxford Brookes Univ, Dept Biol & Med Sci, Gipsy Lane, Oxford OX3 0BP, England..
    Stollewerk, Angelika
    Queen Mary Univ London, Sch Biol & Chem Sci, Mile End Rd, London E1 4NS, England..
    Torres-Oliva, Montserrat
    Univ Goettingen, Johann Friedrich Blumenbach Inst Zool & Anthropol, Dept Dev Biol, GZMB Ernst Caspari Haus, Justus von Liebig Weg 11, D-37077 Gottingen, Germany..
    Turetzek, Natascha
    Univ Goettingen, Johann Friedrich Blumenbach Inst Zool & Anthropol, Dept Dev Biol, GZMB Ernst Caspari Haus, Justus von Liebig Weg 11, D-37077 Gottingen, Germany..
    Vanthournout, Bram
    Aarhus Univ, Dept Biosci, Ny Munkegade 116,Bldg 1540, DK-8000 Aarhus C, Denmark.;Univ Ghent, Dept Biol, Evolut & Opt Nanostruct Grp EON, Ghent, Belgium..
    Werren, John H.
    Univ Rochester, Dept Biol, Rochester, NY 14627 USA..
    Wolff, Carsten
    Humboldt Univ, Inst Biol, Philippstr 13, D-10115 Berlin, Germany..
    Worley, Kim C.
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    Bucher, Gregor
    Georg August Univ, GZMB, Johann Friedrich Blumenbach Inst, Dept Evolutionary Dev Genet, Gottingen Campus,Justus von Liebig Weg 11, D-37077 Gottingen, Germany..
    Gibbs, Richard A.
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    Coddington, Jonathan
    Smithsonian Natl Museum Nat Hist, MRC 163,POB 37012, Washington, DC 20013 USA..
    Oda, Hiroki
    JT Biohist Res Hall, 1-1 Murasaki Cho, Takatsuki, Osaka 5691125, Japan.;Osaka Univ, Grad Sch Sci, Dept Biol Sci, Osaka, Japan..
    Stanke, Mario
    Ernst Moritz Arndt Univ Greifswald, Inst Math & Comp Sci, Walther Rathenau Str 47, D-17487 Greifswald, Germany..
    Ayoub, Nadia A.
    Washington & Lee Univ, Dept Biol, 204 West Washington St, Lexington, VA 24450 USA..
    Prpic, Nikola-Michael
    Univ Goettingen, Johann Friedrich Blumenbach Inst Zool & Anthropol, Dept Dev Biol, GZMB Ernst Caspari Haus, Justus von Liebig Weg 11, D-37077 Gottingen, Germany..
    Flot, Jean-Francois
    ULB, Evolutionary Biol & Ecol, CP 160-12,Ave FD Roosevelt 50, B-1050 Brussels, Belgium..
    Posnien, Nico
    Univ Goettingen, Johann Friedrich Blumenbach Inst Zool & Anthropol, Dept Dev Biol, GZMB Ernst Caspari Haus, Justus von Liebig Weg 11, D-37077 Gottingen, Germany..
    Richards, Stephen
    Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, One Baylor Plaza, Houston, TX 77030 USA..
    McGregor, Alistair P.
    Oxford Brookes Univ, Dept Biol & Med Sci, Gipsy Lane, Oxford OX3 0BP, England..
    The house spider genome reveals an ancient whole-genome duplication during arachnid evolution2017In: BMC Biology, ISSN 1741-7007, E-ISSN 1741-7007, Vol. 15, 62Article in journal (Refereed)
    Abstract [en]

    Background: The duplication of genes can occur through various mechanisms and is thought to make a major contribution to the evolutionary diversification of organisms. There is increasing evidence for a large-scale duplication of genes in some chelicerate lineages including two rounds of whole genome duplication (WGD) in horseshoe crabs. To investigate this further, we sequenced and analyzed the genome of the common house spider Parasteatoda tepidariorum.

    Results: We found pervasive duplication of both coding and non-coding genes in this spider, including two clusters of Hox genes. Analysis of synteny conservation across the P. tepidariorum genome suggests that there has been an ancient WGD in spiders. Comparison with the genomes of other chelicerates, including that of the newly sequenced bark scorpion Centruroides sculpturatus, suggests that this event occurred in the common ancestor of spiders and scorpions, and is probably independent of the WGDs in horseshoe crabs. Furthermore, characterization of the sequence and expression of the Hox paralogs in P. tepidariorum suggests that many have been subject to neo-functionalization and/or sub-functionalization since their duplication.

    Conclusions: Our results reveal that spiders and scorpions are likely the descendants of a polyploid ancestor that lived more than 450 MYA. Given the extensive morphological diversity and ecological adaptations found among these animals, rivaling those of vertebrates, our study of the ancient WGD event in Arachnopulmonata provides a new comparative platform to explore common and divergent evolutionary outcomes of polyploidization events across eukaryotes.

  • Liu, Wei
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Schrott-Fischer, Annelies
    Med Univ Innsbruck, Dept Otolaryngol, Innsbruck, Austria..
    Glueckert, Rudolf
    Med Univ Innsbruck, Dept Otolaryngol, Innsbruck, Austria..
    Benav, Heval
    MED EL GmbH, R&D, Innsbruck, Austria..
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The Human "Cochlear Battery" - Claudin-11 Barrier and Ion Transport Proteins in the Lateral Wall of the Cochlea2017In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 10, 239Article in journal (Refereed)
    Abstract [en]

    Background: The cochlea produces an electric field potential essential for hair cell transduction and hearing. This biological "battery" is situated in the lateral wall of the cochlea and contains molecular machinery that secretes and recycles K+ ions. Its functioning depends on junctional proteins that restrict the para-cellular escape of ions. The tight junction protein Claudin-11 has been found to be one of the major constituents of this barrier that maintains ion gradients (Gow et al., 2004; Kitajiri et al., 2004a). We are the first to elucidate the human Claudin-11 framework and the associated ion transport machinery using super-resolution fluorescence illumination microscopy (SR-SIM). Methods: Archival cochleae obtained during meningioma surgery were used for SR-SIM together with transmission electron microscopy after ethical consent. Results: Claudin-11-expressing cells formed parallel tight junction lamellae that insulated the epithelial syncytium of the stria vascularis and extended to the suprastrial region. Intercellular gap junctions were found between the barrier cells and fibrocytes. Conclusion: Transmission electron microscopy, confocal microscopy and SR-SIM revealed exclusive cell specialization in the various subdomains of the lateral wall of the human cochlea. The Claudin-11-expressing cells exhibited both conductor and isolator characteristics, and these micro-porous separators may selectively mediate the movement of charged units to the intrastrial space in a manner that is analogous to a conventional electrochemical "battery." The function and relevance of this battery for the development of inner ear disease are discussed.

  • Rossen, Jenny
    et al.
    Sophiahemmet Univ, Stockholm, Sweden.;Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden..
    Buman, Matthew P.
    Arizona State Univ, Sch Nutr & Hlth Promot, Coll Hlth Solut, Phoenix, AZ USA..
    Johansson, Unn-Britt
    Sophiahemmet Univ, Stockholm, Sweden.;Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden..
    Yngve, Agneta
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics. Sophiahemmet Univ, Stockholm, Sweden.
    Ainsworth, Barbara
    Arizona State Univ, Sch Nutr & Hlth Promot, Coll Hlth Solut, Phoenix, AZ USA..
    Brismar, Kerstin
    Karolinska Inst, Dept Mol Med & Surg, Karolinska Univ Hosp, Rolf Luft Res Ctr Diabet & Endocrinol, Stockholm, Sweden..
    Hagströmer, Maria
    Karolinska Inst, Div Physiotherapy, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.;Karolinska Univ Hosp, Allied Hlth Profess Funct, Funct Area Occupat Therapy & Physiotherapy, Stockholm, Sweden..
    Reallocating bouted sedentary time to non-bouted sedentary time, light activity and moderate-vigorous physical activity in adults with prediabetes and type 2 diabetes2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 7, e0181053Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to investigate the potential associations of reallocating 30 minutes sedentary time in long bouts (>60 min) to sedentary time in non-bouts, light intensity physical activity (LPA) and moderate-to vigorous physical activity (MVPA) with cardiometabolic risk factors in a population diagnosed with prediabetes or type 2 diabetes.

    Methods: Participants diagnosed with prediabetes and type 2 diabetes (n = 124, 50% men, mean [SD] age = 63.8 [7.5] years) were recruited to the physical activity intervention Sophia Step Study. For this study baseline data was used with a cross-sectional design. Time spent in sedentary behaviors in bouts (>60 min) and non-bouts (accrued in <60 min bouts) and physical activity was measured using the ActiGraph GT1M. Associations of reallocating bouted sedentary time to non-bouted sedentary time, LPA and MVPA with cardiometabolic risk factors were examined using an isotemporal substitution framework with linear regression models.

    Results: Reallocating 30 minutes sedentary time in bouts to MVPA was associated with lower waist circumference (b = -4.30 95% CI:-7.23, -1.38 cm), lower BMI (b = -1.46 95% CI:-2.60, -0.33 kg/m(2)) and higher HDL cholesterol levels (b = 0.11 95% CI: 0.02, 0.21 kg/m(2). Similar associations were seen for reallocation of sedentary time in non-bouts to MVPA. Reallocating sedentary time in bouts to LPA was associated only with lower waist circumference.

    Conclusion: Reallocation of sedentary time in bouts as well as non-bouts to MVPA, but not to LPA, was beneficially associated with waist circumference, BMI and HDL cholesterol in individuals with prediabetes and type 2 diabetes. The results of this study confirm the importance of reallocation sedentary time to MVPA.

  • Farag, Mohamed A.
    et al.
    Cairo Univ, Pharmacognosy Dept, Coll Pharm, Kasr el Aini St,PB 11562, Cairo, Egypt..
    Ali, Sara E.
    German Univ Cairo, Fac Pharm & Biotechnol, Dept Pharmaceut Biol, PB 11835, Cairo, Egypt..
    Hodaya, Rashad H.
    Desert Res Ctr, Plant Prod Dept, PB 11714, Cairo, Egypt..
    El-Seedi, Hesham R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy. Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm 32512, Egypt..
    Sultani, Haider N.
    Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany..
    Laub, Annegret
    Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany..
    Eissa, Tarek E.
    Modern Sci & Arts Univ, Coll Pharm, Pharmacognosy Dept, PB 12566, Cairo, Egypt..
    Abou-Zaid, Fouad O. F.
    Desert Res Ctr, Plant Prod Dept, PB 11714, Cairo, Egypt..
    Wessjohann, Ludger A.
    Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany..
    Phytochemical Profiles and Antimicrobial Activities of Allium cepa Red cv. and A. sativum Subjected to Different Drying Methods: A Comparative MS-Based Metabolomics2017In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, no 5, 761Article in journal (Refereed)
    Abstract [en]

    Plants of the Allium genus produce sulphur compounds that give them a characteristic (alliaceous) flavour and mediate for their medicinal use. In this study, the chemical composition and antimicrobial properties of Allium cepa red cv. and A. sativum in the context of three different drying processes were assessed using metabolomics. Bulbs were dried using either microwave, air drying, or freeze drying and further subjected to chemical analysis of their composition of volatile and non-volatile metabolites. Volatiles were collected using solid phase micro-extraction (SPME) coupled to gas chromatography-mass spectrometry (GC/MS) with 42 identified volatiles including 30 sulphur compounds, four nitriles, three aromatics, and three esters. Profiling of the polar non-volatile metabolites via ultra-performance liquid chromatography coupled to high resolution MS (UPLC/MS) annotated 51 metabolites including dipeptides, flavonoids, phenolic acids, and fatty acids. Major peaks in GC/MS or UPLC/MS contributing to the discrimination between A. sativum and A. cepa red cv. were assigned to sulphur compounds and flavonoids. Whereas sulphur conjugates amounted to the major forms in A. sativum, flavonoids predominated in the chemical composition of A. cepa red cv. With regard to drying impact on Allium metabolites, notable and clear separations among specimens were revealed using principal component analysis (PCA). The PCA scores plot of the UPLC/MS dataset showed closer metabolite composition of microwave dried specimens to freeze dried ones, and distant from air dried bulbs, observed in both A. cepa and A. sativum. Compared to GC/MS, the UPLC/MS derived PCA model was more consistent and better in assessing the impact of drying on Allium metabolism. A phthalate derivative was found exclusively in a commercial garlic preparation via GC/MS, of yet unknown origin. The freeze dried samples of both Allium species exhibited stronger antimicrobial activities compared to dried specimens with A. sativum being in general more active than A. cepa red cv.

  • Österberg, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    Profiling memory accesses on the ODROID-XU42017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Decoupled Access-Execute(DAE) is an innovative approach to optimize energy consumption of computer programs by splitting the program into two tasks; the first task is to access data, this is profoundly memory-bound and can be done with energy efficient cores. The second task is to execute and compute the data, which iscompute-bound and can be done with powerful cores. This thesis work aims todevelop a profiling tool that can measure the efficiency of DAE by investigating thecache misses in the original code and the DAE code (in the access and executephases). This was achieved by measuring the cache loads and memory accesses forthe DAE transformation for the benchmarks done by a previous study that targets DAE on Arm's HMP architecture, big.LITTLE. The data obtained from this study showt hat DAE on big.LITTLE has a potential for energy savings, especially with applications that feature indirection in memory accesses. Arm DynamIQ opens up new possibilities for DAE code transformation. New levels of energy efficiency can be reached with a finer-grained Dynamic Voltage Frequency Scaling(DVFS), a more rapid power, state transition mechanism and a shared cache for 'big' and 'LITTLE' CPUs.

  • Aaboud, M.
    et al.
    Bergeås, Elin Kuutmann
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Brenner, Richard
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ekelöf, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellert, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ferrari, Arnaud
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Gradin, P.O. Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Madsen, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Öhman, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Rangel-Smith, Camilla
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zwalinski, L.
    Measurement of (WW +/-)-W-+/- vector-boson scattering and limits on anomalous quartic gauge couplings with the ATLAS detector2017In: Physical Review D: covering particles, fields, gravitation, and cosmology, ISSN 2470-0010, E-ISSN 2470-0029, Vol. 96, no 1, 012007Article in journal (Refereed)
    Abstract [en]

    This paper presents the extended results of measurements of (WW +/-)-W-+/- jj production and limits on anomalous quartic gauge couplings using 20.3 fb(-1) of proton-proton collision data at root s = 8 TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with two leptons (e or mu) with the same electric charge and at least two jets are analyzed. Production cross sections are determined in two fiducial regions, with different sensitivities to the electroweak and strong production mechanisms. An additional fiducial region, particularly sensitive to anomalous quartic gauge coupling parameters alpha 4 and alpha 5, is introduced, which allows more stringent limits on these parameters compared to the previous ATLAS measurement.

  • Ramnerö, David
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Semi-automatic Training Data Generation for Cell Segmentation Network Using an Intermediary Curator Net2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In this work we create an image analysis pipeline to segment cells from microscopy image data. A portion of the segmented images are manually curated and this curated data is used to train a Curator network to filter the whole dataset. The curated data is used to train a separate segmentation network to improve the cell segmentation. This technique can be easily applied to different types of microscopy object segmentation.

  • Public defence: 2017-12-01 14:00 Enghoffsalen, Ing 50 bv, Akademiska sjukhuset, Uppsala
    Karlsson, Henning
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala university.
    New preclinical strategies for characterization and development of anticancer drugs2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Increased understanding of the molecular mechanisms underlying cancer development has shifted drug discovery towards target driven drug development the last decades, but the development of effective cancer drugs has been hampered by the lack of predictive preclinical models. 3-D cultures, considered to more accurately reflect solid tumors in vivo, have been proposed as one way to increase the predictability of clinical efficacy in cancer drug discovery and development.

    The aims of this thesis were to improve preclinical models for cancer drug development, with focus on colorectal cancer (CRC) and use of multicellular tumor spheroids (MCTS), and also to mechanistically characterize some potentially new anticancer drugs (papers I – IV). The most important technical improvement was the development of direct measurement of green fluorescent protein (GFP) marked cells in spheroids, simplifying live collection of viability data and enabling high-throughput screening (HTS) in the MCTS model (paper I). In paper III and IV, the 3-D model was adapted to enable studies on the interaction between drugs and radiation. Two potentially new anticancer drugs, VLX50 and VLX60, were mechanistically characterized. VLX60, a novel copper containing thiosemicarbazone, induced reactive oxygen species (ROS) formation, was selectively active against BRAF mutated colon cancer cells and exhibited anticancer activity in vivo (paper II). Furthermore, two potentially new anticancer drugs were found suitable for further development for use in combination with radiation (papers III and IV). In paper III, synergy with radiation in spheroids compared to monolayer cultured colon cancer cells was shown with the novel iron-chelating inhibitor of oxidative phosphorylation, VLX600. In paper IV, the antiprotozoal drug nitazoxanide was shown to sensitize quiescent clonogenic colon cancer cells to radiation.

    In conclusion, introduction of measurement of fluorescence of GFP marked cells in spheroids makes clinically relevant 3-D models feasible for HTS experiments and characterization of candidate drugs and radiosensitizers in early cancer drug discovery and development. VLX60 has several characteristics suitable for further development into a cancer drug, notably against BRAF mutated colorectal cancer cells. VLX600 and nitazoxanide show radiosensitizing properties making them promising for further development for use as cancer drugs in combination with radiation.

    List of papers
    1. Loss of cancer drug activity in colon cancer HCT-116 cells during spheroid formation in a new 3-D spheroid cell culture system
    Open this publication in new window or tab >>Loss of cancer drug activity in colon cancer HCT-116 cells during spheroid formation in a new 3-D spheroid cell culture system
    2012 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 318, no 13, 1577-1585 p.Article in journal (Refereed) Published
    Abstract [en]

    Clinically relevant in vitro methods are needed to identify new cancer drugs for solid tumors. We report on a new 3-D spheroid cell culture system aimed to mimic the properties of solid tumors in vivo. The colon cancer cell lines HCT-116 wt and HCT-116 wt/GFP were grown as monolayers and for 3 or 6 days on 96-well NanoCulture (R) plates to form spheroids. Expression of surface markers, genes and hypoxia were assessed to characterize the spheroids and drug induced cytotoxicity was evaluated based on fluorescein diacetate (FDA) conversion by viable cells to fluorescent fluorescein or by direct measurement of fluorescence of GFP marked cells after a 72 h drug incubation. The cells reproducibly formed spheroids in the NanoCulture (R) plates with tight cell-attachment after 6 days. Cells in spheroids showed geno- and phenotypical properties reminiscent of hypoxic stem cells. Monolayer cultured cells were sensitive to standard and investigational drugs, whereas the spheroids gradually turned resistant. Similar results for cytotoxicity were observed using simplified direct measurement of fluorescence of GFP marked cells compared with FDA incubation. In conclusion, this new 3-D spheroid cell culture system provides a convenient and clinically relevant model for the identification and characterization of cancer drugs for solid tumors.

    Keyword
    Tumor cell, Cell culture, Monolayer, Spheroid, Cancer drug, Colon cancer
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-177550 (URN)10.1016/j.yexcr.2012.03.026 (DOI)000305591800011 ()
    Available from: 2012-07-16 Created: 2012-07-16 Last updated: 2017-10-09Bibliographically approved
    2. Mechanistic characterization of a copper containing thiosemicarbazone with potent antitumor activity
    Open this publication in new window or tab >>Mechanistic characterization of a copper containing thiosemicarbazone with potent antitumor activity
    Show others...
    2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 18, 30217-30234 p.Article in journal (Refereed) Published
    Abstract [en]

    Background: The thiosemicarbazone CD 02750 (VLX50) was recently reported as a hit compound in a phenotype-based drug screen in primary cultures of patient tumor cells. We synthesized a copper complex of VLX50, denoted VLX60, and characterized its antitumor and mechanistic properties.

    Materials and Methods: The cytotoxic effects and mechanistic properties of VLX60 were investigated in monolayer cultures of multiple human cell lines, in tumor cells from patients, in a 3-D spheroid cell culture system and in vivo and were compared with those of VLX50.

    Results: VLX60 showed >= 3-fold higher cytotoxic activity than VLX50 in 2-D cultures and, in contrast to VLX50, retained its activity in the presence of additional iron. VLX60 was effective against non-proliferative spheroids and against tumor xenografts in vivo in a murine model. In contrast to VLX50, gene expression analysis demonstrated that genes associated with oxidative stress were considerably enriched in cells exposed to VLX60 as was induction of reactive oxygen. VLX60 compromised the ubiquitin-proteasome system and was more active in BRAF mutated versus BRAF wild-type colon cancer cells.

    Conclusions: The cytotoxic effects of the copper thiosemicarbazone VLX60 differ from those of VLX50 and shows interesting features as a potential antitumor drug, notably against BRAF mutated colorectal cancer.

    Place, publisher, year, edition, pages
    IMPACT JOURNALS LLC, 2017
    Keyword
    cancer drug, thiosemicarbazone, spheroid, VLX60, BRAF
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-323035 (URN)10.18632/oncotarget.16324 (DOI)000400456200055 ()28415818 (PubMedID)
    Funder
    Swedish Cancer SocietySwedish Foundation for Strategic Research
    Available from: 2017-06-01 Created: 2017-06-01 Last updated: 2017-10-09Bibliographically approved
    3. A novel tumor spheroid model identifies selective enhancement of radiation by an inhibitor of oxidative phosphorylation
    Open this publication in new window or tab >>A novel tumor spheroid model identifies selective enhancement of radiation by an inhibitor of oxidative phosphorylation
    Show others...
    (English)In: Article in journal (Other academic) Submitted
    Place, publisher, year, edition, pages
    Uppsala:
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-330981 (URN)
    Available from: 2017-10-09 Created: 2017-10-09 Last updated: 2017-10-09
    4. Selective radiosensitization by nitazoxanide of quiescent clonogenic colon cancer tumor cells
    Open this publication in new window or tab >>Selective radiosensitization by nitazoxanide of quiescent clonogenic colon cancer tumor cells
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-330980 (URN)
    Available from: 2017-10-09 Created: 2017-10-09 Last updated: 2017-10-09
  • Blomqvist, Klara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Malmberg, Isabell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Att förlora ett bröst: En litteraturstudie om kvinnors psykiska hälsa efter mastektomi2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Breast cancer is the most common form of cancer among women today, however, the survival rate has increased due to the development of more effective treatment options. Mastectomy has for a long time been the standard treatment but today, breast conserving surgery along with adjuvant therapy is considered to be an equally good treatment. It is therefore necessary to discuss the effect mastectomy has on mental health in light of these new treatment options. This literature review is important because it may enlighten nurses on this topic and provides conditions for correct handling and care of post-operative women.

     

    Aim: The purpose of this study is to investigate whether and how women’s mental health is affected by undergoing mastectomy as surgical treatment for breast cancer.

     

    Method: A general literature review. The searches were conducted in the databases PubMed, Cochrane, Cinahl and PsychINFO. A total 14 science articles with qualitative and quantitative design were included.  

     

    Results: Mental ill health, such as depression and anxiety, are common after undergoing a mastectomy and seems to be affected more negatively for those undergoing mastectomy than those undergoing breast conserving surgery and/or reconstruction. However, the mental ill health seem to decrease over time from before surgery to after. The body image is also affected negatively, more negatively after mastectomy compared to breast conserving surgery and/or reconstruction. The psychosocial health and quality of life appears to be lower than the general population.

     

    Conclusions: This literature review finds that mental ill health are common among women that have undergone a mastectomy. More research is required in order to understand how mental health changes over time among women undergoing mastectomy.

  • Jansson, Olivia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Magnusson, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vilka anledningar finns till att föräldrar väljer att inte vaccinera sina barn?: En litteraturöversikt2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Vaccine protects both individuals and the society in general. Without vaccines, both herd-immunity and public health are threatened. Around the world, some parents choose not to vaccinate their children. This decision is often based on information the parents have received from internet sources. This study aimed to investigate the reasons why parents refrain from vaccinating their children. This information is important in the nurse's profession as the role involves supporting the patient in his or her self-care. Method: Through a systematic review, articles regarding vaccine resistance and hesitancy have been examined to answer the purpose of this study. A literature search was made in scientific databases, and 13 articles were selected. The articles were reviewed and various reasons for the vaccine resistance were found. Result: Things that parents worried about were side effects, illnesses and the content of the vaccine. Some parents did not believe that the disease exists anymore or thought that the vaccine is not reliable. Most of the parents' decisions aimed to protect their child and were, in most cases, made by lack of information. Conclusion: The conclusion of this review is that more reliable information must be available for parents. The information should come from reliable sources, such as authorities. The authorities should also reach out with information through the internet and social media, as parents tend to rely on the internet whilst making decisions. With information from this study nurses can help the parents make an informed decision regarding vaccinations. 

  • Dahl, Viktor
    et al.
    Publ Hlth Agcy Sweden, Stockholm, Sweden.;European Ctr Dis Prevent & Control ECDC, EPIET, Stockholm, Sweden..
    Wallensten, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Publ Hlth Agcy Sweden, Stockholm, Sweden..
    Self-reported infections during international travel and notifiable infections among returning international travellers, Sweden, 2009-20132017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 7, e0181625Article in journal (Refereed)
    Abstract [en]

    We studied food and water-borne diseases (FWDs), sexually transmitted diseases (STDs), vector-borne diseases (VBDs) and diseases vaccinated against in the Swedish childhood vaccination programme among Swedish international travellers, in order to identify countries associated with a high number of infections. We used the national database for notifiable infections to estimate the number of FWDs (campylobacteriosis, salmonellosis, giardiasis, shigellosis, EHEC, Entamoeba histolytica, yersinosis, hepatitis A, paratyphoid fever, typhoid fever, hepatitis E, listeriosis, cholera), STIs (chlamydia, gonorrhoea and acute hepatitis B), VBDs (dengue fever, malaria, West Nile fever, Japanese encephalitis and yellow fever) and diseases vaccinated against in the Swedish childhood vaccination programme (pertussis, measles, mumps, rubella, diphtheria) acquired abroad 2009-2013. We obtained number and duration of trips to each country from a database that monthly collects travel data from a randomly selected proportion of the Swedish population. We calculated number of infections per country 2009-2013 and incidence/million travel days for the five countries with the highest number of infections. Thailand had the highest number of FWDs (7,697, incidence 191/million travel days), STIs (1,388, incidence 34/million travel days) and VBDs (358, incidence 9/million travel days). France had the highest number of cases of diseases vaccinated against in the Swedish childhood vaccination programme (8, 0.4/million travel days). Swedish travellers contracted most infections in Thailand. Special focus should be placed on giving advice to travellers to this destination.

  • Philipson, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Widfeldt, Sigrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Faktorer som påverkar upplevelsen av bemötande hos personer med substansbrukssyndrom2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Introduction: People who use drugs are particularly vulnerable patients within health care, due to stigmatization and poor attitudes from healthcare professionals. Poor treatment can cause negative consequences for the patient’s overall health. Aim: To explore factors affecting how patients with substance use disorder experience treatment from healthcare professionals. Method: Literature review of qualitative studies. Data is collected from databases PubMed, PsycInfo, Scopus, ScienceDirect and CINAHL. Result: A person centered approach has a positive effect on the experience of treatment. Stigmatization and lack of formal competence are factors contributing to a negative experience of treatment from healthcare professionals. Conclusion: The factors contributing to the experience of treatment from healthcare professionals are if person centered care is applied, if stigmatizing behaviors and attitudes are present, and the formal nursing education levels related to substance use disorders. Individuals with substance use disorders may experience that treatment received by healthcare professionals affect their decision to seek care. Improvement and extension of nurse’s education related to substance use disorder and treatment within health care should be a priority.

  • Arnsäter, Olivia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Janerheim, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Faktorer i samarbetet och kommunikationen mellan sjuksköterskor och undersköterskor som påverkar en patientsäker omvårdnad: En intervjustudie2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Patient safety is a constantly current subject. Collaboration and communication plays an important role for patient safety. Licensed practical nurses, registred nurses and physicians often works separately, without consulting each other. There are great risks with insufficient communication. The most commonly reported cause to adverse events are lack of communication within or between professions, units, shifts and caregivers.

    Aim: The aim of this study was to describe factors in the collaboration and communication between registred nurses and licensed practical nurses that can affect patient safe care on a hospital department.

    Method: The study was conducted using qualitative methods and based on half-structured interview questions with ten nurses, from two different departments and two different hospitals in Sweden. Interviews were recorded and transcribed as well as analyzed by qualitative content analysis.

    Result: The analyze of the responces gave four categories and six subcategories which was Control of care with subcategories Clarity and To have time, Common platform with subcategories Consensus and Reconciliation, Good group dynamics with subcategories Trust and Team spirit and Experience and competence.

    Conclusion: There are many factors in the collaboration and communication between registered nurses and licensed practical nurses that can affect a patient safe care. Factors as to have clarity, contribute to good group dynamics and to have the right competence the individual can impact. Other factors as environment, team training and work load are depending on decisions from higher instances.

  • Bermudez, Fanny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Frida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kvinnans livskvalitet och sexuella funktion efter hysterektomi: En litteraturstudie2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Hysterectomy is a relatively common gynecological surgery that can be performed in three different ways: abdominally, vaginally or laparoscopically. It has been suggested that women with benign cause for a hysterectomy suffers from many symptoms that can lower a woman's overall quality of life and sexual function. Many women experience anxiety prior to the operation concerning the outcomes of the surgery.

     

    Aim: The purpose is to investigate how women estimate their quality of life and sexual function after an elective hysterectomy with a benign cause.

     

    Method: A literature review where 13 quantitative original articles were examined. The result was compiled and analyzed using a content analysis method.

     

    Results: Most of the articles reported that women's quality of life and sexual function improved after the hysterectomy. The women's social function, physical function, mental function and their pain problems had improved. This included that the women’s sexual frequency and sexual activity improved but their sexual desire was unchanged. In a contrary note some women estimated their FSFI higher, whilst in two other studies it was shown that some had FSFI which also concluded an impaired sexual function. Although women estimated their FSFI higher postoperatively their scores still show lower FSFI score than the normal population.

     

    Conclusion: Most women who go through with a hysterectomy because of benign diseases evaluate their quality of life to be higher postoperatively by improving their social function, physical function and mental health. Their sexual function is estimated to be higher than it was preoperatively, even though women still show lower FSFI score than the normal population.

  • Wang, Jinfan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    Forster, Anthony C.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    Translational roles of the C75 2 ' OH in an in vitro tRNA transcript at the ribosomal A, P and E sites2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 6709Article in journal (Refereed)
    Abstract [en]

    Aminoacyl-tRNAs containing a deoxy substitution in the penultimate nucleotide (C75 2'OH -> 2'H) have been widely used in translation for incorporation of unnatural amino acids (AAs). However, this supposedly innocuous modification surprisingly increased peptidyl-tRNA(ugc)(Ala) drop off in biochemical assays of successive incorporations. Here we predict the function of this tRNA 2'OH in the ribosomal A, P and E sites using recent co-crystal structures of ribosomes and tRNA substrates and test these structure-function models by systematic kinetics analyses. Unexpectedly, the C75 2'H did not affect A-to P-site translocation nor peptidyl donor activity of tRNA(ugc)(Ala). Rather, the peptidyl acceptor activity of the A-site Ala-tRNA(ugc)(Ala) and the translocation of the P-site deacylated tRNA(ugc)(Ala) to the E site were impeded. Delivery by EF-Tu was not significantly affected. This broadens our view of the roles of 2'OH groups in tRNAs in translation.

  • Matricon, Pierre
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ranganathan, Anirudh
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, SE-10691 Stockholm, Sweden..
    Warnick, Eugene
    NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA..
    Gao, Zhan-Guo
    NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA..
    Rudling, Axel
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, SE-10691 Stockholm, Sweden..
    Lambertucci, Catia
    Univ Camerino, Scuola Sci Farmaco & Prod Salute, Via S Agostino 1, I-62032 Camerino, MC, Italy..
    Marucci, Gabriella
    Univ Camerino, Scuola Sci Farmaco & Prod Salute, Via S Agostino 1, I-62032 Camerino, MC, Italy..
    Ezzati, Aitakin
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, SE-10691 Stockholm, Sweden..
    Jaiteh, Mariama
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dal Ben, Diego
    Univ Camerino, Scuola Sci Farmaco & Prod Salute, Via S Agostino 1, I-62032 Camerino, MC, Italy..
    Jacobson, Kenneth A.
    NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA..
    Carlsson, Jens
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Fragment optimization for GPCRs by molecular dynamics free energy calculations: Probing druggable subpockets of the A(2A) adenosine receptor binding site2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 6398Article in journal (Refereed)
    Abstract [en]

    Fragment-based lead discovery is becoming an increasingly popular strategy for drug discovery. Fragment screening identifies weakly binding compounds that require optimization to become high-affinity leads. As design of leads from fragments is challenging, reliable computational methods to guide optimization would be invaluable. We evaluated using molecular dynamics simulations and the free energy perturbation method (MD/FEP) in fragment optimization for the A(2A) adenosine receptor, a pharmaceutically relevant G protein-coupled receptor. Optimization of fragments exploring two binding site subpockets was probed by calculating relative binding affinities for 23 adenine derivatives, resulting in strong agreement with experimental data (R-2 = 0.78). The predictive power of MD/FEP was significantly better than that of an empirical scoring function. We also demonstrated the potential of the MD/FEP to assess multiple binding modes and to tailor the thermodynamic profile of ligands during optimization. Finally, MD/FEP was applied prospectively to optimize three nonpurine fragments, and predictions for 12 compounds were evaluated experimentally. The direction of the change in binding affinity was correctly predicted in a majority of the cases, and agreement with experiment could be improved with rigorous parameter derivation. The results suggest that MD/FEP will become a powerful tool in structure-driven optimization of fragments to lead candidates.

  • Bowman, John L
    et al.
    Kohchi, Takayuki
    Yamato, Katsuyuki T
    Jenkins, Jerry
    Shu, Shengqiang
    Ishizaki, Kimitsune
    Yamaoka, Shohei
    Nishihama, Ryuichi
    Nakamura, Yasukazu
    Berger, Frédéric
    Adam, Catherine
    Aki, Shiori Sugamata
    Althoff, Felix
    Araki, Takashi
    Arteaga-Vazquez, Mario A
    Balasubrmanian, Sureshkumar
    Barry, Kerrie
    Bauer, Diane
    Boehm, Christian R
    Briginshaw, Liam
    Caballero-Perez, Juan
    Catarino, Bruno
    Chen, Feng
    Chiyoda, Shota
    Chovatia, Mansi
    Davies, Kevin M
    Delmans, Mihails
    Demura, Taku
    Dierschke, Tom
    Dolan, Liam
    Dorantes-Acosta, Ana E
    Eklund, D. Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Florent, Stevie N
    Flores-Sandoval, Eduardo
    Fujiyama, Asao
    Fukuzawa, Hideya
    Galik, Bence
    Grimanelli, Daniel
    Grimwood, Jane
    Grossniklaus, Ueli
    Hamada, Takahiro
    Haseloff, Jim
    Hetherington, Alexander J
    Higo, Asuka
    Hirakawa, Yuki
    Hundley, Hope N
    Ikeda, Yoko
    Inoue, Keisuke
    Inoue, Shin-Ichiro
    Ishida, Sakiko
    Jia, Qidong
    Kakita, Mitsuru
    Kanazawa, Takehiko
    Kawai, Yosuke
    Kawashima, Tomokazu
    Kennedy, Megan
    Kinose, Keita
    Kinoshita, Toshinori
    Kohara, Yuji
    Koide, Eri
    Komatsu, Kenji
    Kopischke, Sarah
    Kubo, Minoru
    Kyozuka, Junko
    Lagercrantz, Ulf
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Lin, Shih-Shun
    Lindquist, Erika
    Lipzen, Anna M
    Lu, Chia-Wei
    De Luna, Efraín
    Martienssen, Robert A
    Minamino, Naoki
    Mizutani, Masaharu
    Mizutani, Miya
    Mochizuki, Nobuyoshi
    Monte, Isabel
    Mosher, Rebecca
    Nagasaki, Hideki
    Nakagami, Hirofumi
    Naramoto, Satoshi
    Nishitani, Kazuhiko
    Ohtani, Misato
    Okamoto, Takashi
    Okumura, Masaki
    Phillips, Jeremy
    Pollak, Bernardo
    Reinders, Anke
    Rövekamp, Moritz
    Sano, Ryosuke
    Sawa, Shinichiro
    Schmid, Marc W
    Shirakawa, Makoto
    Solano, Roberto
    Spunde, Alexander
    Suetsugu, Noriyuki
    Sugano, Sumio
    Sugiyama, Akifumi
    Sun, Rui
    Suzuki, Yutaka
    Takenaka, Mizuki
    Takezawa, Daisuke
    Tomogane, Hirokazu
    Tsuzuki, Masayuki
    Ueda, Takashi
    Umeda, Masaaki
    Ward, John M
    Watanabe, Yuichiro
    Yazaki, Kazufumi
    Yokoyama, Ryusuke
    Yoshitake, Yoshihiro
    Yotsui, Izumi
    Zachgo, Sabine
    Schmutz, Jeremy
    Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome2017In: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 171, no 2, 287-304 p.Article in journal (Refereed)
    Abstract [en]

    The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP.

  • Public defence: 2017-12-02 09:30 Hedstrandsalen, Uppsala
    Schiza, Aglaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Experimental treatment of patients with disseminated malignant melanoma2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Malignant melanoma (MM) is the deadliest skin cancer with an ever-increasing incidence. New treatments have improved the prognosis for patients with advanced MM. Still, most patients do not respond, and the side effects can be severe, underlining the need for better therapies.

    The overall aim of this thesis was to evaluate new means to improve the treatment for patients with advanced MM. Immunostimulatory gene therapy (AdCD40L) was evaluated in a clinical study and BRAF-inhibitory treatment in rare cases of BRAF-mutated MM.

    Due to its immunogenicity, MM is an attractive target for immunostimulatory gene therapy. AdCD40L is an adenovirus carrying the human gene for CD40 ligand, which in different ways can stimulate the immune system to combat cancer. We conducted a Phase I/IIa study with AdCD40L in patients with metastatic MM having received established treatments. In cohort 1 (n=6), four weekly, intratumoural AdCD40L injections were given. In cohort 2 (n=9), low dose cyclophosphamide was added to increase the immune response. Since irradiation may act synergistically with immunotherapy, patients in cohort 3 (n=9) also received a single fraction of radiotherapy (8 Gy). This fraction was given towards the lesion selected for injections.

    The primary objectives were to assess the feasibility and safety of AdCD40L-treatment and secondarily its anti-tumour effects. Patients were thoroughly assessed for toxicity. The anti-tumour response was evaluated by imaging techniques (FDG-PET/CT, DW-MRI scans), tumour biopsies and blood tests. Plasma protein markers were measured with a multiplex platform. Another objective was to evaluate the potential of DW-MRI and FDG-PET/CT for prediction of AdCD40L treatment response, in terms of overall survival (OS).

    AdCD40L was well tolerated with mild transient reactions. Local and distant responses in PET/CT scans along with a significantly better 6-month survival in the cohorts that received cyclophosphamide conditioning were observed. Effector lymphocyte responses were elicited. All patients had an increased T effector/T regulatory-cell ratio and death receptors were significantly up-regulated post therapy. Inflammatory cytokines and other plasma proteins were altered in favourable ways by the AdCD40L treatment. The analyses support that the functional DWI parameters may be better early predictors of OS than the established metabolic and morphologic criteria of FDG-PET/CT and CT/MRI, respectively.

    In conclusion, the stimulation of the CD40 pathway to initiate anti-tumour immunity is a promising treatment alternative for MM patients. However, further studies with developed treatment schemes are warranted.

    In the first report ever on treatment of a pregnant patient with a BRAF-inhibitor, the therapy was initiated in the second trimester. The treatment with vemurafenib enabled prolonged gestation, hence reducing the risk of immaturity-related complications. Further, we report the first case worldwide of a patient with metastatic conjunctival melanoma who benefitted from treatment with vemurafenib. Additional studies are needed to assess the efficacy of BRAF -inhibitors in the different subtypes of ocular melanoma.

     

    List of papers
    1. Immunostimulatory AdCD40L gene therapy combined with low-dose cyclophosphamide in metastatic melanoma patients
    Open this publication in new window or tab >>Immunostimulatory AdCD40L gene therapy combined with low-dose cyclophosphamide in metastatic melanoma patients
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    2016 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, no 8, 872-880 p.Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Current approaches for treating metastatic malignant melanoma (MM) are not effective enough and are associated with serious adverse events. Due to its immunogenicity, melanoma is an attractive target for immunostimulating therapy. In this phase I/IIa study, local AdCD40L immunostimulatory gene therapy was evaluated in patients with MM.

    METHODS: AdCD40L is an adenovirus carrying the gene for CD40 ligand. Patients that failed standard treatments were enrolled. Six patients received four weekly intratumoral AdCD40L injections. Next, nine patients received low-dose cyclophosphamide conditioning before the first and fourth AdCD40L injection. The blood samples were collected at multiple time points for chemistry, haematology and immunology evaluations. Radiology was performed at enrolment and repeated twice after the treatment.

    RESULTS: AdCD40L was safe with mild transient reactions. No objective responses were recorded by MRI, however, local and distant responses were seen on FDG-PET. The overall survival at 6 months was significantly better when cyclophosphamide was added to AdCD40L. The patients with the best survival developed the highest levels of activated T cells and experienced a pronounced decrease of intratumoral IL8.

    CONCLUSIONS: AdCD40L therapy for MM was well tolerated. Local and distant responses along with better survival in the low-dose cyclophosphamide group are encouraging.

    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-295735 (URN)10.1038/bjc.2016.42 (DOI)000374129200004 ()27031851 (PubMedID)
    Funder
    Swedish Cancer Society
    Available from: 2016-06-09 Created: 2016-06-09 Last updated: 2017-10-15Bibliographically approved
    2. Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients
    Open this publication in new window or tab >>Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients
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    2017 (English)In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 15, no 79Article in journal (Refereed) Published
    Abstract [en]

    Background and aims: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). Methods: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide. Cells were analyzed by flow cytometry while plasma samples were analyzed by a multi-array proteomics. Results: All patients had an increased Teffector/Tregulatory cell ratio post therapy. Simultaneously, the death receptors TNFR1 and TRAIL-R2 were significantly up-regulated post treatment. Stem cell factor (SCF), E-selectin, and CD6 correlated to enhanced overall survival while a high level of granulocytic myeloid-derived suppressor cells (gMDSCs), IL8, IL10, TGFb1, CCL4, PlGF and Fl3t ligand was highest in patients with short survival. Conclusions: AdCD40L intratumoral injection induced desirable systemic immune effects that correlated to prolonged survival. Further studies using CD40 stimulation in malignant melanoma are warranted.

    Keyword
    AdCD40L, Malignant melanoma, Immunotherapy, Proteomics, T regulatory cells, Myeloid-derived suppressor cells
    National Category
    Immunology in the medical area
    Identifiers
    urn:nbn:se:uu:diva-322800 (URN)10.1186/s12967-017-1182-z (DOI)000399786900002 ()28427434 (PubMedID)
    Available from: 2017-06-20 Created: 2017-06-20 Last updated: 2017-10-15Bibliographically approved
    3. Diffusion-Weighted MRI may be better than FDG-PET/CT to assess immunotherapy response in patients with metastatic melanoma
    Open this publication in new window or tab >>Diffusion-Weighted MRI may be better than FDG-PET/CT to assess immunotherapy response in patients with metastatic melanoma
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-330709 (URN)
    Available from: 2017-10-03 Created: 2017-10-03 Last updated: 2017-10-15
    4. Treatment of metastatic malignant melanoma with vemurafenib during pregnancy
    Open this publication in new window or tab >>Treatment of metastatic malignant melanoma with vemurafenib during pregnancy
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    2013 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, Vol. 31, no 11, e192-e193 p.Article in journal (Refereed) Published
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-328673 (URN)10.1200/JCO.2012.45.2870 (DOI)23401457 (PubMedID)
    Available from: 2017-08-29 Created: 2017-08-29 Last updated: 2017-10-15Bibliographically approved
    5. A case report of a patient with metastatic ocular melanoma who experienced a response to treatment with the BRAF inhibitor vemurafenib
    Open this publication in new window or tab >>A case report of a patient with metastatic ocular melanoma who experienced a response to treatment with the BRAF inhibitor vemurafenib
    2016 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 16, 634Article in journal (Refereed) Published
    Abstract [en]

    Background: Conjunctival malignant melanoma (CMM) is a rare malignancy and in the advanced setting there is no effective treatment. In contrast, half of cutaneous melanomas have BRAF mutations and treatment with BRAF inhibitors is established for patients with disseminated disease. The most common form of ocular melanoma, uveal melanoma, lacks these mutations, however, their presence has been reported for CMM. Case presentation: We used the BRAF inhibitor vemurafenib to treat a 53 year-old female suffering from a BRAFV600E mutated metastatic CMM. The patient benefited from the treatment, a response was evident within a week and she experienced a progression free survival of four months. Conclusions: To our knowledge, this is the first described case of response to vemurafenib treatment in a patient with ocular melanoma.

    Keyword
    BRAF inhibitor, BRAF mutation, Conjunctival malignant melanoma, Ocular melanoma, Vemurafenib
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-305937 (URN)10.1186/s12885-016-2657-7 (DOI)000384169800001 ()27520988 (PubMedID)
    Available from: 2016-11-11 Created: 2016-10-24 Last updated: 2017-10-15Bibliographically approved
  • Eriksson, Leif
    et al.
    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). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Bergström, Anna
    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). Institute for Global Health, London, United Kingdom.
    Hoa, Dinh Thi Phuong
    Hanoi School of Public Health, Hanoi, Vietnam.
    Nga, Nguyen Thu
    Research Institute for Child Health, Hanoi, Vietnam.
    Eldh, Ann Catrine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Högskolan Dalarna.
    Sustainability of knowledge implementation in a low- and middle- income context: Experiences from a facilitation project in Vietnam targeting maternal and neonatal health2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 8, e0182626Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In a previous trial in Vietnam, a facilitation strategy to secure evidence-based practice in primary care resulted in reduced neonatal mortality over a period of three years. While little is known as to what ensures sustainability in the implementation of community-based strategies, the aim of this study was to investigate factors promoting or hindering implementation, and sustainability of knowledge implementation strategies, by means of the former Neonatal Knowledge Into Practice (NeoKIP) trial.

    METHODS: In 2014 we targeted all levels in the Vietnamese healthcare system: six individual interviews with representatives at national, provincial and district levels, and six focus group discussions with representatives at the commune level. The interviews were transcribed verbatim, translated to English, and analysed using inductive and deductive thematic analysis.

    RESULTS: To achieve successful implementation and sustained effect of community-based knowledge implementation strategies, engagement of leaders and key stakeholders at all levels of the healthcare system is vital-prior to, during and after a project. Implementation and sustainability require thorough needs assessment, tailoring of the intervention, and consideration of how to attain and manage funds. The NeoKIP trial was characterised by a high degree of engagement at the primary healthcare system level. Further, three years post trial, maternal and neonatal care was still high on the agenda for healthcare workers and leaders, even though primary aspects such as stakeholder engagement at all levels, and funding had been incomplete or lacking.

    CONCLUSIONS: The current study illustrates factors to support successful implementation and sustain effects of community-based strategies in projects in low- and middle-income settings; some but not all factors were represented during the post-NeoKIP era. Most importantly, trials in this and similar contexts require deliberate management throughout and beyond the project lifetime, and engagement of key stakeholders, in order to promote and sustain knowledge implementation.

  • Grandahl, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Larsson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dalianis, Tina
    Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Stenhammar, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tydén, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Westerling, Ragnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Catch-up HPV vaccination status of adolescents in relation to socioeconomic factors, individual beliefs and sexual behaviour2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 11, e0187193Article in journal (Refereed)
    Abstract [en]

    In 2012, human papillomavirus (HPV) vaccination was introduced free of charge in the Swedish national school-based vaccination programme for 10-12-year-old girls, and as catch-up vaccination for young women. In Sweden, there is an ongoing discussion about including boys in the national vaccination programme. Few studies are undertaken about adolescents' knowledge, beliefs and HPV vaccination status in relation to socioeconomic status and sexual experience. Thus, the aim was to examine HPV catch-up vaccination status in adolescents in relation to 1) socioeconomic factors, 2) beliefs and knowledge about HPV prevention, and 3) sexual behaviour. The Health Belief Model was used as a theoretical framework. Upper secondary school students (n = 832) aged 16, randomly chosen from a larger sample, were invited to participate in conjunction with the general health interview with the school nurse. A total of 751/832 (90.3%), girls (n = 391, 52%) and boys (n = 360, 48%) completed the questionnaire. HPV vaccination was associated with ethnicity and the mothers' education level; i.e. girls with a non-European background and girls with a less educated mother were less likely to have received the vaccine (p<0.01 and p = 0.04 respectively). Vaccinated girls perceived HPV infection as more severe (p = 0.01), had more insight into women's susceptibility to the infection (p = 0.02), perceived more benefits of the vaccine as protection against cervical cancer (p<0.01) and had a higher intention to engage in HPV-preventive behaviour (p = 0.01). Furthermore, boys and girls were almost equally sexually experienced, although fewer girls had used condom during first intercourse with their latest partner (p = 0.03). Finally, HPV vaccinated girls were less likely to have unprotected sex (p<0.01). In summary, catch-up HPV vaccination among young girls was associated with a European background and high maternal education level, as well as more favourable beliefs towards HPV prevention and less sexual risk-taking. Further preventive measures should therefore be directed at the migrant population.

  • Weidner, Tim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    Investigating the Scalability of Direct-to-Master Caches2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Upcoming processors will utilize an ever increasing number of transistors bye mploying them as multiple cores. With the growth in number of cores, current cache hierarchies become one of the limiting factors for the scalability of applications utilizing multi-core processors. D2M, a new split cache hierarchy design, provides a unified mechanism for cache searching, eviction, and coherence,that eliminates level-by-level data movement and searches. This work contributesto research on D2M by performing a scalability analysis using High-Performance Computing benchmarks from the SPLASH-2x benchmark suite. By conducting experiments for 2, 4 and 8 cores with the Gem5 full-system simulator, we provide ageneral scalability trend for D2M. The experiments specifically target scalability ofthe metadata hierarchy. MD3 lock granularity and shared region overhead are examined, resulting in a definite number of locks to avoid MD3 lock aliasing for the selected benchmarks. In addition, a detailed performance comparison between D2M and a generic standard cache hierarchy model is given for all core configurations.

  • Nilsson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Peric, Alexandra
    AstraZeneca Gothenburg, Cardiovasc & Metab Dis, Innovat Med & Early Dev, Gothenburg, Sweden..
    Strimfors, Marie
    AstraZeneca Gothenburg, Cardiovasc & Metab Dis, Innovat Med & Early Dev, Gothenburg, Sweden..
    Goodwin, Richard J. A.
    AstraZeneca Cambridge, Mass Spectrometry Imaging, Innovat Med & Early Dev, Drug Safety & Metab, Cambridge, England..
    Hayes, Martin A.
    AstraZeneca Gothenburg, Cardiovasc & Metab Dis, Innovat Med & Early Dev, Gothenburg, Sweden..
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hilgendorf, Constanze
    AstraZeneca Gothenburg, Cardiovasc & Metab Dis, Innovat Med & Early Dev, Gothenburg, Sweden.;AstraZeneca Gothenburg, Innovat Med & Early Dev, Drug Safety & Metab, Safety & ADME Translat Sci, Gothenburg, Sweden..
    Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 6352Article in journal (Refereed)
    Abstract [en]

    Knowledge about the region-specific absorption profiles from the gastrointestinal tract of orally administered drugs is a critical factor guiding dosage form selection in drug development. We have used a novel approach to study three well-characterized permeability and absorption marker drugs in the intestine. Propranolol and metoprolol (highly permeable compounds) and atenolol (low-moderate permeability compound) were orally co-administered to rats. The site of drug absorption was revealed by high spatial resolution matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and complemented by quantitative measurement of drug concentration in tissue homogenates. MALDI-MSI identified endogenous molecular markers that illustrated the villi structures and confirmed the different absorption sites assigned to histological landmarks for the three drugs. Propranolol and metoprolol showed a rapid absorption and shorter transit distance in contrast to atenolol, which was absorbed more slowly from more distal sites. This study provides novel insights into site specific absorption for each of the compounds along the crypt-villus axis, as well as confirming a proximal-distal absorption gradient along the intestine. The combined analytical approach allowed the quantification and spatial resolution of drug distribution in the intestine and provided experimental evidence for the suggested absorption behaviour of low and highly permeable compounds.

  • Melander, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    Study of Bandwidth Partitioning for Co-executing GPU Kernels2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Co-executing GPU kernels on a partitioned GPU has been shown to improve utilization efficiency of poorly scaling tasks. While kernels can be executed in parallel, data transfers to the GPU are serial which can negatively impact parallelism and predictability of the kernels.In this work we implement a fairness-based approach to memory transfers by chunking data sets and transferring them interleaved and evaluate the overhead of this approach. Then we develop a model to predict when kernels will start using this implementation. We found that chunked transfers in a single CUDA stream have onlya small overhead compared to serial transfers, while event synchronized transfers in several streams have larger overhead particularly for chunk sizes less than 500 KB.The prediction models accurately estimate kernel starting times and return transfertimes with less than 2.7% relative error.

  • Lövgren, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    Simulating Energy-Efficient Hardware The Software Out-of-order Processor2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The modern trends for technology scaling are not extremely bright. The cost of transistors have leveled off recently, effectively halting the ability to put additional transistors on a chip for the same price. In addition, Dennard Scaling, what has allowed for switching additional transistors whilst scaling to smaller nodes isslowing significantly. This thesis, with focus on the hardware, proposes anenhanced stall-on-use in-order core hardware/software co-design which improves performance and energy efficiency by allowing out-of-program-order executionthrough allowing the hardware and software to communicate with one another --allowing the hardware to make dynamic decisions on how to direct execution flowto expose additional memory- and instruction level parallelism.The results are very promising where we see an increase in both performance (upto 3.7x speedup) and energy efficiency (up to 59% increase). While additional worki is needed to evaluate the extent of the benefits across a wide range of applications, SWOOP looks to be a good option for energy efficiency without compromisingperformance for memory-bound applications with MLP.

  • Lejdung, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    System and database design for a research application to diagnostic laser-doppler instruments2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Perimed AB is interested in developing a new generation research platform, for thei rmost recent medical instrument, PF 6000. With thedevelopment of this platform, they are looking for innovative and practical ways to meet the requirements from the medical research community. Other than a versatile and easy-to-use system, Perimed has noticed a particular needto store and process the large amounts of data generatedby their instruments. With the use of a database, the platform can provide a searchable, trackable and versatile system. The database assures that all information is not only easily attained, but also shareable through various connections. After testinga total of four different databases against the requirementsof the system, a database was chosen to be implemented with the platform. A system design was detailed with the use of six different UML diagram-types. The design promoted a modular system and focused heavily on the data flow, from and to the instrument and database. The system design and the chosen database was then used to implement a prototype. Through the prototype, the database and system design were proven as a feasible solution for how to design and develop the system. Together with the diagrams, the prototype will serve as an excellent source of documentationfor Perimed during the development of the platform.

  • Yeo, Astrid
    et al.
    GlaxoSmithKline Med Res Ctr, Dept Genet, Stevenage, Herts, England..
    Li, Li
    GlaxoSmithKline Med Res Ctr, Dept Genet, Res Triangle Pk, NC USA.;PAREXEL Int, Genom Med, Durham, NC USA..
    Warren, Liling
    GlaxoSmithKline Med Res Ctr, Dept Genet, Res Triangle Pk, NC USA.;Teva Pharmaceut, Raleigh, NC USA..
    Aponte, Jennifer
    GlaxoSmithKline Med Res Ctr, Dept Genet, Res Triangle Pk, NC USA.;PAREXEL Int, Genom Med, Durham, NC USA..
    Fraser, Dana
    GlaxoSmithKline Med Res Ctr, Dept Genet, Res Triangle Pk, NC USA.;PAREXEL Int, Genom Med, Durham, NC USA..
    King, Karen
    GlaxoSmithKline Med Res Ctr, Dept Genet, Res Triangle Pk, NC USA.;PAREXEL Int, Genom Med, Durham, NC USA..
    Johansson, Kelley
    GlaxoSmithKline Med Res Ctr, Dept Genet, Res Triangle Pk, NC USA.;PAREXEL Int, Genom Med, Durham, NC USA..
    Barnes, Allison
    GlaxoSmithKline Med Res Ctr, Clin Stat, Res Triangle Pk, NC USA.;PAREXEL Int, Biostat, Durham, NC USA..
    MacPhee, Colin
    GlaxoSmithKline Med Res Ctr, Dept Vasc Biol & Thrombosis, King Of Prussia, PA USA..
    Davies, Richard
    GlaxoSmithKline Med Res Ctr, Metab Pathways & Cardiovasc Therapeut Area, King Of Prussia, PA USA..
    Chissoe, Stephanie
    GlaxoSmithKline Med Res Ctr, Dept Genet, Res Triangle Pk, NC USA.;GlaxoSmithKline, Elliott Ave, Seattle, WA USA..
    Tarka, Elizabeth
    GlaxoSmithKline Med Res Ctr, Metab Pathways & Cardiovasc Therapeut Area, King Of Prussia, PA USA.;Janssen Pharmaceut, Spring House, PA USA..
    O'Donoghue, Michelle L.
    Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Waterworth, Dawn
    GlaxoSmithKline Med Res Ctr, Dept Genet, Philadelphia, PA USA..
    Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 7, e0182115Article in journal (Refereed)
    Abstract [en]

    Darapladib, a lipoprotein-associated phospholipase A2 (Lp-PLA(2)) inhibitor, failed to demonstrate efficacy for the primary endpoints in two large phase III cardiovascular outcomes trials, one in stable coronary heart disease patients (STABILITY) and one in acute coronary syndrome (SOLID-TIMI 52). No major safety signals were observed but tolerability issues of diarrhea and odor were common (up to 13%). We hypothesized that genetic variants associated with Lp-PLA(2) activity may influence efficacy and tolerability and therefore performed a comprehensive pharmacogenetic analysis of both trials. We genotyped patients within the STABILITY and SOLID-TIMI 52 trials who provided a DNA sample and consent (n = 13,577 and 10,404 respectively, representing 86% and 82% of the trial participants) using genomewide arrays with exome content and performed imputation using a 1000 Genomes reference panel. We investigated baseline and change from baseline in Lp-PLA(2) activity, two efficacy endpoints (major coronary events and myocardial infarction) as well as tolerability parameters at genome-wide and candidate gene level using a meta-analytic approach. We replicated associations of published loci on baseline Lp-PLA2 activity (APOE, CELSR2, LPA, PLA2G7, LDLR and SCARB1) and identified three novel loci (TOMM5, FRMD5 and LPL) using the GWAS-significance threshold P <= 5E-08. Review of the PLA2G7 gene (encoding Lp-PLA(2)) within these datasets identified V279F null allele carriers as well as three other rare exonic null alleles within various ethnic groups, however none of these variants nor any other loci associated with Lp-PLA(2) activity at baseline were associated with any of the drug response endpoints. The analysis of darapladib efficacy endpoints, despite low power, identified six low frequency loci with main genotype effect (though with borderline imputation scores) and one common locus (minor allele frequency 0.24) with genotype by treatment interaction effect passing the GWAS-significance threshold. This locus conferred risk in placebo subjects, hazard ratio (HR) 1.22 with 95% confidence interval (CI) 1.11-1.33, but was protective in darapladib subjects, HR 0.79 ( 95% CI 0.71-0.88). No major loci for tolerability were found. Thus, genetic analysis confirmed and extended the influence of lipoprotein loci on Lp-PLA(2) levels, identified some novel null alleles in the PLA2G7 gene, and only identified one potentially efficacious subgroup within these two large clinical trials.

  • Sundequist Blomdahl, Kristofer
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    An evaluation of random-walk based clustering of multiplex networks2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    A network, or a graph, is a mathematical construct used for modeling relationships between different entities. An extension of an ordinary network is a multiplex network. A multiplex network enables one to model different kinds of relationships between the same entities, or even to model how relationships between entities change over time. A common network analysis task is to find groups of nodes that are unusually tightly connected. This is called community detection, and is a form of clustering. The multiplex extension complicates both the notion of what a community is, and the process of finding them.This project focuses on a random-walk based local method that can be used to find communities centered around supplied seed nodes. An implementation of the methodis made which is used to evaluate its ability to detect communities in different kinds of multiplex networks.

  • Andersson, Martin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Mårtensson, Gustaf
    EMSL, MC2, Chalmers University of Technology, Göteborg, Sweden.
    Klintberg, Lena
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Flowing and pressurizing a solid-liquid two phase monodispersed fluid with high solid content in a transparent microfluidic high-pressure chip2017Conference paper (Other academic)
  • Scherman, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    Extending the Scope of Compile-time Optimizations Across Synchronization Operations2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    With the rise of multiprocessor computers, parallel computing has become a necessity in order to achieve high performance. Modern compilers are conservative in applying classical compiler optimizations to parallel programs, as the compiler might require expensive whole-code analysis in order to preserve the semantics and correctness of the code, to ensure no data races are introduced through optimizations. Extended data-race-free regions (xDRF) is a compile-time analysis that gives the guarantee that variables accessed within the xDRF region cannot be modified by other threads. This guarantee enables safe traditional compiler optimizations on larger regions of code. The extended data-race free regions are used to make stronger alias analysis statements, which allows the traditional compiler optimizations to use the information gained from the extended data-race-free analysis directly without any other changes of the optimization step. Results show a varied utilization of the extended data-race-free, with two out of seventeen benchmarks being unable to find any extended data race-free region, and one benchmark having as many as 23 regions. Usingthe xDRF analysis, the compiler was able to increase by up to 2% the number of load instructions hoisted or deleted. No benchmark show a consistent run-time improvement from the additional transformations. Future work will focus on expanding the usage of the xDRF analysis, forexample for improving Capture Tracking and Escape Analysis, which we expect will lead to a run-time improvement.

  • Andersson, Martin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Stocklassa, Jesper
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Klintberg, Lena
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Control Systems For Gas-Expanded Liquids In Microreactors2017Conference paper (Other academic)
  • Escher, David
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    Parallel Performance Comparison between Encore and OpenMP using Pedestrian Simulation2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Parallel programming has become ubiquitous and more than a preference, it is a necessity for utilizing hardware resources (multiple cores)  in order to speed-up computation. However, developing parallel programs is difficult and error-prone. In ordert o make development of parallel programs easier and less error-prone,new programming languages are being developed. This thesis compares Encore, a new programming language, against C++ with OpenMP for parallelizing program execution. The focus of this comparison is the respective run-times and parallel scalability, when running a pedestrian simulation program.

  • Dubik, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    A comparative evaluation of state-of-the-art community detection algorithms for multiplex networks2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Community detection is the study of discovering groups of nodes more connected toeach other than to other nodes inside a network. These groups give insight into the inner workings of a network and their discovery has practical applications in many fields of science.A multiplex network is a special type of multilayer network where multiple graphs co-exist on different layers that are stacked on top of each other into one structure where each node in a single layer has representation on every other layer in themultiplex. These networks are sophisticated attempts to model real world systems and the research in this area has contributed to increased insight and knowledge too ther fields of science such as social network analysis, medicine, finance and physics. In this thesis, we will provide an overview of three different multiplex community detection algorithms and a fair evaluation in regards to their resource usage and accuracy in a unified computing environment. The algorithms are tested against synthetically generated datasets and real life networks.

  • Malmberg, Anders
    et al.
    Uppsala University, University Board and Chief Officers.
    Kettis, ÅsaUppsala University, University Administration, Division for Quality Enhancement.Maandi, CamillaUppsala University, University Administration, Division for Quality Enhancement.
    Quality and Renewal 2017 (Kvalitet och förnyelse 2017): Research Environment Evaluation at Uppsala University2017Collection (editor) (Other (popular science, discussion, etc.))
    Abstract [en]

    This is the final report of the enhancement-led research evaluation Quality and Renewal 2017, Q&R17 (in Swedish, Kvalitet och förnyelse, KoF17), carried out at Uppsala University between February 2016 and October 2017. The project has been a major undertaking, aiming to strengthen research at Uppsala University through a broad analysis of the functioning of its various research environments, with particular focus on the preconditions and processes that underpin research quality and renewal. 

    To this end, an internet-based survey was carried out, in which around 3,700 active researchers at Uppsala University shared their perceptions of and opinions on their local research environments at the University. Together with some bibliometric analyses, the survey results served as background material for departmental self-evaluations, which in turn were subjected to external peer review. In this process, almost 130 ‘critical friends’, most of them from outside Sweden, evaluated 54 evaluation units to assess strengths and weaknesses and make recommendations.

    Q&R17 is the third major research evaluation at Uppsala University. The two previous evaluations, Q&R07 and Q&R11, primarily aimed to identify strong research activities and research initiatives with potential to develop into strong future areas of research, thereby aiding the university management in its continuous strategic decision-making process. In contrast to those two evaluations, Q&R17 has not resulted in any sort of grading of the research carried out at Uppsala University, either in its totality or in its parts. Nevertheless, the panel reports include numerous testimonies of the perceived strength and excellence of research at Uppsala University. 

    More importantly, given the purpose of Q&R17, a number of areas have been identified where action is needed if Uppsala University is to take steps towards reaching its full potential. These relate to: leadership and strategic renewal; talent attraction and retention; quality culture and control; inter-national milieu; external collaboration and outreach; and research-teaching linkages. The conclusions and recommendations coming out of Q&R17 will form the basis for a number of actions throughout the University aiming to further strengthen the international standing of Uppsala University.

  • Faust, Ellika
    et al.
    Univ Gothenburg, Dept Marine Sci Tjarno, S-45296 Stromstad, Sweden..
    Andre, Carl
    Univ Gothenburg, Dept Marine Sci Tjarno, S-45296 Stromstad, Sweden..
    Meurling, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Kochmann, Judith
    Senckenberg Biodiversitat & Klima Forschungszentr, Senckenberg Gesell Nat Forsch, D-60325 Frankfurt, Germany..
    Christiansen, Henrik
    Univ Gothenburg, Dept Marine Sci Tjarno, S-45296 Stromstad, Sweden.;Katholieke Univ Leuven, Lab Biodivers & Evolutionary Genom, B-3000 Leuven, Belgium..
    Jensen, Lasse Fast
    Fisheries & Maritime Museum, DK-6710 Esbjerg V, Denmark..
    Charrier, Gregory
    Univ Bretagne Occidentale, Lab Sci Environm Marin LEMAR, UMR 6539, UBO,CNRS,IRD,Ifremer,IUEM, F-29280 Plouzane, France..
    Laugen, Ane T.
    Novia Univ Appl Sci, Ekenas 10600, Finland.;Swedish Univ Agr Sci, Dept Ecol, S-75007 Uppsala, Sweden..
    Strand, Asa
    Univ Gothenburg, Dept Marine Sci Tjarno, S-45296 Stromstad, Sweden..
    Origin and route of establishment of the invasive Pacific oyster Crassostrea gigas in Scandinavia2017In: Marine Ecology Progress Series, ISSN 0171-8630, E-ISSN 1616-1599, Vol. 575, 95-105 p.Article in journal (Refereed)
    Abstract [en]

    Identifying the routes and rates of introductions is fundamental for the understanding of marine invasions. Recurring introductions over the last 50 yr have led to the establishment of feral Pacific oyster Crassostrea gigas populations throughout Europe. In the northern countries, Sweden and Norway, the species first occurred in large numbers in 2006. Here, we investigated the relative importance of introduction via re-laying of cultured oysters imported for consumption from France, Ireland or the Netherlands, and dispersal of oyster larvae by ocean currents from wild oyster populations in Denmark. Using microsatellite DNA markers, we estimated genetic differentiation among Pacific oysters collected at 4 Swedish locations, 3 Norwegian locations and 9 potential source locations in Denmark, Ireland, the Netherlands and France. All Swedish samples and 1 Norwegian sample(Tromlingene) were genetically similar to each other and the Danish samples and showed significant genetic differentiation from all other populations. Consequently, it appears that the Pacific oyster populations in Sweden, Denmark and Tromlingene are closely connected and/or share a recent origin. The 2 remaining Norwegian samples(Hui and Espevik) differed from each other and all other populations, but showed similarities to wild oyster samples from Scandinavia and Ireland, respectively. Overall, the results underline a complex origin of Norwegian oysters, with gene flow from Swedish/Danish populations, as well as other unidentified sources. The apparent connectivity among most of the Scandinavian populations has implications for regional management of this invasive species, and highlights possible scenarios for other marine invasive species with a similar life history.

  • Zillikens, M. Carola
    et al.
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NCI, NL-2593 Leiden, Netherlands..
    Demissie, Serkalem
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Hsu, Yi-Hsiang
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Harvard Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA 02115 USA..
    Yerges-Armstrong, Laura M.
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA..
    Chou, Wen-Chi
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst, Cambridge, MA 02142 USA..
    Stolk, Lisette
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NCI, NL-2593 Leiden, Netherlands..
    Livshits, Gregory
    Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-6997801 Tel Aviv, Israel.;Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London WC2R 2LS, England..
    Broer, Linda
    Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Johnson, Toby
    Univ Lausanne, Dept Med Genet, CH-1011 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Inst Social & Prevent Med, Ctr Hosp Univ CHUV, CH-1010 Lausanne, Switzerland..
    Koller, Daniel L.
    Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA..
    Kutalik, Zoltyn
    Univ Lausanne, Dept Med Genet, CH-1011 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Inst Social & Prevent Med, Ctr Hosp Univ CHUV, CH-1010 Lausanne, Switzerland..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England..
    Malkin, Ida
    Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-6997801 Tel Aviv, Israel..
    Ried, Janina S.
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany..
    Smith, Albert V.
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland..
    Thorleifsson, Gudmar
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England..
    Zhang, Weihua
    Imperial Coll, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England.;Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England..
    Aghdassi, Ali
    Ernst Moritz Arndt Univ Greifswald, Dept Med A, D-17489 Greifswald, Germany..
    Akesson, Kristina
    Lund Univ, Dept Clin Sci, S-22362 Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, S-20502 Malmo, Sweden..
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Baier, Leslie J.
    NIH, Phoenix Epidemiol & Clin Res Branch, Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ 85014 USA..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Saffron Walden CB10 1SA, Essex, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Inst Met Sci, Cambridge CB2 OQQ, England.;Univ Cambridge, Addenbrookes Hosp, Inst Met Sci, Metab Res Labs, Cambridge CB2 OQQ, England..
    Bennett, David A.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA..
    Bertram, Lars
    Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt, Inst Neurogenet & Expt & Integrat Gen, D-23562 Lubeck, Germany.;Imperial Coll London, Fac Med, Sch Publ Hlth, London W6 8RP, England..
    Biffar, Rainer
    Ernst Moritz Arndt Univ Greifswald, Ctr Oral Hlth, Dept Prosthet Dent Gerodontol & Biomat, D-17489 Greifswald, Germany..
    Bochud, Murielle
    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Inst Social & Prevent Med, Ctr Hosp Univ CHUV, CH-1010 Lausanne, Switzerland..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Borecki, Ingrid B.
    Washington Univ, Div Stat Gen, Dept Genet, Sch Med, St Louis, MO 63110 USA.;Washington Univ, Div Biostat, Sch Med, St Louis, MO 63110 USA..
    Buchman, Aron S.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA..
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Obanda, Natalia Campos
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands..
    Cauley, Jane A.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA..
    Cawthon, Peggy M.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA..
    Cederberg, Henna
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Chen, Zhao
    Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85714 USA..
    Cho, Nam H.
    Ajou Univ, Sch Med, Dept Prevent Med, Suwon 16499, South Korea..
    Choi, Hyung Jin
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 03080, South Korea.;Chungbuk Natl Univ Hosp, Dept Internal Med, Cheongju, South Korea..
    Claussnitzer, Melina
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst, Cambridge, MA 02142 USA.;MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.;Tech Univ Munich, Inst Human Genet, MRI, D-81675 Munich, Germany.;Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA..
    Collins, Francis
    Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Cummings, Steven R.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA..
    De Jager, Philip L.
    Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiatr Genom, Boston, MA 02115 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Demuth, Ilja
    Charite, Res Grp Geriatr, Berlin Aging Study 2, D-13353 Berlin, Germany.;Charite, Inst Med & Human Genet, D-13353 Berlin, Germany..
    Dhonukshe-Rutten, Rosalie A. M.
    Wageningen Univ, Dept Human Nutr, POB 17, NL-6700 AA Wageningen, Netherlands..
    Diatchenko, Luda
    McGill Univ, Alan Edwards Ctr Res Pain, Montreal H3A 0G1, PQ, Canada.;Univ N Carolina, Sch Dent, Reg Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA..
    Eiriksdottir, Gudny
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland..
    Enneman, Anke W.
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands..
    Erdos, Mike
    Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Eriksson, Johan G.
    Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki 00014, Finland.;Univ Helsinki, Cent Hosp, Unity Gen Practice, Helsinki 00014, Finland.;Folkhalsan Res Ctr, Helsinki 00250, Finland.;Vasa Cent Hosp, Vaasa 65130, Finland.;Nat Inst Hlth & Welf, Helsinki 00271, Finland..
    Eriksson, Joel
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Estrada, Karol
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Evans, Daniel S.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA..
    Feitosa, Mary F.
    Washington Univ, Div Stat Gen, Dept Genet, Sch Med, St Louis, MO 63110 USA..
    Fu, Mao
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA..
    Garcia, Melissa
    Natl Inst Aging, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA..
    Gieger, Christian
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany..
    Girke, Thomas
    Univ Calif Riverside, Inst Integrat Genome Biol, Dept Bot & Plant Sci, Riverside, CA 92521 USA.;Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA..
    Glazer, Nicole L.
    Boston Univ, Sch Med & Publ Hlth, Dept Med, Boston, MA 02118 USA.;Boston Univ, Sch Med & Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA..
    Grallert, Harald
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, CCG Type Diabet 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, CCG Nutrigen & Type Diabet 2, D-85764 Neuherberg, Germany..
    Grewal, Jagvir
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY, England..
    Han, Bok-Ghee
    Osong Hlth Technol Adm Complex, Ctr Genome Sci, Natl Inst Hlth, Chungcheongbuk Do 28159, South Korea..
    Hanson, Robert L.
    NIH, Phoenix Epidemiol & Clin Res Branch, Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ 85014 USA..
    Hayward, Caroline
    Univ Edinburgh, IGMM, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Hofman, Albert
    NCHA, NCI, NL-2593 Leiden, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Hoffman, Eric P.
    SUNY Binghamton, Dept Pharmaceut Sci, Binghamton, NY 13902 USA..
    Homuth, Georg
    Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, D-17487 Greifswald, Germany..
    Hsueh, Wen-Chi
    NIH, Phoenix Epidemiol & Clin Res Branch, Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ 85014 USA..
    Hubal, Monica J.
    George Washington Univ, Dept Exercise & Nutr Sci, Washington, DC 20052 USA.;Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20052 USA..
    Hubbard, Alan
    Univ Calif Berkeley, Div Biostat, Sch Publ Hlth, Berkeley, CA 94720 USA..
    Huffman, Kim M.
    Duke Univ, Sch Med, Div Rheumatol, Dept Med,Duke Mol Physiol Inst, Durham, NC 27710 USA..
    Husted, Lise B.
    Aarhus Univ Hosp, Endocrinol & Internal Med, DK-8000 Aarhus, Denmark..
    Illig, Thomas
    Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Hannover Med Sch, Dept Human Genet, D-30625 Hannover, Germany.;Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Ittermann, Till
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17489 Greifswald, Germany..
    Jansson, John-Olov
    Univ Gothenburg, Dept Physiol, Inst Neurosci & Physiol, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Jordan, Joanne M.
    Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC 27517 USA..
    Jula, Antti
    Nat Inst Hlth & Welf, Helsinki 00271, Finland..
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci & Orthopaed, Skane Univ Hosp SUS, S-22362 Malmo, Sweden..
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England..
    Kilpainen, Tuomas O.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England.;Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, DK-2100 Copenhagen, Denmark.;Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA..
    Klopp, Norman
    Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany..
    Kloth, Jacqueline S. L.
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands..
    Koistinen, Heikki A.
    Univ Helsinki, Dept Med, Helsinki 00029, Finland.;Helsinki Univ Cent Hosp, Helsinki 00029, Finland.;Univ Helsinki, Abdominal Ctr, Endocrinol, Helsinki 00029, Finland.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki 00271, Finland.;Minerva Fdn, Helsinki 00290, Finland..
    Kraus, William E.
    Duke Univ, Sch Med, Div Cardiol, Dept Med,Duke Mol Physiol Inst, Durham, NC 27710 USA..
    Kritchevsky, Stephen
    Sticht Ctr Aging, Wake Forest Sch Med, Winston Salem, NC 27157 USA..
    Kuulasmaa, Teemu
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Laakso, Markku
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Lahti, Jari
    Univ Helsinki, Inst Behav Sci, FI-00014 Helsinki, Finland..
    Lang, Thomas
    Univ Calif San Francisco, San Francisco, CA 94143 USA..
    Langdahl, Bente L.
    Aarhus Univ Hosp, Endocrinol & Internal Med, DK-8000 Aarhus, Denmark..
    Launer, Lenore J.
    Natl Inst Aging, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA..
    Lee, Jong-Young
    Osong Hlth Technol Adm Complex, Ctr Genome Sci, Natl Inst Hlth, Chungcheongbuk Do 28159, South Korea..
    Lerch, Markus M.
    Ernst Moritz Arndt Univ Greifswald, Dept Med A, D-17489 Greifswald, Germany..
    Lewis, Joshua R.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.;Univ Sydney, Ctr Kidney Res, Sch Publ Hlth, Sydney, NSW 2006, Australia..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden..
    Lindgren, Cecilia
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Liu, Yongmei
    Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27517 USA..
    Liu, Tian
    Max Planck Inst Mol Genet, D-14195 Berlin, Germany.;Max Planck Inst Human Dev, D-14195 Berlin, Germany..
    Liu, Youfang
    Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC 27517 USA..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Luben, Robert N.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England..
    Maixner, William
    Univ N Carolina, Sch Dent, Reg Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA..
    McGuigan, Fiona E.
    Lund Univ, Dept Clin Sci, S-22362 Malmo, Sweden..
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, MRI, D-81675 Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, D-85764 Neuherberg, Germany..
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Melov, Simon
    Buck Inst Res Aging, Novato, CA 94945 USA.;Univ Southern Calif, Leonard Davis Sch Gerontol, Los Angeles, CA 90089 USA..
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mitchell, Braxton D.
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.;Baltimore Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Liverpool, Inst Tradit Med, Liverpool L69 3BX, Merseyside, England..
    Mosekilde, Leif
    Aarhus Univ Hosp, Endocrinol & Internal Med, DK-8000 Aarhus, Denmark..
    Newman, Anne
    Univ Pittsburgh, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA..
    Nielson, Carrie M.
    Oregon Hlth & Sci Univ, Portland, OR 97239 USA..
    O'Connell, Jeffrey R.
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA..
    Oostra, Ben A.
    Erasmus MC, Dept Clin Genet, NL-300 CA Rotterdam, Netherlands.;Ctr Med Syst Biol & Netherlands Consortium Hlth A, RC-2300 Leiden, Netherlands..
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Portland, OR 97239 USA..
    Palotie, Aarno
    Harvard Med Sch, Boston, MA 02115 USA.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland.;Univ Helsinki, Dept Med Genet, FI-00014 Helsinki, Finland.;Univ Cent Hosp, FI-00014 Helsinki, Finland..
    Parker, Stephan
    Univ Michigan, Human Genet & Computat Med & Bioinformat, Ann Arbor, MI 48109 USA..
    Peacock, Munro
    Indiana Univ, Dept Med, Sch Med, Indianapolis, IN 46202 USA..
    Perola, Markus
    Nat Inst Hlth & Welf, Helsinki 00271, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland.;Univ Helsinki, Diabet & Obes Res Program, FI-00014 Helsinki, Finland.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Peters, Annette
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany..
    Polasek, Ozren
    Univ Split, Fac Med, Dept Publ Hlth, Split 21000, Croatia..
    Prince, Richard L.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.;Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Perth, WA 6009, Australia..
    Raikkonen, Katri
    Univ Helsinki, Inst Behav Sci, FI-00014 Helsinki, Finland..
    Ralston, Stuart H.
    Western Gen Hosp, Mol Med Ctr, MRC Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Ripatti, Samuli
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland.;Univ Helsinki, Hjelt Inst, Helsinki, Finland.;Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England..
    Robbins, John A.
    Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA..
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Salomaa, Veikko
    Nat Inst Hlth & Welf, Helsinki 00271, Finland..
    Satterfield, Suzanne
    Univ Tennessee, Dept Prevent Med, Hlth Sci Ctr, Memphis, TN 38163 USA..
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Inst Genom & Multiscale Biol, New York, NY 10029 USA..
    Schipf, Sabine
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17489 Greifswald, Germany..
    Scott, Laura
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Sehmi, Joban
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY, England..
    Shen, Jian
    Oregon Hlth & Sci Univ, Portland, OR 97239 USA..
    Shin, Chan Soo
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 03080, South Korea..
    Sigurdsson, Gunnar
    Natl Univ Hosp Iceland, Landspitali, Dept Endocrinol & Metab, IS-101 Reykjavik, Iceland..
    Smith, Shad
    Duke Univ, Med Ctr, Ctr Translat Pain Med, Dept Anesthesiol, Durham, NC 27110 USA..
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England..
    Stancakova, Alena
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Steinhagen-Thiessen, Elisabeth
    Charite, Res Grp Geriatr, Berlin Aging Study 2, D-13353 Berlin, Germany..
    Streeten, Elizabeth A.
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.;Vet Adm Med Ctr, GRECC, Baltimore, MD 21201 USA..
    Styrkarsdottir, Unnur
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Swart, Karin M. A.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, BT-1081 Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst, BT-1081 Amsterdam, Netherlands..
    Tan, Sian-Tsung
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY, England..
    Tarnopolsky, Mark A.
    McMaster Univ, Med Ctr, Dept Med, Hamilton, ON L8N 3Z5, Canada..
    Thompson, Patricia
    Stony Brook Sch Med, Dept Pathol, Stony Brook, NY 11794 USA..
    Thomson, Cynthia A.
    Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85714 USA..
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Tikkanen, Emmi
    Nat Inst Hlth & Welf, Helsinki 00271, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland.;Western Gen Hosp, Mol Med Ctr, MRC Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Tranah, Gregory J.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA..
    Tuomilehto, Jaakko
    Vasa Cent Hosp, Vaasa 65130, Finland.;Danube Univ Krems, Dept Neurosci & Prevent Med, A-3500 Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah 12589, Saudi Arabia.;Dasman Diabet Inst, Dasman 15462, Kuwait..
    van Schoor, Natasja M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, BT-1081 Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst, BT-1081 Amsterdam, Netherlands..
    Verma, Arjun
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England..
    Vollenweider, Peter
    CHU Vaudois, Dept Med & Internal Med, CH-1011 Lausanne, Switzerland..
    Voelzke, Henry
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17489 Greifswald, Germany..
    Wactawski-Wende, Jean
    SUNY Buffalo, Univ Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14214 USA..
    Walker, Mark
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England..
    Weedon, Michael N.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter EX1 2LU, Devon, England..
    Welch, Ryan
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Wichman, H. -Erich
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, D-81377 Munich, Germany.;Tech Univ, Inst Med Stat & Epidemiol, D-81675 Munich, Germany..
    Widen, Elisabeth
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland..
    Williams, Frances M. K.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London WC2R 2LS, England..
    Wilson, James F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.;Univ Edinburgh, IGMM, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Wright, Nicole C.
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA..
    Xie, Weijia
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter EX1 2LU, Devon, England..
    Yu, Lei
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA..
    Zhou, Yanhua
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Chambers, John C.
    Imperial Coll, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England.;Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Royal Brompton & Harefield NHS Fdn Trust, NIHR Cardiovasc Biomed Res Unit, London SW3 6NP, England.;Imperial Coll, London SW3 6NP, England.;Imperial Coll Healthcare NHS Trust, London W2 1NY, England..
    Doring, Angela
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, D-85764 Neuherberg, Germany..
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands.;Ctr Med Syst Biol & Netherlands Consortium Hlth A, RC-2300 Leiden, Netherlands..
    Econs, Michael J.
    Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA.;Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA..
    Gudnason, Vilmundur
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland..
    Kooner, Jaspal S.
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY, England.;Imperial Coll Healthcare NHS Trust, London W2 1NY, England..
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Dept Med Hlth Serv, Seattle, WA 98101 USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London WC2R 2LS, England..
    Stefansson, Kari
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NCI, NL-2593 Leiden, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NCI, NL-2593 Leiden, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England..
    Ossowski, Vicky
    NIH, Phoenix Epidemiol & Clin Res Branch, Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ 85014 USA..
    Waterworth, Dawn
    GlaxoSmithKline, Med Genet, Philadelphia, PA 19112 USA..
    Loos, Ruth J. F.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Inst Child Hlth & Dev, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA..
    Karasik, David
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Bar Ilan Univ, Fac Med Galilee, IL-1311502 Safed, Israel..
    Harris, Tamara B.
    Natl Inst Aging, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Kiel, Douglas P.
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA..
    Large meta-analysis of genome-wide association studies identifies five loci for lean body mass2017In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, 80Article in journal (Refereed)
    Abstract [en]

    Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.

  • André, Rasmus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Department of Theology.
    Differently different?: – Changing the perception of ‘US & THEM’2017Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This study uses a longitudinal case study approach to observe change in ‘US and THEM-thinking’. Its purpose is to increase awareness of identity processes among participants and to test if the Attitude-Behaviour-Context-Triangle (the ABC-triangle) may be a way to achieve that. The ABC-triangle is modified as an ‘identity-analysis tool’ rather than a ‘conflict-analysis tool’.               Aspects relating to recognition of multiple identity affiliations compared to singular-identity categorisation is of interest. The traditional identity theories suggest that high identity salience increase singular-identity categorisation and thereby increase positive emotions for ingroup and negative emotions for outgroup. This study is partly based on the social identity perspective but complements it with Thoits’ identity-accumulation hypothesis and Hogg’s uncertainty-identity theory. Hogg’s theory locates uncertainty reduction as a main contributor to singular-identity categorisation together with its’ implied negative consequences. Hogg’s solutions are located both in multiple identity affiliations, as do Thoits, and in perceived cognitive ability to deal with uncertainty. This study emphasises awareness of identity processes to be the single most important factor for decreasing negative views of ‘THEM’. Overlooked in the more dominant theories of this area, it finds that recognition of multiple identity affiliations influences the perceived singular-identity terms imposed by an ‘US and THEM-situation’. Thereby, challenging imposed identity-restrictions and perceived intergroup competition. Furthermore, it questions the theoretical importance given to identity salience in previous research and theories since high identity salience, in this case, does not equal a singular-identity categorisation or increase negative views of ‘others’. 

  • Public defence: 2017-12-01 09:15 Fåhræussalen, Rudbecklaboratoriet, Uppsala
    Eriksson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Preclinical evaluation of immunostimulatory gene therapy for pancreatic cancer2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Pancreatic cancer is characterized by its desmoplastic tumor microenvironment and the infiltration of immunosuppressive cells. It is a devastating disease where most patients are diagnosed at a late stage and the treatment options are few. The development of new treatments is surly needed. One treatment option explored is the use of immunotherapy with the intent to activate the immune system and change the balance from pro-tumor to anti-tumor. This thesis presents the idea of using oncolytic adenoviruses called LOAd-viruses that are armed with immunostimulatory- and microenvironment-modulating transgenes. For effective treatment of pancreatic cancer, the virus needs to be able to be given in addition to standard therapy, the chemotherapy gemcitabine. In paper I, the immunomodulatory effect of gemcitabine was evaluated in blood from pancreatic cancer patients receiving their first 28-day cycle of treatment with infusions day 1, 8 and 15 followed by a resting period. Gemcitabine reduced the level of immunosup-pressive cells and molecules but the effect did not last throughout the resting period. On the other hand, gemcitabine did not affect the level or proliferative function of effector T cells indicating that gemcitabine could be combined with immunotherapy.

    The LOAd700 virus expresses a novel membrane-bound trimerized form of CD40L (TMZ-CD40L). In paper II, LOAd700 showed to be oncolytic in pancreatic cancer cell lines as well as being immunostimulatory as shown by its capacity to activate dendritic cells (DCs), myeloid cells, endothelium, and to promote expansion of antigen-specific T cells. In paper III, LOAd703 armed with both 4-1BBL and TMZ-CD40L was evaluated. LOAd703 gave a more profound effect than LOAd700 on activation of DCs and the virus was also capable of reducing factors in stellate cells connected to the desmo-plastic and immunosuppressive microenvironment. In paper IV, LOAd713 armed with TMZ-CD40L in combination with a single-chain variable fragment against IL-6R was evaluated. The virus could kill pancreatic cancer cells lines through oncolysis and could also reduce factors involved in desmoplasia in stellate cells. Most interestingly, LOAd713 could reduce the up-regulation of PD-1/PD-L1 in DCs after CD40 activation. Taken together, LOAd703 and LOAd713 seem to have interesting features with their combination of immunostimulation and microenvironment modulation. At present, LOAd703 is evaluated in a clinical trial for pancreatic cancer (NCT02705196).

    List of papers
    1. Gemcitabine reduces MDSCs, tregs and TGF beta-1 while restoring the teff/treg ratio in patients with pancreatic cancer
    Open this publication in new window or tab >>Gemcitabine reduces MDSCs, tregs and TGF beta-1 while restoring the teff/treg ratio in patients with pancreatic cancer
    Show others...
    2016 (English)In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 14, 282Article in journal (Refereed) Published
    Abstract [en]

    Background: Cancer immunotherapy can be potentiated by conditioning regimens such as cyclophosphamide, which reduces the level of regulatory T cells (tregs). However, myeloid suppressive cells are still remaining. Accordingly to previous reports, gemcitabine improves immune status of cancer patients. In this study, the role of gemcitabine was further explored to map its immunological target cells and molecules in patients with pancreatic cancer.

    Methods: Patient blood was investigated by flow cytometry and cytokine arrays at different time points during gemcitabine treatment.

    Results: The patients had elevated myeloid-derived suppressor cells (MDSCs), and Tregs at diagnosis. Myeloid cells were in general decreased by gemcitabine. The granulocytic MDSCs were significantly reduced while monocytic MDSCs were not affected. In vitro, monocytes responding to IL-6 by STAT3 phosphorylation were prevented to respond in gemcitabine medium. However, gemcitabine could not prevent STAT3 phosphorylation in IL-6-treated tumor cell lines. TGF beta-1 was significantly reduced after only one treatment and continued to decrease. At the same time, the effector T cell:Treg ratio was increased and the effector T cells had full proliferative capacity during the gemcitabine cycle. However, after a resting period, the level of suppressor cells and TGF beta-1 had been restored showing the importance of continuous conditioning.

    Conclusions: Gemcitabine regulates the immune system in patients with pancreatic cancer including MDSCs, Tregs and molecules such as TGF beta-1 but does not hamper the ability of effector lymphocytes to expand to stimuli. Hence, it may be of high interest to use gemcitabine as a conditioning strategy together with immunotherapy.

    Keyword
    Gemcitabine, Pancreatic cancer, Tregs, MDSCs, TGF beta
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-306753 (URN)10.1186/s12967-016-1037-z (DOI)000384600600002 ()27687804 (PubMedID)
    Funder
    Swedish Cancer Society
    Available from: 2016-11-16 Created: 2016-11-03 Last updated: 2017-10-10Bibliographically approved
    2. Activation of myeloid and endothelial cells by CD40L gene therapy supports T-cell expansion and migration into the tumor microenvironment
    Open this publication in new window or tab >>Activation of myeloid and endothelial cells by CD40L gene therapy supports T-cell expansion and migration into the tumor microenvironment
    Show others...
    2017 (English)In: Gene Therapy, ISSN 0969-7128, E-ISSN 1476-5462, Vol. 24, no 2, 92-103 p.Article in journal (Refereed) Published
    Abstract [en]

    CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate T-helper 1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer. Further, the CD40L mechanisms of action were elucidated in cancer models. The results demonstrated that the virus transferring TMZ-CD40L had oncolytic capacity in pancreatic cancer cells and could control tumor progression. TMZ-CD40L was a potent stimulator of human myeloid cells and T-cell responses. Further, CD40L-mediated stimulation increased tumor-infiltrating T cells in vivo, which may be due to a direct activation of endothelial cells to upregulate receptors for lymphocyte attachment and transmigration. In conclusion, CD40L-mediated gene therapy is an interesting concept for the treatment of tumors with high levels of M2 macrophages, such as pancreatic cancer, and an oncolytic virus as carrier of CD40L may further boost tumor killing and immune activation.

    National Category
    Other Medical Biotechnology
    Research subject
    Immunology
    Identifiers
    urn:nbn:se:uu:diva-318170 (URN)10.1038/gt.2016.80 (DOI)000394682800006 ()27906162 (PubMedID)
    Funder
    Swedish Cancer Society
    Available from: 2017-03-23 Created: 2017-03-23 Last updated: 2017-10-10Bibliographically approved
    3. Shaping the Tumor Stroma and Sparking Immune Activation by CD40 and 4-1BB Signaling Induced by an Armed Oncolytic Virus.
    Open this publication in new window or tab >>Shaping the Tumor Stroma and Sparking Immune Activation by CD40 and 4-1BB Signaling Induced by an Armed Oncolytic Virus.
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    2017 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    Purpose: Pancreatic cancer is a severe indication with short expected survival despite surgery and/or combination chemotherapeutics. Checkpoint blockade antibodies are approved for several cancer indications, but pancreatic cancer has remained refractory. However, there are clinical data suggesting that stimulation of the CD40 pathway may be of interest for these patients. Oncolytic viruses armed with immunostimulatory genes represent an interesting approach. Herein, we present LOAd703, a designed adenovirus armed with trimerized CD40L and 4-1BBL that activates the CD40 and 4-1BB pathways, respectively. As many cells in the tumor stroma, including stellate cells and the infiltrating immune cells, express CD40 and some 4-1BB, we hypothesize that LOAd703 activates immunity and simultaneously modulates the biology of the tumor stroma.Experimental Design: Tumor, stellate, endothelial, and immune cells were infected by LOAd703 and investigated by flow cytometry, proteomics, and functional analyses.Results: LOAd703-infected pancreatic cell lines were killed by oncolysis, and the virus was more effective than standard-of-care gemcitabine. In in vivo xenograft models, LOAd703 efficiently reduced established tumors and could be combined with gemcitabine for additional effect. Infected stellate and tumor cells reduced factors that promote tumor growth (Spp-1, Gal-3, HGF, TGFβ and collagen type I), while chemokines were increased. Molecules involved in lymphocyte migration were upregulated on infected endothelial cells. Dendritic cells were robustly stimulated by LOAd703 to produce costimulators, cytokines and chemokines, and such DCs potently expanded both antigen-specific T cells and NK cells.Conclusions: LOAd703 is a potent immune activator that modulates the stroma to support antitumor responses. Clin Cancer Res; 1-12. ©2017 AACR.

    National Category
    Cancer and Oncology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
    Identifiers
    urn:nbn:se:uu:diva-330158 (URN)10.1158/1078-0432.CCR-17-0285 (DOI)28536305 (PubMedID)
    Available from: 2017-09-27 Created: 2017-09-27 Last updated: 2017-10-10
    4. An oncolytic virus for pancreatic cancer targeting interleukin-6 signaling and driving CD40-mediated immune activation
    Open this publication in new window or tab >>An oncolytic virus for pancreatic cancer targeting interleukin-6 signaling and driving CD40-mediated immune activation
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    (English)In: Article in journal (Other academic) Submitted
    National Category
    Cancer and Oncology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
    Identifiers
    urn:nbn:se:uu:diva-330161 (URN)
    Available from: 2017-09-27 Created: 2017-09-27 Last updated: 2017-10-10
  • Simons, Greg
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Uppsala Centre for Russian and Eurasian Studies.
    The Role of ‘NGOs’ in Knowledge Management of Conflicts2017In: Государственное управление. Электронный вестник, ISSN 2070-1381, no 64, 362-376 p.Article in journal (Other academic)
  • Public defence: 2017-12-01 09:00 Friessalen, Uppsala
    Andersson, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Extent and limitations of functional redundancy among bacterial communities towards dissolved organic matter2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    One of the key processes in the carbon cycle on our planet is the degradation of dissolved organic matter (DOM) in aquatic environments. The use of organic matter by bacteria links energy from DOM to higher trophic levels of the ecosystem when bacteria are consumed by other organisms. This is referred to as the microbial loop. In this thesis I examined if the communities were functionally redundant in their ability to utilize organic matter, or if variation in bacterial composition and richness is of importance. To test this overarching question several experiments were conducted that include methods such as illumina sequencing of the 16S rRNA gene for taxonomic identification of bacterial communities, flow cytometry to follow the growth of communities and spectroscopic measurement to describe the composition of the organic matter pool. Initially we demonstrated how to optimally sterilize organic matter for experimental studies in order to preserve its natural complexity. In further experiments we found that bacterial communities are redundant in their utilization of organic matter and can maintain optimal performance towards a range of organic matter pools. Related to this we found that pre-adaptation to organic matter played a small role as communities performed equally well regardless of their environmental history. We saw a small effect of richness and composition of bacterial communities on the efficiency of organic matter use, but conclude that this is of minor importance relative to abiotic factors. Still, we also show that organic matter can put strong selection pressure on bacterial communities with regards to richness and composition. Additionally we found that the supply rate of a carbon compound greatly influenced the energy utilization of the compound, i.e. a higher growth rate can be maintained if substrate is delivered in pulses relative to a continuous flow. Finally we conclude that the variation in bacterial communities is unlikely to have a major influence on carbon cycling in boreal lakes, but to enable a finer understanding, the genetics underlying the carbon utilization needs to be further explored. 

    List of papers
    1. Effects of sterilization on composition and bacterial utilization of dissolved organic carbon
    Open this publication in new window or tab >>Effects of sterilization on composition and bacterial utilization of dissolved organic carbon
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Sterilization of dissolved organic carbon (DOC) is an essential step in research on interactions between DOC and organisms, for example where the effect of different microbial communities on DOC is studied or vice versa. Few studies have, however, gone beyond acknowledging that sterilization of DOC influences its characteristics. Here we aimed to provide further knowledge that enables scientists to better tailor their sterilization methods to their research question. To meet this aim, we conducted a sterilization experiment with DOC from 4 boreal lakes treated with 4 sterilization methods, 2 filtrations (0.2 µm, 0.1 µm) and 2 autoclaving approaches (single autoclaving and double with intermediate pH adjustment). Quantity and spectroscopic properties of DOC were compared before and after sterilization and DOC was further tested as a substrate for bacterial growth. We found that the filtration methods better preserved the qualities of DOC, particularly the 0.2 µm filtration. On the contrary, autoclaving caused major inconsistent shifts in both qualitative and quantitative measurements of DOC as well as an increase of the maximum abundance of bacteria in growth experiments. Nonetheless, there remains a trade-off between retaining the quality of DOC and achieving sterile conditions. Therefore, the sterilization method of choice should be guided by the scientific question at hand.    

    Keyword
    sterilization, autoclave, filtration, dissolved organic carbon, excitation emission matrices, parallel factor analysis
    National Category
    Biological Sciences
    Research subject
    Microbiology
    Identifiers
    urn:nbn:se:uu:diva-331676 (URN)
    Available from: 2017-10-16 Created: 2017-10-16 Last updated: 2017-10-23
    2. Influence of pulsed and continuous substrate inputs on freshwater bacterial community composition and functioning in bioreactors
    Open this publication in new window or tab >>Influence of pulsed and continuous substrate inputs on freshwater bacterial community composition and functioning in bioreactors
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Aquatic environments are typically not homogenous, but characterized by changing substrate concentration gradients and nutrient patches. This heterogeneity in substrate availability creates a multitude of niches allowing bacteria with different substrate utilization strategies to hypothetically coexist even when competing for the same substrate. To study the impact of heterogeneous distribution of organic substrates on bacterioplankton, bioreactors with freshwater bacterial communities were fed artificial freshwater medium with acetate supplied either continuously or in pulses. After a month-long incubation, bacterial biomass and community-level substrate uptake rates were twice as high in the pulsed treatment compared to the continuously fed reactors even if the same total amount of acetate was supplied to both treatments. The composition of the bacterial communities emerging in the two treatments differed significantly with specific taxa overrepresented in the respective treatments. The higher estimated growth yield in cultures that received pulsed substrate inputs, imply that such conditions enable bacteria to use resources more efficiently for biomass production. This finding agrees with established concepts of basal maintenance energy requirements and high energetic costs to assimilate substrates at low concentration. Our results further imply that degradation of organic matter is influenced by temporal and spatial heterogeneity in substrate availability. 

    National Category
    Biological Sciences
    Research subject
    Microbiology
    Identifiers
    urn:nbn:se:uu:diva-331692 (URN)
    Available from: 2017-10-17 Created: 2017-10-17 Last updated: 2017-10-23
    3. Response and effect interactions between bacterial communities and organic matter
    Open this publication in new window or tab >>Response and effect interactions between bacterial communities and organic matter
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The interaction between bacteria and dissolved organic matter (DOM) is crucial for the global carbon cycling. Despite decades of research there are, however, few consistent patterns regarding the relationship between bacterial diversity and community composition and DOM. Here we hypothesized that one reason for such inconsistences among studies is that bacterial communities can adapt to a DOM source over time, whereby a change in the functioning of a community can be, at least partly, decoupled from its composition and diversity. To test this idea we performed a reciprocal transplant experiment with medium (i.e. DOM source) and bacterial communities from two boreal lakes. In this experiment the two communities were allowed to adapt to their indigenous and their foreign source of DOM over 42 days. Bacterial community composition (BCC) was measured throughout the experiment. In addition we measured the capacity of the communities to use DOM, in repeated short (5 days) separated bioassays. The results show a response of bacterial community composition to the DOM sources which was influenced by the origin of the community. In contrast, we could not show an effect of BCC on DOM-processing and functional performance. Indeed, communities of different origin processed the two DOM sources equally well even at the beginning of the experiment. This work demonstrates that the DOM pool can be a strong selective force for BCC but not vice versa. 

    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-331696 (URN)
    Available from: 2017-10-17 Created: 2017-10-17 Last updated: 2017-10-23
    4. The relative importance of richness and BCC for DOC degradation
    Open this publication in new window or tab >>The relative importance of richness and BCC for DOC degradation
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The importance of biodiversity has been of primary interest for ecologist the last 20 years, giving rise to biodiversity ecosystem function (BEF) studies. Within the traditional field of ecology reoccurring patterns have emerged but within microbial ecology the importance of species richness for functioning is still poorly understood with few consistent patterns. In this study we examined the effect of species richness for dissolved organic matter degradation in lakes. This was examined within a smaller span of species richness compared to what is typically in microbial BEF experiments. Bacterial communities of reduced species richness were exposed to a range of DOC environments to test if reduced richness changed the functioning of communities and if the effect was similar among DOC environments. This was conducted in a full factorial design of 3 levels, with 6 dilutions, 5 media and 3 inocula resulting in 90 treatments. Overall, richness and community composition appeared to have effects on DOC degradation, but these effects were minor compared to the variation caused by the different DOC sources. Further, the importance of species richness varied among media and, thus, the chemical complexity of the environment influenced the biodiversity-ecosystem functioning relationship. 

    National Category
    Biological Sciences
    Research subject
    Microbiology
    Identifiers
    urn:nbn:se:uu:diva-331693 (URN)
    Available from: 2017-10-17 Created: 2017-10-17 Last updated: 2017-10-23
  • Lind, Jonna
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Tribology of polymer composites for elevated temperature applications2017Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Polymers as construction material are common in the industry. Although more recently the use of polymer composites in more demanding applications has increased, requiring more of them mechanically, tribologically and thermally. To enhance the properties various fillers are used, from common glass fibers to more advanced nanoparticles. For this study three types of base polymers have been studied: poly-amide (PA), poly-phenylene-sulphide (PPS) and poly-ether-ether-ketone (PEEK). They have been filled with glass fibers, carbon fibers, poly-tetra-fluoro-ethylene (PTFE), graphite and thermally conductive modifier in various combinations. Fibers are used to increase the mechanical properties, PTFE and graphite are added as lubricating additives to reduce the friction, and the thermally conductive modifier to increase the thermal conductivity. Five general groups of polymer composites were studied.

    • Pure PEEK
    • PPS, PA and PEEK filled with fibers
    • PPS, PA and PEEK filled with fibers and lubricating additives
    • PA filled with lubricating additives
    • PEEK filled with fibers and additives for lubrication and thermal conductivity

    The polymer composites have been tribologically tested in a reciprocating sliding test set-up. Friction, wear and surface damage have been studied. Three types of counter surfaces have been used: ball bearing steel balls, stainless steel cylinders and anodized aluminum cylinders. Load, surface temperature of the polymer composites and number of cycles were varied to study any changes in friction and wear. The wear marks on the polymer composites were studied using an SEM. Cross sections of some tested samples were prepared to study any subsurface damage.

    From the tests the polymer composites showed similarities in friction. Lubricating additives gave lower friction, often around 0.05-0.15, while pure and only reinforced gave higher, often around 0.4-0.5. The wear was also less for polymer composites with lubricating additives. There was no clear influence of temperature but for most tests an increase in temperature gave lower friction. The only influence of load was that higher load gave wider wear tracks. Since no cross sections were prepared to compare subsurface damage due to different loads there might be a possibility that there were some differences below the surface as well. Otherwise cross sections showed that polymer composites with only fibers had cracks and cracked fibers below the surface due to the high stresses the polymer composite had been subjected to. With lubricating additives there was no large subsurface damage and it seems as if the lubricating additives formed a protective tribofilm in the wear track, giving both lower friction and wear. The presence of such a tribofilm was confirmed by XPS analysis that showed a surface layer containing F from PTFE.

    The conclusions are that the tribological properties of a polymer composite are strongly dependent on its fillers. Lubricating additives form a tribofilm that lowers friction and wear. Elevated temperatures might drastically change the tribological behavior of a polymer composite why it is important to do tests at higher temperatures. Cross sections can give information about subsurface damage and might help to understand the wear mechanisms and deformation of polymer composites better. More microscopy and mechanism studies are required in order to further understand the tribological behavior of polymer composites.

    List of papers
    1. Friction and wear studies of some PEEK materials
    Open this publication in new window or tab >>Friction and wear studies of some PEEK materials
    2015 (English)In: Tribologia - Finnish Journal of Tribology, ISSN 0780-2285, Vol. 33, no 2, 20-28 p.Article in journal, Editorial material (Refereed) Published
    Abstract [en]

    The friction and wear behavior of several types of PEEK polymers and composites were studied. The influence of carbon fiber, lubricant and thermally conductive fillers were evaluated, as well as the effects of contact load and temperature. The tests were done using a reciprocating ball-on-disc set-up. The materials were tested under the load of 5 N and 15 N, at room temperature, 80 °C, 120 °C and 150 °C. The difference between the materials was substantial, with a friction coefficient varying between 0.03 and 0.3 for the different materials at 120 °C. PEEK with carbon fiber filler showed an improvement in both friction and wear compared to unfilled PEEK. When adding lubricant, PTFE, to the composite the friction and wear were improved even more. PEEK with thermally conductive filler on the other hand had both highest friction and wear. Increasing the temperature slightly decreased both friction and wear for most of the PEEK materials. At 150 °C, only the composite with PTFE lubricant had a low friction and wear.

    Keyword
    PEEK, carbon fiber, friction, wear
    National Category
    Textile, Rubber and Polymeric Materials
    Research subject
    Engineering Science with specialization in Tribo Materials
    Identifiers
    urn:nbn:se:uu:diva-267460 (URN)
    Available from: 2015-12-02 Created: 2015-11-23 Last updated: 2017-11-08
    2. Cross section microscopy studies of wear tested polymer composites
    Open this publication in new window or tab >>Cross section microscopy studies of wear tested polymer composites
    2016 (English)Conference paper, Oral presentation with published abstract (Other academic)
    National Category
    Textile, Rubber and Polymeric Materials Composite Science and Engineering
    Research subject
    Engineering Science with specialization in Tribo Materials
    Identifiers
    urn:nbn:se:uu:diva-307578 (URN)
    Conference
    17th Nordic Symposium on Tribology (NordTrib), 2016
    Available from: 2016-12-16 Created: 2016-11-17 Last updated: 2017-11-08
    3. Surface and subsurface deformation of polyamide and poly-ether-ether-ketone composites sliding against steel cylinders
    Open this publication in new window or tab >>Surface and subsurface deformation of polyamide and poly-ether-ether-ketone composites sliding against steel cylinders
    (English)Manuscript (preprint) (Other academic)
    National Category
    Materials Engineering
    Research subject
    Engineering Science with specialization in Tribo Materials
    Identifiers
    urn:nbn:se:uu:diva-332986 (URN)
    Available from: 2017-11-08 Created: 2017-11-08 Last updated: 2017-11-08
    4. Effect of PTFE on the tribological behaviour of PPS with glass fiber
    Open this publication in new window or tab >>Effect of PTFE on the tribological behaviour of PPS with glass fiber
    2014 (English)In: 1st International conference on polymer tribology (PolyTrib), 2014Conference paper, Oral presentation with published abstract (Other academic)
    National Category
    Textile, Rubber and Polymeric Materials Composite Science and Engineering
    Research subject
    Engineering Science with specialization in Tribo Materials
    Identifiers
    urn:nbn:se:uu:diva-234191 (URN)
    Conference
    PolyTrib, Bled, September 11-12, 2014
    Available from: 2014-11-25 Created: 2014-10-15 Last updated: 2017-11-08
    5. Friction and wear of PA66-PPA composites sliding against anodized aluminium cylinders
    Open this publication in new window or tab >>Friction and wear of PA66-PPA composites sliding against anodized aluminium cylinders
    2015 (English)Conference paper, Poster (with or without abstract) (Refereed)
    Keyword
    Polymer composites, friction, wear.
    National Category
    Textile, Rubber and Polymeric Materials
    Research subject
    Engineering Science with specialization in Tribo Materials
    Identifiers
    urn:nbn:se:uu:diva-267458 (URN)
    Conference
    20th International Conference on Wear of Materials, Toronto, Canada, 12-16 April, 2015
    Available from: 2015-12-02 Created: 2015-11-23 Last updated: 2017-11-08Bibliographically approved
    6. Effect of temperature on the performance of some polymer composites
    Open this publication in new window or tab >>Effect of temperature on the performance of some polymer composites
    2015 (English)Conference paper, Poster (with or without abstract) (Refereed)
    Keyword
    Polymer composites, friction, wear.
    National Category
    Textile, Rubber and Polymeric Materials
    Research subject
    Engineering Science with specialization in Tribo Materials
    Identifiers
    urn:nbn:se:uu:diva-267459 (URN)
    Conference
    International Tribology Conference, Tokyo, 16-20 September, 2015
    Available from: 2015-12-02 Created: 2015-11-23 Last updated: 2017-11-08Bibliographically approved
    7. Cross sections studies of polymer composites
    Open this publication in new window or tab >>Cross sections studies of polymer composites
    2016 (English)Conference paper, Oral presentation with published abstract (Other academic)
    National Category
    Composite Science and Engineering Textile, Rubber and Polymeric Materials
    Research subject
    Engineering Science with specialization in Tribo Materials
    Identifiers
    urn:nbn:se:uu:diva-307579 (URN)
    Conference
    2nd International conference on Polymer Tribology (PolyTrib), 2016
    Available from: 2016-12-16 Created: 2016-11-17 Last updated: 2017-11-08
  • Dalmar, Abdirisak Ahmed
    et al.
    Benadir Univ, Fac Med, Mogadishu, Somalia..
    Hussein, Abdullahi Sheik
    Benadir Univ, Fac Med, Mogadishu, Somalia..
    Walhad, Said Ahmed
    Amoud Univ, Coll Hlth Sci, Borama, Somaliland, Somalia..
    Ibrahim, Abdirashid Omer
    Amoud Univ, Coll Hlth Sci, Borama, Somaliland, Somalia..
    Abdi, Abshir Ali
    East Africa Univ, Fac Med, Bosasso, Somalia..
    Ali, Mohamed Khalid
    East Africa Univ, Fac Med, Bosasso, Somalia..
    Ereg, Derie Ismail
    Univ Hargeisa, Coll Med, Hargeisa, Somalia..
    Egal, Khadra Ali
    Univ Hargeisa, Coll Med, Hargeisa, Somalia..
    Shirwa, Abdulkadir Mohamed
    Galkayo Univ, Coll Med, Galkayo, Somalia..
    Aden, Mohamed Hussain
    Puntland Univ Sci & Technol, Med Coll, Galkayo, Somalia..
    Yusuf, Marian Warsame
    Somali Swedish Researchers Assoc, Stockholm, Sweden..
    Abdi, Yakoub Aden
    Somali Swedish Researchers Assoc, Stockholm, Sweden..
    Freij, Lennart
    Somali Swedish Researchers Assoc, Stockholm, Sweden..
    Johansson, Annika
    Somali Swedish Researchers Assoc, Stockholm, Sweden..
    Mohamud, Khalif Bile
    Somali Swedish Researchers Assoc, Stockholm, Sweden..
    Abdulkadir, Yusuf
    Somali Swedish Researchers Assoc, Stockholm, Sweden..
    Emmelin, Maria
    Lund Univ, Unit Social Med & Global Hlth, Lund, Sweden..
    Eriksen, Jaran
    Karolinska Inst, Div Clin Pharmacol, Stockholm, Sweden..
    Erlandsson, Kerstin
    Dalarna Univ, Falun, Sweden..
    Gustafsson, Lars L.
    Karolinska Inst, Div Clin Pharmacol, Stockholm, Sweden..
    Ivarsson, Anneli
    Umea Univ, Unit Epidemiol & Global Hlth, Umea, Sweden..
    Klingberg-Allvin, Marie
    Dalarna Univ, Falun, Sweden..
    Kinsman, John
    Umea Univ, Unit Epidemiol & Global Hlth, Umea, Sweden..
    Källestål, Carina
    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).
    Målqvist, Mats
    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).
    Osman, Fatumo
    Persson, Lars-Åke
    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).
    Sahlen, Klas-Goran
    Umea Univ, Unit Epidemiol & Global Hlth, Umea, Sweden..
    Wall, Stig
    Umea Univ, Unit Epidemiol & Global Hlth, Umea, Sweden..
    Rebuilding research capacity in fragile states: the case of a Somali-Swedish global health initiative2017In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 10, no 1, 1348693Article in journal (Refereed)
    Abstract [en]

    This paper presents an initiative to revive the previous Somali-Swedish Research Cooperation, which started in 1981 and was cut short by the civil war in Somalia. A programme focusing on research capacity building in the health sector is currently underway through the work of an alliance of three partner groups: six new Somali universities, five Swedish universities, and Somali diaspora professionals. Somali ownership is key to the sustainability of the programme, as is close collaboration with Somali health ministries. The programme aims to develop a model for working collaboratively across regions and cultural barriers within fragile states, with the goal of creating hope and energy. It is based on the conviction that health research has a key role in rebuilding national health services and trusted institutions.

  • Shorawi, Roshna
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Sociology.
    Holm, Annika
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Sociology.
    Ovisshet från dag till dag: En studie om ensamstående föräldrar med en osäker anställningsform: allmän visstidsanställning2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Studiens syfte är att undersöka hur formen visstidsanställning samspelar med ensamstående föräldrars privatliv och yrkesliv samt om och i så fall hur det kan bidra till någon form av upplevd ohälsa. Första teorin som vi har valt att använda oss av är Robert Karaseks Krav-kontrollmodell. De centrala begreppen i denna teori är lågt- och högt handlingsutrymme och stress. Den andra teorin är intersektionalitet, där vi exemplifierar begreppen makt och ojämlikhet och hur det samverkar med under- och överordning i relation till två grupper det vill säga visstidsanställda och tillsvidareanställda och hur de i sin tur ställs mot varandra. Vi kommer att stärka begreppet handlingsutrymme med Max Webers förklaring till det. För att få svar på vårt syfte och frågeställningar har vi valt att genomföra en analys av datamaterial från tio kvalitativa semistrukturerade intervjuer med ensamstående föräldrar som har en visstidsanställning. Resultatet av vår studie visar att en visstidsanställning kan ge konsekvenser i privatlivet såsom dåligt samvete, instabil ekonomi och minskad tid tillsammans med familjen, på grund av att de “måste” ta de arbetspassen som de blir tilldelade som ofta är de obekväma arbetstiderna som blir “över”. Vårt material kan påvisa att konsekvenserna i arbetslivet kan vara utanförskap, minskad kontroll över arbetet samt att de blir tillfrågade de obekväma arbetstiderna som blir “över” efter att tillsvidareanställa har blivit tilldelade sitt schema. Resultatet visar också att upplevelserna skiljer sig åt något mellan kvinnor och män i meningen att kvinnor verkar uppleva större ohälsa än män.

  • Helén, Lina
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Sociology.
    Våldtog och våldtogs under livesändning: En diskursanalytisk studie om diskursen kring sexualbrott på diskussionsforumet Flashback2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • Larsson, David
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Design and Test of: Wide Band and Highly Polarized Antenna for 60GHz2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    In this work  high gain antennas are investigated for the 60 GHz frequency. The goal is to produce a high bandwidth point-to-point wireless network that could enable improved and new features in embedded systems used to detect particles in high energy physics.

    A literature study was performed aiming at simple, high gain, highly polarised antennas. Complex designs were grouped into three different groups: flat antenna design, build-up design and multi-antenna design. The multi-antenna design was found to have the simplest design and manufacturing but also feature larger antenna area.

    Three different designs were produced and tested, standard patch antenna, long patch antenna and a Vivaldi antenna. Manufacturing of a 4-patch antenna was also tested. All three demonstrated expected properties, the Vivaldi shows the best gain while the long patch antenna is slightly below the standard patch antenna.

    A forth design implementation was also tested using a 3D-printed lens. A lens can increase gain and allow changing beam direction. A lens was design and tested, the results showed an increased gain but with varying results at angels.

    Antennas were designed and manufactured using simple etching technique showing that further research can be done using simple and easily accessible techniques. Both antenna and lens show good properties and should be further investigated and validated.