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  • Public defence: 2018-09-19 09:15 B7:101a, Uppsala
    de Kock, Neil
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Mass spectrometry based analysis of endogenous sterols and hormones2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Bioanalytical applications using supercritical fluid chromatography (SFC) as analytical technique are of increasing interest. In essence, bioanalysis involves measurement of bioactive or endogenous compounds in biological matrices. SFC has emerged as an excellent choice for bioanalytical analysis, attributable to its speed, selectivity and efficiency compared with high performance liquid chromatography. Moreover, coupling of SFC with mass spectrometry (MS) provides the additional benefits of specificity and sensitivity.

    The aim of this thesis was to exploit these features by developing methods for the analysis of endogenous steroids, cholesterol oxidation products (COPs) and thyroid hormones (THs) by using ultra-performance supercritical fluid chromatography–tandem mass spectrometry (UPSFC–MS/MS) as analytical technique.

    Endogenous steroids control many physiological processes, including reproduction, maturation, gene expression and neurological functions in humans and animals. In the first study, three steroids were measured in domesticated White Leghorn (WL) chickens and ancestral Red Junglefowl (RJF) birds. Restraining stress caused a significantly larger increase in corticosterone levels in RJF than in WL, indicating a blunted hypothalamic–pituitary–adrenal (HPA) axis activity in domesticated chickens. The second study was a continuation of the first study and corticosterone levels from the F12 generation of an intercross between WL and RJF birds were measured before and after physical restraint stress. The expression levels of the glucocorticoid receptor (GR) in the hypothalamus and several genes in the adrenal glands were correlated with the post-stress levels of corticosterone in plasma. In the third study, the measurement of steroids was extended to assess more endogenous steroids from the four major classes, i.e. estrogens, androgens, progestogens and corticosterone.

    Endogenous COPs are of interest in pathophysiology. COPs are more readily disposed by cells than cholesterol. Therefore, cholesterol is oxidised to the more polar COPs and are generally more bioactive than cholesterol. Moreover, if their production in cells and tissues and/or their introduction with dietary animal fat are excessive, COPs could indeed contribute to the pathogenesis of various disease processes. Fourteen COPs were included in the fourth study and a novel method for their separation was developed.

    The last study in this thesis, involved the analysis of five THs. These hormones are vital for growth, developmental and metabolic processes of vertebrate life and play an important role in energy homeostasis. Measurements of circulating thyroid hormone levels are used in thyroid disorder diagnoses or treatment status monitoring. Two rapid methods for the separation of five THs were developed.

    In summary, the work in this thesis demonstrates the applicability of UPSFC–MS/MS as an analytical technique in bioanalysis of endogenous compounds.

    List of papers
    1. Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens
    Open this publication in new window or tab >>Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens
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    2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 15345Article in journal (Refereed) Published
    Abstract [en]

    Understanding the genetic basis of phenotypic diversity is a challenge in contemporary biology. Domestication provides a model for unravelling aspects of the genetic basis of stress sensitivity. The ancestral Red Junglefowl (RJF) exhibits greater fear-related behaviour and a more pronounced HPA-axis reactivity than its domesticated counterpart, the White Leghorn (WL). By comparing hormones (plasmatic) and adrenal global gene transcription profiles between WL and RJF in response to an acute stress event, we investigated the molecular basis for the altered physiological stress responsiveness in domesticated chickens. Basal levels of pregnenolone and dehydroepiandrosterone as well as corticosterone response were lower in WL. Microarray analysis of gene expression in adrenal glands showed a significant breed effect in a large number of transcripts with over-representation of genes in the channel activity pathway. The expression of the best-known steroidogenesis genes were similar across the breeds used. Transcription levels of acute stress response genes such as StAR, CH25 and POMC were upregulated in response to acute stress. Dampened HPA reactivity in domesticated chickens was associated with changes in the expression of several genes that presents potentially minor regulatory effects rather than by means of change in expression of critical steroidogenic genes in the adrenal.

    National Category
    Chemical Sciences Genetics
    Identifiers
    urn:nbn:se:uu:diva-265144 (URN)10.1038/srep15345 (DOI)000362885300001 ()
    Funder
    Swedish Research Council, 621-2011-4731Swedish Research Council Formas, 221-2011-1088EU, European Research Council, 322206
    Available from: 2015-10-23 Created: 2015-10-23 Last updated: 2018-08-06Bibliographically approved
    2. QTL mapping of stress related gene expression in a cross between domesticated chickens and ancestral red junglefowl
    Open this publication in new window or tab >>QTL mapping of stress related gene expression in a cross between domesticated chickens and ancestral red junglefowl
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    2017 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 446, no C, p. 52-58Article in journal (Refereed) Published
    Abstract [en]

    Domestication of animals is associated with numerous alterations in physiology, morphology, and behavior. Lower reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and reduced fearfulness is seen in most studied domesticates, including chickens. Previously we have shown that the physiological stress response as well as expression levels of hundreds of genes in the hypothalamus and adrenal glands are different between domesticated White Leghorn and the progenitor of modern chickens, the Red Junglefowl. To map genetic loci associated with the transcription levels of genes involved in the physiological stress response, we conducted an eQTL analysis in the F12 generation of an inter-cross between White Leghorn and Red Junglefowl. We selected genes for further studies based on their known function in the regulation of the HPA axis or sympathoadrenal (SA) system, and measured their expression levels in the hypothalamus and the adrenal glands after a brief stress exposure (physical restraint). The expression values were treated as quantitative traits for the eQTL mapping. The plasma levels of corticosterone were also assessed. We analyzed the correlation between gene expression and corticosterone levels and mapped eQTL and their potential effects on corticosterone levels. The effects on gene transcription of a previously found QTL for corticosterone response were also investigated. The expression levels of the glucocorticoid receptor (GR) in the hypothalamus and several genes in the adrenal glands were correlated with the post-stress levels of corticosterone in plasma. We found several cis- and transacting eQTL for stress-related genes in both hypothalamus and adrenal. In the hypothalamus, one eQTL for c-FOS and one QTL for expression of GR were found. In the adrenal tissue, we identified eQTL for the genes NROB1, RGS4, DBH, MAOA, GRIN1, GABRB2, GABRB3, and HSF1. None of the found eQTL were significant predictors of corticosterone levels. The previously found QTL for corticosterone was associated with GR expression in hypothalamus. Our data suggests that domestication related modification in the stress response is driven by changes in the transcription levels of several modulators of the HPA and SA systems in hypothalamus and adrenal glands and not by changes in the expression of the steroidogenic genes. The presence of eQTL for GR in hypothalamus combined with the negative correlation between GR expression and corticosterone response suggests GR as a candidate for further functional studies regarding modification of stress response during chicken domestication.

    Keywords
    Animal domestication, Stress response, HPA axis, QTL, eQTL
    National Category
    Medical Genetics Biochemistry and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
    Identifiers
    urn:nbn:se:uu:diva-322082 (URN)10.1016/j.mce.2017.02.010 (DOI)000399509600006 ()
    Funder
    Swedish Research Council, 621-2011-4731Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, 221-2011-1088EU, European Research Council, Genewell 322206
    Available from: 2017-05-18 Created: 2017-05-18 Last updated: 2018-08-24Bibliographically approved
    3. A novel targeted analysis of peripheral steroids by ultra–performance supercritical fluid chromatography hyphenated to mass spectrometry
    Open this publication in new window or tab >>A novel targeted analysis of peripheral steroids by ultra–performance supercritical fluid chromatography hyphenated to mass spectrometry
    (English)In: Article in journal (Other academic) Submitted
    National Category
    Analytical Chemistry
    Research subject
    Chemistry with specialization in Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-356766 (URN)
    Available from: 2018-08-06 Created: 2018-08-06 Last updated: 2018-08-06
    4. A novel ultra-performance supercritical fluid chromatography–tandem mass spectrometry method for separation of fourteen cholesterol oxidation products
    Open this publication in new window or tab >>A novel ultra-performance supercritical fluid chromatography–tandem mass spectrometry method for separation of fourteen cholesterol oxidation products
    (English)Manuscript (preprint) (Other academic)
    Keywords
    COPs, oxycholesterols, supercritical fluid chromatography–tandem mass spectrometry
    National Category
    Analytical Chemistry
    Research subject
    Chemistry with specialization in Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-356763 (URN)
    Available from: 2018-08-06 Created: 2018-08-06 Last updated: 2018-08-24
    5. Rapid mass spectrometric methods for separation of five thyroid hormones by ultra-performance supercritical fluid chromatography and ultra-performance liquid chromatography
    Open this publication in new window or tab >>Rapid mass spectrometric methods for separation of five thyroid hormones by ultra-performance supercritical fluid chromatography and ultra-performance liquid chromatography
    (English)Manuscript (preprint) (Other academic)
    Keywords
    thyroid hormones, UPSFC–MS/MS, UPLC–MS/MS, derivatisation
    National Category
    Analytical Chemistry
    Research subject
    Chemistry with specialization in Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-356765 (URN)
    Available from: 2018-08-06 Created: 2018-08-06 Last updated: 2018-08-24
  • Public defence: 2018-09-20 15:00 Geijersalen, Uppsala
    Franzén, Nils
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Philosophy, Logic and Metaphysics. Uppsala University.
    Sense and Sensibility: Four Essays on Evaluative Discourse2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The subject of this thesis is the nature of evaluative terms and concepts. It investigates various phenomena that distinguish evaluative discourse from other types of language use. Broadly, the thesis argues that these differences are best explained by the hypothesis that evaluative discourse serves to communicate that the speaker is in a particular emotional or affective state of mind.

    The first paper, “Aesthetic Evaluation and First-hand Experience”, examines the fact that it sounds strange to make evaluative aesthetic statements while at the same time denying that you have had first-hand experience with the object being discussed. It is proposed that a form of expressivism about aesthetic discourse best explains the data.

    The second paper, “Evaluative Discourse and Affective States of Mind”, discusses the problem of missing Moorean infelicity for expressivism. It is argued that evaluative discourse expresses states of mind attributed by sentences of the form “Nils finds it wrong to tell lies”. These states, the paper argues, are non-cognitive, and the observation therefore addresses the problem of missing infelicity.

    The third paper, “Sensibilism and Evaluative Supervenience”, argues that contemporary theories about why the moral supervenes on the non-moral have failed to account for the full extent of the phenomenon. Supervenience pertains not just to the moral but to the evaluative in general, it is a conceptual truth and it involves a relationship with a certain directionality. While all these points have been individually recognized at various points in the literature on moral supervenience, no theory accounts for all them. It is suggested that a kind of sensibilist semantics, according to which the extensions of evaluative terms are determined by how we feel about things, explains the full phenomenon.

    The fourth paper, “Sensibilism and Imaginative Resistance”, discusses why we refuse to accept strange evaluative claims as being true in fictions, even though we are happy to accept other types of absurdities as fictionally true. The paper argues that the sensibilist semantics outlined in the third article offers a good diagnosis of the puzzle and compares this to other approaches.

    List of papers
    1. Aesthetic Evalution and First-hand Experience
    Open this publication in new window or tab >>Aesthetic Evalution and First-hand Experience
    (English)In: Australasian Journal of Philosophy, ISSN 0004-8402, E-ISSN 1471-6828Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    Evaluative aesthetic discourse communicates that the speaker has had first-hand experience of what is talked about. If you call a book bewitching, it will be assumed that you have read the book. If you say that a building is beautiful, it will be assumed that you have had some visual experience with it. According to an influential view, this is because knowledge is a norm for assertion, and aesthetic knowledge requires first-hand experience. This paper criticizes this view and argues for an alternative view, according to which aesthetic discourse expresses affective states of mind, analogously to how assertions express beliefs. It is because these affective states require first-hand experience that aesthetic discourse communicates that such acquaintance is at hand. The paper furthermore argues that the lack of an experience requirement for aesthetic belief ascriptions constitutes a problem for the kind of expressivist who claims that evaluative belief states are covert non-cognitive states.

    Keywords
    KEYWORDS: first-hand experience, aesthetic evaluation, evaluative discourse, acquaintance inference, expressivism, aesthetic knowledge
    National Category
    Philosophy
    Research subject
    Philosophy
    Identifiers
    urn:nbn:se:uu:diva-341025 (URN)
    Available from: 2018-02-06 Created: 2018-02-06 Last updated: 2018-08-07
    2. Evaluative Discourse and Affective States of Mind
    Open this publication in new window or tab >>Evaluative Discourse and Affective States of Mind
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Expressivists maintain that evaluative discourse expresses non-cognitve states of mind in a similar way to how ordinary descriptive language expresses beliefs. Conjoining an ordinary assertion that p with the denial of being in the corresponding belief-state that p famously gives rise to Moorean infelicity:

    (i) ?? It’s raining but I don’t believe that it’s raining.

    If expressivists are right, then conjoining evaluative statements with the denial of being in the requite non-cognitive state of mind should give rise to similar infelicity. However, as several theorists have pointed out, this does not seem to be the case. Statements like the following are not infelicitious:

    (ii) Murder is wrong but I don’t disapprove of it.

    In this paper, I argue that evaluative discourse expresses the kind of states which are attributed by ‘find’- constructions in English, and that these states are non-cognitive in nature. This addresses the problem of missing Moorean infelicity for expressivism, and it also tells us some interesting things about evaluative discourse in general.

    Keywords
    Expressivism; Anti-realism; Evaluative Discourse; Aesthetic Discourse; Moral Discourse; Predicates of personal taste
    National Category
    Humanities and the Arts
    Research subject
    Theoretical Philosophy
    Identifiers
    urn:nbn:se:uu:diva-356593 (URN)
    Available from: 2018-08-02 Created: 2018-08-02 Last updated: 2018-08-07Bibliographically approved
    3. Sensibilism and Evaluative Supervenience
    Open this publication in new window or tab >>Sensibilism and Evaluative Supervenience
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    This paper argues that the current literature on the supervenience of the evaluative on the non-

    Keywords
    aesthetic predicates, anti-realism, expressivism, moral predicates, predicates of personal taste, R.M Hare, supervenience, sensibilism
    National Category
    Philosophy
    Research subject
    Theoretical Philosophy
    Identifiers
    urn:nbn:se:uu:diva-356566 (URN)
    Available from: 2018-08-01 Created: 2018-08-01 Last updated: 2018-08-09
    4. Sensibilism and Imaginative Resistance
    Open this publication in new window or tab >>Sensibilism and Imaginative Resistance
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    This article discusses why it is that we refuse to accept strange evaluative claims as being true in fictions, even though weare happy to accept other types of absurdities in such stories. For instance, we would refuse to accept the following statement as true in a fiction:

    (i)             In killing her baby, Giselda did the right thing; after all, it was a girl.

    The diagnosis of the puzzle is the following: when entering a fictional story, we leave our beliefs about what the world is like behind, while taking our emotional attitudes with us into the fiction. If sensibilism is true, the way we feel about things is what settles their evaluative properties. Thus, imagining a scenario were the configuration of the relevant facts and properties are the same, we refuse to go along with that evaluative properties are instantiated according to a different pattern. It is the attitudes we hold in the actual world that fixes the extension of evaluative properties, even at non-actual worlds.

    Keywords
    Sensibilism; Evaluative discourse; Philosophy of fiction; Aesthetic predicates; Moral predicates; Predicates of personal taste; Imaginative resistance; David Hume
    National Category
    Humanities and the Arts
    Research subject
    Philosophy
    Identifiers
    urn:nbn:se:uu:diva-356594 (URN)
    Available from: 2018-08-02 Created: 2018-08-02 Last updated: 2018-08-07Bibliographically approved
  • Public defence: 2018-09-21 09:15 Humanistiska teatern, UPPSALA
    Englund, Josefin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of History.
    Som folk är mest: Könsideal i svenska kontaktannonser 1890–19802018Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This thesis investigates 5,000 descriptions of men and women in search for a life partner of the opposite sex through classifieds 1890-1980. The advertisers’ descriptions of who they are and what they want sketches a picture of the expectations everyday people have had on how men and women should be over almost a hundred years. Previous accounts of 20th century gender relations are based on governmental and political materials.

    The bipartite structure of the personals advertisements is used methodologically to differentiate between the so-called “ego-descriptions” and the “alter-descriptions” - what the advertiser had to offer and what the advertiser wanted. Men's descriptions of themselves – ego descriptions – is compared to women's descriptions of the man – alter description –, and women’s descriptions of themselves – ego-description – is compared to men’s descriptions of women – alter description. Six categories were created to capture the content of the personal advertisements: 1) Breadwinner qualifications 2) Parenting qualifications 3) Homemaker qualifications 4) Bodily aspects 5) Leisure 6) Personal interests and qualifications.

    This study shows that men and women increasingly are described on the grounds of similar qualifications, and that both men and women are increasingly depicted with characteristics that earlier was coded as female. It also shows that children and the family became more important. Stability and security were highly appreciated in the beginning of the period, but gave way to values as mobility and opportunity in the late 1900’s. Both women and men shift from favouring material conditions to an increased focus on feelings and thoughts, and in the end of the period the life partner relationship was more about emotional closeness and the company of a like-minded individual.

    However, despite these more general results, it is clear that neither the images of the man nor the images woman was unambiguous, and that men and women for most of the time didn't share the same ideals. When thousands of men and women describe their dreams and needs based on the lives they live, unlike government surveys, for example, a multitude of images of the nineteenth century man and woman appear.

  • Public defence: 2018-09-21 09:15 Universitetshuset, sal IX, Uppsala
    Viberg Johansson, Jennifer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    INDIVIDUAL GENETIC RESEARCH RESULTS: Uncertainties, Conceptions, and Preferences2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis contributes to the ethical discussion on how to handle incidental findings in biomedical research using sequencing technologies from a theoretical and an empirical perspective. Study I and II are theoretical studies that used conceptual analysis. Study I demonstrates that the argument for disclosure based on the principle of beneficence ignores the complexity and uncertain predictive value of genetic risk information. The argument neglects the distinction between an incidentally discovered disease and an incidentally discovered risk for disease with unclear predictive value. Study II investigates the proposal to let participants express their preferences to incidental genetic findings in the consent form. The study argues that this freedom of choice is problematic because it is uncertain whether the opportunity to choose in the consent phase enables people to express what they truly prefer. Participants might be steered to a specific answer depending on mood, triggered feelings, and the framing of the question.

    The second part of the thesis is empirical and used both a qualitative and a quantitative approach. Study III investigates research participants’ understanding of genetic risk and used a phenomenographic approach and focus group interviews. One result was that participants understood genetic risk in binary terms. This understanding involved an either/or concept of genetic risk. Participants tend not to understand genetic risk as a probability. They also interpreted the information in terms of their past, present, and future life. Study IV used a questionnaire with a stated preference technique called Discrete Choice Experiments (DCE) to investigate participants’ preferences for genetic risk information. An effective preventive measure was the most important characteristic for research participants in their decision to be given genetic risk information. When the disease was life threatening, had a high penetrance probability, and had effective preventive measures, 98% of the participants wanted to know their incidental genetic risk information.

    As genetic risk information has many different characteristics and includes many uncertainties, ethical discussions and empirical studies of people’s attitudes and preferences need to explicitly engage the complexity of genetic incidental findings.

    List of papers
    1. Incidental Findings: The Time Is not yet Ripe for a Policy for Biobanks
    Open this publication in new window or tab >>Incidental Findings: The Time Is not yet Ripe for a Policy for Biobanks
    2015 (English)In: Ethics, Law and Governance of Biobanking: National, European and International Approaches / [ed] Mascalzoni, Deborah, Springer, 2015Chapter in book (Refereed)
    Place, publisher, year, edition, pages
    Springer, 2015
    Series
    International Library of Ethics Law and Technology, ISSN 1875-0044 ; 14
    National Category
    Medical Ethics
    Identifiers
    urn:nbn:se:uu:diva-244975 (URN)9789401795739 (ISBN)
    Available from: 2015-02-23 Created: 2015-02-23 Last updated: 2018-08-01Bibliographically approved
    2. Freedom of Choice about Incidental Findings can frustrate participants’ true preferences
    Open this publication in new window or tab >>Freedom of Choice about Incidental Findings can frustrate participants’ true preferences
    2016 (English)In: Bioethics, ISSN 0269-9702, E-ISSN 1467-8519, Vol. 30, no 3, p. 203-209Article in journal (Refereed) Published
    Abstract [en]

    Ethicists, regulators and researchers have struggled with the question of whether incidental findings in genomics studies should be disclosed to participants. In the ethical debate, a general consensus is that disclosed information should benefit participants. However, there is no agreement that genetic information will benefit participants, rather it may cause problems such as anxiety. One could get past this disagreement about disclosure of incidental findings by letting participants express their preferences in the consent form. We argue that this freedom of choice is problematic.

    In transferring the decision to participants, it is assumed that participants will understand what they decide about and that they will express what they truly want. However, psychological findings about people's reaction to probabilities and risk have been shown to involve both cognitive and emotional challenges. People change their attitude to risk depending on what is at stake. Their mood affects judgments and choices, and they over- and underestimate probabilities depending on whether they are low or high. Moreover, different framing of the options can steer people to a specific choice.

    Although it seems attractive to let participants express their preferences to incidental findings in the consent form, it is uncertain if this choice enables people to express what they truly prefer. In order to better understand the participants' preferences, we argue that future empirical work needs to confront the participant with the complexity of the uncertainty and the trade-offs that are connected with the uncertain predictive value of genetic risk information.

    National Category
    Medical Ethics
    Identifiers
    urn:nbn:se:uu:diva-244971 (URN)10.1111/bioe.12160 (DOI)000371487500010 ()
    Funder
    Riksbankens Jubileumsfond, PR2013-0123EU, FP7, Seventh Framework Programme, 305444Swedish Research CouncilSwedish Heart Lung Foundation
    Available from: 2015-02-23 Created: 2015-02-23 Last updated: 2018-08-01Bibliographically approved
    3. Making sense of genetic risk: A qualitative focus-group study of healthy participants in genomic research
    Open this publication in new window or tab >>Making sense of genetic risk: A qualitative focus-group study of healthy participants in genomic research
    Show others...
    2018 (English)In: Patient Education and Counseling, ISSN 0738-3991, E-ISSN 1873-5134, Vol. 101, no 3, p. 422-427Article in journal (Refereed) Published
    Abstract [en]

    Objective

    It is well known that research participants want to receive genetic risk information that is about high risks, serious diseases and potential preventive measures. The aim of this study was to explore, by qualitative means, something less well known: how do healthy research participants themselves make sense of genetic risk information?

    Method

    A phenomenographic approach was chosen to explore research participants’ understanding and assessment of genetic risk. We conducted four focus-group (N = 16) interviews with participants in a research programme designed to identify biomarkers for cardiopulmonary disease.

    Results

    Among the research participants, we found four ways of understanding genetic risk: as a binary concept, as an explanation, as revealing who I am (knowledge of oneself) and as affecting life ahead.

    Conclusion

    Research participants tend to understand genetic risk as a binary concept. This does not necessarily imply a misunderstanding of, or an irrational approach to, genetic risk. Rather, it may have a heuristic function in decision-making.

    Practical implications

    Risk communication may be enhanced by tailoring the communication to the participants’ own lay conceptions. For example, researchers and counselors should address risk in binary terms, maybe looking out for how individual participants search for threshold figures.

    Keywords
    Lay understanding; Conception of genetic risk; Making sense of genetic risk in research; Genetic risk communication
    National Category
    Medical Genetics
    Identifiers
    urn:nbn:se:uu:diva-330221 (URN)10.1016/j.pec.2017.09.009 (DOI)000427826300007 ()
    Available from: 2017-09-27 Created: 2017-09-27 Last updated: 2018-08-01Bibliographically approved
    4. Research participants’ preferences for receiving incidental genetic risk information: a discrete choice experiment
    Open this publication in new window or tab >>Research participants’ preferences for receiving incidental genetic risk information: a discrete choice experiment
    Show others...
    (English)In: Genetics in Medicine, ISSN 1098-3600, E-ISSN 1530-0366Article in journal (Refereed) Submitted
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology Other Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-356552 (URN)
    Available from: 2018-08-01 Created: 2018-08-01 Last updated: 2018-08-01
  • Public defence: 2018-09-21 09:30 Polhemsalen, Uppsala
    Sturesson, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology, Ångström Space Technology Centre (ÅSTC). Försvarshögskolan/Swedish National Defence College.
    Sense, Actuate and Survive: Ceramic Microsystems for High-Temperature Aerospace Applications2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In aerospace applications, but also in manufacturing, mining, energy industry and natural hazards, high temperature, corrosion, erosion and radiation, challenge the performance and being of hardware.

    In this work, high-temperature co-fired ceramic (HTCC) alumina and platinum have been used for a range of devices intended for aerospace applications at up to 1000°C.

    The thermomechanics of a pressure sensor was investigated, and the interfacing was attained by wireless powering and reading. However, read range was limited and sensitivity decreased with temperature. Silver, electroplated after sintering, was found to remedy this until it eventually alloyed with platinum.

    Copper was electroplated and oxidized for oxygen storage in a microcombustor, intended for sample preparation for optogalvanic spectroscopy (OGS) to indicate extraterrestrial life. Despite delamination, caused by residual stresses, the device operated successfully.

    Conversely, pre-firing metallization by integration of platinum wires was studied. Freely suspended, and despite heat-induced shape irregularities, these were found advantageous over screen printed elements for gas heating, and temperature and pressure sensing. By fusing off the wires, spherical tips, allowing for impedance monitoring of microplasma sources in, e.g., OGS, were formed.

    Microplasma sources can also be used for gas heating. This, together with screen printed and suspended resistive heaters, was evaluated in a microthruster, showing that plasma heating is the most effective, implying fuel consumption reduction in satellite propulsion.

    In conclusion, HTCC alumina microdevices are thermally stable and could benefit several aerospace applications, especially with the complementary metallization schemes devised here.

    Future developments are expected to include both processing and design, all with the intention of sensing, actuating and surviving in high-temperature environments.

    List of papers
    1. Thermomechanical properties and performance of ceramic resonators for wireless pressure reading in high temperatures
    Open this publication in new window or tab >>Thermomechanical properties and performance of ceramic resonators for wireless pressure reading in high temperatures
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    2015 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 25, no 9, article id 095016Article in journal (Refereed) Published
    Abstract [en]

    This paper reports on the design, fabrication and thermomechanical study of ceramic LC resonators for wireless pressure reading, verified at room temperature, at 500 °C and at 1000 °C for pressures up to 2.5 bar. Five different devices were fabricated of high-temperature co-fired ceramics (HTCC) and characterized. Alumina green tape sheets were screen printed with platinum paste, micromachined, laminated and fired. The resulting samples were 21 x 19 mm2 with different thicknesses. An embedded communicator part was integrated with either a passive backing part or with a pressure-sensing element, including an 80 μm thick and 6 mm diameter diaphragm. The study includes measuring thermally and mechanically induced resonance frequency shifts, and thermally induced deformations. For the pressure sensor device, contributions from changes in the relative permittivity and from expanding air, trapped in the cavity, were extracted. The devices exhibited thermomechanical robustness during heating, regardless of the thickness of the backing. The pressure sensitivity decreased with increasing temperature from 15 050 ppm/bar at room temperature to 2400 ppm/bar at 1000°C, due to the decreasing pressure difference between the external pressure and the air pressure inside the cavity. 

    Keywords
    Wireless Reading, HTCC, Pressure sensing, Harsh Environments, Thermomechanical properties
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:uu:diva-253555 (URN)10.1088/0960-1317/25/9/095016 (DOI)000365167700023 ()
    Funder
    Knut and Alice Wallenberg Foundation
    Available from: 2015-05-29 Created: 2015-05-29 Last updated: 2018-08-03Bibliographically approved
    2. Ceramic Pressure Sensor for High Temperatures – Investigation of the Effect of Metallizationon on Read Range
    Open this publication in new window or tab >>Ceramic Pressure Sensor for High Temperatures – Investigation of the Effect of Metallizationon on Read Range
    2017 (English)In: IEEE Sensors Journal, ISSN 1530-437X, E-ISSN 1558-1748, Vol. 17, no 8, p. 2411-2421Article in journal (Refereed) Published
    Abstract [en]

    A study on the relationship between circuit metallization, made by double-layer screen printing of platinum and electroplating of silver on top of platinum, and its impact on practical read range of ceramic LC resonators for high-temperature pressure measurements is presented. Also included is the first realization of membranes by draping a graphite insert with ceramic green body sheets. As a quality factor circuit reference, two-port microstrip meander devices were positively evaluated and to study interdiffusion between silver and platinum, test samples were annealed at 500 degrees C, 700 degrees C, and 900 degrees C for 4, 36, 72, and 96 h. The LC resonators were fabricated with both metallization methods, and the practical read range at room temperature was evaluated. Pressure-sensitive membranes were characterized for pressures up to 2.5 bar at room temperature, 500 degrees C and up to 900 degrees C. Samples electroplated with silver exhibited performance equal to or better than double-layer platinum samples for up to 60 h at 500 degrees C, 20 h at 700 degrees C, and for 1 h at 900 degrees C, which was correlated with the degree of interdiffusion as determined from cross-sectional analysis. The LC resonator samples with double-layer platinum exhibited a read range of 61 mm, and the samples with platinum and silver exhibited a read range of 59 mm. The lowest sheet resistance, and, thereby, the highest read range of 86 mm, was obtained with a silver electroplated LC resonator sample after 36 h of annealing at 500 degrees C.

    Keywords
    Alternative metallization, ceramic membrane, harsh environment sensor, high temperature co-fired ceramics (HTCC), HTCC processing, LC resonator, pressure sensor, wireless reading
    National Category
    Accelerator Physics and Instrumentation Engineering and Technology
    Research subject
    Engineering Science with specialization in Microsystems Technology
    Identifiers
    urn:nbn:se:uu:diva-302852 (URN)10.1109/JSEN.2017.2671418 (DOI)000398890800016 ()
    Available from: 2016-09-11 Created: 2016-09-11 Last updated: 2018-08-03Bibliographically approved
    3. Manufacturing and characterization of a ceramic microcombustor with integrated oxygen storage and release element
    Open this publication in new window or tab >>Manufacturing and characterization of a ceramic microcombustor with integrated oxygen storage and release element
    Show others...
    2015 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 25, no 10, article id 104006Article in journal (Refereed) Published
    Abstract [en]

    A microscale ceramic high-temperature combustor with a built-in temperature sensor and source of oxygen has been designed, manufactured and characterized. The successful in situ electroplating and oxidation of copper, and the use of copper oxide as the source of oxygen were demonstrated. It was shown that residual stresses from electroplating, copper oxidation and oxide decomposition did not cause much deformation of the substrate but influenced mainly the integrity and adhesion of the metal films. The process had influence on the electrical resistances, however. Calibration of the temperature sensor and correlation with IR thermography up to 1000°C revealed a nearly linear sensor behavior. Demonstration of combustion in a vacuum chamber proved that no combustion had occurred before release of oxygen from the metal oxide resource.

    Place, publisher, year, edition, pages
    Institute of Physics (IOP), 2015
    Keywords
    isotopic analysis, HTCC, combustor, EDS, TGA, RGA, oxygen release
    National Category
    Engineering and Technology
    Research subject
    Engineering Science with specialization in Microsystems Technology
    Identifiers
    urn:nbn:se:uu:diva-264147 (URN)10.1088/0960-1317/25/10/104006 (DOI)000366827400007 ()
    Funder
    Swedish National Space Board
    Available from: 2015-10-06 Created: 2015-10-06 Last updated: 2018-08-03Bibliographically approved
    4. Pirani Microgauge Fabricated of High-Temperature Co-fired Ceramics with Integrated Platinum Wires
    Open this publication in new window or tab >>Pirani Microgauge Fabricated of High-Temperature Co-fired Ceramics with Integrated Platinum Wires
    (English)In: Sensors and Actuators A-Physical, ISSN 0924-4247, E-ISSN 1873-3069Article in journal (Refereed) Submitted
    Abstract [en]

    This paper presents the integration and pressure sensor operation of platinum bond wires in High-Temperature Co-fired alumina (HTCC). Devices were fabricated with a 50 µm diameter wire suspended across a 500 µm wide cavity in green-body state HTCC, electrically connected to screen printed alumina conductors. The substrate shrinkage during sintering to a cavity width of 400 µm causes the wire element to elevate from the cavity´s bottom surface. Resulting devices were compared with reference devices, containing screen-printed sensor elements, as Pirani gauges operated at 100 °C in constant-resistance mode, and in dynamic mode with a feeding current of 1 A in a pressure range from 10-4 Torr to atmospheric pressure. Also, devices with wire lengths between 500 and 3500 µm were operated and studied in constant-resistance and dynamic mode. Lastly, a device is demonstrated in operation at a mean temperature of 830 °C. The results include wire elements with a consistent elevation from their substrate surfaces, with irregularities along the wires. The wire devices exhibit a faster pressure response in dynamic mode than the reference devices do but operate similarly in constant-resistance mode. Increasing the wire element length shows an increasing dynamic pressure range but a decreasing maximum sensitivity. The sensitivity is retained in high temperature mode, but the dynamic range is extended from about 10 Torr to about 700 Torr.

    National Category
    Ceramics
    Research subject
    Engineering Science with specialization in Microsystems Technology
    Identifiers
    urn:nbn:se:uu:diva-356481 (URN)
    Available from: 2018-07-30 Created: 2018-07-30 Last updated: 2018-08-03
    5. Manufacturing Miniature Langmuir probes by Fusing Platinum Bond Wires
    Open this publication in new window or tab >>Manufacturing Miniature Langmuir probes by Fusing Platinum Bond Wires
    2015 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 25, no 10, article id 105012Article in journal (Refereed) Published
    Abstract [en]

    This paper reports on a novel method for manufacturing microscopic Langmuir probes with spherical tips from platinum bond wires for plasma characterization in microplasma sources by fusing. Here, the resulting endpoints, formed by droplets of a fused wire, are intended to act as a spherical Langmuir probe. For studying the fusing behavior, bond wires were wedge-bonded over a 2 mm wide slit, to emulate the final application, and fused at different currents and voltages. For electrical isolation, a set of wires were coated with a 4 µm thick layer of Parylene before they were fused. After fusing, the gap size, as well as the shape and area of the ends of the remaining stubs were measured. The yield of the process was also investigated, and the fusing event was studied using a high-speed camera for analyzing the dynamics of fusing. Four characteristic tip shapes were observed: spherical, semi-spherical, serpentine shaped and folded. The stub length leveled out at ~420µm. The fusing of the coated wires required a higher power for attaining a spherical shape. Finally, a Parylene coated bond wire was integrated into a stripline split-ring resonator (SSRR) microplasma source, and fused to form two Langmuir probes with spherical endpoints. These probes were used for measuring the I-V characteristics of a plasma generated by the SSRR. In a voltage range between -60 V and 60 V, the fused stubs exhibited the expected behavior of spherical Langmuir probes and will be considered for future integration.

    Keywords
    Langmuir probe; bond wire; fusing; microplasma source
    National Category
    Physical Sciences Engineering and Technology
    Research subject
    Engineering Science with specialization in Microsystems Technology
    Identifiers
    urn:nbn:se:uu:diva-251306 (URN)10.1088/0960-1317/25/10/105012 (DOI)000366827400028 ()
    Funder
    Swedish National Space BoardKnut and Alice Wallenberg Foundation
    Available from: 2015-04-15 Created: 2015-04-15 Last updated: 2018-08-03Bibliographically approved
    6. Effect of Resistive and Plasma Heating on the Specific Impulse of a Ceramic Cold Gas Thruster
    Open this publication in new window or tab >>Effect of Resistive and Plasma Heating on the Specific Impulse of a Ceramic Cold Gas Thruster
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    (English)In: Journal of microelectromechanical systems, ISSN 1057-7157, E-ISSN 1941-0158Article in journal (Refereed) Submitted
    Abstract [en]

    Research and development of small satellites has continued to expand over the last decades. However, propulsion systems with adequate performance have persisted to be a great challenge. In this paper, the effects of three different heaters on the specific impulse and overall thrust efficiency of a cold gas microthruster are presented. They consisted of a conventional, printed resistive thick-film element, a freely suspended wire, and a stripline split-ring resonator microplasma source and were integrated in a single device made from high-temperature co-fired ceramics (HTCC). The devices were evaluated in two setups, where the first measured thrust and the other shock cell geometry. In addition, the resistive elements were evaluated as gas temperature sensors. The microplasma source was found to provide the greatest improvement in both specific impulse and thrust efficiency, increasing the former from an un-heated level of 44 s to 55 s when heating with a power of 1.1 W. This corresponded to a thrust efficiency of 53 %. This could be compared to the results from the wire and printed heaters which were 50 s and 18 %, and 45 s and 14 %, respectively. The combined results also showed that imaging the shock cells of a plasma heated thruster was a simple and effective way to determine its performance compared to the traditional thrust balance method.

    Keywords
    Microthruster, HTCC, Resistive Heating, Plasma Heating, Specific Impulse, Shock Cells
    National Category
    Aerospace Engineering
    Research subject
    Engineering Science with specialization in Microsystems Technology
    Identifiers
    urn:nbn:se:uu:diva-356675 (URN)
    Available from: 2018-08-02 Created: 2018-08-02 Last updated: 2018-08-03
    7. On the Applicability and Military Utility of Microsystems in Military Jet Engines
    Open this publication in new window or tab >>On the Applicability and Military Utility of Microsystems in Military Jet Engines
    (English)Manuscript (preprint) (Other academic)
    Keywords
    HTCC, jet engine control, applicability, military utility
    National Category
    Aerospace Engineering
    Identifiers
    urn:nbn:se:uu:diva-356691 (URN)
    Available from: 2018-08-03 Created: 2018-08-03 Last updated: 2018-08-03
  • Public defence: 2018-09-21 10:15 ITC 2446, Uppsala
    Mukha, Timofey
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Scientific Computing. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Numerical Analysis.
    Modelling Techniques for Large-Eddy Simulation of Wall-Bounded Turbulent Flows2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Large-eddy simulation (LES) is a highly accurate turbulence modelling approach in which a wide range of spatial and temporal scales of the flow are resolved. However, LES becomes prohibitively computationally expensive when applied to wall-bounded flows at high Reynolds numbers, which are typical of many industrial applications. This is caused by the need to resolve very small, yet dynamically important flow structures found in the inner region of turbulent boundary layers (TBLs). To remove the restrictive resolution requirements, coupling LES with special models for the flow in the inner region has been proposed. The predictive accuracy of this promising approach, referred to as wall-modelled LES (WMLES), requires further analysis and validation. 

    In this work, systematic simulation campaigns of canonical wall-bounded flows have been conducted to support the development of a complete methodology for highly accurate WMLES on unstructured grids. Two novel algebraic wall-stress models are also proposed and shown to be more robust and precise than the classical approaches of the same type. 

    For turbulence simulations, it is often challenging to provide accurate conditions at the inflow boundaries of the domain. Here, a novel methodology is proposed for generating an inflow TBL using a precursor simulation of turbulent channel flow. A procedure for determining the parameters of the precursor based on the Reynolds number of the inflow TBL is given. The proposed method is robust and easy to implement, and its accuracy is demonstrated to be on par with other state-of-the-art approaches. 

    To make the above investigations possible, several software packages have been developed in the course of the work on this thesis. This includes a Python package for post-processing the flow simulation results, a Python package for inflow generation methods, and a library for WMLES based on the general-purpose software for computational fluid dynamics OpenFOAM. All three codes are publicly released under an open-source licence to facilitate their use by other research groups.

    List of papers
    1. The generation of turbulent inflow boundary conditions using precursor channel flow simulations
    Open this publication in new window or tab >>The generation of turbulent inflow boundary conditions using precursor channel flow simulations
    2017 (English)In: Computers & Fluids, ISSN 0045-7930, E-ISSN 1879-0747, Vol. 156, p. 21-33Article in journal (Refereed) Published
    National Category
    Computational Mathematics
    Identifiers
    urn:nbn:se:uu:diva-302801 (URN)10.1016/j.compfluid.2017.06.020 (DOI)000411848100003 ()
    Projects
    eSSENCE
    Available from: 2017-06-23 Created: 2016-09-09 Last updated: 2018-08-05Bibliographically approved
    2. Eddylicious: A Python package for turbulent inflow generation
    Open this publication in new window or tab >>Eddylicious: A Python package for turbulent inflow generation
    2018 (English)In: SoftwareX, ISSN 2352-7110, Vol. 7, p. 112-114Article in journal (Refereed) Published
    National Category
    Computational Mathematics
    Identifiers
    urn:nbn:se:uu:diva-302803 (URN)10.1016/j.softx.2018.04.001 (DOI)
    Available from: 2018-04-17 Created: 2016-09-09 Last updated: 2018-08-05Bibliographically approved
    3. Effect of wall-stress model and mesh-cell topology on the predictive accuracy of LES for wall-bounded flows
    Open this publication in new window or tab >>Effect of wall-stress model and mesh-cell topology on the predictive accuracy of LES for wall-bounded flows
    2018 (English)In: Proc. 7th European Conference on Computational Fluid Dynamics, European Community on Computional Methods in Applied Sciences (ECCOMAS), 2018Conference paper, Published paper (Refereed)
    Place, publisher, year, edition, pages
    European Community on Computional Methods in Applied Sciences (ECCOMAS), 2018
    National Category
    Fluid Mechanics and Acoustics Computational Mathematics
    Identifiers
    urn:nbn:se:uu:diva-356047 (URN)
    Conference
    ECFD 2018, June 11–15, Glasgow, UK
    Available from: 2018-06-12 Created: 2018-07-12 Last updated: 2018-08-05Bibliographically approved
    4. A-priori study of wall modeling in large eddy simulation
    Open this publication in new window or tab >>A-priori study of wall modeling in large eddy simulation
    2018 (English)In: Proc. 7th European Conference on Computational Fluid Dynamics, European Community on Computional Methods in Applied Sciences (ECCOMAS), 2018Conference paper, Published paper (Refereed)
    Place, publisher, year, edition, pages
    European Community on Computional Methods in Applied Sciences (ECCOMAS), 2018
    National Category
    Fluid Mechanics and Acoustics Computational Mathematics
    Identifiers
    urn:nbn:se:uu:diva-356045 (URN)
    Conference
    ECFD 2018, June 11–15, Glasgow, UK
    Available from: 2018-06-12 Created: 2018-07-12 Last updated: 2018-08-05Bibliographically approved
    5. Turbulucid: A Python package for post-processing of fluid flow simulations
    Open this publication in new window or tab >>Turbulucid: A Python package for post-processing of fluid flow simulations
    2018 (English)In: Journal of Open Research Software, E-ISSN 2049-9647Article in journal (Other academic) Submitted
    National Category
    Computational Mathematics
    Identifiers
    urn:nbn:se:uu:diva-356438 (URN)
    Available from: 2018-07-25 Created: 2018-07-27 Last updated: 2018-08-05Bibliographically approved
    6. A library for wall-modelled large-eddy simulation based on OpenFOAM technology
    Open this publication in new window or tab >>A library for wall-modelled large-eddy simulation based on OpenFOAM technology
    2018 (English)In: Computer Physics Communications, ISSN 0010-4655, E-ISSN 1879-2944Article in journal (Other academic) Submitted
    National Category
    Fluid Mechanics and Acoustics Computational Mathematics
    Identifiers
    urn:nbn:se:uu:diva-356462 (URN)
    Available from: 2018-07-31 Created: 2018-07-27 Last updated: 2018-08-05Bibliographically approved
  • Public defence: 2018-09-21 13:00 Polhemsalen, 10134, Ångströmslaboratoriet, Uppsala
    Alghamdi, Azza
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics.
    Approximation of pluricomplex Green functions: A probabilistic approach2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This PhD thesis focuses on probabilistic methods of approximation of pluricomplex Green functions and is based on four papers.

    The thesis begins with a general introduction to the use of pluricomplex Green functions in multidimensional complex analysis and a review of their main properties. This is followed by short description of the main results obtained in the enclosed papers.

    In Paper I, we study properties of the metric space of pluriregular sets, that is zero sets of continuous pluricomplex Green functions. The best understood non-trivial examples of such sets are composite Julia sets, obtained by iteration of finite families of polynomial mappings in several complex variables. We prove that the so-called chaos game is applicable in the case of such sets. We also visualize some composite Julia sets using escape time functions and Monte Carlo simulation.

    In Paper II, we extend results in Paper I to the case of infinite compact families of proper polynomials mappings. With composition as the semigroup operation, we generate families of infinite iterated function systems with compact attractors. We show that such attractors can be approximated probabilistically in a manner of the classic chaos game.

    In Paper III, we study numerical approximation and visualisation of pluricomplex Green functions based on the Monte-Carlo integration. Unlike alternative methods that rely on locating a sequence of carefully chosen finite sets of points satisfying some optimal conditions for approximation purposes, our approach is simpler and more direct by relying on generation of pseudorandom points. We examine numerically the errors of approximation for some simple geometric shapes for which the pluricomplex Green functions are known. If the pluricomplex Green functions are not known, the errors in Monte Carlo integration can be expressed with the aid of statistics in terms of confidence intervals.

    Finally, in Paper IV, we study how perturbations of an orthonomalization procedure influence the resulting approximate Bergman functions. To this end we consider the concept of near orthonormality of a finite set of vectors in an inner product space, understood as closeness of the Gram matrix of those vectors to the identity matrix. We provide estimates for the errors resulting from using nearly orthogonal bases instead of orthogonal ones. The motivation for this work comes from Paper III: when Gram matrices are calculated via Monte Carlo integration, the outcomes of standard orthogonalisation algorithms are nearly orthonormal bases.

    List of papers
    1. Probabilistic approximation of partly filled-in composite Julia sets
    Open this publication in new window or tab >>Probabilistic approximation of partly filled-in composite Julia sets
    2017 (English)In: Annales Polonici Mathematici, ISSN 0066-2216, E-ISSN 1730-6272, Vol. 119, no 3, p. 203-220Article in journal (Refereed) Published
    Abstract [en]

    We study properties of the metric space of pluriregular sets and of contractions on that space induced by finite families of proper polynomial mappings of several complex variables. In particular, we show that closed balls in the space of pluriregular sets do not have to be compact and we give a simple proof of applicability of the so-called chaos game in the case of composite Julia sets. Part of the construction of those sets also leads to a computationally viable approximation by simpler sets based on Monte-Carlo simulation.

    Keywords
    composite Julia sets, pluricomplex Green functions, iterated function system, the chaos game, complex dynamics, Monte-Carlo simulation
    National Category
    Mathematics
    Identifiers
    urn:nbn:se:uu:diva-339527 (URN)10.4064/ap4100-8-2017 (DOI)000417986400002 ()
    Available from: 2018-01-22 Created: 2018-01-22 Last updated: 2018-07-06Bibliographically approved
    2. Attractors of compactly generated semigroups of regular polynomial mappings.
    Open this publication in new window or tab >>Attractors of compactly generated semigroups of regular polynomial mappings.
    (English)Manuscript (preprint) (Other academic)
    Keywords
    Julia sets, pluricomplex Green function, iterated function systems.
    National Category
    Mathematical Analysis
    Identifiers
    urn:nbn:se:uu:diva-355806 (URN)
    Available from: 2018-07-05 Created: 2018-07-05 Last updated: 2018-07-06
    3. Approximation of pluricomplex Green functions based on Monte Carlo integration
    Open this publication in new window or tab >>Approximation of pluricomplex Green functions based on Monte Carlo integration
    (English)Manuscript (preprint) (Other academic)
    Keywords
    Pluricomplex Green functions, pluriregular sets, Bernstein-Markov property, orthogonal polynomials, Monte Carlo simulation
    National Category
    Computational Mathematics
    Research subject
    Mathematics
    Identifiers
    urn:nbn:se:uu:diva-355808 (URN)
    Available from: 2018-07-05 Created: 2018-07-05 Last updated: 2018-07-06
    4. Bergman Functions and Nearly Orthonormal Polynomials
    Open this publication in new window or tab >>Bergman Functions and Nearly Orthonormal Polynomials
    (English)Manuscript (preprint) (Other academic)
    Keywords
    Bergman function, nearly orthonormal polynomials, orthogonal polynomials, Monte Carlo simulation.
    National Category
    Mathematical Analysis
    Identifiers
    urn:nbn:se:uu:diva-355809 (URN)
    Available from: 2018-07-05 Created: 2018-07-05 Last updated: 2018-07-06
  • Public defence: 2018-09-21 13:00 B22, BMC, Uppsala
    Cao, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Exposure to xenobiotic chemicals disrupts metabolism, rhythmicity and cell proliferation in Drosophila melanogaster2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Most species are constantly exposed to xenobiotic chemicals through multiple routes. Among all categories of xenobiotics, phthalates and bisphenols are two of the most widely used plasticizers and can be found in polyvinyl chloride (PVC) materials, medical devices and even drinking water. In paper I, we found that bis-(2-ethylhexyl) phthalate (DEHP) exposure caused a significant decrease in circulating carbohydrates and insulin-related genes. The Multidrug-Resistance like Protein 1 (MRP1, MRP in Drosophila) belongs to the ATP-binding cassette transporter family, and previous studies revealed the importance of MRP1 for transporting xenobiotics. However, the function of MRP1 in metabolism and other biological processes is still unclear. Therefore, in paper II, we showed that knocking down MRP expression in Malpighian tubules, the physiological equivalence of the vertebrate kidney, led to disrupted lipid homeostasis and oxidative resistance. In paper III and IV, we initially used whole transcriptome sequencing to assess the genetic interferences of exposure to Dibutyl Phthalate (DBP) and Bisphenol A Diglycidyl Ether (BADGE). The reproductive and developmental disruptions of DBP had been reported in many studies. However, the mechanism is still unclear. In paper III, we observed that DBP interfered with neuronal systems associated circadian genes, including in vrille (vri, human NFIL3), timeless (tim, human TIMELESS), period (per, human PER3) and Pigment-dispersing factor (Pdf). Furthermore, we demonstrated that the evolutionarily conserved gene, Hormone receptor-like in 38 (Hr38, human NR4A2) was involved in responding to DBP and regulated Pdf expression as a consequence. In paper IV, BADGE, a BPA-substitute, was tested for its disruptive effects on Drosophila. Based on the transcriptome sequencing, we found that several mitotic genes, including string (stg, human CDC25A), Cyclin B (CycB, human CCNB1), Cyclin E (CycE, human CCNE1), and pan gu (png, human NEK11), had detectable overexpression by BADGE exposure. Developmental exposure to BADGE induced a large increase of hemocytes in fly 3rd instar larvae, while it did not damage the morphological structure of lymph gland and blood circulation. To summarize, our studies describe the potential disruptions of the industrial xenobiotics and provide the mechanistic hints for future investigations.

    List of papers
    1. Bis-(2-ethylhexyl) Phthalate Increases Insulin Expression and Lipid Levels in Drosophila melanogaster
    Open this publication in new window or tab >>Bis-(2-ethylhexyl) Phthalate Increases Insulin Expression and Lipid Levels in Drosophila melanogaster
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    2016 (English)In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 119, no 3, p. 309-316Article in journal (Refereed) Published
    Abstract [en]

    Bis-(2-ethylhexyl) phthalate (DEHP) is one of the most widely used plasticizers, and human beings are exposed to DEHP via polyvinyl chloride (PVC) materials, medical equipment and even drinking water. While DEHP has been implicated to influence metabolism and endocrine functions, important questions remain about the molecular mechanisms of these effects. We employed the model organism Drosophila melanogaster and examined physiological, molecular and behavioural effects from DEHP-contaminated food. We found that DEHP, at levels comparable to human exposure, made male flies more resistant to starvation and increased lipid levels, while decreasing circulating carbohydrates. Moreover, DEHP-fed male flies had higher expression levels of an insulin-like peptide known to regulate metabolism, as well as the insulin receptor. Our results suggest that long-term DEHP feeding may induce diabetes-like dysfunctions. These findings provide a molecular background of how DEHP may have detrimental effects on metabolic functions.

    National Category
    Pharmacology and Toxicology
    Identifiers
    urn:nbn:se:uu:diva-303019 (URN)10.1111/bcpt.12587 (DOI)000380889500011 ()27009472 (PubMedID)
    External cooperation:
    Funder
    Swedish Research Council
    Available from: 2016-09-14 Created: 2016-09-14 Last updated: 2018-07-31Bibliographically approved
    2. Multidrug-Resistance like Protein 1 activity in Malpighian tubules regulates lipid homeostasis in Drosophila
    Open this publication in new window or tab >>Multidrug-Resistance like Protein 1 activity in Malpighian tubules regulates lipid homeostasis in Drosophila
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Multidrug-Resistance like Proteins (MRPs) are ubiquitously expressed essential transporters required for many biological processes. Previous studies revealed that MRPs are pivotal for transporting endo- and xenobiotics, conferring resistance to anti-cancer agents and contributing to clearance of oxidative products. Nonetheless, their functions in other biological processes are still unclear. In our investigation, we suppress the expression of Drosophila Multidrug resistance like Protein 1 (MRP) in Malpighian tubules, the functional equivalent to the human kidney, and find this is sufficient to cause abnormal lipid accumulation, as well as disrupt normal feeding patterns. In addition, we suggest that the elevation of lipid contents may be a result of increasing Hr96 (homolog of human Pregnane X receptor) expression, which is known to play a role in detoxification and lipid metabolism processes. Finally, we validate that Malpighian tubules-specific MRP deficiency increases oxidative resistance in fruit flies. In summary, our results demonstrate that inadequate MRP expression in Malpighian tubules can lead to disrupted lipid homeostasis and feeding behavior. However, it may also elevate the oxidative resistance of the flies.

    National Category
    Biochemistry and Molecular Biology Genetics
    Identifiers
    urn:nbn:se:uu:diva-356540 (URN)
    Available from: 2018-07-31 Created: 2018-07-31 Last updated: 2018-07-31
    3. Dibutyl phthalate exposure disrupts conserved circadian rhythm signaling systems in Drosophila
    Open this publication in new window or tab >>Dibutyl phthalate exposure disrupts conserved circadian rhythm signaling systems in Drosophila
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Due to their common use as industrial plasticizers, agents in cosmetics and inclusion in skin care products, people are constantly exposed to phthalate xenobiotics. Although much research has focused on their ability to disrupt endocrine signaling, leading to developmental, reproductive and metabolic defects, how phthalates interfere with these biological functions is still unclear. Using whole transcriptome analysis, we demonstrate that exposing the genetically-tractable model system Drosophila melanogaster to the xenobiotic Dibutyl Pthalate (DBP) throughout development interferes with neuronal systems associated with vision and circadian rhythm. Of note, while DBP did not influence with eye development, it inhibited the expression of signaling systems regulating vision, including Rhodopsin 5 (Rh5) and Rhodopsin 6 (Rh6), two light-sensing G-protein coupled receptors involved in the daily resetting of circadian rhythm. Furthermore, DBP influenced the expression of genes central to circadian rhythm regulation, including vrille (vri, human NFIL3), timeless (tim, human TIMELESS), period (per, human PER3) and Pigment-dispersing factor (Pdf). Finally, we demonstrate that DBP disrupts circadian rhythm by interacting with the evolutionarily conserved nuclear receptor Hormone receptor-like in 38 (Hr38, human NR4A2), which in turn regulates Pdf expression. Our results are the first to provide comprehensive evidence that DBP interferes with the circadian rhythm system.

    National Category
    Neurosciences Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-356541 (URN)
    Available from: 2018-07-31 Created: 2018-07-31 Last updated: 2018-07-31
    4. Developmental bisphenol A diglycidyl ether (BADGE) exposure causes cell over-proliferation in Drosophila
    Open this publication in new window or tab >>Developmental bisphenol A diglycidyl ether (BADGE) exposure causes cell over-proliferation in Drosophila
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Since the estrogenic activity of bisphenol A had been reported, the industry started to find a proper replacement. Bisphenol A diglycidyl ether (BADGE) is one of the derivatives of BPA which is used widely in epoxy resin manufactory. Recently, some studies have demonstrated the adverse effects of BADGE on reproduction and development. However, the knowledge of BADGE is still scarce. Because of its hydrolytic property, BADGE is usually detected at a low level in commodities and the influences seem to be underestimated. In our study, we use the whole transcriptome sequencing to assess the effects of developmental BADGE exposure on Drosophila melanogaster. Notably, the genes related to cell proliferation are significantly affected by BADGE exposure. More detailed, a group of mitotic genes, including string (stg, human CDC25A), Cyclin B (CycB, human CCNB1), Cyclin E (CycE, human CCNE1), and pan gu (png, human NEK11), are detectable overexpressed. Phenotypically, we observe that BADGE induces severe hemocytes over-proliferation in the 3rd instar larvae, but does not cause morphological damage of the larval lymph gland and blood circulation. In conclusion, we provide evidence to show the carcinogenic potential of BADGE and raise the concern of better understanding of xenobiotics. 

    National Category
    Biochemistry and Molecular Biology Pharmacology and Toxicology
    Identifiers
    urn:nbn:se:uu:diva-356544 (URN)
    Available from: 2018-07-31 Created: 2018-07-31 Last updated: 2018-07-31
  • Public defence: 2018-09-21 13:00 Auditorium Minus, Uppsala
    Molin, Carl Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    New Biomarkers for Neuromuscular Function and Myasthenia Gravis2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Myasthenia gravis (MG) is an autoimmune disorder, which is caused by autoantibodies against the acetylcholine receptor (AChR). The cardinal symptom is muscle fatigue, which can range from slight weakness of the extraocular muscles (causing droopy eyelids or double vision), to paralysis of the respiratory muscles. Antibodies towards other muscle proteins have been discovered, and MG is now considered a very heterogeneous disease with several subgroups. The severity of symptoms in MG patients is often fluctuating, and the antibody titers do not correlate with disease severity or treatment response. Therefore, there is a great need for reliable biomarkers in MG, both for assessing neuromuscular function, but also for clinical aspects such as disease progression and subgrouping.

    In Study I, the use of compound motor action potential (CMAP) as a biomarker for muscle status was examined in trained and untrained individuals. We found that trained individuals have a higher CMAP in proximal muscles, and the CMAP value in the biceps correlate with muscle strength in these individuals, indicating that CMAP can be used as a biomarker for muscle function. In Study II, subjects from study I were examined with ultrasound to assess the effect of high-resistance strength training (HRST) on peripheral nerves, and to compare muscle thickness. We did not find a difference in nerve cross-sectional area between the two groups. Trained individuals had thicker biceps muscles. The results from study I and II has led to CMAP and ultrasound being used to evaluate the result of physical exercise as an intervention in MG patients.

    In Study III, the expression of inflammatory proteins in the sera of MG patients was compared to healthy controls, in search for possible biomarkers. We found eleven proteins to be elevated, which provide new insight to the inflammatory response in MG and have possible functions as new biomarkers of inflammatory activity.

    In Study IV, the effect of thymectomy on the potential microRNA MG biomarkers miR-150-5p and miR-21-5p was examined. A decrease in miR-150-5p was seen 24 months after thymectomy, which further validate the use of miR-150-5p as a disease-specific biomarker for clinical outcome in AChR positive MG patients.

    List of papers
    1. Compound Motor Action Potential: Electrophysiological Marker for Muscle Training
    Open this publication in new window or tab >>Compound Motor Action Potential: Electrophysiological Marker for Muscle Training
    2016 (English)In: Journal of clinical neurophysiology, ISSN 0736-0258, E-ISSN 1537-1603, Vol. 33, no 4, p. 340-345Article in journal (Refereed) Published
    Abstract [en]

    Purpose:The compound motor action potential (CMAP) represents the summated action potentials of all stimulated motor endplates and potentially reflects muscle hypertrophy and increased muscle contractions. Since electrophysiological biomarkers for high-resistance strength training are lacking, the authors evaluated whether the CMAP of distal and proximal muscles differs between healthy men and women who perform and do not perform high-resistance muscle training.Methods:Motor neurography was performed with stimulation of the median nerve (recording of abductor pollicis brevis muscle), peroneal nerve (recording of extensor digitorum brevis muscle), femoral nerve (recording of rectus femoris muscle) and musculocutaneous nerve (recording of biceps brachii muscle), and isometric muscle strength, measured with a hand-held dynamometer, were performed on 83 healthy subjects (52 women).Results:Trained women had 25% higher CMAP amplitude in the rectus femoris muscle than untrained women (P < 0.001), whereas CMAP amplitude in the trained male cohort was 25% higher in the biceps (P = 0.005) compared with untrained men. In the trained group, CMAP amplitude in the biceps correlated with isometric muscle strength (R = 0.30; P = 0.046).Conclusions:The authors' propose the CMAP as an objective neurophysiological parameter for proximal muscle status and training effects in future interventional studies of patients with neuromuscular disorders.

    Keywords
    Compound motor action potential, CMAP, Electrophysiological marker, Muscle training, Isometric muscle strength
    National Category
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-304429 (URN)10.1097/WNP.0000000000000252 (DOI)000382523700013 ()26744834 (PubMedID)
    Funder
    Swedish Society of Medicine, SLS-330141Swedish Research Council, VR-523-2014-2048
    Available from: 2016-10-05 Created: 2016-10-05 Last updated: 2018-08-01Bibliographically approved
    2. High-resistance strength training does not affect nerve cross sectional area – An ultrasound study
    Open this publication in new window or tab >>High-resistance strength training does not affect nerve cross sectional area – An ultrasound study
    2017 (English)In: Clinical Neurophysiology Practice, ISSN 2467-981X, Vol. 2, p. 163-169Article in journal (Refereed) Published
    Abstract [en]

    ObjectiveThe aim was to study the effect of high-resistance strength training on peripheral nerve morphology, by examining properties of peripheral nerves as well as distal and proximal muscle thickness with ultrasound, comparing healthy individuals who perform and do not perform high-resistance strength training.

    MethodsNeuromuscular ultrasound was used to examine cross sectional area (CSA) of the median and musculocutaneous nerves, and muscle thickness of the abductor pollicis brevis muscle, biceps brachii muscle, quadriceps muscle and extensor digitorum brevis muscle, in 44 healthy individuals, of whom 22 performed regular high-resistance strength training.

    ResultsNo difference in nerve CSA was found between trained and untrained individuals although trained individuals had thicker biceps brachii muscles. The CSA of the median nerve in the forearm correlated with participants’ height and was significantly larger in men than women.

    ConclusionsIn this cohort, CSA of the median and musculocutaneous nerves was not affected by strength training, whereas gender had a prominent effect both on CSA and muscle thickness.

    SignificanceThis is the first study to examine the effect of high-resistance strength training on peripheral nerves with neuromuscular ultrasound.

    Keywords
    High-resistance strength training, Muscle thickness, Reference values, Nerve remodeling, Nerve cross sectional area
    National Category
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-356114 (URN)
    Available from: 2018-07-14 Created: 2018-07-14 Last updated: 2018-08-01
    3. Profile of upregulated inflammatory proteins in sera of Myasthenia Gravis patients.
    Open this publication in new window or tab >>Profile of upregulated inflammatory proteins in sera of Myasthenia Gravis patients.
    2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 39716Article in journal (Refereed) Published
    Abstract [en]

    This study describes specific patterns of elevated inflammatory proteins in clinical subtypes of myasthenia gravis (MG) patients. MG is a chronic, autoimmune neuromuscular disease with antibodies most commonly targeting the acetylcholine receptors (AChRab), which causes fluctuating skeletal muscle fatigue. MG pathophysiology includes a strong component of inflammation, and a large proportion of patients with early onset MG additionally present thymus hyperplasia. Due to the fluctuating nature and heterogeneity of the disease, there is a great need for objective biomarkers as well as novel potential inflammatory targets. We examined the sera of 45 MG patients (40 AChRab seropositive and 5 AChRab seronegative), investigating 92 proteins associated with inflammation. Eleven of the analysed proteins were significantly elevated compared to healthy controls, out of which the three most significant were: matrix metalloproteinase 10 (MMP-10; p = 0.0004), transforming growth factor alpha (TGF-α; p = 0.0017) and extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE) (also known as protein S100-A12; p = 0.0054). Further, levels of MMP-10, C-X-C motif ligand 1 (CXCL1) and brain derived neurotrophic factor (BDNF) differed between early and late onset MG. These novel targets provide valuable additional insight into the systemic inflammatory response in MG.

    National Category
    Medical and Health Sciences Neurology
    Research subject
    Immunology; Neurology
    Identifiers
    urn:nbn:se:uu:diva-314679 (URN)10.1038/srep39716 (DOI)000391148300002 ()28045063 (PubMedID)
    Funder
    Swedish Research Council, 2014-02048Swedish Research Council, 2014-07603Swedish Society of Medicine, SLS-499271Futurum - Academy for Health and Care, Jönköping County Council, Sweden, 520281
    Available from: 2017-02-04 Created: 2017-02-04 Last updated: 2018-08-01Bibliographically approved
    4. Thymectomy lowers the myasthenia gravis biomarker miR-150-5p.
    Open this publication in new window or tab >>Thymectomy lowers the myasthenia gravis biomarker miR-150-5p.
    Show others...
    2018 (English)In: Neurology(R) neuroimmunology & neuroinflammation, ISSN 2332-7812, Vol. 5, no 3, article id e450Article in journal (Refereed) Published
    Abstract [en]

    Objective: The aim of the study was to analyze the effect of thymectomy on the proposed disease-specific microRNA (miRNA) biomarkers miR-150-5p and miR-21-5p in patients from the prospective randomized trial of thymectomy in myasthenia gravis (MGTX trial) and to evaluate the longitudinal changes in clinical patterns compared with these miRNA levels.

    Methods: Serum samples were obtained from 80 patients with MG who were included in the MGTX trial. Thirty-eight patients were randomized to thymectomy plus prednisone treatment, and 42 patients were randomized to prednisone treatment. Serum samples were analyzed for the expression of miR-150-5p and miR-21-5p, with quantitative reverse transcriptase PCR at baseline and at 12, 24, and 36 months after randomization. The inclusion criteria for participation in the MGTX trial were age 18-65 years, generalized myasthenia gravis (Myasthenia Gravis Foundation of America Class II-IV), disease duration of less than 5 years, and seropositivity for acetylcholine receptor antibodies (AChR+).

    Results: Patients treated with thymectomy had lower levels of miR-150-5p at 24 months, both compared with baseline values (p = 0.0011) and the prednisone group (p = 0.04). No change in miRNA levels was found in the prednisone group. Levels of miR-21-5p displayed a negative correlation with the prednisone dose within the prednisone-only group (p ≤ 0.001).

    Conclusions: Thymectomy lowers the levels of the proposed biomarker miR-150-5p, which strengthens its position as a potential disease-specific biomarker for AChR+ MG.

    National Category
    Neurology
    Research subject
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-356113 (URN)10.1212/NXI.0000000000000450 (DOI)29511707 (PubMedID)
    Available from: 2018-07-14 Created: 2018-07-14 Last updated: 2018-08-01
  • Public defence: 2018-09-21 13:15 Häggsalen, Uppsala
    Remouit, Flore
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Electricity.
    Automation of underwater operations on wave energy converters using remotely operated vehicles2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the last fifteen years, the Division of Electricity at Uppsala University has been developing a wave energy converter (WEC) concept. The concept is based on a point-absorbing buoy with a directly driven linear generator placed on the seabed. Several units are connected to a marine substation, whose role is to collect and smooth the power absorbed from the waves and then bring it to the shore through one single cable.

    A big challenge in the project is to reduce the costs related to the deployment and maintenance of the WECs and substation. Currently, those operations are performed by divers, which is costly and entail considerable risks. A possibility is to replace divers with automated solutions using small robots called remotely operated vehicles (ROVs). This PhD thesis proposes and analyses a method for deployment and maintenance of underwater devices with no use of diving operations.

    Existing ROVs need additional modules and equipment in order to carry out operations with the required force and precision. Typical missions are inspection, shackles or slings removal, valve closing, and cable connection. The latter demands especially high precision in the positioning: 5 mm in distance and 5◦ in heading angle. In addition, this operation involves forces up to 200 N. This combination power-precision is not reached by existing ROVs. This PhD thesis presents a positioning system for underwater robot to enable autonomous positioning of the vehicle before cable connection.

    The positioning system is composed of two green lasers and a monocular camera, and is based on image processing. Experimental results from laboratory testing show that the mean absolute error in distance measurement is as low as 6 mm at 0.7 m from the target, whereas the heading is minimized to 2◦. The computational time for the image processing is 13.6 ms per image, meaning the possibility of a 30 Hz measurement system. Used together with a closed-loop path-following unit, this positioning system can support autonomous docking. This PhD thesis presents the model of an autopilot and results from docking simulations, showing the performance of the positioning system used in closed-loop.

    List of papers
    1. Wave Energy Research at Uppsala University and The Lysekil Research Site, Sweden: A Status Update
    Open this publication in new window or tab >>Wave Energy Research at Uppsala University and The Lysekil Research Site, Sweden: A Status Update
    Show others...
    2015 (English)Conference paper, Published paper (Refereed)
    Abstract [en]

    This paper provides a summarized status update ofthe Lysekil wave power project. The Lysekil project is coordinatedby the Div. of Electricity, Uppsala University since 2002, with theobjective to develop full-scale wave power converters (WEC). Theconcept is based on a linear synchronous generator (anchored tothe seabed) driven by a heaving point absorber. This WEC has nogearbox or other mechanical or hydraulic conversion systems,resulting in a simpler and robust power plant. Since 2006, 12 suchWECs have been build and tested at the research site located atthe west coast of Sweden. The last update includes a new andextended project permit, deployment of a new marine substation,tests of several concepts of heaving buoys, grid connection,improved measuring station, improved modelling of wave powerfarms, implementation of remote operated vehicles forunderwater cable connection, and comprehensive environmentalmonitoring studies.

    Keywords
    Wave energy, point absorber, experiments, arrays, generators, ROVs
    National Category
    Electrical Engineering, Electronic Engineering, Information Engineering Ocean and River Engineering
    Identifiers
    urn:nbn:se:uu:diva-265218 (URN)
    Conference
    Proceedings of the 11th European Wave and Tidal Energy Conference. Nantes, France, September 2015
    Available from: 2015-10-26 Created: 2015-10-26 Last updated: 2018-08-07Bibliographically approved
    2. Variability Assessment and Forecasting of Renewables: A Review for Solar, Wind, Wave and Tidal Resources
    Open this publication in new window or tab >>Variability Assessment and Forecasting of Renewables: A Review for Solar, Wind, Wave and Tidal Resources
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    2015 (English)In: Renewable & sustainable energy reviews, ISSN 1364-0321, E-ISSN 1879-0690, Vol. 44, p. 356-375Article in journal (Refereed) Published
    National Category
    Energy Engineering Engineering and Technology
    Research subject
    Engineering Science with specialization in Science of Electricity; Engineering Science with specialization in Solid State Physics
    Identifiers
    urn:nbn:se:uu:diva-225870 (URN)10.1016/j.rser.2014.12.019 (DOI)000351324300025 ()
    Available from: 2014-06-09 Created: 2014-06-09 Last updated: 2018-08-01
    3. Automation of subsea connections for clusters of wave energy converters
    Open this publication in new window or tab >>Automation of subsea connections for clusters of wave energy converters
    Show others...
    2015 (English)In: The Proceedings of the Twenty-fifth (2015) International Ocean and Polar Engineering Conference, 2015Conference paper, Published paper (Refereed)
    Abstract [en]

    To make wave power a viable energy source, large clusters of wave energy converters should be deployed. For most of the farms the output power of the WECs should be aggregated in a marine substation and then transmitted to the grid. The need for cost effective underwater cable connection operations is one of the main issues in offshore operations. Underwater connections can be conducted with wet- or dry-mateable connectors, performed by divers or ROVs. Although there are existing solutions used by the oil and gas industry that could be employed, the capital expenditure needed is not compatible with the offshore renewable energy industry.

     

    The objective of this research is to decrease costs and minimize working hazards associated with sub-sea work when performing these underwater electrical connections. This article presents a solution using small ROV’s instead of divers to execute the task. The main idea is to perform the connection underwater, but using dry-mateable connectors. A solution to make this possible is to install air pockets at the substation enclosing the connectors. These boxes are meant to be filled with air and hence create a dry environment in which to perform the connections. This is achieved with help of two tools. First a docking system allows the operator to fix the ROV at the substation before doing the connection. Then a gripper tool added to the ROV grasps the cable and connects it to the substation in the air pocket. The procedure and design of this low-cost solution are described, and the different prototypes that have been tested for offshore operation are also shown.

    Keywords
    Wave energy, ROV, subsea connection, gripper, substation
    National Category
    Engineering and Technology
    Research subject
    Engineering Science with specialization in Science of Electricity
    Identifiers
    urn:nbn:se:uu:diva-259835 (URN)978-1-880653-89-0 (ISBN)
    Conference
    The Twenty-fifth International Ocean and Polar Engineering Conference, June 21-26, Kona, Hawaii, USA
    Projects
    Lysekil project
    Available from: 2015-08-12 Created: 2015-08-12 Last updated: 2018-08-01Bibliographically approved
    4. Review of Electrical Connectors for Underwater Applications
    Open this publication in new window or tab >>Review of Electrical Connectors for Underwater Applications
    2017 (English)In: IEEE Journal of Oceanic Engineering, ISSN 0364-9059, E-ISSN 1558-1691Article in journal (Refereed) Accepted
    Abstract [en]

    The history of underwater electrical connectors is relativelynew: In 1858, the first transatlantic communication cable was created. Sincethen, the need for subsea electrical connectors has been growing very fastin the offshore industry. Today numerous companies offer a large choiceof underwater connectors and assemblies, and it can be intricate to distinguish the different technologies employed for each of them. However theuse, deployment, maintenance, and lifetime of any subsea equipment, froma simple sonar to a wave energy converter, relies on its connectors. Hencethe design of an underwater electrical connector is to be carefully lookedat, and especially for tailor-made applications that have more specific requirements. To produce a good connector, it is necessary to account for thermal, electrical, and mechanical properties, as well as to determine thebest materials that should be used for the application. Finally, connector issues go hand in hand with the deployment and operation of any electrical equipment, and it is of interest to review the different techniques for cable connection, as well as the challenges related to cable layout. Those challenges can be of different nature, but they should all be taken into account for any subsea connection.

    Keywords
    Cable, connector, electrical, review, subsea, underwater
    National Category
    Engineering and Technology Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:uu:diva-334294 (URN)10.1109/JOE.2017.2745598 (DOI)
    Available from: 2017-11-22 Created: 2017-11-22 Last updated: 2018-08-01
    5. Deployment and Maintenance of Wave Energy Converters at the Lysekil Research Site: A Comparative Study on the Use of Divers and Remotely-Operated Vehicles
    Open this publication in new window or tab >>Deployment and Maintenance of Wave Energy Converters at the Lysekil Research Site: A Comparative Study on the Use of Divers and Remotely-Operated Vehicles
    Show others...
    2018 (English)In: Journal of Marine Science and Engineering, E-ISSN 2077-1312, Vol. 6, no 2, article id 39Article in journal (Refereed) Published
    Abstract [en]

    Ocean renewable technologies have been rapidly developing over the past years. However, current high installation, operation, maintenance, and decommissioning costs are hindering these offshore technologies to reach a commercialization stage. In this paper we focus on the use of divers and remotely-operated vehicles during the installation and monitoring phase of wave energy converters. Methods and results are based on the wave energy converter system developed by Uppsala University, and our experience in offshore deployments obtained during the past eleven years. The complexity of underwater operations, carried out by either divers or remotely-operated vehicles, is emphasized. Three methods for the deployment of wave energy converters are economically and technically analyzed and compared: one using divers alone, a fully-automated approach using remotely-operated vehicles, and an intermediate approach, involving both divers and underwater vehicles. The monitoring of wave energy converters by robots is also studied, both in terms of costs and technical challenges. The results show that choosing an autonomous deployment method is more advantageous than a diver-assisted method in terms of operational time, but that numerous factors prevent the wide application of robotized operations. Technical solutions are presented to enable the use of remotely-operated vehicles instead of divers in ocean renewable technology operations. Economically, it is more efficient to use divers than autonomous vehicles for the deployment of six or fewer wave energy converters. From seven devices, remotely-operated vehicles become advantageous.

    National Category
    Marine Engineering
    Identifiers
    urn:nbn:se:uu:diva-348816 (URN)10.3390/jmse6020039 (DOI)000436558500011 ()
    Funder
    StandUpEU, FP7, Seventh Framework Programme, 607656Swedish Energy Agency
    Available from: 2018-04-17 Created: 2018-04-17 Last updated: 2018-09-17Bibliographically approved
    6. Optical System for Underwater Positioning of Observation Class Remotely Operated Vehicle
    Open this publication in new window or tab >>Optical System for Underwater Positioning of Observation Class Remotely Operated Vehicle
    2016 (English)Conference paper, Published paper (Refereed)
    Abstract [en]

    To make wave power a viable energy source, large clusters of wave energy converters (WECs) will be deployed into large farms. For most of these farms, the output power of the WECs will be aggregated in a marine substation and then transmitted to the grid. The need for cost effective underwater connection operations is one of the main challenges with this kind of offshore installation. Our research is related to underwater connection with help of Observation Class Remotely Operated Vehicles (OC ROVs). The main idea is to use a docking system in order for the small and light ROV to perform the connection, using the reaction force from its docking point instead of the motors propulsion, the latter being too little. This docking operation has to be very accurate and needs both an autopilot and a good positioning tool. In this paper we present an optical positioning system made of green lasers that together with the ROV’s camera measure the distances to the docking point. This is obtained by tracking the laser beams on the images captured from the camera and using triangulation of the points extracted. The tool has been implemented into an OCROV and tested in a tank.

    Keywords
    ROV, positioning, underwater connections, wave energy converters
    National Category
    Other Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:uu:diva-302641 (URN)
    External cooperation:
    Conference
    3rd Asian Wave and Tidal Energy Conference, AWTEC, Singapore
    Available from: 2016-09-07 Created: 2016-09-07 Last updated: 2018-08-01Bibliographically approved
    7. Laser-based relative positioning system for underwater remotely operated vehicle
    Open this publication in new window or tab >>Laser-based relative positioning system for underwater remotely operated vehicle
    (English)In: IEEE Journal of Oceanic Engineering, ISSN 0364-9059, E-ISSN 1558-1691Article in journal (Refereed) Submitted
    Abstract [en]

    This paper addresses the development, testing and verification of a relative positioning system for underwater vehicles. The position and orientation of the vehicle relative to a plane based target is estimated through a laser-based optical system. The sensor package consists of two green line-lasers and a camera. The image processing algorithm is built on the probabilistic Hough transform and a light but robust filtering method. This decreases the computational time to 13.6 ms per image. Experimental results from laboratory testing show that the mean absolute error in distance measurement is as low as 6 mm at 0.7 m from the target, whereas in heading is 2°.

    Keywords
    Optical positioning, Green lasers, Image processing, Relative positioning, Remotely operated vehicle
    National Category
    Robotics
    Identifiers
    urn:nbn:se:uu:diva-356535 (URN)
    Available from: 2018-07-31 Created: 2018-07-31 Last updated: 2018-08-07
    8. Autonomous docking based on optical positioning system for remotely operated vehicle
    Open this publication in new window or tab >>Autonomous docking based on optical positioning system for remotely operated vehicle
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Underwater docking is of high interest as it could be used to chargeunderwater robots while on a mission, thus extending their range of ac-tion, or to upload data without retrieving the vehicle, thus increasing itsmemory capacity. In this paper, the purpose of the docking system is toperform cable connections using remotely operated vehicles. The modelof an autopilot for autonomous docking is presented and the performancesof its components are analysed. This autopilot is based on measurementsfrom an optical positioning system which localizes the vehicle based onfeature detection from image processing. It shows that this positioning system could be integrated to the modelled autopilot and used in closed-loop for autonomous docking.

    Keywords
    Optical positioning; closed-loop; Image processing; Remotely operated vehicle; Autonomous docking.
    National Category
    Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:uu:diva-356562 (URN)
    Available from: 2018-08-01 Created: 2018-08-01 Last updated: 2018-08-01
  • Public defence: 2018-09-21 13:15 A1:111a, Uppsala
    Granberg, Albina
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics. Högskolan Kristianstad.
    Koka sjuda steka: Ett sociokulturellt perspektiv på matlagning i hem- och konsumentkunskap på grundsärskolan2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In Swedish schools, the subject Home Economics (HE) is the formal setting for teaching and learning about food and how to cook. All students are obliged to learn HE, but in schools for students with mild intellectual disabilities (ID) students are offered four times as much teaching in the subject than students in regular schools. However, this learning context is underexplored. This thesis aims to create an understanding of what cooking in HE is by studying the teaching content in regard to HE cooking practices for students with mild ID through a sociocultural standpoint. Accompanying observations and qualitative semi-structured interviews were used for data collection. The observations included 16 lessons in HE in schools for students with mild ID. The interviews were conducted with 22 qualified and experienced HE teachers. Field notes from the observations and transcripts from the interviews were analyzed using a thematic analysis. A sociocultural perspective, along with the concept of cuisine, constituted the theoretical framework. The findings reveal that the teaching of cooking in HE is focused on one particular artifact, the recipe. This causes difficulties for the students concerning skills related to the design, purport and arithmetic of the recipe. The prominent role of the recipe in cooking in HE was hence captured in a novel concept, recipe literacy. The teachers also reported using a task-centered approach to teaching certain techniques and methods, such as frying, kneading and simmering. The cuisine that is represented in the data from the observations and interviews is framed within baking, primarily sweet baking. The focus on sweet baking and the students’ various difficulties when using recipes limited the possibilities for students to learn how to cook proper meals for everyday life. Thereby, a conscious choice of dishes and attention to didactics is necessary to improve the validity of the subject. By overcoming such obstacles, opportunities can therefore be created for students with mild ID to learn how to cook.

    List of papers
    1. To use a recipe - not a piece of cake: Students with mild intellectual disabilities use of recipes in home economics
    Open this publication in new window or tab >>To use a recipe - not a piece of cake: Students with mild intellectual disabilities use of recipes in home economics
    2014 (English)In: International Journal of Consumer Studies, ISSN 1470-6423, E-ISSN 1470-6431, Vol. 38, no 4, p. 412-418Article in journal (Refereed) Published
    Abstract [en]

    Recipes are not only part of today's cooking culture, they are also part of the Swedish syllabus of home economics. The aim of this study was to investigate what kinds of difficulties students with mild intellectual disabilities have using recipes during cooking lessons in home economics. We conducted an ethnographically inspired approach, with a total of 44 h of accompanying observations. Three compulsory schools for students with intellectual disabilities were enrolled in the study, and 37 students and three teachers were included. The socio-cultural theory of learning has been used as a theoretical framework. The findings reveal both that recipes are central artefacts during the cooking lessons and that the students have various difficulties using the recipes. The difficulties vary, and they concern both how the recipes are designed and the purport of the recipes. Difficulties in relation to the design included, for example, the separation of ingredients and instructions in the text and the large amount of information given in both the whole and the parts of the recipes. The difficulties in relation to the purport – that is, the meaning or sense of the recipe – were the ingredients, the kitchen utensils and the knowledge of how to perform a specific task. These difficulties can be considered special in relation to the use of the recipes. We suggest the concept of ‘recipe literacy’ to capture the complex knowledge of using recipes.

    National Category
    Other Social Sciences not elsewhere specified
    Research subject
    Food, Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-229036 (URN)10.1111/ijcs.12109 (DOI)000340240200012 ()
    Available from: 2014-07-28 Created: 2014-07-28 Last updated: 2018-08-03Bibliographically approved
    2. Knowing how to use and understand recipes: What Arithmetical Understanding Is Needed When Students With Mild Intellectual Disabilities Use Recipes In Practical Cooking Lessons In Home Economics?
    Open this publication in new window or tab >>Knowing how to use and understand recipes: What Arithmetical Understanding Is Needed When Students With Mild Intellectual Disabilities Use Recipes In Practical Cooking Lessons In Home Economics?
    2017 (English)In: International Journal of Consumer Studies, ISSN 1470-6423, E-ISSN 1470-6431, Vol. 41, no 5, p. 494-500Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to explore what arithmetical understanding is needed when students with mild intellectual disabilities use recipes during practical cooking lessons in Home Economics. The settings were compulsory schools in Sweden attended by students with intellectual disabilities. Sixteen lessons in Home Economics during which cooking took place were observed. In total, 37 students and three teachers participated. All students had a mild intellectual disability. Their ages varied, but most were between 13 and 14 years old. The sociocultural perspective on learning, combined with a literacy framework, was used as a theoretical foundation for the study. Main findings are that students need an arithmetical understanding of (i) how to interpret numbers, (ii) how to interpret and use units, and (iii) how to compute when using recipes. The knowledge and skills needed to be able to use a recipe are featured in the concept recipe literacy, capturing both theoretical, declarative knowledge and the more practical, procedural knowledge. Recipe literacy can be used to theorize the use of recipes when learning to cook, as in Home Economics.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2017
    National Category
    Social Sciences
    Identifiers
    urn:nbn:se:uu:diva-318552 (URN)10.1111/ijcs.12357 (DOI)000409879600006 ()
    Available from: 2017-03-25 Created: 2017-03-25 Last updated: 2018-08-03
    3. Teaching and learning cooking skills in Home Economics: What do teachers for students with mild intellectual disabilities consider important to learn?
    Open this publication in new window or tab >>Teaching and learning cooking skills in Home Economics: What do teachers for students with mild intellectual disabilities consider important to learn?
    2017 (English)In: British Food Journal, ISSN 0007-070X, E-ISSN 1758-4108, Vol. 119, no 5, p. 1067-1078Article in journal (Refereed) Published
    Abstract [en]

    Purpose - The purpose of this paper is to explore which elements of cooking skills Home Economics (HE) teachers in schools for students withmild intellectual disability (ID) consider important for their students to learn.

    Design/methodology/approach - In total, 22 qualitative interviews with HE teachers of students with mild ID were conducted. The transcripts were analyzed thematically using the sociocultural approach on learning and knowledge as a theoretical framework.

    Findings - The elements of cooking skills that were emphasized included mastering the language of cooking, measuring, following recipes, representing an instrumental and task-centered - knowledge on cooking.

    Practical implications - The results of this study provide an insight into cooking lessons in HE in schools, not only regarding the focus that teachers give to cooking skills, but also to how cooking skills can be understood on a theoretical level. This has implications for both regular schools and schools for students with mild IDs since the elements that teachers consider important then guide what the students are given to learn. Teachers should be conscious that the planning of lessons should also be based on the students' specific circumstances and context.

    Originality/value - To the authors' knowledge, this is the first study that provides knowledge about how HE teachers reason regarding which cooking skills they consider important for students to learn. HE is taught to both children and adolescents, and it is important to investigate teachers' perceptions about the subject and how the teaching is organized, including cooking skills.

    Place, publisher, year, edition, pages
    EMERALD GROUP PUBLISHING LTD, 2017
    Keywords
    Teaching, Cooking skills, Home Economics, Sociocultural theory on learning
    National Category
    Pedagogy
    Identifiers
    urn:nbn:se:uu:diva-328289 (URN)10.1108/BFJ-09-2016-0435 (DOI)000402881100009 ()
    Funder
    Swedish Research Council
    Available from: 2017-08-21 Created: 2017-08-21 Last updated: 2018-08-03
    4. Using the Concept of Cuisine to Understand Learning Opportunities within the Subject of Home Economics: A Qualitative Study in the School for Students with Mild Intellectual Disabilities
    Open this publication in new window or tab >>Using the Concept of Cuisine to Understand Learning Opportunities within the Subject of Home Economics: A Qualitative Study in the School for Students with Mild Intellectual Disabilities
    (English)In: International Journal of Home Economics, ISSN 1999-561X, E-ISSN 1999-561XArticle in journal (Refereed) Submitted
    National Category
    Social Sciences
    Research subject
    Food, Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-356548 (URN)
    Available from: 2018-07-31 Created: 2018-07-31 Last updated: 2018-08-15
  • Public defence: 2018-09-24 10:15 Humanistiska teatern, Uppsala
    Eriksson, Rose
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History, Textile Studies.
    Retorik och praktik.: en studie av Gestriklands hemslöjdsförening 1912-19302018Doctoral thesis, monograph (Other academic)
    Abstract [en]

    The principal aim of this dissertation, Rhetoric and Practice: A Study of the Handicraft Society of Gestrikland 1912-1930, has been to investigate how the rhetoric of the Society – in its early years, as well in the subsequent writings which relate the Society’s history – compares to its actual practices, and to undertake a critical review of the meaning and practical application of the Society’s official slogans. One area of focus is the way Gestrikland’s Handicraft society employed the motto of “helping people to help themselves” – the idea, that is to say, of generating income for the poor. Another focus is the concept of “local character” as applied to the most typical handicraft products for a particular region. Both concepts were central to the Swedish handicraft movement.

    The study of archivial records as well as the analyses of textile objects, conducted from the point of view my own practical expertise, has led to significant new knowledge which clearly shows the discrepancy between the rhetoric and the reality of the early Handicraft movement. By problematizing and analysing the central concepts of the movement, “helping people to help themselves” and “local character”, I have been able to give a more relevant understanding of the practice. Specifically, I show that the origin of “local character” does not derive from the qualities of the surrounding natural environment, but rather from the creative initiative of particular individuals. Similarly, the idea of “helping people to help themselves”, which in the official rhetoric was understood to describe an initiative to supplement the income of the poorer folk of the countryside, has also in practice been shown to create occupation also for the women of the elite, and to help them find a place in public life. The handicraft movement thus became an organisation of middle-class women for women of all classes. One might say the organisation even existed to “help one’s own people help themselves”.

     

  • Public defence: 2018-09-27 14:00 Lindahlsalen, Uppsala
    Liu, Xiaodong
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Mechanisms of speciation in Silene2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A fundamental question in the field of evolutionary biology is how new species originate. Investigating speciation benefits from an integrated approach, which requires a solid understanding of ecology, reproductive biology, geographical distribution, underlying genetic architecture of reproductive isolation (RI), demographic history and genomic divergence. In this thesis, I studied the evolution of reproductive isolation in the sister species Silene dioica (L.) Clairv. and S. latifolia Poiret. The aims of the thesis are to investigate (1) the individual and cumulative contributions of extrinsic and intrinsic reproductive barriers between S. dioica and S. latifolia, (2) the genetic architecture of traits associated with reproductive barriers (3) the demographic history of lineage-split between the two species, (4) genomic patterns of divergence between the species.

    I found that multiple extrinsic pre- and postzygotic barriers resulting from ecological differentiation contributed most to total RI, while intrinsic barriers had substantial individual strength but contributed weakly to total RI. QTL mapping revealed evidence for genetic coupling of QTLs controlling traits associated with RI, although QTLs were overall widely distributed. QTLs related to sexually dimorphic traits were located on or near the pseudo-autosomal region of the sex chromosomes. The best-supported demographic model suggests heterogeneous population size and migration rates among genome-wide loci and points to the presence of barrier loci. Genomic divergence (measured using FST and dXY) was commonly accentuated around the middle of linkage groups and near QTLs for traits associated with reproductive barriers.

    In summary, the results in my thesis indicate that the speciation process is driven by multiple interacting and complex reproductive barriers. The genomic divergence landscape is shaped by interplay of the magnitude of gene flow, the strength and timing of selection, and other  confounding factors such as genomic features.

    List of papers
    1. Ecological divergence plays an important role in strong but complex reproductive isolation in campions (Silene).
    Open this publication in new window or tab >>Ecological divergence plays an important role in strong but complex reproductive isolation in campions (Silene).
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Keywords
    adaptation, germination, reproductive barrier, species distribution modeling, speciation
    National Category
    Biological Sciences
    Research subject
    Biology with specialization in Ecological Botany
    Identifiers
    urn:nbn:se:uu:diva-356985 (URN)
    Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-09
    2. Genetic architecture of traits associated with reproductive barriers in Silene: Coupling, sex chromosomes and variation
    Open this publication in new window or tab >>Genetic architecture of traits associated with reproductive barriers in Silene: Coupling, sex chromosomes and variation
    2018 (English)In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294XArticle in journal (Refereed) Published
    Abstract [en]

    The evolution of reproductive barriers and their underlying genetic architecture is ofcentral importance for the formation of new species. Reproductive barriers can becontrolled either by few large-effect loci suggesting strong selection on key traits,or by many small-effect loci, consistent with gradual divergence or with selection onpolygenic or multiple traits. Genetic coupling between reproductive barrier loci fur-ther promotes divergence, particularly divergence with ongoing gene flow. In thisstudy, we investigated the genetic architectures of ten morphological, phenologicaland life history traits associated with reproductive barriers between the hybridizingsister species Silene dioica and S. latifolia; both are dioecious with XY-sex determina-tion. We used quantitative trait locus (QTL) mapping in two reciprocal F2crosses.One to six QTLs per trait, including nine major QTLs (PVE > 20%), were detectedon 11 of the 12 linkage groups. We found strong evidence for coupling of QTLs foruncorrelated traits and for an important role of sex chromosomes in the geneticarchitectures of reproductive barrier traits. Unexpectedly, QTLs detected in the twoF2crosses differed largely, despite limited phenotypic differences between themand sufficient statistical power. The widely dispersed genetic architectures of traitsassociated with reproductive barriers suggest gradual divergence or multifariousselection. Coupling of the underlying QTLs likely promoted divergence with geneflow in this system. The low congruence of QTLs between the two crosses furtherpoints to variable and possibly redundant genetic architectures of traits associatedwith reproductive barriers, with important implications for the evolutionary dynam-ics of divergence and speciation.

    Keywords
    adaptation, ddRAD-seq, genetic coupling, QTL, reproductive barrier, speciation
    National Category
    Natural Sciences
    Research subject
    Biology with specialization in Evolutionary Genetics
    Identifiers
    urn:nbn:se:uu:diva-356980 (URN)10.1111/mec.14562 (DOI)
    Funder
    Swedish Research Council
    Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-09
    3. Genomic divergence and reproductive isolation in Silene
    Open this publication in new window or tab >>Genomic divergence and reproductive isolation in Silene
    (English)Manuscript (preprint) (Other academic)
    National Category
    Biological Sciences
    Research subject
    Biology with specialization in Evolutionary Genetics
    Identifiers
    urn:nbn:se:uu:diva-356986 (URN)
    Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-09
    4. Pseudo-autosomal region on the sex chromosomes of Silene controls sexually dimorphic traits
    Open this publication in new window or tab >>Pseudo-autosomal region on the sex chromosomes of Silene controls sexually dimorphic traits
    (English)Manuscript (preprint) (Other academic)
    National Category
    Biological Sciences
    Research subject
    Biology with specialization in Evolutionary Genetics
    Identifiers
    urn:nbn:se:uu:diva-356987 (URN)
    Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-09
  • Public defence: 2018-09-28 09:00 Skoogsalen, ing 78/79, Uppsala
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Methodological aspects of quantitative cardiac molecular imaging2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The objective of this research was to facilitate the use of quantitative cardiac molecular imaging by developing and validating methods and applications. More specifically:

    we determined the optimal tracer kinetic model for analysis of 11C-PIB and evaluated the performance of two simpler measures, retention index (RI) and standardized uptake value (SUV), in the quantification of cardiac 11C-PIB uptake in amyloidosis. An irreversible two-tissue (2Tirr) model best described the 11C-PIB uptake in cardiac amyloidosis. RI and SUV showed high correlation with quantitative results from this kinetic model and also a better discrimination between amyloidosis patients and controls than a 2Tirr model with population averaged metabolite correction. RI and SUV are furthermore more feasible for use in clinical routine and therefore the preferred measure to use in PET diagnosis of cardiac amyloidosis. We also tested the feasibility of a semiautomatic software to analyze RI and visualize cardiac uptake of 11C-PIB in amyloidosis. The RI values were comparable with RI based on manual segmentation, showing significantly higher 11C-PIB RI in amyloidosis patients than in healthy volunteers. A fast and accurate semiautomatic analysis process is thus feasible to use for PET in cardiac amyloidosis instead of the laborious manual analyses that were used so far.

    Furthermore, we assessed the quantitative accuracy of cardiac perfusion measurements with 15O-water PET in a digital time-of-flight PET-MR scanner. A high correlation and agreement between PET-MR based and PET-CT based MBF was found; cardiac perfusion measurements with 15O-water can therefore be performed accurately with the fully integrated Signa PET-MR scanner. 

    Finally, we assessed the quantitative accuracy of cardiac perfusion measurements using dynamic contrast-enhanced MRI with simultaneous 15O-water PET as reference at rest and during adenosine-induced hyperemia with a fully integrated PET-MR scanner. The correlations between global and regional MRI- and PET-based MBF values were good and the biases were negliable for both global and regional MBF comparisons, but the limits of agreement were wide for both global and regional MBF, with larger variability for high MBF-values indicating that MRI-based quantitative MBF measurement based on widely available acquisition protocols is not yet ready for clinical introduction.

    List of papers
    1. Quantification of (11)C-PIB kinetics in cardiac amyloidosis
    Open this publication in new window or tab >>Quantification of (11)C-PIB kinetics in cardiac amyloidosis
    Show others...
    2018 (English)In: J Nucl CardiolArticle in journal (Refereed) Epub ahead of print
    Abstract [en]

    BACKGROUND: The purpose of this work was to determine the optimal tracer kinetic model of (11)C-PIB and to validate the use of the simplified methods retention index (RI) and standardized uptake value (SUV) for quantification of cardiac (11)C-PIB uptake in amyloidosis. METHODS AND RESULTS: Single-tissue, reversible and irreversible two-tissue models were fitted to data from seven cardiac amyloidosis patients who underwent (11)C-PIB PET scans and arterial blood sampling for measurement of blood radioactivity and metabolites. The irreversible two-tissue model (2Tirr) best described cardiac (11)C-PIB uptake. RI and SUV showed high correlation with the rate of irreversible binding (Ki) from the 2Tirr model (r(2 )=0.95 and r(2 )=0.94). Retrospective data from 10 amyloidosis patients and 5 healthy controls were analyzed using RI, SUV, as well as compartment modelling with a population-average metabolite correction. All measures were higher in amyloidosis patients than in healthy controls (p=.001), but with an overlap between groups for Ki. CONCLUSION: An irreversible two-tissue model best describes the (11)C-PIB uptake in cardiac amyloidosis. RI and SUV correlate well with Ki from the 2Tirr model. RI and SUV discriminate better between amyloidosis patients and controls than Ki based on population-average metabolite correction.

    Keywords
    11c-pib, Cardiac amyloidosis, absolute quantification, retention index, standardized uptake value
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-356695 (URN)1532-6551 (Electronic) 1071-3581 (Linking) (ISBN)
    Note

    Kero, Tanja Sorensen, Jens Antoni, Gunnar Wilking, Helena Carlson, Kristina Vedin, Ola Rosengren, Sara Wikstrom, Gerhard Lubberink, Mark eng J Nucl Cardiol. 2018 Jul 23. pii: 10.1007/s12350-018-1349-x. doi: 10.1007/s12350-018-1349-x.

    Available from: 2018-08-03 Created: 2018-08-03 Last updated: 2018-08-05
    2. Accurate analysis and visualization of cardiac (11)C-PIB uptake in amyloidosis with semiautomatic software
    Open this publication in new window or tab >>Accurate analysis and visualization of cardiac (11)C-PIB uptake in amyloidosis with semiautomatic software
    2016 (English)In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 23, no 4, p. 741-750Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: (11)C-PIB PET is a promising non-invasive diagnostic tool for cardiac amyloidosis. Semiautomatic analysis of PET data is now available but it is not known how accurate these methods are for amyloid imaging. The aim of this study was to evaluate the feasibility of one semiautomatic software tool for analysis and visualization of (11)C-PIB left ventricular retention index (RI) in cardiac amyloidosis.

    METHODS AND RESULTS: Patients with systemic amyloidosis and cardiac involvement (n = 10) and healthy controls (n = 5) were investigated with dynamic (11)C-PIB PET. Two observers analyzed the PET studies with semiautomatic software to calculate the left ventricular RI of (11)C-PIB and to create parametric images. The mean RI at 15-25 min from the semiautomatic analysis was compared with RI based on manual analysis and showed comparable values (0.056 vs 0.054 min(-1) for amyloidosis patients and 0.024 vs 0.025 min(-1) in healthy controls; P = .78) and the correlation was excellent (r = 0.98). Inter-reader reproducibility also was excellent (intraclass correlation coefficient, ICC > 0.98). Parametric polarmaps and histograms made visual separation of amyloidosis patients and healthy controls fast and simple.

    CONCLUSION: Accurate semiautomatic analysis of cardiac (11)C-PIB RI in amyloidosis patients is feasible. Parametric polarmaps and histograms make visual interpretation fast and simple.

    Keywords
    Amyloid; PET imaging; C-11 PIB; cardiac amyloidosis
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-266308 (URN)10.1007/s12350-015-0149-9 (DOI)000381082100016 ()26173894 (PubMedID)
    Available from: 2015-11-06 Created: 2015-11-06 Last updated: 2018-08-05Bibliographically approved
    3. Quantitative myocardial blood flow imaging with integrated time-of-flight PET-MR
    Open this publication in new window or tab >>Quantitative myocardial blood flow imaging with integrated time-of-flight PET-MR
    Show others...
    2017 (English)In: EJNMMI physics, ISSN 2197-7364, Vol. 4, no 1Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: The use of integrated PET-MR offers new opportunities for comprehensive assessment of cardiac morphology and function. However, little is known on the quantitative accuracy of cardiac PET imaging with integrated time-of-flight PET-MR. The aim of the present work was to validate the GE Signa PET-MR scanner for quantitative cardiac PET perfusion imaging. Eleven patients (nine male; mean age 59 years; range 46-74 years) with known or suspected coronary artery disease underwent (15)O-water PET scans at rest and during adenosine-induced hyperaemia on a GE Discovery ST PET-CT and a GE Signa PET-MR scanner. PET-MR images were reconstructed using settings recommended by the manufacturer, including time-of-flight (TOF). Data were analysed semi-automatically using Cardiac VUer software, resulting in both parametric myocardial blood flow (MBF) images and segment-based MBF values. Correlation and agreement between PET-CT-based and PET-MR-based MBF values for all three coronary artery territories were assessed using regression analysis and intra-class correlation coefficients (ICC). In addition to the cardiac PET-MR reconstruction protocol as recommended by the manufacturer, comparisons were made using a PET-CT resolution-matched reconstruction protocol both without and with TOF to assess the effect of time-of-flight and reconstruction parameters on quantitative MBF values.

    RESULTS: Stress MBF data from one patient was excluded due to movement during the PET-CT scanning. Mean MBF values at rest and stress were (0.92 ± 0.12) and (2.74 ± 1.37) mL/g/min for PET-CT and (0.90 ± 0.23) and (2.65 ± 1.15) mL/g/min for PET-MR (p = 0.33 and p = 0.74). ICC between PET-CT-based and PET-MR-based regional MBF was 0.98. Image quality was improved with PET-MR as compared to PET-CT. ICC between PET-MR-based regional MBF with and without TOF and using different filter and reconstruction settings was 1.00.

    CONCLUSIONS: PET-MR-based MBF values correlated well with PET-CT-based MBF values and the parametric PET-MR images were excellent. TOF and reconstruction settings had little impact on MBF values.

    Keywords
    PET-MR, Myocardial blood flow (MBF), O-15-water, Quantification, Time-of-flight (TOF)
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-312386 (URN)10.1186/s40658-016-0171-2 (DOI)000397119200001 ()28058674 (PubMedID)
    Available from: 2017-01-09 Created: 2017-01-09 Last updated: 2018-08-05Bibliographically approved
    4. Evaluation of quantitative CMR perfusion imaging by comparison with simultaneous 15O-water-PET
    Open this publication in new window or tab >>Evaluation of quantitative CMR perfusion imaging by comparison with simultaneous 15O-water-PET
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background

    The aim of the present work was to assess the quantitative accuracy of cardiac perfusion measurements using dynamic contrast-enhanced MRI with simultaneous 15O-water PET as reference at rest and during adenosine-induced hyperemia with a fully integrated PET-MR scanner. 

    Methods

    15 patients with known or suspected coronary artery disease (9 male, mean age 66 years; range 51-75) underwent simultaneous gadolinium-DOTA-perfusion MRI and 15O-water PET scans at rest and during adenosine-induced hyperaemia on a GE Signa PET-MR scanner. Global and regional MBF at rest and during adenosine stress were calculated for MRI and PET. Correlation and agreement between MRI- and PET-based global and regional MBF values were assessed using correlation and Bland Altman analysis.

    Results

    Three subjects were excluded due to technical problems during the PET-MR scan. Global mean (± SD) MBF values at rest and stress were 0.97 ± 0.27 and 3.19 ± 0.70 mL/g/min for MRI and 1.02 ± 0.28 and 3.13 ± 1.16 mL/g/min for PET (p=0.66 and p=0.81). The correlations between global and regional MRI- and PET-based MBF values were strong (r=0.86 and r=0.75). The biases were negliable for both global and regional MBF comparisons (0.01 and 0.00 mL/min/g for both), but the limits of agreement were wide for both global and regional MBF, with larger variability for high MBF-values.

    Conclusion

    The correlation between simultaneous quantitative MBF measurements with single bolus DCE MRI and 15O-water PET measured in an integrated PET-MRI was strong but the agreement was only moderate indicating that MRI-based quantitative MBF measurements is not ready for clinical introduction.   

    Keywords
    myocardial perfusion, myocardial blood flow, cardiac magnetic resonance imaging, positron emission tomography, quantitative modeling
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-356696 (URN)
    Available from: 2018-08-03 Created: 2018-08-03 Last updated: 2018-08-05
  • Public defence: 2018-09-28 09:30 Rudbeckssalen, Rudbeck entréplan, C11, Uppsala
    Kamble, Prasad G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Role of nuclear receptors in the regulation of human adipose tissue metabolism2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Nuclear receptors modulate expression of genes involved in adipose tissue (AT) metabolism. Their improved understanding may provide new treatment options for metabolic disorders such as obesity, insulin resistance (IR) and type 2 diabetes (T2D).

    This thesis explored the role of nuclear receptors, mainly, glucocorticoid and estrogen receptors (GR and ER, respectively) and peroxisome proliferator-activated receptor gamma (PPARγ), and their interplay in the regulation of metabolic function and dysfunction in human AT.

    In Paper I, the regulation of adipokine lipocalin 2 (LCN2) expression by synthetic glucocorticoid, dexamethasone and effect of LCN2 on glucose and lipid metabolism in AT were studied. In pre-menopausal but not post-menopausal women or men, dexamethasone upregulated LCN2 gene expression, which also correlated with markers of obesity and IR. LCN2 inhibited adipocyte glucose uptake.

    In Paper II, the effect of estrogen (E2) and its interaction with GR in LCN2 regulation in AT from post-menopausal women were examined. E2 increased LCN2 expression, what seems to be mediated by ERβ. E2 and dexamethasone co-treatment increased LCN2 gene expression in presence of ERα but not ERβ antagonist. Dexamethasone decreased ERα, while increased ERβ gene expression.

    In Paper III and IV, the feasibility of genotype-based recall (GBR), a participant recruitment approach, was tested by undertaking clinical and AT phenotyping of different PPARγ Pro12Ala carriers. The baseline characteristics were comparable between genotypes. Compared to fasting, a decreased hormone-sensitive lipase gene expression in Pro/Pro group also accompanied with a higher antilipolytic effect of insulin after oral glucose. Adipocyte glucose uptake and adipogenesis remained unchanged between genotypes.

    Overall, LCN2 can induce IR in human AT and may mediate metabolic defects by excess glucocorticoids in pre-menopausal women. GR selectively interacts with ERα and ERβ, the latter two acts oppositely to control LCN2 expression in AT. PPARγ Pro12Ala had no major effect on clinical and adipose phenotype, likely due to a small sample size in relation to the modest effect the Ala variant or tissues other than adipose could be critical in conferring protection by Pro12Ala against T2D risk. Further, the GBR approach deemed feasible, however, would be more suitable in the characterization of rare genetic variants.

    List of papers
    1. Lipocalin 2 produces insulin resistance and can be upregulated by glucocorticoids in human adipose tissue
    Open this publication in new window or tab >>Lipocalin 2 produces insulin resistance and can be upregulated by glucocorticoids in human adipose tissue
    Show others...
    2016 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 427, p. 124-132Article in journal (Refereed) Published
    Abstract [en]

    The adipokine lipocalin 2 is linked to obesity and metabolic disorders. However, its role in human adipose tissue glucose and lipid metabolism is not explored. Here we show that the synthetic glucocorticoid dexamethasone dose-dependently increased lipocalin 2 gene expression in subcutaneous and omental adipose tissue from pre-menopausal females, while it had no effect in post-menopausal females or in males. Subcutaneous adipose tissue from both genders treated with recombinant human lipocalin 2 showed a reduction in protein levels of GLUT1 and GLUT4 and in glucose uptake in isolated adipocytes. In subcutaneous adipose tissue, lipocalin 2 increased IL-6 gene expression whereas expression of PPAR gamma and adiponectin was reduced. Our findings suggest that lipocalin 2 can contribute to insulin resistance in human adipose tissue. In pre-menopausal females, it may partly mediate adverse metabolic effects exerted by glucocorticoid excess.

    Keywords
    Glucocorticoids, Lipocalin 2, Human adipose tissue, Type 2 diabetes, Insulin resistance, PPAR gamma
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-297263 (URN)10.1016/j.mce.2016.03.011 (DOI)000375335500013 ()26973291 (PubMedID)
    Funder
    Swedish Diabetes AssociationEXODIAB - Excellence of Diabetes Research in SwedenAstraZenecaSwedish Society for Medical Research (SSMF)
    Available from: 2016-06-23 Created: 2016-06-22 Last updated: 2018-08-12Bibliographically approved
    2. Effect of estrogen and its interaction with glucocorticoids in the regulation of lipocalin 2 in human adipose tissue: a role for estrogen receptor β pathway in insulin resistance?
    Open this publication in new window or tab >>Effect of estrogen and its interaction with glucocorticoids in the regulation of lipocalin 2 in human adipose tissue: a role for estrogen receptor β pathway in insulin resistance?
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-357118 (URN)
    Available from: 2018-08-12 Created: 2018-08-12 Last updated: 2018-08-12
    3. Genotype-based recall to study metabolic effects of genetic variation: a pilot study of PPARG Pro12Ala carriers
    Open this publication in new window or tab >>Genotype-based recall to study metabolic effects of genetic variation: a pilot study of PPARG Pro12Ala carriers
    Show others...
    2017 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 4, p. 234-242Article in journal (Refereed) Published
    Abstract [en]

    AIM: To assess practical implications of genotype-based recall (GBR) studies, an increasingly popular approach for in-depth characterization of genotype-phenotype relationships.

    METHODS: We genotyped 2500 participants from the Swedish EpiHealth cohort and considered loss-of-function and missense variants in genes with relation to cardiometabolic traits as the basis for our GBR study. Therefore, we focused on carriers and non-carriers of the PPARG Pro12Ala (rs1801282) variant, as it is a relatively common variant with a minor allele frequency (MAF) of 0.14. It has also been shown to affect ligand binding and transcription, and carriage of the minor allele (Ala12) is associated with a reduced risk of type 2 diabetes. We re-invited 39 Pro12Pro, 34 Pro12Ala, and 30 Ala12Ala carriers and performed detailed anthropometric and serological assessments.

    RESULTS: The participation rates in the GBR study were 31%, 44%, and 40%, and accordingly we included 12, 15, and 13 individuals with Pro12Pro, Pro12Ala, and Ala12Ala variants, respectively. There were no differences in anthropometric or metabolic variables among the different genotype groups.

    CONCLUSIONS: Our report highlights that from a practical perspective, GBR can be used to study genotype-phenotype relationships. This approach can prove to be a valuable tool for follow-up findings from large-scale genetic discovery studies by undertaking detailed phenotyping procedures that might not be feasible in large studies. However, our study also illustrates the need for a larger pool of genotyped or sequenced individuals to allow for selection of rare variants with larger effects that can be examined in a GBR study of the present size.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2017
    Keywords
    Genotype-based recall, PPARG Pro12Ala, metabolism
    National Category
    Endocrinology and Diabetes Medical Genetics
    Identifiers
    urn:nbn:se:uu:diva-342240 (URN)10.1080/03009734.2017.1405127 (DOI)000423294800005 ()29303622 (PubMedID)
    Funder
    Swedish Research Council, 2015-02907Göran Gustafsson Foundation for Research in Natural Sciences and MedicineSwedish Heart Lung Foundation, 20140422Knut and Alice Wallenberg Foundation, 2013.0126Swedish Diabetes Association
    Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2018-08-12Bibliographically approved
    4. Role of peroxisome proliferator-activated receptor gamma Pro12Ala polymorphism in human adipose tissue: assessment of adipogenesis and adipocyte glucose and lipid turnover.
    Open this publication in new window or tab >>Role of peroxisome proliferator-activated receptor gamma Pro12Ala polymorphism in human adipose tissue: assessment of adipogenesis and adipocyte glucose and lipid turnover.
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    2018 (English)In: Adipocyte, ISSN 2162-3945, E-ISSN 2162-397XArticle in journal (Refereed) Epub ahead of print
    Abstract [en]

    Protective mechanisms of peroxisome proliferator-activated receptor gamma (PPARγ) Pro12Ala polymorphism in type 2 diabetes (T2D) are unclear. We obtained adipose tissue (AT) before and 3 h after oral glucose (OGTT) in carriers and non-carriers of the Ala allele (12 Pro/Pro, 15 Pro/Ala, and 13 Ala/Ala). Adipogenesis, adipocyte glucose uptake and lipolysis as well as PPARγ target genes expression were investigated and compared between the genotype groups. On fasting and post-OGTT, neither basal nor insulin-stimulated adipocyte glucose uptake differed between genotypes. Compared to fasting, a decreased hormone-sensitive lipase gene expression in Pro/Pro (p<0.05) also accompanied with a higher antilipolytic effect of insulin post-OGTT (p<0.01). The adipocyte size was similar across groups. Preadipocyte differentiation rates between Pro/Pro and Ala/Ala were unchanged. In conclusion, no major differences in AT differentiation, glucose uptake, lipolysis or expression of PPARγ target genes were observed between different PPARγ Pro12Ala genotypes. Albeit small, our study may suggest that other pathways in AT or effects exerted in other tissues might contribute to the Pro12Ala-mediated protection against T2D.

    Keywords
    PPARG Pro12Ala, human adipose tissue, metabolism and adipogenesis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-357116 (URN)10.1080/21623945.2018.1503030 (DOI)30064293 (PubMedID)
    Available from: 2018-08-12 Created: 2018-08-12 Last updated: 2018-08-12
  • Public defence: 2018-09-28 09:30 Polhemssalen, Uppsala
    Donzel-Gargand, Olivier
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    The Multiple Faces of Interfaces: Electron microscopy analysis of CuInSe2 thin-film solar cells2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The CIS solar cell family features both a high stability and world-class performances. They can be deposited on a wide variety of substrates and absorb the entire solar spectrum only using a thickness of a few micrometers. These particularities allow them to feature the most positive Energy returned on energy invested (EROI) values and the shortest Energy payback times (EPBT) of all the main photovoltaic solar cells. Using mainly electron microscopy characterization techniques, this thesis has explored the questions related to the interface control in thin-film photovoltaic solar cells based on CuInSe2 (CIS) absorber materials. Indeed, a better understanding of the interfaces is essential to further improve the solar cell conversion efficiency (currently around 23%), but also to introduce alternative substrates, to implement various alloying (Ga-CIS (CIGS), Ag-CIGS (ACIGS)…) or even to assess alternative buffer layers.

    The thread of this work is the understanding and the improvement of the interface control. To do so, the passivation potential of Al2O3 interlayers has been studied in one part of the thesis. While positive changes were generally measured, a subsequent analysis has revealed that a detrimental interaction could occur between the NaF precursor layer and the rear Al2O3 passivation layer. Still within the passivation research field, incorporation of various alkali-metals to the CIS absorber layer has been developed and analyzed. Large beneficial effects were ordinarily reported. However, similar KF-post deposition treatments were shown to be potentially detrimental for the silver-alloyed CIGS absorber layer. Finally, part of this work dealt with the limitations of the thin-barrier layers usually employed when using steel substrates instead of soda-lime glass ones. The defects and their origin could have been related to the steel manufacturing process, which offered solutions to erase them.

    Electron microscopy, especially Transmission electron microscopy (TEM), was essential to scrutinize the local changes occurring at the different interfaces within a few nanometers. The composition variation was measured with both Electron energy loss spectroscopy (EELS) and Energy dispersive X-ray spectroscopy (EDS) techniques. Finally, efforts have been invested in controlling and improving the FIB sample preparation, which was required for the TEM observations in our case.

    List of papers
    1. On the assessment of CIGS surface passivation by photoluminescence
    Open this publication in new window or tab >>On the assessment of CIGS surface passivation by photoluminescence
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    2015 (English)In: Physica Status Solidi. Rapid Research Letters, ISSN 1862-6254, E-ISSN 1862-6270, Vol. 9, no 5, p. 288-292Article in journal (Refereed) Published
    Abstract [en]

    An optimized test structure to study rear surface passivation in Cu(In,Ga)Se-2 (CIGS) solar cells by means of photoluminescence (PL) is developed and tested. The structure - illustrated in the abstract figure - is examined from the rear side. To enable such rear PL assessment, a semi-transparent ultrathin Mo layer has been developed and integrated in place of the normal rear contact. The main advantages of this approach are (i) a simplified representation of a rear surface passivated CIGS solar cell is possible, (ii) it is possible to assess PL responses originating close to the probed rear surface, and (iii) a stable PL response as a function of air exposure time is obtained. In this work, PL measurements of such structures with and without rear surface passivation layers have been compared, and the measured improvement in PL intensity for the passivated structures is associated with enhanced CIGS rear interface properties. [GRAPHICS] Transmission electron microscope (TEM) bright field cross-section image of the rear illuminated test structure fabricated for PL characterization.

    Keywords
    solar cells, thin films, CuInGaSe2, surface passivation, photoluminescence
    National Category
    Environmental Engineering Physical Sciences
    Identifiers
    urn:nbn:se:uu:diva-256541 (URN)10.1002/pssr.201510081 (DOI)000354888300002 ()
    Available from: 2015-06-25 Created: 2015-06-24 Last updated: 2018-08-12Bibliographically approved
    2. Surface defect passivation by a thin metallic barrier for Cu(InxGa1-x)Se2 co-evaporation on Cr-steel substrates
    Open this publication in new window or tab >>Surface defect passivation by a thin metallic barrier for Cu(InxGa1-x)Se2 co-evaporation on Cr-steel substrates
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    2016 (English)In: Thin Solid Films, ISSN 0040-6090, E-ISSN 1879-2731, Vol. 619, p. 220-226Article in journal (Refereed) Published
    Abstract [en]

    The use of Cr-steel substrates for the fabrication of Cu(In,Ga)Se2 (CIGS) solar cells is highly desirable and is a topic of considerable research interest. However, solar cells on non-treated steel substrates often exhibit decreased performance compared to their homologues on soda lime glass substrates. This is partly attributed to out-diffusion of steel components (Fe, Cr, Mn, etc.) into the solar cell. To avoid this contamination, thin film barriers can be added on top of the steel surface, but they do not always prevent the diffusion completely. In this paper we study the potential of using Cr and Ti as thin barrier layers. We find that local surface defects on the steel, several micrometers in height, lead to cracks in the back contact as well as in the barrier layers. Advanced transmission electron microscopy (TEM) techniques reveal that elemental diffusion and chemical reactions occur at these openings during heat treatments in Se atmosphere. TEM-energy dispersive X-ray spectroscopy (TEM-EDX) analysis in combination with calculation of the solid state diffusion coefficient demonstrate that a Cr-barrier sacrificially protects the Cr-steel substrate, blocking most of the Fe out-diffusion, whereas a Ti-barrier is less efficient.

    Place, publisher, year, edition, pages
    Elsevier, 2016
    Keywords
    Back contact; Thin film; Solar cell; Steel substrate; CuInGaSe2; Electron microscopy; Diffusion; Barrier
    National Category
    Metallurgy and Metallic Materials Condensed Matter Physics Energy Systems
    Research subject
    Engineering Science with specialization in Materials Analysis; Engineering Science with specialization in Materials Science
    Identifiers
    urn:nbn:se:uu:diva-307368 (URN)10.1016/j.tsf.2016.10.063 (DOI)000389610900033 ()
    Available from: 2016-11-14 Created: 2016-11-14 Last updated: 2018-08-12Bibliographically approved
    3. Rear Surface Optimization of CZTS Solar Cells by Use of a Passivation Layer With Nanosized Point Openings
    Open this publication in new window or tab >>Rear Surface Optimization of CZTS Solar Cells by Use of a Passivation Layer With Nanosized Point Openings
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    2016 (English)In: IEEE Journal of Photovoltaics, ISSN 2156-3381, E-ISSN 2156-3403, Vol. 6, no 1, p. 332-336Article in journal (Refereed) Published
    Abstract [en]

    Previously, an innovative way to reduce rear interface recombination in Cu(In, Ga)(S, Se)(2) (CIGSSe) solar cells has been successfully developed. In this work, this concept is established in Cu-2(Zn, Sn)(S, Se)(4) (CZTSSe) cells to demonstrate its potential for other thin-film technologies. Therefore, ultrathin CZTS cells with an Al2O3 rear surface passivation layer having nanosized point openings are fabricated. The results indicate that introducing such a passivation layer can have a positive impact on open-circuit voltage (V-OC; +17% rel.), short-circuit current (J(SC); +5% rel.), and fill factor (FF; +9% rel.), compared with corresponding unpassivated cells. Hence, a promising efficiency improvement of 32% rel. is obtained for the rear passivated cells.

    Keywords
    Aluminum oxide, Cu(In, Ga)(S, Se)(2), Cu-2(Zn, Sn)(S, Se)(4), nanosized point contacts, solar cells, surface passivation layer, thin-film
    National Category
    Environmental Engineering
    Identifiers
    urn:nbn:se:uu:diva-274909 (URN)10.1109/JPHOTOV.2015.2496864 (DOI)000367251900048 ()
    Funder
    Swedish Research CouncilSwedish Energy AgencyEU, FP7, Seventh Framework Programme, 300998EU, FP7, Seventh Framework Programme, 327367
    Available from: 2016-01-27 Created: 2016-01-26 Last updated: 2018-08-12Bibliographically approved
    4. Deep surface Cu depletion induced by K in high-efficiency Cu(In,Ga)Se2 solar cell absorbers
    Open this publication in new window or tab >>Deep surface Cu depletion induced by K in high-efficiency Cu(In,Ga)Se2 solar cell absorbers
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    2018 (English)In: Progress in Photovoltaics, ISSN 1062-7995, E-ISSN 1099-159XArticle in journal (Refereed) Epub ahead of print
    Abstract [en]

    In this work, we used K‐rich glass substrates to provide potassium during the coevaporation of Cu(In,Ga)Se2 (CIGS) absorber layers. Subsequently, we applied a postdeposition treatment (PDT) using KF or RbF to some of the grown absorbers. It was found that the presence of K during the growth of the CIGS layer led to cell effi- ciencies beyond 17%, and the addition of a PDT pushed it beyond 18%. The major finding of this work is the observation of discontinuous 100‐ to 200‐nm‐deep Cu‐ depleted patches in the vicinity of the CdS buffer layer, correlated with the presence of K during the growth of the absorber layer. The PDT had no influence on the forma- tion of these patches. A second finding concerns the composition of the Cu‐depleted areas, where an anticorrelation between Cu and both In and K was measured using scanning transmission electron microscopy. Furthermore, a steeper Ga/(In+Ga) ratio gradient was measured for the absorbers grown with the presence of K, suggesting that K hinders the group III element interdiffusion. Finally, no Cd in‐diffusion to the CIGS layer could be detected. This indicates that if CdCu substitution occurs, either their concentration is below our instrumental detection limit or its presence is contained within the first 6 nm from the CdS/CIGS interface.

    Keywords
    CIGS, Cu depletion, EELS, OVC, Raman, solar cell, TEM
    National Category
    Other Materials Engineering Energy Systems
    Identifiers
    urn:nbn:se:uu:diva-357120 (URN)10.1002/pip.3010 (DOI)
    Available from: 2018-08-12 Created: 2018-08-12 Last updated: 2018-09-04Bibliographically approved
    5. Surface Modification And Secondary Phase Formation From a High Dose KF-Post Deposition Treatment of (Ag,Cu)(In,Ga)Se2 Solar Cell Absorbers
    Open this publication in new window or tab >>Surface Modification And Secondary Phase Formation From a High Dose KF-Post Deposition Treatment of (Ag,Cu)(In,Ga)Se2 Solar Cell Absorbers
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    (English)In: Progress in Photovoltaics, ISSN 1062-7995, E-ISSN 1099-159XArticle in journal (Refereed) Submitted
    Abstract [en]

    In this study we assessed the potential of KF-Post Deposition Treatment (PDT) performed on a silver-alloyed Cu(Inx,Ga1-x)Se2 (ACIGS) solar absorber. ACIGS absorbers with Ag/Ag+Cu ratio (Ag/I) close to 20% were co-evaporated on a Mo-coated glass substrate and exposed to in-situ KF-PDT of various intensities. The current-voltage characteristics indicated that an optimized PDT can be beneficial, increasing in our study the median Voc and efficiency values by +48 mV and +0.9 %abs (from 728 mV and 16.1 % efficiency measured for the sample without PDT), respectively. However, an increased KF-flux during PDT resulted in a net deterioration of the performance leading to median Voc and efficiency values as low as 503 mV and 4.7 %. The chemical composition analysis showed that while the reference absorber without any PDT was homogeneous, the KF-PDT induced a clear change within the first 10 nm from the surface. Here, the surface layer composition was richer in K and In with an increased Ag/I ratio, and its thickness seemed to follow the KF exposure intensity. Additionally, high-dose KF-PDT resulted in substantial formation of secondary phases for the ACIGS. The secondary phase precipitates were also richer in Ag, K and In, and Electron and X-ray diffraction data match with the monoclinic C 1 2/c 1 space group adopted by the Ag-alloyed KInSe2 (AKIS) phase. It could not be concluded whether the performance loss for the solar cell devices originated from the thicker surface layer or the presence of secondary phases, or both for the high-dose KF-PDT sample.

    Keywords
    TEM, EDS, ACIGS, XPS, KF-PDT, KInSe
    National Category
    Energy Systems Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:uu:diva-357122 (URN)
    Available from: 2018-08-12 Created: 2018-08-12 Last updated: 2018-08-13Bibliographically approved
    6. Effect of different Na supply methods on thin Cu(In,Ga)Se2 solar cells with Al2O3 rear passivation layers
    Open this publication in new window or tab >>Effect of different Na supply methods on thin Cu(In,Ga)Se2 solar cells with Al2O3 rear passivation layers
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    2018 (English)In: Solar Energy Materials and Solar Cells, ISSN 0927-0248, E-ISSN 1879-3398Article in journal (Refereed) Published
    Abstract [en]

    In this work, rear-contact passivated Cu(In,Ga)Se2 (CIGS) solar cells were fabricated without any intentional contact openings between the CIGS and Mo layers. The investigated samples were either Na free or one of two Na supply methods was used, i) a NaF precursor on top of the Al2O3 rear passivation layer or ii) an in situ post- deposition treatment with NaF after co-evaporation of the CIGS layer. The thickness of the ALD-Al2O3 passi- vation layer was also varied in order to find an optimal combination of Na supply and passivation layer thickness. Our results from electrical characterization show remarkably different solar cell behavior for different Na supplies. For up to 1nm thick Al2O3 layers an electronically good contact could be confirmed independently of Na deposition method and content. When the Al2O3 thickness exceeded 1 nm, the current was blocked on all samples except on the samples with the NaF precursor. On these samples the current was not blocked up to an Al2O3 layer thickness of about 6 nm, the maximum thickness we could achieve without the CIGS peeling off the Al2O3 layer. Transmission electron microscopy reveals a porous passivation layer for the samples with a NaF precursor. An analysis of the dependence of the open circuit voltage on temperature (JVT) indicates that a thicker NaF precursor layer lowers the height of the hole barrier at the rear contact for the passivated cells. This energy barrier is also lower for the passivated sample, compared to an unpassivated sample, when both samples have been post-deposition treated.

    Keywords
    Alkali Back contact CIGS Passivation Thin films Rear contact Tunneling
    National Category
    Electrical Engineering, Electronic Engineering, Information Engineering Energy Systems Other Materials Engineering
    Identifiers
    urn:nbn:se:uu:diva-357123 (URN)10.1016/j.solmat.2018.07.017 (DOI)
    Available from: 2018-08-12 Created: 2018-08-12 Last updated: 2018-08-12
  • Public defence: 2018-09-28 10:15 Sal IV, Uppsala
    Lidén, Moa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Confirmation Bias in Criminal Cases2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Confirmation bias is a tendency to selectively search for and emphasize information that is consistent with a preferred hypothesis, whereas opposing information is ignored or downgraded. This thesis examines the role of confirmation bias in criminal cases, primarily focusing on the Swedish legal setting. It also examines possible debiasing techniques.

    Experimental studies with Swedish police officers, prosecutors and judges (Study I-III) and an archive study of appeals and petitions for new trials (Study IV) were conducted. The results suggest that confirmation bias is at play to varying degrees at different stages of the criminal procedure. Also, the explanations and possible ways to prevent the bias seem to vary for these different stages. In Study I police officers’ more guilt presumptive questions to apprehended than non-apprehended suspects indicate a confirmation bias. This seems primarily driven by cognitive factors and reducing cognitive load is therefore a possible debiasing technique. In Study II prosecutors did not display confirmation bias before but only after the decision to press charges, as they then were less likely to consider additional investigation necessary and suggested more guilt confirming investigation. The driving forces need further examination. Study III suggests that pretrial detentions influence judges’ perception of the evidence strength, making them more likely to convict, in cases where they themselves detained. This is indicative of a confirmation bias with social explanations, which, possibly, can be mitigated by changing decision maker between detention and main hearing. The confirmatory reasoning in Study I-III can be considered rational or irrational, following different types of rationality, like probabilistic or judicial rationality. In Study IV, statistical estimates based on empirical data from the Apellate Courts and the Supreme Court indicate that far from all wrongfully convicted who appeal or petition for a new trial are acquitted. A robustness analysis confirmed that these overall conclusions hold over a wide variety of assumptions regarding unknown parameters.                         

    Also, the usage of empirical methods to study law and legal phenomena is discussed. The concept of Evidence-Based Law (EBL) is used to exemplify how empirical legal research may benefit both legal scholarship and law in a wider sense.

    List of papers
    1. The Presumption of Guilt in Suspect Interrogations: Apprehension as a Trigger of Confirmation Bias and Debiasing Techniques
    Open this publication in new window or tab >>The Presumption of Guilt in Suspect Interrogations: Apprehension as a Trigger of Confirmation Bias and Debiasing Techniques
    2018 (English)In: Law and human behavior, ISSN 0147-7307, E-ISSN 1573-661X, Vol. 42, no 4, p. 336-354Article in journal (Refereed) Published
    Abstract [en]

    This research tests whether a police officer’s decision to apprehend a suspect triggers confirmation bias during an interrogation. The study also tests two strategies to reduce confirmation bias: (1) decoupling decision to apprehend from interrogation and (2) reducing cognitive load for the interrogating police officer. In Experiment 1, Swedish police officers (N = 60) were faced with 12 scenarios in which they either had to decide for themselves whether to apprehend a suspect or were informed about the corresponding decision by another police officer or a prosecutor. Participants then prepared questions for a suspect interrogation and evaluated the trustworthiness of the suspect’s denial or confession. The same method was used in Experiment 2 but with law and psychology students (N = 60) as participants. In Experiment 3, psychology students (N = 60) prepared interrogation questions either by freely producing their own or by choosing questions from a preset list. Overall, apprehended suspects were interrogated in a more guilt presumptive way and rated as less trustworthy than non apprehended suspects. However, the tested debiasing techniques, primarily reducing cognitive load for the interrogating police officer, hold some potential in mitigating this bias.

    Keywords
    confirmation bias, cognitive bias, debias, police, interrogation, apprehension, investigation
    National Category
    Law and Society
    Research subject
    Jurisprudence
    Identifiers
    urn:nbn:se:uu:diva-351671 (URN)10.1037/lhb0000287 (DOI)
    Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-21
    2. From Devil's Advocate to Crime Fighter: Confirmation Bias and Debiasing Techniques in Prosecutorial Decision Making
    Open this publication in new window or tab >>From Devil's Advocate to Crime Fighter: Confirmation Bias and Debiasing Techniques in Prosecutorial Decision Making
    2018 (English)In: Psychology, Crime and Law, ISSN 1068-316X, E-ISSN 1477-2744Article in journal (Refereed) Submitted
    Abstract [en]

    This research examines the role of confirmation bias in prosecutorial decisions

    before, during and after the prosecution. It also evaluates whether confirmation

    bias is reduced by changing decision maker between arrest and prosecution. In

    Experiment 1, Swedish prosecutors (N = 40) assessed 8 scenarios where they

    either decided themselves or were informed about a colleague’s decision to arrest

    or not arrest a suspect. Participants then rated how trustworthy the suspect’s

    statement was as well as the strength of new ambiguous evidence and the total

    evidence. They also decided whether to prosecute and what additional

    investigative measures to undertake. In Experiment 2 the same method was used

    with Law and Psychology students (N = 60). Overall, prosecutors’ assessments

    before the prosecution indicated that they were able to act as their own devil’s

    advocate. Also, their assessments while deciding about whether to prosecute were

    reasonably balanced. However, after pressing charges, they displayed a more

    guilt-confirming mindset, suggesting they then took on the role as crime fighters.

    This differed from the student sample in which higher levels of guilt confirmation

    was displayed in relation to arrested suspects consistently before, during and after

    a prosecution decision. The role of prosecutors’ working experience is discussed.

    Keywords
    confirmation bias, cognitive bias, criminal procedure, arrest, prosecute, debiasing
    National Category
    Law and Society
    Research subject
    Jurisprudence
    Identifiers
    urn:nbn:se:uu:diva-351673 (URN)
    Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-21
    3. "Guilty, No Doubt": Detention Provoking Confirmation Bias in Judges' Guilt Assessments and Debiasing Techniques
    Open this publication in new window or tab >>"Guilty, No Doubt": Detention Provoking Confirmation Bias in Judges' Guilt Assessments and Debiasing Techniques