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  • Disputation: 2018-01-23 09:00 ITC/2446, Uppsala
    Zeljić, Aleksandar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för datorteknik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Datalogi.
    From Machine Arithmetic to Approximations and back again: Improved SMT Methods for Numeric Data Types2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Safety-critical systems, especially those found in avionics and automotive industries, rely on machine arithmetic to perform their tasks: integer arithmetic, fixed-point arithmetic or floating-point arithmetic (FPA). Machine arithmetic exhibits subtle differences in behavior compared to the ideal mathematical arithmetic, due to fixed-size representation in memory. Failure of safety-critical systems is unacceptable, due to high-stakes involving human lives or huge amounts of money, time and effort. By formally proving properties of systems, we can be assured that they meet safety requirements. However, to prove such properties it is necessary to reason about machine arithmetic. SMT techniques for machine arithmetic are lacking scalability. This thesis presents approaches that augment or complement existing SMT techniques for machine arithmetic.

    In this thesis, we explore approximations as a means of augmenting existing decision procedures. A general approximation refinement framework is presented, along with its implementation called UppSAT. The framework solves a sequence of approximations. Initially very crude, these approximations are fairly easy to solve. Results of solving approximate constraints are used to either reconstruct a solution of original constraints, obtain a proof of unsatisfiability or to refine the approximation. The framework preserves soundness, completeness, and termination of the underlying decision procedure, guaranteeing that eventually, either a solution is found or a proof that solution does not exist. We evaluate the impact of approximations implemented in the UppSAT framework on the state-of-the-art in SMT for floating-point arithmetic.

    A novel method to reason about the theory of fixed-width bit-vectors called mcBV is presented. It is an instantiation of the model constructing satisfiability calculus, mcSAT, and uses a new lazy representation of bit-vectors that allows both bit- and word-level reasoning. It uses a greedy explanation generalization mechanism capable of more general learning compared to traditional approaches. Evaluation of mcBV shows that it can outperform bit-blasting on several classes of problems.

    Delarbeten
    1. Deciding bit-vector formulas with mcSAT
    Öppna denna publikation i ny flik eller fönster >>Deciding bit-vector formulas with mcSAT
    2016 (Engelska)Ingår i: Theory and Applications of Satisfiability Testing: SAT 2016, Springer, 2016, 249-266 s.Konferensbidrag, Publicerat paper (Refereegranskat)
    Ort, förlag, år, upplaga, sidor
    Springer, 2016
    Serie
    Lecture Notes in Computer Science, ISSN 0302-9743 ; 9710
    Nationell ämneskategori
    Datavetenskap (datalogi)
    Identifikatorer
    urn:nbn:se:uu:diva-305182 (URN)10.1007/978-3-319-40970-2_16 (DOI)000387430600016 ()978-3-319-40969-6 (ISBN)
    Konferens
    SAT 2016, July 5–8, Bordeaux, France
    Projekt
    UPMARC
    Tillgänglig från: 2016-06-11 Skapad: 2016-10-12 Senast uppdaterad: 2018-01-14Bibliografiskt granskad
    2. An approximation framework for solvers and decision procedures
    Öppna denna publikation i ny flik eller fönster >>An approximation framework for solvers and decision procedures
    2017 (Engelska)Ingår i: Journal of automated reasoning, ISSN 0168-7433, E-ISSN 1573-0670, Vol. 58, nr 1, 127-147 s.Artikel i tidskrift (Refereegranskat) Published
    Nationell ämneskategori
    Datavetenskap (datalogi)
    Identifikatorer
    urn:nbn:se:uu:diva-305180 (URN)10.1007/s10817-016-9393-1 (DOI)000392387400006 ()
    Projekt
    UPMARC
    Tillgänglig från: 2016-11-10 Skapad: 2016-10-12 Senast uppdaterad: 2018-01-14Bibliografiskt granskad
    3. Exploring Approximations for Floating-Point Arithmetic using UppSAT
    Öppna denna publikation i ny flik eller fönster >>Exploring Approximations for Floating-Point Arithmetic using UppSAT
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    We consider the problem of solving floating-point constraints obtained from software verification. We present UppSAT --- a new implementation of a systematic approximation refinement framework [ZWR17] as an abstract SMT solver. Provided with an approximation and a decision procedure (implemented in an off-the-shelf SMT solver), UppSAT yields an approximating SMT solver. Additionally, UppSAT includes a library of predefined approximation components which can be combined and extended to define new encodings, orderings and solving strategies. We propose that UppSAT can be used as a sandbox for easy and flexible exploration of new approximations. To substantiate this, we explore several approximations of floating-point arithmetic. Approximations can be viewed as a composition of an encoding into a target theory, a precision ordering, and a number of strategies for model reconstruction and precision (or approximation) refinement. We present encodings of floating-point arithmetic into reduced precision floating-point arithmetic, real-arithmetic, and fixed-point arithmetic (encoded into the theory of bit-vectors in practice). In an experimental evaluation, we compare the advantages and disadvantages of approximating solvers obtained by combining various encodings and decision procedures (based on existing, state-of-the-art SMT solvers for floating-point, real, and bit-vector arithmetic).

    Nyckelord
    SAT, SMT, approximations, model construction, floating-point arithmetic
    Nationell ämneskategori
    Datavetenskap (datalogi)
    Forskningsämne
    Datavetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-334564 (URN)
    Tillgänglig från: 2017-11-24 Skapad: 2017-11-24 Senast uppdaterad: 2018-01-13
  • Disputation: 2018-01-24 09:15 Hambergsalen, Uppsala
    Vallot, Dorothée
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Luft-, vatten och landskapslära.
    Modelling calving and sliding of Svalbard outlet glaciers: Spatio-temporal changes and interactions2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Future sea level rise associated to global warming is one of the greatest societal and environmental challenges of tomorrow. A large part of the contribution comes from glaciers and ice sheets discharging ice and meltwater into the ocean and the recent worldwide increase is worrying. Future predictions of sea level rise try to encompass the complex processes of ice dynamics through glacier modelling but there are still large uncertainties due to the lack of observations or too coarse parameterisation, particularly for processes occurring at the glacier interfaces with the bed (sliding) and with the ocean (calving). This thesis focuses on modelling these processes from two marine-terminating glaciers in Svalbard, Kronebreen and Tunabreen. By inverting three years of high temporal resolution time-series of surface velocities on Kronebreen, basal properties are retrieved with the ice flow model Elmer/Ice in Paper I. Results suggest that surface melt during the summer greatly influences the dynamics of the following season and that sliding laws for such glaciers should be adapted to local and global processes changing in space and time. The subglacial drainage system, fed by the surface melt, is modelled in Paper II during two melting seasons. Results show different configurations of efficient and inefficient drainage systems between years and the importance of using a sliding law dependent on spatio-temporal changes in effective pressure. The interaction with the ocean is incorporated in Paper III by combining a series of models, including an ice flow model, a plume model and a particle model for discrete calving and compares the output with observations. Results show the importance of glacier geometry, sliding and undercutting on calving rate and location. However, more observations and analytic methods are needed. Time-lapse imagery placed in front of Tunabreen have been deployed and a method of automatic detection for iceberg calving is presented in Paper IV. Results show the influence of the rising plume in calving and the front destabilisation of the local neighbourhood.

    Delarbeten
    1. Basal dynamics of Kronebreen, a fast-flowing tidewater glacier in Svalbard: non-local spatio-temporal response to water input
    Öppna denna publikation i ny flik eller fönster >>Basal dynamics of Kronebreen, a fast-flowing tidewater glacier in Svalbard: non-local spatio-temporal response to water input
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    2017 (Engelska)Ingår i: Journal of Glaciology, ISSN 0022-1430, E-ISSN 1727-5652, 1-13 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    We evaluate the variability in basal friction for Kronebreen, Svalbard, a fast-flowing tidewater glacier. We invert 3 years (2013–15) of surface velocities at high temporal resolution (generally 11 days), to estimate the changing basal properties of the glacier. Our results suggest that sliding behaviour of Kronebreen within a year is primarily influenced by changes in water input patterns during the meltwater season and basal friction is highly variable from a year to another. At present, models usually employ parameterisations to encompass the complex physics of glacier sliding by mathematically simulate their net effect. For such ice masses with strong seasonal variations of surface melt, the spatio-temporal patterns of basal friction imply that it is neither possible nor appropriate to use a parameterisation for bed friction that is fixed in space and/or time, at least in a timescale of a few years. Basal sliding may not only be governed by local processes such as basal topography or summer melt, but also be mediated by factors that vary over a larger distance and over a longer time period such as subglacial hydrology organisation, ice-thickness changes or calving front geometry.

    Nyckelord
    Arctic glaciology, glacier modelling, ice dynamics, ice velocity, subglacial processes
    Nationell ämneskategori
    Naturgeografi
    Forskningsämne
    Geovetenskap med inriktning mot naturgeografi
    Identifikatorer
    urn:nbn:se:uu:diva-334293 (URN)10.1017/jog.2017.69 (DOI)
    Tillgänglig från: 2017-11-22 Skapad: 2017-11-22 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
    2. Modelled subglacial hydrology and basal sliding at Kronebreen, a tidewater glacier in Svalbard
    Öppna denna publikation i ny flik eller fönster >>Modelled subglacial hydrology and basal sliding at Kronebreen, a tidewater glacier in Svalbard
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Multidisciplinär geovetenskap
    Forskningsämne
    Geovetenskap med inriktning mot naturgeografi
    Identifikatorer
    urn:nbn:se:uu:diva-334778 (URN)
    Tillgänglig från: 2017-11-27 Skapad: 2017-11-27 Senast uppdaterad: 2017-11-27
    3. Effects of undercutting and sliding on calving: a global approach applied to Kronebreen, Svalbard
    Öppna denna publikation i ny flik eller fönster >>Effects of undercutting and sliding on calving: a global approach applied to Kronebreen, Svalbard
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    2017 (Engelska)Ingår i: The Cryosphere Discussions, ISSN 1994-0432, E-ISSN 1994-0440, ISSN 1994-0416Artikel i tidskrift (Refereegranskat) Submitted
    Nationell ämneskategori
    Naturvetenskap Multidisciplinär geovetenskap
    Forskningsämne
    Geovetenskap med inriktning mot naturgeografi
    Identifikatorer
    urn:nbn:se:uu:diva-334771 (URN)10.5194/tc-2017-166 (DOI)
    Tillgänglig från: 2017-11-27 Skapad: 2017-11-27 Senast uppdaterad: 2017-11-29
    4. Automatic detection of calving events from time-lapse imagery at Tunabreen, Svalbard
    Öppna denna publikation i ny flik eller fönster >>Automatic detection of calving events from time-lapse imagery at Tunabreen, Svalbard
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Multidisciplinär geovetenskap
    Forskningsämne
    Geovetenskap med inriktning mot naturgeografi
    Identifikatorer
    urn:nbn:se:uu:diva-334776 (URN)
    Tillgänglig från: 2017-11-27 Skapad: 2017-11-27 Senast uppdaterad: 2017-11-27
  • Disputation: 2018-01-27 10:00 Geijersalen: Eng/6-1023, Uppsala
    Palmer, Ryan
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Språkvetenskapliga fakulteten, Engelska institutionen.
    Enchanting Irruptions: Wonder, Noir, and the Environmental Imaginary2017Doktorsavhandling, monografi (Övrigt vetenskapligt)
    Abstract [en]

    This thesis investigates narratives of re-enchantment and disenchantment in three contemporary U.S. novels, Lydia Millet’s Mermaids in Paradise, Karen Tei Yamashita’s Tropic of Orange, and Thomas Pynchon’s Inherent Vice. Drawing on key concepts from ecocritcism and affect theory, I argue that these novels interrogate narratives and affects associated with questions central to the Anthropocene: climate-related dilemmas, questions of environmental justice, and animal ethics. Situating these texts in relation to environmental discourses, I show how affects of wonder and re-enchantment are produced within them through the insertion of anti-mimetic narrative objects into otherwise representationally realistic fictional worlds. These incursions, and the affective shifts they produce, challenge and interrupt in the novels narratives of ecological dread and disenchantment, which I link to the techniques and affects of noir. In each chapter of this study, I show how the dialogical interplay between disenchantment and re-enchantment disrupts preconceptions and assumptions about aspects of ecological crisis, and engenders or reinforces political commitments to environmentally related issues. Chapter One focuses on interspecies politics and animal rights in Mermaids in Paradise, environmental justice is central to the analysis of Tropic of Orange in Chapter Two, and the political dynamics of countercultural environmentalism inform my reading of Inherent Vice in Chapter Three. Throughout, I explore the potential of re-enchantment to suggest an alternative to disenchanted and apocalyptic narratives concerning the environment, and to articulate a productive politics for contemporary ecofiction. 

  • Disputation: 2018-01-27 10:15 Ihresalen, Uppsala
    Sjösvärd, Thomas
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Litteraturvetenskapliga institutionen.
    En himmel av sten: Willy Kyrklund och det grekiska2018Doktorsavhandling, monografi (Övrigt vetenskapligt)
    Abstract [en]

    The aim of this dissertation is to investigate the notion of the ‘Greek’ in the work of Willy Kyrklund [1921–2009].

    Kyrklund authorship can be interpreted as a dialogue with the mythology and literature of ancient Greece. There is also the representation of Greece as both a physical and imaginary location, as well as the depiction of a modern nation. The focus of my study is on the way in which Greek mythology, Greek history, or Greece as a geographical concept function within the context of his fiction in particular.

    The theoretical foundation of the analysis is divided into three sections. The first deals with philology, and philological interpretation as a model for general hermeneutics. The second examines myth, what is perceived as mythical, and which phenomena that are posed as its opposite. The third section explores the literary representation and ideological dimension of geographical space.

    In Kyrklund’s early short prose collections the past is associated with suppressed desire and violence. These notions appear in Kyrklund’s fiction with a suddenness that creates a kind of rupture in the text.

    The novel Polyfem förvandlad [Polyphemus metamorphosed] (1964) develops these themes in a complex arrangement of 15 intertwined episodes.

    In the play Medea från Mbongo [Medea from Mbongo] (dated 1965), it is not primarily the origin of the individual subject’s genesis that is at stake, but that Western civilization. The paradoxes characterising the scenes of the play, in which a so-called civilization is demonstrated to be both violent and mythical in its nature.

    In Elpënor [Elpënor] (1986), an arrangement of a short epic story and two essays, the central intertexts are the Homeric songs. Whereas the ‘fictive’ narrative appears to recount the ‘true’ story of the events depicted in the Odyssey, the paratext ruptures this and makes all readings open to doubt.

    Om godheten [On Goodness] (1988) contains an important metaphor: “Arching above us is a heaven made of stone”. This can be interpreted as an expression of the inability to imagine the state of the world as nothing but created by an existing, albeit indifferent, God.

  • Disputation: 2018-01-29 09:15 Room B42, Uppsala
    Maturi, Varun
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Gene regulation by different proteins of TGFβ superfamily2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The present thesis discusses how gene regulation by transforming growth factor β (TGFβ) family cytokines is affected by post-translational modifications of different transcription factors. The thesis also focuses on gene regulation by transcription factors involved in TGFβ signaling.

    The importance of the poly ADP-ribose polymerase (PARP) family in controlling gene expression in response to TGFβ and bone morphogenetic protein (BMP) is analyzed first. PARP2, along with PARP1, ADP-ribosylates Smad2 and Smad3, the signaling mediators of TGFβ. On the other hand, poly ADP-ribose glycohydrolase (PARG) removes the ADP-ribose from Smad2/3 and antagonizes PARP1 and PARP2. ADP-ribosylation of Smads in turn affects their DNA binding capacity. We then illustrate how PARP1 and PARG can regulate gene expression in response to BMP that signals via Smad1, 5. Over-expression of PARP1 suppressed the transcriptional activity of Smad1/5. Knockdown of PARP1 or over-expression of PARG enhanced the transcriptional activity of BMP-Smads on target genes. Hence our data suggest that ADP-ribosylation of Smad proteins controls both TGFβ and BMP signaling. 

    I then focus on elucidating novel genes that are regulated by ZEB1 and Snail1, two key transcriptional factors in TGFβ signaling, known for their ability to induce EMT and cancer metastasis. Chromatin immunoprecipitation-sequencing (ChIP-seq) and targeted whole genome transcriptomics in triple negative breast cancer cells were used, to find binding regions and the functional impact of ZEB1 and Snail1 throughout the genome. ZEB1 binds to the regulatory sequences of a wide range of genes, not only related to cell invasion, pointing to new functions of ZEB1. On the other hand, Snail1 regulated only a few genes, especially related to signal transduction and cellular movement. Further functional analysis revealed that ZEB1 could regulate the anchorage-independent growth of the triple negative breast cancer cells, whereas Snail1 could regulate the expression of BMP6 in these cells. We have therefore elucidated novel functional roles of the two transcription factors, Snail1 and ZEB1 in triple negative breast cancer cells.

    Delarbeten
    1. Fine-Tuning of Smad Protein Function by Poly(ADP-Ribose) Polymerases and Poly(ADP-Ribose) Glycohydrolase during Transforming Growth Factor β Signaling
    Öppna denna publikation i ny flik eller fönster >>Fine-Tuning of Smad Protein Function by Poly(ADP-Ribose) Polymerases and Poly(ADP-Ribose) Glycohydrolase during Transforming Growth Factor β Signaling
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    2014 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 8, e103651- s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND:

    Initiation, amplitude, duration and termination of transforming growth factor β (TGFβ) signaling via Smad proteins is regulated by post-translational modifications, including phosphorylation, ubiquitination and acetylation. We previously reported that ADP-ribosylation of Smads by poly(ADP-ribose) polymerase 1 (PARP-1) negatively influences Smad-mediated transcription. PARP-1 is known to functionally interact with PARP-2 in the nucleus and the enzyme poly(ADP-ribose) glycohydrolase (PARG) can remove poly(ADP-ribose) chains from target proteins. Here we aimed at analyzing possible cooperation between PARP-1, PARP-2 and PARG in regulation of TGFβ signaling.

    METHODS:

    A robust cell model of TGFβ signaling, i.e. human HaCaT keratinocytes, was used. Endogenous Smad3 ADP-ribosylation and protein complexes between Smads and PARPs were studied using proximity ligation assays and co-immunoprecipitation assays, which were complemented by in vitro ADP-ribosylation assays using recombinant proteins. Real-time RT-PCR analysis of mRNA levels and promoter-reporter assays provided quantitative analysis of gene expression in response to TGFβ stimulation and after genetic perturbations of PARP-1/-2 and PARG based on RNA interference.

    RESULTS:

    TGFβ signaling rapidly induces nuclear ADP-ribosylation of Smad3 that coincides with a relative enhancement of nuclear complexes of Smads with PARP-1 and PARP-2. Inversely, PARG interacts with Smads and can de-ADP-ribosylate Smad3 in vitro. PARP-1 and PARP-2 also form complexes with each other, and Smads interact and activate auto-ADP-ribosylation of both PARP-1 and PARP-2. PARP-2, similar to PARP-1, negatively regulates specific TGFβ target genes (fibronectin, Smad7) and Smad transcriptional responses, and PARG positively regulates these genes. Accordingly, inhibition of TGFβ-mediated transcription caused by silencing endogenous PARG expression could be relieved after simultaneous depletion of PARP-1.

    CONCLUSION:

    Nuclear Smad function is negatively regulated by PARP-1 that is assisted by PARP-2 and positively regulated by PARG during the course of TGFβ signaling.

    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:uu:diva-231920 (URN)10.1371/journal.pone.0103651 (DOI)000341302700014 ()25133494 (PubMedID)
    Tillgänglig från: 2014-09-11 Skapad: 2014-09-11 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    2. Regulation of Bone Morphogenetic Protein Signaling by ADP-ribosylation
    Öppna denna publikation i ny flik eller fönster >>Regulation of Bone Morphogenetic Protein Signaling by ADP-ribosylation
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    2016 (Engelska)Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, nr 24, 12706-12723 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    We previously established a mechanism of negative regulation of transforming growth factor beta signaling mediated by the nuclear ADP-ribosylating enzyme poly-(ADP-ribose) polymerase 1 (PARP1) and the deribosylating enzyme poly-(ADP-ribose) glycohydrolase (PARG), which dynamically regulate ADP-ribosylation of Smad3 and Smad4, two central signaling proteins of the pathway. Here we demonstrate that the bone morphogenetic protein (BMP) pathway can also be regulated by the opposing actions of PARP1 and PARG. PARG positively contributes to BMP signaling and forms physical complexes with Smad5 and Smad4. The positive role PARG plays during BMP signaling can be neutralized by PARP1, as demonstrated by experiments where PARG and PARP1 are simultaneously silenced. In contrast to PARG, ectopic expression of PARP1 suppresses BMP signaling, whereas silencing of endogenous PARP1 enhances signaling and BMP-induced differentiation. The two major Smad proteins of the BMP pathway, Smad1 and Smad5, interact with PARP1 and can be ADP-ribosylated in vitro, whereas PARG causes deribosylation. The overall outcome of this mode of regulation of BMP signal transduction provides a fine-tuning mechanism based on the two major enzymes that control cellular ADP-ribosylation.

    Nationell ämneskategori
    Cell- och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-299724 (URN)10.1074/jbc.M116.729699 (DOI)000378119900024 ()27129221 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, K2010-67X-14936-07-3 K2013-66X-14936-10-5
    Tillgänglig från: 2016-07-26 Skapad: 2016-07-26 Senast uppdaterad: 2018-01-10Bibliografiskt granskad
    3. Genome-wide binding of transcription factor ZEB1 in triple-negative breast cancer cells
    Öppna denna publikation i ny flik eller fönster >>Genome-wide binding of transcription factor ZEB1 in triple-negative breast cancer cells
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    ZEB1, EMT, ChIP-seq, CRISPR-Cas9
    Nationell ämneskategori
    Cellbiologi
    Forskningsämne
    Biokemi; Biologi med inriktning mot molekylär cellbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-334438 (URN)
    Tillgänglig från: 2017-11-23 Skapad: 2017-11-23 Senast uppdaterad: 2017-11-30
    4. Genome-wide binding of transcription factor Snail1 in triple-negative breast cancer cells
    Öppna denna publikation i ny flik eller fönster >>Genome-wide binding of transcription factor Snail1 in triple-negative breast cancer cells
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    ChIP-Seq, Snail1, Ampliseq, EMtT, BMP6
    Nationell ämneskategori
    Cellbiologi
    Forskningsämne
    Biokemi; Biologi med inriktning mot molekylär cellbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-334433 (URN)
    Tillgänglig från: 2017-11-23 Skapad: 2017-11-23 Senast uppdaterad: 2017-11-30
  • Disputation: 2018-02-02 09:00 Rudbecksalen, Uppsala
    Čančer, Matko
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    From Genes to Therapy: Modeling and Novel Therapeutic Strategies for Brain Tumors2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Medulloblastoma is the most common malignant pediatric brain tumor and is molecularly divided into four subgroups – WNT, SHH, Group 3 and Group 4. Two thirds of medulloblastoma patients survive, but survivors often suffer from severe, lifelong side-effects. The MYCN oncogene is deregulated in many medulloblastoma patients. Glioblastoma is the most common malignant brain tumor in adults, with a median survival of about one year. Glioblastoma is a highly heterogeneous tumor where targeted therapy has, so far, not been successful and most glioblastoma patients unfortunately die.

    In our first study we developed three novel humanized models of MYCN-driven SHH medulloblastoma. Histologically and molecularly these models closely resembled the infant class of SHH tumors. Further, we identified a set of clinically relevant genes that had prognostic significance among patients. mTOR signaling pathway was identified as a major contributor to invasion and dissemination, and we showed that mTOR specific inhibition suppressed migration and viability in vitro.

    In the second study we performed a forward genetic screen of retrovirally-induced murine PDGFB-driven gliomas and identified more than fifty candidate cancer-causing genes, of which many were mutated or deregulated in glioblastoma. One of the genes identified in this screen was PPFIBP1, found to be differentially expressed from obstructive retroviral integrations in PDGFB-driven glioma clones. Lower PPFIBP1 expression significantly decreased survival of mice and was found to be suppressed in glioblastoma patients. We propose PPFIBP1 to be a novel tumor suppressor gene that contributes to glioblastoma development.

    In the last study we used a panel of 19 patient-derived glioblastoma cell lines and identified a characteristic expression signature that predicts sensitivity to BET inhibition. BET inhibition resulted in apoptosis and senescence, cell cycle arrest and modulation of DNA damage response. The inhibitory effects of BET inhibition were further enhanced in combination with temozolomide, suggesting a promising future therapy for distinct subgroups of glioblastoma patients.

    This thesis addresses novel molecular findings in medulloblastoma and glioblastoma development, presents clinically relevant brain tumor models, and promising therapeutic approaches that can be used in future clinical trials in malignant pediatric and adult brain tumors.

    Delarbeten
    1. MYCN Drives Disparate Medulloblastoma from Human Embryonic and iPSC-Derived Stem Cells
    Öppna denna publikation i ny flik eller fönster >>MYCN Drives Disparate Medulloblastoma from Human Embryonic and iPSC-Derived Stem Cells
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Cell- och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-334659 (URN)
    Tillgänglig från: 2017-11-25 Skapad: 2017-11-25 Senast uppdaterad: 2018-01-13
    2. An RCAS/tva Forward Genetic Screen Identifies Novel Candidate Genes Involved in Gliomagenesis
    Öppna denna publikation i ny flik eller fönster >>An RCAS/tva Forward Genetic Screen Identifies Novel Candidate Genes Involved in Gliomagenesis
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Cell- och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-334660 (URN)
    Tillgänglig från: 2017-11-25 Skapad: 2017-11-25 Senast uppdaterad: 2018-01-13
    3. BET Inhibition in Combination with Temozolomide Targets Human Glioblastoma Cells
    Öppna denna publikation i ny flik eller fönster >>BET Inhibition in Combination with Temozolomide Targets Human Glioblastoma Cells
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Cell- och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-334661 (URN)
    Tillgänglig från: 2017-11-25 Skapad: 2017-11-25 Senast uppdaterad: 2018-01-13
  • Disputation: 2018-02-02 09:15 Polhemssalen, Ångströmlaboratoriet, Uppsala
    von Fieandt, Linus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Oorganisk kemi.
    Cutting Edge Titanium-based CVD Hard Coatings2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Modern tools for metal cutting applications, such as turning or milling, are typically improved with a thin protective coating. Despite being only a few microns thick, the coating can increase the lifetime of the tool by more than 100 times compared to an uncoated tool. Two different types of techniques are normally used to deposit the coatings, i.e. chemical vapor deposition (CVD) or physical vapor deposition (PVD). A CVD coated tool often includes several different layers. TiN-Ti(C,N)-Al2O3-TiN is a common combination. The research in this thesis has focused on deposition, characterization, and optimization of TiN and Ti(C,N) layers. CVD has been used to deposit all coatings studied in this thesis. They were characterized with a variety of techniques such as: X-ray diffraction, electron microscopy and X-ray photoelectron spectroscopy.

    TiN was deposited on three different substrates, Co, Fe and Ni. It was found that the TiN coating was strongly affected by the substrate. TiN deposited on Fe substrates resulted in a porous interface caused by substrate etching by the reaction gas mixture. CVD of TiN on Ni substrates resulted in an unwanted intermetallic phase (Ni3Ti) in addition to TiN. Etching or corrosion of the Fe substrates could be reduced by lowering the deposition temperature. In addition, the formation of (Ni3Ti) could be significantly reduced by adjusting the partial pressure of the reactant gases. This shows that CVD of TiN on cutting tools with Fe or Ni as a binder phase needs to be optimized with respect to the process parameters.

    Thermodynamic calculations of the Ti(C,N) CVD process indicates that the major growth species using CH3CN, TiCl4 and H2 as precursors, was HCN and TiCl3. They were formed in the gas phase by homogeneous reactions. Furthermore, it was found that by adjusting the composition of the reaction gas mixture, the preferred orientation, morphology, and micro-structure of the Ti(C,N) coatings could be tailored. As a result, the tribological/mechanical properties of the Ti(C,N) coatings could be significantly improved. A hardness of 40 GPa, i.e. close to super hard could for instance be achieved. The origin of the mechanical improvements was attributed to a more ordered crystallographic orientation in the <111> direction as well as a high defect density close to the coating surface. In addition to the excellent mechanical properties, the Ti(C,N) coatings were also found to have a high corrosion resistance in sea water, thanks to a formation of a passivating surface layer (TiO2).

    Delarbeten
    1. Chemical vapor deposition of TiN on transition metal substrates
    Öppna denna publikation i ny flik eller fönster >>Chemical vapor deposition of TiN on transition metal substrates
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    (Engelska)Ingår i: Surface and Coatings TechnologyArtikel i tidskrift (Refereegranskat) Epub ahead of print
    Nationell ämneskategori
    Materialkemi
    Identifikatorer
    urn:nbn:se:uu:diva-335908 (URN)10.1016/j.surfcoat.2017.11.063 (DOI)
    Forskningsfinansiär
    Stiftelsen för strategisk forskning (SSF), RMA15-0048
    Tillgänglig från: 2017-12-10 Skapad: 2017-12-10 Senast uppdaterad: 2017-12-10
    2. Texture formation in chemical vapor deposition of Ti(C,N)
    Öppna denna publikation i ny flik eller fönster >>Texture formation in chemical vapor deposition of Ti(C,N)
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    Growth model, Titanium compounds, Chemical vapor deposition process, X-ray diffraction
    Nationell ämneskategori
    Materialkemi
    Identifikatorer
    urn:nbn:se:uu:diva-335894 (URN)
    Forskningsfinansiär
    Stiftelsen för strategisk forskning (SSF), RMA15-0048Stiftelsen för strategisk forskning (SSF), RIF14-0053Vetenskapsrådet, C0514401
    Tillgänglig från: 2017-12-09 Skapad: 2017-12-09 Senast uppdaterad: 2017-12-10
    3. On the growth, orientation and hardness of chemical vapor deposited Ti(C,N)
    Öppna denna publikation i ny flik eller fönster >>On the growth, orientation and hardness of chemical vapor deposited Ti(C,N)
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    2018 (Engelska)Ingår i: Thin Solid Films, ISSN 0040-6090, E-ISSN 1879-2731, Vol. 645, nr Supplement C, 19-26 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Abstract Chemical vapor deposition (CVD) of Ti(C,N) from a reaction gas mixture of TiCl4, CH3CN, H2 and N2 was investigated with respect to gas phase composition and kinetics. The gas phase composition was modelled by thermodynamic calculations and the growth rate of the CVD process was measured when replacing H2 for N2 while the sum of partial pressures H2+N2 was kept constant. The N2/H2 molar ratio was varied from 0 to 19. Single crystal c-sapphire was used as substrates. It was found that low molar ratios (N2/H2 molar ratio below 0.6) lead to an increased Ti(C,N) growth rate with up to 22%, compared to deposition without added N2. The mechanism responsible for the increased growth rate was attributed to the formation and increased gas phase concentration of one major growth species, HCN, in the gas phase. The texture of the Ti(C,N) films were also studied. ⟨211⟩ textured layers were deposited at N2/H2 molar ratios below 9. At higher molar ratios, ⟨111⟩ oriented Ti(C,N) layers were deposited and the grain size increased considerably. The films deposited at a N2/H2 ratio above 9 exhibited superior hardness, reaching 37GPa. The increased hardness is attributed to an almost epitaxial orientation between the layer and the substrate. The absence of grain twinning in the ⟨111⟩ oriented layer also contributed to the increased hardness.The Ti(C,N) layers were characterized by elastic recoil detection analysis, X-ray photo electron spectroscopy, scanning electron microscopy, X-ray diffraction and nanoindentation.

    Nyckelord
    CVD, Ti(C, N), Hard coating, Thermodynamic modelling
    Nationell ämneskategori
    Materialkemi
    Forskningsämne
    Kemi med inriktning mot oorganisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-334644 (URN)10.1016/j.tsf.2017.10.037 (DOI)
    Forskningsfinansiär
    Stiftelsen för strategisk forskning (SSF), RMA15-0048Stiftelsen för strategisk forskning (SSF), RIF14-0053Vetenskapsrådet, C0514401
    Tillgänglig från: 2017-11-24 Skapad: 2017-11-24 Senast uppdaterad: 2017-12-10Bibliografiskt granskad
    4. Deformation mechanism of highly oriented Ti(C,N) coatings
    Öppna denna publikation i ny flik eller fönster >>Deformation mechanism of highly oriented Ti(C,N) coatings
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Materialkemi
    Identifikatorer
    urn:nbn:se:uu:diva-335906 (URN)
    Forskningsfinansiär
    Stiftelsen för strategisk forskning (SSF), RMA15-0048
    Tillgänglig från: 2017-12-10 Skapad: 2017-12-10 Senast uppdaterad: 2017-12-10
    5. Tribological properties of highly oriented Ti(C,N) deposited by chemical vapor deposition
    Öppna denna publikation i ny flik eller fönster >>Tribological properties of highly oriented Ti(C,N) deposited by chemical vapor deposition
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    (Engelska)Ingår i: Tribology InternationalArtikel i tidskrift (Refereegranskat) Epub ahead of print
    Nationell ämneskategori
    Materialkemi
    Identifikatorer
    urn:nbn:se:uu:diva-335909 (URN)10.1016/j.triboint.2017.11.040 (DOI)
    Forskningsfinansiär
    Stiftelsen för strategisk forskning (SSF), RMA15-0048
    Tillgänglig från: 2017-12-10 Skapad: 2017-12-10 Senast uppdaterad: 2017-12-10
    6. Corrosion properties of CVD grown Ti(C,N) coatings in artificial seawater environment
    Öppna denna publikation i ny flik eller fönster >>Corrosion properties of CVD grown Ti(C,N) coatings in artificial seawater environment
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    Corrosion, Ti(C, N), CVD, XPS
    Nationell ämneskategori
    Materialkemi
    Forskningsämne
    Kemi med inriktning mot oorganisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-335893 (URN)
    Forskningsfinansiär
    Stiftelsen för strategisk forskning (SSF), RMA15-0048
    Tillgänglig från: 2017-12-09 Skapad: 2017-12-09 Senast uppdaterad: 2017-12-10
  • Disputation: 2018-02-02 09:30 Enghoffsalen, Uppsala
    Sidibeh, Cherno Omar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Novel mechanisms of glucocorticoid-induced insulin resistance in human adipose tissue2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The global prevalence of obesity and type 2 diabetes (T2D) is increasing. From a public health perspective, it is therefore of interest to identify common underlying mechanisms of these comorbidities. Glucocorticoids are steroid hormones that are important in stress regulation in mammals. Elevated glucocorticoid levels are associated with insulin resistance (IR) and T2D-like phenotypes. Here, glucocorticoids are used to model a state of IR in human adipose tissue to identify potential pharmacological targets.

    In Paper I the impact of T2D on lipid turnover was examined in a cohort of 20 T2D subjects and 20 healthy controls. Plasma levels of non-esterified fatty acids (NEFA) were shown to be elevated in T2D subjects during oral glucose tolerance test (OGTT) compared to healthy controls. In vitro lipolysis and assessments of mRNA and metabolites in subcutaneous adipose tissue (SAT) were performed. Results showed that elevated NEFA levels in T2D subjects could be attributed to impaired lipid storage.

    In Paper II we explored the role of cannabinoid receptor type 1 (CNR1) in glucocorticoid-induced IR. The CNR1 gene was upregulated after exposure to glucocorticoids in SAT. Moreover, CNR1 gene expression in SAT was associated with markers of IR and elevated in T2D subjects compared to healthy controls. Furthermore, using a CNR1-specific antagonist, we found that CNR1 may mediate lipolysis in SAT.

    In Paper III-IV, we examined the role of FK506 protein 5 (FKBP51) in glucocorticoid-induced IR. Its corresponding gene, FKBP5, was found to be upregulated in SAT and omental adipose tissue (OAT) following glucocorticoid-exposure. In addition, FKBP5 gene expression in SAT was associated with markers of IR and tended to be elevated in T2D subjects compared to healthy controls. Furthermore, co-incubating an FKBP51-specific inhibitor with glucocorticoids in SAT partly prevented glucocorticoid-impaired adipocyte glucose uptake.

    We identified CNR1 and FKBP51 as potential pharmacological targets in T2D and glucocorticoid-induced IR. Both were shown to be elevated in human adipose tissue after glucocorticoid-exposure. Their SAT gene expression levels were also associated with markers of IR and tended to be elevated in T2D. Both may be involved in perturbations of adipocyte metabolism, including glucose and lipid metabolism.

    Delarbeten
    1. Impaired adipose tissue lipid storage, but not altered lipolysis, contributes to elevated levels of NEFA in type 2 diabetes. Degree of hyperglycemia and adiposity are important factors
    Öppna denna publikation i ny flik eller fönster >>Impaired adipose tissue lipid storage, but not altered lipolysis, contributes to elevated levels of NEFA in type 2 diabetes. Degree of hyperglycemia and adiposity are important factors
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    2016 (Engelska)Ingår i: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 65, nr 12, 1768-1780 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background. Elevated levels of circulating non-esterified fatty acids (NEFA) mediate many adverse metabolic effects. In this work we aim to determine the impact of type 2 diabetes (T2D), glycemic control and obesity on lipolysis regulation. Design and Participants. 20 control and 20 metformin-treated T2D subjects were matched for sex (10 M/10 F), age (58 +/- 11 vs 58 +/- 9 y) and BMI (30.8 +/- 4.6 vs 30.7 +/- 4.9 kg/m(2)). In vivo lipolysis was assessed during a 3 h-OGTT with plasma glycerol and NEFA levels. Subcutaneous adipose tissue (SAT) biopsies were obtained to measure mRNA and metabolite levels of factors related to lipolysis and lipid storage and to assess in vitro lipolysis in isolated subcutaneous adipocytes. Results. Plasma NEFA AUC during the OGTT where higher 30% (P = 0.005) in T2D than in control subjects, but plasma glycerol AUC and subcutaneous adipocyte lipolysis in vitro were similar, suggesting that adipose tissue lipolysis is not altered. Expression in SAT of genes involved in lipid storage (FABP4, DGAT1, FASN) were reduced in T2D subjects compared with controls, but no differences were seen for genes involved in lipolysis. T2D subjects had elevated markers of beta-oxidation, alpha-hydroxybutyrate (1.4-fold, P < 0.01) and p-hydroxybutyrate (1.7-fold, P < 0.05) in plasma. In multivariate analysis, HbA1c, visceral adipose tissue volume and sex (male) were significantly associated with NEFA AUC in T2D subjects. Conclusions. In T2D subjects, NEFA turnover is impaired, but not due to defects in lipolysis or lipid beta-oxidation. Impaired adipose NEFA re-esterification or de novo lipogenesis is likely to contribute to higher NEFA plasma levels in T2D. The data suggest that hyperglycemia and adiposity are important contributing factors for the regulation of plasma NEFA concentrations.

    Nyckelord
    Lipolysis, Type 2 diabetes, Adipose tissue, Metabolism, Lipid storage
    Nationell ämneskategori
    Endokrinologi och diabetes
    Identifikatorer
    urn:nbn:se:uu:diva-311176 (URN)10.1016/j.metabol.2016.09.008 (DOI)000388158700007 ()27832864 (PubMedID)
    Forskningsfinansiär
    AstraZenecaDiabetesförbundet
    Tillgänglig från: 2016-12-22 Skapad: 2016-12-22 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    2. Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance
    Öppna denna publikation i ny flik eller fönster >>Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance
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    2017 (Engelska)Ingår i: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 55, nr 3, 839-852 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone. CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity. Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue. Subcutaneous adipose tissue was obtained from well-controlled type 2 diabetes subjects and controls. Subcutaneous adipose tissue gene expression levels of CNR1 and endocannabinoid synthesizing and degrading enzymes were assessed. Furthermore, paired human subcutaneous adipose tissue and omental adipose tissue from non-diabetic volunteers undergoing kidney donation or bariatric surgery, was incubated with or without dexamethasone. Subcutaneous adipose tissue obtained from volunteers through needle biopsy was incubated with or without dexamethasone and in the presence or absence of the CNR1-specific antagonist AM281. CNR1 gene and protein expression, lipolysis and glucose uptake were evaluated. Subcutaneous adipose tissue CNR1 gene expression levels were 2-fold elevated in type 2 diabetes subjects compared with control subjects. Additionally, gene expression levels of CNR1 and endocannabinoid-regulating enzymes from both groups correlated with markers of insulin resistance. Dexamethasone increased CNR1 expression dose-dependently in subcutaneous adipose tissue and omental adipose tissue by up to 25-fold. Dexamethasone pre-treatment of subcutaneous adipose tissue increased lipolysis rate and reduced glucose uptake. Co-incubation with the CNR1 antagonist AM281 prevented the stimulatory effect on lipolysis, but had no effect on glucose uptake. CNR1 is upregulated in states of type 2 diabetes and insulin resistance. Furthermore, CNR1 is involved in glucocorticoid-regulated lipolysis. Peripheral CNR1 could be an interesting drug target in type 2 diabetes and dyslipidemia.

    Ort, förlag, år, upplaga, sidor
    SPRINGER, 2017
    Nyckelord
    Type 2 diabetes, Glucocorticoids, Insulin resistance, Adipose tissue, Endocannabinoid system
    Nationell ämneskategori
    Endokrinologi och diabetes
    Identifikatorer
    urn:nbn:se:uu:diva-320351 (URN)10.1007/s12020-016-1172-6 (DOI)000394966900021 ()27858284 (PubMedID)
    Forskningsfinansiär
    AstraZenecaHjärt-Lungfonden, 20100648Diabetesförbundet
    Tillgänglig från: 2017-04-19 Skapad: 2017-04-19 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    3. FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance
    Öppna denna publikation i ny flik eller fönster >>FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance
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    2014 (Engelska)Ingår i: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 63, nr 9, 1198-1208 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective

    To study effects of dexamethasone on gene expression in human adipose tissue aiming to identify potential novel mechanisms for glucocorticoid-induced insulin resistance.

    Materials/methods

    Subcutaneous and omental adipose tissue, obtained from non-diabetic donors (10 M/15 F; age: 28–60 years; BMI: 20.7–30.6 kg/m2), was incubated with or without dexamethasone (0.003–3 μmol/L) for 24 h. Gene expression was assessed by microarray and real time-PCR and protein expression by immunoblotting.

    Results

    FKBP5 (FK506-binding protein 5) and CNR1 (cannabinoid receptor 1) were the most responsive genes to dexamethasone in both subcutaneous and omental adipose tissue (~ 7-fold). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots. The gene product, FKBP51 protein, was 10-fold higher in the omental than in the subcutaneous depot, whereas the mRNA levels were similar. Higher FKBP5 gene expression in omental adipose tissue was associated with reduced insulin effects on glucose uptake in both depots. Furthermore, FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter and negatively with plasma HDL-cholesterol. FKBP5 SNPs were found to be associated with type 2 diabetes and diabetes-related phenotypes in large population-based samples.

    Conclusions

    Dexamethasone exposure promotes expression of FKBP5 in adipose tissue, a gene that may be implicated in glucocorticoid-induced insulin resistance.

    Nationell ämneskategori
    Endokrinologi och diabetes
    Identifikatorer
    urn:nbn:se:uu:diva-232423 (URN)10.1016/j.metabol.2014.05.015 (DOI)000340864400014 ()24997500 (PubMedID)
    Tillgänglig från: 2014-09-17 Skapad: 2014-09-17 Senast uppdaterad: 2017-12-06
    4. FKBP5 expression in human adipose tissue: Potential role in glucose and lipid metabolism, adipogenesis and type 2 diabetes
    Öppna denna publikation i ny flik eller fönster >>FKBP5 expression in human adipose tissue: Potential role in glucose and lipid metabolism, adipogenesis and type 2 diabetes
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    2017 (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Abstract [en]

    Background and aims

    High levels of glucocorticoids can contribute to dyslipidemia, obesity, insulin resistance (IR) and the onset of diabetes with properties similar to type 2 diabetes (T2D). We recently showed that the FKBP5 is one of the genes with the greatest increase in human adipose tissue following exposure to the synthetic glucocorticoid dexamethasone. FKBP5 codes for FKBP51, a co-chaperone of the glucocorticoid receptor (GR) complex. Here, we explore the involvement of FKBP51 in glucocorticoid-induced IR in human subcutaneous adipose tissue (SAT), including its potential role in T2D. Moreover, we assess the metabolic effects of reducing the activity of FKBP51 by the use of the specific inhibitor SAFit1.

    Materials and Methods

    FKBP5 gene expression was assessed in fresh SAT explants in a separate cohort of 20 T2D subjects group-wise matched by gender, age and BMI to 20 non-diabetic subjects. In addition, human SAT was obtained from non-diabetic volunteers (19F/9M) by needle biopsies of the lower abdominal region. SAT was incubated for 24 h with or without dexamethasone and the FKBP51-specific inhibitor SAFit1. Incubated SAT was used to measure the glucose uptake rate of isolated adipocytes (n=19) or to measure the expression levels of genes known to be regulated by the GR-complex (n=9).

    Results

    The FKBP5 gene expression levels in SAT showed a tendency of being about 10% higher in T2D subjects compared to non-diabetic subjects (p=0.088). In addition, FKBP5 gene expression levels positively correlated with several markers of IR, including glucose area under the curve during oral glucose tolerance test (r=0.33, p<0.05). FKBP5 gene expression levels were found to inversely correlate with lipolytic, lipogenic and adipogenic genes. These included ATGL, PLIN3, DGAT2 PPARG and CEBPA (r=-0.50, r=-0.47, r=-0.44, r=-0.43, r=-0.50, respectively, p<0.01 for all). Dexamethasone was shown to up- or downregulate several genes known to be regulated by the GR-complex. Co-incubation with the FKBP51-selective inhibitor, SAFit1, had no effect on these gene expression levels. SAFit1 was partly able to prevent the inhibitory effects of dexamethasone on glucose uptake.

    Nationell ämneskategori
    Endokrinologi och diabetes
    Identifikatorer
    urn:nbn:se:uu:diva-334197 (URN)
    Tillgänglig från: 2017-12-06 Skapad: 2017-12-06 Senast uppdaterad: 2017-12-06
  • Disputation: 2018-02-02 10:00 Hambergsalen, Geocentrum, Uppsala
    Brodic, Bojan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Geofysik.
    Three-component digital-based seismic landstreamer: Methodologies for infrastructure planning applications2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    To support urban infrastructure planning projects, along with various other near-surface applications, a multicomponent landstreamer was developed. The landstreamer was built with broadband (0-800 Hz), three-component (3C) micro-electro-mechanical system (MEMS) sensors. The digital nature of the MEMS sensors makes the developed landstreamer insensitive to electric/electromagnetic noise.

    The landstreamer’s design and its seismic imaging capabilities, along with the MEMS technical specifications, were evaluated in several studies. When comparing signals recorded with the streamer with planted MEMS sensors, no negative effects of the design were noted. Compared to different geophones tested, the streamer produced higher quality and broader signal bandwidth data. Additionally, a seismic study conducted in a tunnel demonstrated its electric/electromagnetic noise insensitivity. The streamer combined with wireless seismic recorders was used to survey logistically challenging areas for improved imaging and characterizations and avoid interference with traffic.

    For example, at the Stockholm Bypass site, the landstreamer recorded data were used for traveltime tomography with results showing a well delineated bedrock level and potential low-velocity zones matching with inferred poor-quality-class rocks. The seismic response of fractures and their extent between a tunnel and the surface was studied at the Äspö Hard Rock Laboratory site. The velocity model obtained using the traveltime tomography approach showed known well-characterized fracture systems and potential additional formerly unknown ones. Additionally, compressional- and shear-wave velocities, seismic quality factors, Vp/Vs and dynamic Poisson’s ratios of the known fracture zones were obtained. Fractures and/or weakness zones in the bedrock were imaged using refraction and reflection imaging methods at a site contaminated with a cancerogenic pollutant in southwest Sweden, illustrating the potential of the streamer for environmental-related applications. In southern Finland, the landstreamer was used for SH-wave reflection seismic imaging from a vertically oriented impact source with the results showing a well-delineated bedrock level and weak reflections correlating well with geology. At the same site, its potential for multichannel analysis of surface waves (MASW) was demonstrated. The surface-wave obtained shear-wave velocities match well with the borehole based stratigraphy of the site and are complementary to the SH-wave reflectivity and previous investigations at the site.

    Studies conducted in this thesis demonstrate the landstreamer’s potential for various near-surface applications and show the benefits and need for 3C seismic data recording. 

    Delarbeten
    1. Multicomponent broadband digital-based seismic landstreamer for near-surface applications
    Öppna denna publikation i ny flik eller fönster >>Multicomponent broadband digital-based seismic landstreamer for near-surface applications
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    2015 (Engelska)Ingår i: Journal of Applied Geophysics, ISSN 0926-9851, E-ISSN 1879-1859, Vol. 123, 227-241 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    During the last few decades there has been an increased demand for infrastructure, along with a greater awareness of environmental issues in the construction industry. These factors have contributed to an increased interest in using seismic methods for near surface characterization, particularly in urban environments. Seismic sensors not affected by anthropogenic electromagnetic noise are therefore important, as well as an acquisition system that is easy to deploy, move and non-invasive. To address some of these challenges, a multicomponent broadband MEMS (micro-electro mechanical system) based landstreamer system was developed. The landstreamer system is fully digital, therefore it is less sensitive to electrical or electromagnetic noise. Crosstalk, leakage and tilting tests show that the system is superior to its predecessors. The broadband nature of the sensors (theoretically 0–800 Hz), 3C (three-component) recording and the close spacing of the sensors enable high-resolution imaging. The current streamer configuration consists of 20 sensors 4 m apart and 80 sensors 2 m apart. The streamer can easily be combined with wireless recorders for simultaneous data acquisition. In this study, we present results from testing of the streamer with various sources, such as a shear wave vibrator and different types of impact sources. MEMS-sensors and their high sensitivity allowed recording clear reflections that were not observed with coil-based sensors. A complementary test was also carried out at a planned access ramp for an urban tunnel where potential poor quality rocks had been identified by drilling. First-break traveltime tomography showed that these poor quality rocks correlate with low velocity zones. The presented landstreamer system has great potential for characterizing the subsurface in noisy environments.

    Nyckelord
    Landstreamer, MEMS, Tomography, Near-surface, Urban environment
    Nationell ämneskategori
    Geofysik
    Identifikatorer
    urn:nbn:se:uu:diva-267390 (URN)10.1016/j.jappgeo.2015.10.009 (DOI)000366073400022 ()
    Forskningsfinansiär
    Forskningsrådet Formas, 252-2012-1907
    Tillgänglig från: 2015-11-21 Skapad: 2015-11-21 Senast uppdaterad: 2017-12-10Bibliografiskt granskad
    2. Delineating fracture zones using surface-tunnel-surfaceseismic data, P-S, and S-P mode conversions
    Öppna denna publikation i ny flik eller fönster >>Delineating fracture zones using surface-tunnel-surfaceseismic data, P-S, and S-P mode conversions
    2017 (Engelska)Ingår i: Journal of Geophysical Research - Solid Earth, ISSN 2169-9313, E-ISSN 2169-9356, Vol. 122, nr 7, 5493-5516 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A surface-tunnel-surface seismic experiment was conducted at the Äspö Hard Rock Laboratoryto study the seismic response of major fracture systems intersecting the tunnel. A newly developedthree-component microelectromechanical sensor-based seismic landstreamer was deployed inside the noisytunnel along with conventional seismic receivers. In addition to these, wireless recorders were placed on thesurface. This combination enabled simultaneous recording of the seismic wavefield both inside the tunneland on the surface. The landstreamer was positioned between two geophone-based line segments, alongthe interval where known fracture systems intersect the tunnel. First arrival tomography produced a velocitymodel of the rock mass between the tunnel and the surface with anomalous low-velocity zones correlatingwell with locations of known fracture systems. Prominent wave mode converted direct and reflected signals,P-S and S-P waves, were observed in numerous source gathers recorded inside the tunnel. Forward traveltime and 2-D finite difference elastic modeling, based on the known geometry of the fracture systems, showthat the converted waves are generated at these systems. Additionally, the landstreamer data were used toestimate Vp/Vs, Poisson’s ratio, and seismic attenuation factors (Qp and Qs) over fracture sets that havedifferent hydraulic conductivities. The low-conductivity fracture sets have greater reductions in P wavevelocities and Poisson’s ratio and are more attenuating than the highly hydraulically conductive fracture set.Our investigations contribute to fracture zone characterization on a scale corresponding to seismicexploration wavelengths.

    Nationell ämneskategori
    Geofysik
    Forskningsämne
    Geofysik med inriktning mot fasta jordens fysik
    Identifikatorer
    urn:nbn:se:uu:diva-327949 (URN)10.1002/2017JB014304 (DOI)000409366700040 ()
    Tillgänglig från: 2017-08-14 Skapad: 2017-08-14 Senast uppdaterad: 2017-12-20Bibliografiskt granskad
    3. Multi-component digital-based seismic landstreamer and boat-towed radio-magnetotelluric acquisition systems for improved subsurface characterization in the urban environment
    Öppna denna publikation i ny flik eller fönster >>Multi-component digital-based seismic landstreamer and boat-towed radio-magnetotelluric acquisition systems for improved subsurface characterization in the urban environment
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    2017 (Engelska)Ingår i: First Break, ISSN 0263-5046, E-ISSN 1365-2397, Vol. 35, nr 8, 41-47 s.Artikel i tidskrift (Övrigt vetenskapligt) Published
    Abstract [en]

    It is estimated that urban life will be the norm for around 60% of the world’s population by 2040, leading to a more centralized distribution of people and making the city as the main place of residence (Whiteley, 2009). This population centralization inherently implies rapidly expanding cities and imposes the need for more infrastructure within, around and between the present city boundaries. However, infrastructure projects nowadays have to follow strict civil engineering standards that require detailed knowledge of subsurface conditions during different stages of the construction processes. Since direct methods conventionally used for site characterization (e.g., drilling and/or core testing) are still relatively expensive the focus in the last two decades has been on non-invasive, geophysical methods. However, geophysical site characterization in urban areas is not an easy task owing to numerous challenges and various types of noise sources. Challenges such as electric/electromagnetic (EM) noise, pipelines and other subsurface objects (sometimes even unknown or undocumented), the inability to properly couple sensors because of pavement, traffic noises and limited space are common in urban environment. Since geophysical surveys need to be done with the least amount of disturbances to the environment, residents and traffic, new geophysical techniques for fast, non-invasive and high-resolution site characterization are needed. To overcome some of these challenges, a nationwide joint industry-academia project was launched in 2012 TUST GeoInfra, www.trust-geoinfra.se). As a component in the project, Uppsala University developed two new data acquisition systems. These are a fully digital MEMS-based (Micro-machined Electro-Mechanical Sensor) three component (3C) seismic landstreamer and a boat-towed radio-magnetotelluric (RMT) acquisition system. Both systems were specifically designed to address urban environments with the RMT system particularly aiming at efficient and cost-effective geophysical surveying on shallow-water bodies, which constitute 7% of Scandinavia. In this article, we will describe the two systems and present two case studies illustrating their potential. A number of published accounts are now available from the two systems showing what type of problems they can address (e.g., Bastani et al., 2015; Brodic et al., 2015; Malehmir et al., 2015a, 2015b, 2016a, 2016b, 2017; Dehghannejad et al., 2017; Maries et al., 2017; Mehta et al., 2017; Brodic et al., 2017).

    Ort, förlag, år, upplaga, sidor
    Amsterdam, Netherlands: , 2017
    Nationell ämneskategori
    Geofysik
    Identifikatorer
    urn:nbn:se:uu:diva-327951 (URN)
    Projekt
    TRUST Geoinfra
    Tillgänglig från: 2017-08-14 Skapad: 2017-08-14 Senast uppdaterad: 2017-12-10Bibliografiskt granskad
    4. 3C seismic landstreamer study of an esker architecture through shear- and surface-wave imaging
    Öppna denna publikation i ny flik eller fönster >>3C seismic landstreamer study of an esker architecture through shear- and surface-wave imaging
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    As a continuation of a seismic experiment to test the capability of a newly developed 3C(three component) MEMS-based (microelectro-mechanical system) seismic landstreamer fordelineating an esker core (porous glacial sediments), depth to water table and bedrock insouthwestern Finland, additional analysis of the same dataset was performed. The seismic sourceused was a 500-kg vertical impact drophammer. We report results from one of the horizontalcomponents of the landstreamer data, the transverse (SH-wave) component. In addition to this,we complement the interpretation conducted previously on P-wave stacked section with surfacewavederived shear-wave velocities and Vp/Vs ratios along the entire profile.Although the seismic source used is of vertical-type nature, peculiarly, the data inspectionshowed clear bedrock reflection on the SH-wave component. This observation led us toscrutinize the transverse component data through side-by-side inspection of the shot records onall the three components and particle motion (hodograms) analysis to confirm the pure shearnature of the reflection. Using the apparent moveout velocity of the reflection, as well as knowndepth to bedrock based on drilling, we employed finite-difference synthetic modelling to furtherverify the nature of the reflection. Compared to the P-wave seismic section, bedrock is moreaccurately delineated on the SH-wave section. Some structures connected to the MUKH(morphologically undetectable kettle hole) imaged on the P-wave results are also notable on theSH-wave section, and particularly on the surface-wave derived shear-wave velocity model. Ourresults indicate that the SH-wave energy is generated at the source location itself. This study isencouraging and illustrates why multicomponent seismic data should be acquired and analyzedfor near-surface applications.

    Nyckelord
    landstreamer, shear-waves, surface-waves, MASW
    Nationell ämneskategori
    Geofysik
    Forskningsämne
    Geofysik med inriktning mot fasta jordens fysik
    Identifikatorer
    urn:nbn:se:uu:diva-335429 (URN)
    Tillgänglig från: 2017-12-05 Skapad: 2017-12-05 Senast uppdaterad: 2017-12-10
  • Disputation: 2018-02-02 10:15 Sal IX, Universitetshuset, Uppsala
    Johansson, Caroline
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Juridiska fakulteten, Juridiska institutionen.
    Tjänstepensionen möter EU-rätten: Om relationen mellan svenska kollektivavtal och den inre marknaden2018Doktorsavhandling, monografi (Övrigt vetenskapligt)
    Abstract [en]

     

    The occupational pension constitutes an important part of the total pension for most employees in Sweden. The large part of the occupational pension plans are decided through collective agreement on confederate level and the social partners are given a large scope regarding contributions, requirements and administration. The main focus of the thesis regards the relation between the Swedish collectively bargained, occupational pension and EU internal market law. The aim is to describe how they interrelate and identify tensions between the two. Before that, the Swedish occupational pension is examined. First, a historical account is given regarding both the occupational and the public pension. Thereafter, the occupational pension’s modern structure is analysed, set out from the pension plan for white collar workers in the private sector. The occupational pension then serves as the basis for the analysis of the EU internal market law. This part contains one chapter on competition law and collective agreements, one chapter on the free movement of financial services and one chapter on the free movement of workers and occupational pension rights. To conclude, the thesis connects to overarching questions regarding the scope for different welfare solutions within the EU.

  • Disputation: 2018-02-02 13:00 Lecture hall, Falun
    Källman, Hans-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Dose Management in Diagnostic Radiology - application of the DICOM imaging standard and a Monte Carlo dose engine for exposure surveillance2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Ionizing radiation is used in diagnostic radiology with a large contribution to the health of the patients. The regulations to limit the detrimental effects, e.g. cancer induction, are based on recommendations from the International Commission on Radiological Protection (ICRP). Epidemiological evidence for radiation induced cancer is expressed as a function of absorbed dose in the irradiated organs. The committee for Biological Effects of Ionizing Radiation has favored the use of Lifetime Attributable Risk, a risk estimator applicable to individuals exposed in medical applications. The imaging in radiology complies with a technical standard that potentiates the retrieval of exposure information that can be used in optimization of patient exposure. The information can also be used as input in organ dose calculations.

    The aims were to apply the benefits of the technical image standard to radiation safety management by automated collection and analysis of exposure data and to adapt a Therapy Planning System (TPS) for radiotherapy to calculate dose for a Computed Tomography (CT) machine.

    An automated workflow for extraction, communication and analysis of exposure data from the image files in the central image archive was defined and implemented at the institution (papers I-II). A source model for Monte Carlo simulation of the CT was developed taking into consideration the energy spectrum of the photons, the spiral movement of the X-ray beam, the beam shaping filter and the tube current modulation (paper III). The source model was used exploring the possibilities to utilize the tissue characterization methods and segmentation tools available in the TPS to devise a strategy to automate organ dose calculations for patients undergoing thorax examinations in a CT (paper IV).

    The exposure data workflow was finalized showing that the technical standard for images could supply a framework for automated assembly and analysis of the data, supporting the local implementation of optimization. The CT was modeled with regard to its irradiation characteristics with uncertainties in the dose calculations below 4%. Dose calculations with the tissue characterization methods available in the TPS deviated by less than 2% from measurements and a strategy for automation of organ dose calculations was devised that could facilitate individual risk estimates in CT.

    Delarbeten
    1. DICOM Metadata repository for technical information in digital medical images
    Öppna denna publikation i ny flik eller fönster >>DICOM Metadata repository for technical information in digital medical images
    2009 (Engelska)Ingår i: Acta Oncologica, Vol. 48, nr 2, 285-288 s.Artikel i tidskrift (Refereegranskat) Published
    Ort, förlag, år, upplaga, sidor
    Taylor & Francis, 2009
    Nationell ämneskategori
    Annan fysik
    Identifikatorer
    urn:nbn:se:uu:diva-335529 (URN)
    Tillgänglig från: 2017-12-06 Skapad: 2017-12-06 Senast uppdaterad: 2017-12-08
    2. Automated detection of changes in patient exposure in digital projection radiography using exposure index from DICOM header metadata
    Öppna denna publikation i ny flik eller fönster >>Automated detection of changes in patient exposure in digital projection radiography using exposure index from DICOM header metadata
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    2011 (Engelska)Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, nr 6, 960-965 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Purpose. Automated collection of image data from DICOM headers enables monitoring of patient dose and image quality parameters. Manual monitoring is time consuming, owing to the large number of exposure scenarios, thus automated methods for monitoring needs to be investigated. The aim of the present work was to develop and optimise such a method. Material and methods. Exposure index values from digital systems in projection radiography were collected over a period of five years, representing data from 1.2 million projection images. The exposure index values were converted to detector dose and an automated method for detection of sustained level shifts in the resulting detector dose time series was applied using the statistical analysis tool R. The method combined handling of outliers, filtering and estimation of variation in combination with two different statistical rank tests for level shift detection. A set of 304 time series representing central body parts was selected and the level shift detection method was optimised using level shifts identified by ocular evaluation as the gold standard. Results. Two hundred and eighty-one level changes were identified that were deemed in need of further investigation. The majority of these changes were abrupt. The sensitivity and specificity of the optimised and automated detection method concerning the ocular evaluation were 0.870 and 0.997, respectively, for detected abrupt changes. Conclusions. An automated analysis of exposure index values, with the purpose of detecting changes in exposure, can be performed using the R software in combination with a DICOM header metadata repository containing the exposure index values from the images. The routine described has good sensitivity and acceptable specificity for a wide range of central body part projections and can be optimised for more specialised purposes.

    Nationell ämneskategori
    Radiologi och bildbehandling
    Identifikatorer
    urn:nbn:se:uu:diva-156931 (URN)10.3109/0284186X.2011.579622 (DOI)000292841500029 ()
    Tillgänglig från: 2011-08-20 Skapad: 2011-08-11 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
    3. Source modeling for Monte Carlo dose calculation of CT examinations with a radiotherapy treatment planning system
    Öppna denna publikation i ny flik eller fönster >>Source modeling for Monte Carlo dose calculation of CT examinations with a radiotherapy treatment planning system
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    2016 (Engelska)Ingår i: Medical physics (Lancaster), ISSN 0094-2405, Vol. 43, nr 11, 6118-6128 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Purpose: Radiation dose to patients undergoing examinations with Multislice Computed Tomography (MSCT) as well as Cone Beam Computed Tomography (CBCT) is a matter of concern. Risk management could benefit from efficient replace rational dose calculation tools. The paper aims to verify MSCT dose calculations using a Treatment Planning System (TPS) for radiotherapy and to evaluate four different variations of bow-tie filter characterizations for the beam model used in the dose calculations. Methods: A TPS (RayStation (TM), RaySearch Laboratories, Stockholm, Sweden) was configured to calculate dose from a MSCT (GE Healthcare, Wauwatosa, WI, USA). The x-ray beam was characterized in a stationary position the by measurements of the Half-Value Layer (HVL) in aluminum and kerma along the principal axes of the isocenter plane perpendicular to the beam. A Monte Carlo source model for the dose calculation was applied with four different variations on the beam-shaping bow-tie filter, taking into account the different degrees of HVL information but reconstructing the measured kerma distribution after the bow-tie filter by adjusting the photon sampling function. The resulting dose calculations were verified by comparison with measurements in solid water as well as in an anthropomorphic phantom. Results: The calculated depth dose in solid water as well as the relative dose profiles was in agreement with the corresponding measured values. Doses calculated in the anthropomorphic phantom in the range 26-55 mGy agreed with the corresponding thermo luminescence dosimeter (TLD) measurements. Deviations between measurements and calculations were of the order of the measurement uncertainties. There was no significant difference between the different variations on the bow-tie filter modeling. Conclusions: Under the assumption that the calculated kerma after the bow-tie filter replicates the measured kerma, the central specification of the HVL of the x-ray beam together with the kerma distribution can be used to characterize the beam. Thus, within the limits of the study, a flat bow-tie filter with an HVL specified by the vendor suffices to calculate the dose distribution. The TPS could be successfully configured to replicate the beam movement and intensity modulation of a spiral scan with dose modulation, on the basis of the specifications available in the metadata of the digital images and the log file of the CT.

    Nyckelord
    radiation exposure, radiation oncology, tomography, x-ray computed, Monte Carlo method, risk management
    Nationell ämneskategori
    Radiologi och bildbehandling
    Identifikatorer
    urn:nbn:se:uu:diva-310771 (URN)10.1118/1.4965043 (DOI)000387007500033 ()27806588 (PubMedID)
    Tillgänglig från: 2016-12-19 Skapad: 2016-12-19 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
    4. Towards automated and personalized organ dose determination in CT examinations – influence of tissue data representations for Monte Carlo dose calculation with a Therapy Planning System
    Öppna denna publikation i ny flik eller fönster >>Towards automated and personalized organ dose determination in CT examinations – influence of tissue data representations for Monte Carlo dose calculation with a Therapy Planning System
    (Engelska)Ingår i: Medical physics (Lancaster), ISSN 0094-2405Artikel i tidskrift (Refereegranskat) Submitted
    Nationell ämneskategori
    Annan fysik
    Identifikatorer
    urn:nbn:se:uu:diva-335555 (URN)
    Tillgänglig från: 2017-12-06 Skapad: 2017-12-06 Senast uppdaterad: 2017-12-08
  • Disputation: 2018-02-02 13:00 Polhemsalen, Uppsala
    Hultman, Erik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Elektricitetslära.
    Robotized Production Methods for Special Electric Machines2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    A research project on renewable energy conversion from ocean waves to electricity was started at the Division of Electricity at Uppsala University (UU) in 2001. The Wave Energy Converter (WEC) unit developed in this project is intended to be used in large offshore WEC farms and has therefore been designed with large-scale production in mind. The concept has now also been commercialized by the spin-off company Seabased Industry AB.

    An essential part of the UU WEC is the linear direct-drive generator. This thesis presents the pilot work on developing robotized production methods for this special electric machine. The generator design is here investigated and four different backbreaking, monotone, potentially hazardous and time consuming manual production tasks are selected for automation. A robot cell with special automation equipment is then developed and constructed for each task. Simplicity, reliability and flexibility are prioritized and older model pre-owned industrial robots are used throughout the work. The robot cells are evaluated both analytically and experimentally, with focus on full scale experiments. It is likely that the developed production methods can be applied also for other similar electric machines.

    The main focus in the thesis is on robotized stator cable winding. The here presented robot cell is, to the knowledge of the author, the first fully automated stator cable winding setup. Fully automated winding with high and consistent quality and high flexibility is demonstrated. Significant potential cost savings compared to manual winding are also indicated. The robot cell is well prepared for production, but further work is required to improve its reliability.

    The other three developed robot cells are used for stator stacking, surface mounting of permanent magnets on translators and machining of rubber discs. All robot cell concepts are experimentally validated and considerable potential cost savings compared to manual production are indicated. Further work is however required with regards to autonomy and reliability.

    Finally, the thesis presents a pedagogical development work connected to the research on robotized production methods. A first cycle course on automation and robot engineering is here completely reworked, as it is structured around three real-world group project tasks. The new course is evaluated from the examination results, the students’ course evaluations and the feedback from the teachers during six years. The students greatly appreciated the new course. It is indicated that the developed teaching approach is effective in teaching both classical and modern engineering skills.

    Delarbeten
    1. Electromagnetic, Mechanical and Manufacturing Properties for Cable Wound Direct-Drive PM Linear Generators for Offshore Environments
    Öppna denna publikation i ny flik eller fönster >>Electromagnetic, Mechanical and Manufacturing Properties for Cable Wound Direct-Drive PM Linear Generators for Offshore Environments
    2012 (Engelska)Ingår i: Proceedings of the ASME 31st International Conference on Ocean, Offshore and Arctic Engineering, 2012, VOL 4, 2012, 441-447 s.Konferensbidrag, Publicerat paper (Refereegranskat)
    Abstract [en]

    Renewable energy conversion in offshore environments, such as wave, wind and tidal energy, can potentially give a considerable contribution to the global electric energy demand. These harsh environments require robust generators with minimal need for maintenance at competitive costs. To reduce the generator cost, the electromagnetic design must be done with manufacturing in mind. An optimal design provides high electric efficiency, long device life-time, little need for maintenance and low manufacturing costs. Modern simulation tools can be used to optimize the electromagnetic design of a generator for a specific task and operation mode. Hereby both electromagnetic losses and material stresses can be reduced. Industrial robots might provide new possibilities to automate generator-specific manufacturing tasks. A generator design with a cable wound stator, surface mounted permanent magnets on the translator and direct-drive linear technology is investigated in this article. This concept has a simpler and more robust mechanical design, while both the electromagnetic losses and the need for maintenance are reduced. By reducing the number of generator assembly steps, manufacturing might also be facilitated. Further work is however needed in developing automated assembly methods and comparing them to conventional generator manufacturing.

    Nationell ämneskategori
    Teknik och teknologier
    Forskningsämne
    Teknisk fysik med inriktning mot elektricitetslära
    Identifikatorer
    urn:nbn:se:uu:diva-190222 (URN)000324655900049 ()978-0-7918-4491-5 (ISBN)
    Konferens
    31st International Conference on Ocean, Offshore and Arctic Engineering, Jul 1-6, 2012, Rio de Janeiro, Brazil
    Tillgänglig från: 2013-01-07 Skapad: 2013-01-07 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    2. Status Update of the Wave Energy Research at Uppsala University
    Öppna denna publikation i ny flik eller fönster >>Status Update of the Wave Energy Research at Uppsala University
    Visa övriga...
    2013 (Engelska)Konferensbidrag, Publicerat paper (Refereegranskat)
    Ort, förlag, år, upplaga, sidor
    Aalborg, Denmark: , 2013
    Nationell ämneskategori
    Teknik och teknologier
    Forskningsämne
    Teknisk fysik med inriktning mot elektricitetslära
    Identifikatorer
    urn:nbn:se:uu:diva-212701 (URN)
    Konferens
    10th European Wave and Tidal Conference (EWTEC)
    Tillgänglig från: 2013-12-13 Skapad: 2013-12-13 Senast uppdaterad: 2017-12-07
    3. Preparing the Uppsala University wave energy converter generator for large-scale production
    Öppna denna publikation i ny flik eller fönster >>Preparing the Uppsala University wave energy converter generator for large-scale production
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    2014 (Engelska)Konferensbidrag, Publicerat paper (Övrigt vetenskapligt)
    Ort, förlag, år, upplaga, sidor
    Halifax, Canada: , 2014
    Nationell ämneskategori
    Teknik och teknologier
    Identifikatorer
    urn:nbn:se:uu:diva-237554 (URN)
    Konferens
    5th International Conference on Ocean Energy
    Tillgänglig från: 2014-12-03 Skapad: 2014-12-03 Senast uppdaterad: 2017-12-07
    4. Utilizing cable winding and industrial robots to facilitate the manufacturing of electric machines
    Öppna denna publikation i ny flik eller fönster >>Utilizing cable winding and industrial robots to facilitate the manufacturing of electric machines
    2013 (Engelska)Ingår i: Robotics and Computer-Integrated Manufacturing, ISSN 0736-5845, E-ISSN 1879-2537, Vol. 29, nr 1, 246-256 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Cable wound electric machines are used mainly for high voltage and direct-drive applications. They can be found in areas such as wind power, hydropower, wave power and high-voltage motors. Compared to conventional winding techniques, cable winding includes fewer manufacturing steps and is therefore likely to be better suited for automated production. Automation of the cable winding production step is a crucial task in order to lower the manufacturing costs of these machines. This article presents a production method using industrial robots for automation of cable winding of electric machine stators. The concept presented is validated through computer simulations and full-scale winding experiments, including a constructed robot-held cable feeder tool prototype. A cable wound linear stator section of an Uppsala University Wave Energy Converter and its winding process is used as a reference in this article. From this example, it is shown that considerable production cycle time and manufacturing cost savings can be anticipated compared to manual winding. The suggested automation method is very flexible. It can be used for the production of cable wound stators with different shapes and sizes, for different cable dimensions and with different winding patterns.

    Nyckelord
    Stator winding, Automated production, Industrial robot, Electric machine assembly, Powerformer, Wave energy converter
    Nationell ämneskategori
    Teknik och teknologier
    Forskningsämne
    Teknisk fysik med inriktning mot elektricitetslära
    Identifikatorer
    urn:nbn:se:uu:diva-187001 (URN)10.1016/j.rcim.2012.06.005 (DOI)000310116400021 ()
    Tillgänglig från: 2012-12-03 Skapad: 2012-12-03 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    5. Six-Degrees-of-Freedom (6-DOF) Work Object Positional Calibration Using a Robot-Held Proximity Sensor
    Öppna denna publikation i ny flik eller fönster >>Six-Degrees-of-Freedom (6-DOF) Work Object Positional Calibration Using a Robot-Held Proximity Sensor
    2013 (Engelska)Ingår i: Machines, Vol. 1, nr 2, 63-80 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Industrial automation has been recognized as a fundamental key to build and keep manufacturing industries in developed countries. In most automation tasks, knowing the exact position of the objects to handle is essential. This is often done using a positional calibration system, such as a camera-based vision system. In this article, an alternative six-degrees-of-freedom work object positional calibration method using a robot-held proximity sensor, is presented. A general trigonometry-based measurement and calculation procedure, which, step-by-step, adjusts a work object coordinate system to the actual work object position, is explained. For suitable robot tasks and work object geometries, the benefits with the presented method include its robustness, large work area and low investment cost. Some drawbacks can be longer cycle time and its limited capacity to handle unsorted and complicated objects. To validate the presented method, it was implemented in an experimental robot setup. In this robot cell, it was used to calibrate the position of a stator section work object, which is used in the Uppsala University Wave Energy Converter generator. Hereby the function of the positional calibration procedure was validated. Sufficient positioning accuracy for the stator winding task was achieved and theoretically validated based on the experiments.

    Nationell ämneskategori
    Teknik och teknologier
    Forskningsämne
    Teknisk fysik med inriktning mot elektricitetslära
    Identifikatorer
    urn:nbn:se:uu:diva-212667 (URN)10.3390/machines1020063 (DOI)
    Tillgänglig från: 2013-12-13 Skapad: 2013-12-13 Senast uppdaterad: 2017-12-07
    6. A cable feeder tool for robotized cable winding
    Öppna denna publikation i ny flik eller fönster >>A cable feeder tool for robotized cable winding
    2014 (Engelska)Ingår i: Robotics and Computer-Integrated Manufacturing, ISSN 0736-5845, E-ISSN 1879-2537, Vol. 30, nr 6, 577-588 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Cable winding is an alternative technology to create stator windings in large electrical machines. Today such cable winding is performed manually, which is very repetitive, time-consuming and therefore also expensive. This paper presents the design, function and control system of a developed cable feeder tool for robotized stator cable winding. The presented tool was able to catch a cable inside a cable guiding system and to grab the cable between two wheels. One of these wheels was used to feed cable through the feeder. A control system was integrated in the tool to detect feeding slippage and to supervise the feeding force on the cable. Functions to calculate the cable feed length, to release the cable from the tool and for positional calibration of the stator to be wound were also integrated in the tool. In validating the function of the cable feeder tool, the stator of the linear generator used in the Wave Energy Converter generator developed at Uppsala University was used as an example. Through these experiments, it was shown that the developed robot tool design could be used to achieve automated robotized cable winding. These results also complied with the cycle time assumptions for automated cable winding from earlier research. Hence, it was theoretically indicated that the total winding cycle time for one Uppsala University Wave Energy Converter stator could be reduced from about 80 h for manual winding with four personnel to less than 20 h in a fully developed cable winding robot cell. The same robot tool and winding automation could also be used, with minor adjustments, for other stator designs.

    Nyckelord
    Cable feeder, Cable winding, Stator assembly, Powerformer, Wave Energy Converter
    Nationell ämneskategori
    Robotteknik och automation Datavetenskap (datalogi)
    Forskningsämne
    Teknisk fysik med inriktning mot elektricitetslära
    Identifikatorer
    urn:nbn:se:uu:diva-230907 (URN)10.1016/j.rcim.2014.04.003 (DOI)000340219600001 ()
    Tillgänglig från: 2014-09-04 Skapad: 2014-09-01 Senast uppdaterad: 2018-01-11Bibliografiskt granskad
    7. Automated Cable Preparation for Robotized Stator Cable Winding
    Öppna denna publikation i ny flik eller fönster >>Automated Cable Preparation for Robotized Stator Cable Winding
    2017 (Engelska)Ingår i: MACHINES, ISSN 2075-1702, Vol. 5, nr 2, 14Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A method for robotized cable winding of the Uppsala UniversityWave Energy Converter generator stator has previously been presented and validated. The purpose of this study is to present and validate further developments to the method: automated stand-alone equipment for the preparation of the winding cables. The cable preparation consists of three parts: feeding the cable from a drum, forming the cable end and cutting the cable. Forming and cutting the cable was previously done manually and only small cable drums could be handled. Therefore the robot cell needed to be stopped frequently. The new equipment was tested in an experimental robot stator cable winding setup. Through the experiments, the equipment was validated to be able to perform fully automated and robust cable preparation. Suggestions are also given on how to further develop the equipment with regards to performance, robustness and quality. Hence, this work represents another important step towards demonstrating completely automated robotized stator cable winding.

    Nyckelord
    cable winding, industrial automation, industrial robot, electric machine assembly, wave energy converter
    Nationell ämneskategori
    Robotteknik och automation
    Identifikatorer
    urn:nbn:se:uu:diva-324239 (URN)10.3390/machines5020014 (DOI)000401525400004 ()
    Tillgänglig från: 2017-06-15 Skapad: 2017-06-15 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    8. An updated cable feeder tool design for robotized stator cable winding
    Öppna denna publikation i ny flik eller fönster >>An updated cable feeder tool design for robotized stator cable winding
    (Engelska)Ingår i: Mechatronics (Oxford), ISSN 0957-4158, E-ISSN 1873-4006Artikel i tidskrift (Refereegranskat) Submitted
    Abstract [en]

    We have previously suggested a method for robotized stator winding of cable wound electric machines and demonstrated the method successfully in full-scale experiments. The cable feeder tool used to handle the cable during the complete winding process is an essential component of this robot cell. To take the robot winding method to the next level, into an industrial product, require further developments regarding durability, independency, flexibility and implementability. In this paper, we present an updated cable feeder tool design. This tool is designed to be used in a robot cell for cable winding of the third-generation design of the Uppsala University Wave Energy Converter generator stator. In this work, three cable feeder tool prototypes have been constructed, experimentally evaluated and validated for the intended application. Key performance parameters are presented and discussed, including suggestions for further developments. We completed a durable, compact, high performance tool design, with fully integrated control into industrial robot controllers. The experimental results presented in this article are very promising and hence, the updated cable feeder tool design represents another important step towards an industrial solution for robotized stator cable winding.

    Nationell ämneskategori
    Teknik och teknologier
    Identifikatorer
    urn:nbn:se:uu:diva-334553 (URN)
    Tillgänglig från: 2017-11-23 Skapad: 2017-11-23 Senast uppdaterad: 2017-12-07
    9. Robotized stator cable winding
    Öppna denna publikation i ny flik eller fönster >>Robotized stator cable winding
    (Engelska)Ingår i: Robotics and Computer-Integrated Manufacturing, ISSN 0736-5845, E-ISSN 1879-2537Artikel i tidskrift (Refereegranskat) Submitted
    Abstract [en]

    Automated stator winding assembly has been available for small and medium sized conventional electric machines for a long time. Cable winding is an alternative technology developed for medium and large sized machines in particular. In this paper we present, evaluate and validate the first fully automated stator cable winding assembly equipment in detail. A full-scale prototype stator cable winding robot cell has been constructed, based on extensive previous work and experience, and used in the experiments. While the prototype robot cell is adapted for the third design generation of the Uppsala University Wave Energy Converter generator stator, the winding method can be adapted for other stator designs. The presented robot cell is highly flexible and well prepared for future integration in a smart production line. Potential cost savings are indicated compared to manual winding, which is a backbreaking task. However, further work is needed to improve the reliability of the robot cell, especially when it comes to preventing the kinking of the winding cable during the assembly.

    Nationell ämneskategori
    Teknik och teknologier
    Identifikatorer
    urn:nbn:se:uu:diva-334554 (URN)
    Tillgänglig från: 2017-11-23 Skapad: 2017-11-23 Senast uppdaterad: 2017-12-07
    10. Robotized stacking of the Uppsala University wave energy converter generator stator
    Öppna denna publikation i ny flik eller fönster >>Robotized stacking of the Uppsala University wave energy converter generator stator
    2014 (Engelska)Ingår i: 33Rd International Conference On Ocean, Offshore And Arctic Engineering, 2014, Vol 9A: Ocean Renewable Energy, 2014Konferensbidrag, Publicerat paper (Refereegranskat)
    Nationell ämneskategori
    Teknik och teknologier
    Identifikatorer
    urn:nbn:se:uu:diva-237544 (URN)000363499000001 ()978-0-7918-4553-0 (ISBN)
    Konferens
    33rd International Conference on Ocean, Offshore and Arctic Engineering
    Tillgänglig från: 2014-12-03 Skapad: 2014-12-03 Senast uppdaterad: 2017-12-07
    11. Robotized Surface Mounting of Permanent Magnets
    Öppna denna publikation i ny flik eller fönster >>Robotized Surface Mounting of Permanent Magnets
    2014 (Engelska)Ingår i: Machines, Vol. 2, nr 4, 219-232 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Using permanent magnets on a rotor can both simplify the design and increase the efficiency of electric machines compared to using electromagnets. A drawback, however, is the lack of existing automated assembly methods for large machines. This paper presents and motivates a method for robotized surface mounting of permanent magnets on electric machine rotors. The translator of the Uppsala University Wave Energy Converter generator is used as an example of a rotor. The robot cell layout, equipment design and assembly process are presented and validated through computer simulations and experiments with prototype equipment. A comparison with manual assembly indicates substantial cost savings and an improved work environment. By using the flexibility of industrial robots and a scalable equipment design, it is possible for this assembly method to be adjusted for other rotor geometries and sizes. Finally, there is a discussion on the work that remains to be done on improving and integrating the robot cell into a production line.

    Nationell ämneskategori
    Elektroteknik och elektronik
    Identifikatorer
    urn:nbn:se:uu:diva-237449 (URN)10.3390/machines2040219 (DOI)
    Tillgänglig från: 2014-12-02 Skapad: 2014-12-02 Senast uppdaterad: 2017-12-07
    12. Robotized manufacturing of rubber components for commercialization of the Uppsala University wave energy converter concept
    Öppna denna publikation i ny flik eller fönster >>Robotized manufacturing of rubber components for commercialization of the Uppsala University wave energy converter concept
    2016 (Engelska)Konferensbidrag, Publicerat paper (Övrigt vetenskapligt)
    Ort, förlag, år, upplaga, sidor
    Glasgow, UK: , 2016
    Nationell ämneskategori
    Teknik och teknologier
    Identifikatorer
    urn:nbn:se:uu:diva-334547 (URN)
    Konferens
    2nd International Conference on Offshore Renewable Energy
    Tillgänglig från: 2017-11-23 Skapad: 2017-11-23 Senast uppdaterad: 2017-12-07
    13. Integration of real-world project tasks in a course on automation and robot engineering
    Öppna denna publikation i ny flik eller fönster >>Integration of real-world project tasks in a course on automation and robot engineering
    (Engelska)Ingår i: European Journal of Engineering Education, ISSN 0304-3797, E-ISSN 1469-5898Artikel i tidskrift (Refereegranskat) Submitted
    Abstract [en]

    The modern engineering profession requires classical technical skills combined with creativity and a high proficiency in cooperation and sustainable development. Research indicates that the engineering education should adapt better to this. This paper presents and evaluates the integration of open-ended real-world project group tasks in an introduction course on automation and robot engineering. We used extensive written student course evaluations, the students’ examination results and the teachers’ experience for evaluation. Six occasions of the updated course are evaluated against the previous classical course. Both the students and the teachers greatly appreciated the new course. There was a strong indication that the students’ theoretical knowledge and understanding of the subject had improved, both with regards to the technical depth and to the increasingly important non-technical engineering skills. This was achieved without increasing their work load. It is likely that the presented teaching approach can be used also in other engineering courses.

    Nationell ämneskategori
    Teknik och teknologier
    Identifikatorer
    urn:nbn:se:uu:diva-334555 (URN)
    Tillgänglig från: 2017-11-23 Skapad: 2017-11-23 Senast uppdaterad: 2017-12-07
  • Disputation: 2018-02-02 13:00 Room IV, University Main Building, Uppsala
    Lloyd, Christina
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Teologiska fakulteten, Teologiska institutionen.
    Moments of meaning – Towards an assessment of protective and risk factors for existential vulnerability among young women with mental ill-health concerns: A mixed methods project in clinical psychology of religion and existential health2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Detta sequential mixed-methods projekt genomfördes inom området för klinisk religionspsykologi och existentiell hälsa. Det centrala syftet med studien var att undersöka kliniskt relevanta områden för en bedömning av skydds- och riskfaktorer för existentiell sårbarhet och dysfunktionellt existentiellt meningsskapande i ett kliniskt urval av unga kvinnor med psykisk ohälsa. Tre teoretiska områden applicerades och operationaliserades för studien: Existentiellt meningsskapande; Ontologisk trygghet; och Känsloreglering. Undersökningsgruppen bestod av kvinnliga deltagare vid en psykodynamisk psykoterapimottagning för unga vuxna i Sverige, med depression som den vanligaste preliminära diagnosen. Studie I, kvantitativ, bestod av en online-enkät med etablerade bedömningsinstrument, som besvarades av 53 kvinnor (17-30 år, M = 22,4 år). Depressionsrelaterade personlighetsdrag utforskades som möjliga underliggande variabler i relationen mellan psykisk ohälsa och en dysfunktionell existentiellt meningsskapande process, genom en jämförelse av grupper med olika nivåer av depressionsrelaterade personlighetsdrag, avseende de undersökta områdena. Studie II, kvalitativ, omfattade en djupintervju med ett urval av informanter (n = 10, intervall 21-25 y, M = 22,7) från den föregående studien, representativa för dem med höga värden på depressionsrelaterade personlighetsskalor. Interrelationer mellan existentiellt meningsskapande och känsloreglering undersöktes i förhållande till vardagsliv, kritiska livshändelser och livets yttersta frågor genom en systematisk textkondenseringsprocess. Studie III, multimetod, omfattade flera bedömningssteg av data från urvalsgruppen, och en bedömning av interbedömarreliabilitet (IRR). Möjliga funktionella (skydds-) faktorer och dysfunktionella (risk-) faktorer för psykisk ohälsa undersöktes via den Existentiella världsbildens funktion, operationaliserad som sambandet mellan existentiell världsbild, ontologisk trygghet och självbild. Enligt vår hypotes var höga värden på den depressionsrelaterade personlighetsskalan Aggressionshämning starkt relaterade till en mindre funktionell existentiellt meningsskapande process i detta urval av unga kliniska kvinnor. Bland dem med höga värden framträdde en meningskris med avseende på svag eller ingen tillgång till tillräckliga kulturella eller existentiella resurser i intergenerationella, känslomässigt stödjande relationer. Resultatet indikerade vidare en generell brist på en utvecklad och funktionell existentiell världsbild åtföljd av en låg grad av reflektion gällande existentiella världsbildsfrågor bland majoriteten av informanterna och deras föräldrar.

    Delarbeten
    1. Psychological and existential vulnerability among clinical young women: a quantitative comparison of depression-related subgroups
    Öppna denna publikation i ny flik eller fönster >>Psychological and existential vulnerability among clinical young women: a quantitative comparison of depression-related subgroups
    2015 (Engelska)Ingår i: Mental Health, Religion & Culture, ISSN 1367-4676, E-ISSN 1469-9737, Vol. 18, nr 4, 259-272 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The objective was to explore psychological and existential vulnerability among clinical young women in Sweden. Females (n = 53) with depression as the most common preliminary diagnosis were investigated through an online questionnaire. Included measures were Karolinska Scales of Personality, Self-concept, Strategies to Handle Negative Emotions, Sense of Coherence, and questions pertaining to existential meaning-making, including religious/spiritual belief. The sample was divided into High (n = 35) and Low/Inter (n = 18) groups according to scores on the anxiety- and depression-related personality scale Inhibition of aggression. Using independent samples t-test, the High group showed signs of significantly higher psychological and existential vulnerability than the Low/Inter group. Salutogenic factors being (1) coming from socially and societally engaged families and (2) being in a functional existential meaning-making process. The conclusion is that vulnerabilities in the psychological and existential domains are linked, especially in individuals high on depression-like aspects of personality. However, no significant differences for religion/spirituality were found. Treatment implications were addressed.

    Ort, förlag, år, upplaga, sidor
    London: Routledge Mental Health, 2015
    Nyckelord
    Clinical young women; psychological vulnerability; existential meaning-making; depression; sense of coherence; self-concept; emotion regulation
    Nationell ämneskategori
    Psykiatri Religionsvetenskap
    Forskningsämne
    Religionspsykologi
    Identifikatorer
    urn:nbn:se:uu:diva-276769 (URN)10.1080/13674676.2015.1021313 (DOI)000356237600003 ()
    Tillgänglig från: 2016-02-15 Skapad: 2016-02-15 Senast uppdaterad: 2017-12-08
    2. Emotion Regulation and Existential Meaning-Making in Young Women with Mental Ill-Health Concerns–A Qualitative Study
    Öppna denna publikation i ny flik eller fönster >>Emotion Regulation and Existential Meaning-Making in Young Women with Mental Ill-Health Concerns–A Qualitative Study
    2016 (Engelska)Ingår i: Psychological and Behavioral Sciences International Journal, Vol. 1, nr 1, 001-010 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Increasing rates of psychiatric problems, like anxiety, worry, and anguish among Swedish youth–especially among females, are considered a serious public mental health concern. To explore psychological and existential vulnerability and needs among female youths with mental ill-health concerns, a qualitative in-depth interview study was done with a sample comprised of ten females on the waiting-list at an outpatient psychotherapy clinic. In relation to everyday life, critical events, and ultimate concerns, two areas were explored: Emotion regulation and Existential meaning-making, and their interrelations were examined. Results indicated that these areas appear to be strongly related processes in this sample, possibly due to frequent experiences of relational losses and disruptions. Such experiences, if not repaired, might fuel existential issues like fear of death, loneliness, and alienation, increasing the vulnerability for mental ill-health. Psychotherapeutic implications were discussed.

    Ort, förlag, år, upplaga, sidor
    Juniper Publisher, 2016
    Nyckelord
    Emotion regulation – existential meaning-making – moments of meaning – young women – mental health
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Religionspsykologi
    Identifikatorer
    urn:nbn:se:uu:diva-315272 (URN)
    Tillgänglig från: 2017-02-13 Skapad: 2017-02-13 Senast uppdaterad: 2017-12-08
    3. An Assessment of Existential Worldview Function among Young Women at Risk for Depression and Anxiety—A Multi-Method Study
    Öppna denna publikation i ny flik eller fönster >>An Assessment of Existential Worldview Function among Young Women at Risk for Depression and Anxiety—A Multi-Method Study
    2017 (Engelska)Ingår i: Archive for the Psychology of Religion/ Archiv für Religionspsychologie, ISSN 0084-6724, E-ISSN 1573-6121, Vol. 39, nr 2, 165-203 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Increasing rates of psychiatric problems like depression and anxiety among Swedish youth, predominantly among females, are considered a serious public mental health concern. Multiple studies confirm that psychological as well as existential vulnerability manifest in different ways for youths in Sweden. This multi-method study aimed at assessing existential worldview function by three factors: 1) existential worldview, 2) ontological security, and 3) self-concept, attempting to identify possible protective and risk factors for mental ill-health among female youths at risk for depression and anxiety. The sample comprised ten females on the waiting list at an outpatient psychotherapy clinic for teens and young adults. Results indicated that both functional and dysfunctional factors related to mental health were present, where the quality and availability of significant interpersonal relations seemed to have an important influence. Examples of both an impaired worldview function and a lack of an operating existential worldview were found. Psychotherapeutic implications are discussed.

    Ort, förlag, år, upplaga, sidor
    Brill Academic Publishers, 2017
    Nyckelord
    existential worldview function, ontological security, self-concept, young women, meaning, belonging, depression, anxiety
    Nationell ämneskategori
    Medicin och hälsovetenskap Religionsvetenskap Psykologi
    Forskningsämne
    Religionspsykologi
    Identifikatorer
    urn:nbn:se:uu:diva-333574 (URN)10.1163/15736121-12341337 (DOI)000408056700004 ()
    Tillgänglig från: 2017-11-15 Skapad: 2017-11-15 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
  • Disputation: 2018-02-02 13:15 Humanistiska teatern, Uppsala
    Novak, Judit
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Fakulteten för utbildningsvetenskaper, Institutionen för pedagogik, didaktik och utbildningsstudier.
    Juridification of Educational Spheres: The Case of Swedish School Inspection2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    This dissertation argues that the great transformation of education policy and governance that we have witnessed in the last few decades can only be properly understood by taking into account a process of juridification. In and of itself, this is not a novel assertion; what is argued here is that what this entails concretely has been only partially understood. The mounting importance of positive rights in the welfare state as a means of preserving and legitimating the State’s role is underlined, and particular focus is directed to the Swedish Schools Inspectorate (SSI) as an intermediary body between the State and educational institutions. The main argument that this dissertation advances is that the Swedish 2010 Education Act, along with the changes that its enforcement brought to state school inspection, is an instructive expression of the institutionalization of a juridified school system. Central to this argument is the idea that the legitimacy of the postmodern State in the eyes of its citizens can no longer be taken for granted. Juridification can be seen as a strategy of compensatory legitimation. Drawing on earlier research on governance and juridification, respectively, the dissertation sketches out the general thrust for the examination of the relation between the two and, in particular, just what the theoretical perspective of juridification adds to our understanding of the transformation of education policy and practice. We still know rather little about the latter, i.e., about what the functions and implications of a “juridified” mode of education governance may be more precisely. Against the backdrop of three empirical studies, it advances the argument that a good part of the evolutionary process that is here called “the juridification of educational spheres” comprises operations, institutions and actors deeply involved in locally or regionally situated issues and struggles. It further argues that state school inspection processes as such provide some means of intermediation – the means of making ideologies become real and policies come true. The final discussion is conducted in light of the specific case of the SSI, particularly how the actions and decisions involved in the Inspectorate’s enactment of policy actually constitute policy by giving it certain forms and specific content. These considerations take us beyond the sphere of governance and to the heart of what we may think schooling is or ought to be about. 

    Delarbeten
    1. Skolan och rättssäkerheten: vad har en elev rätt att kunna?
    Öppna denna publikation i ny flik eller fönster >>Skolan och rättssäkerheten: vad har en elev rätt att kunna?
    2016 (Svenska)Ingår i: Vad ska en svensk kunna?: Utbildningens dilemma - intressenas spel / [ed] Michael Gustavsson, Tove Österman, Elinor Hållén, Göteborg: Daidalos, 2016, 105-131 s.Kapitel i bok, del av antologi (Refereegranskat)
    Ort, förlag, år, upplaga, sidor
    Göteborg: Daidalos, 2016
    Nyckelord
    Juridifiering, oförytterliga värden, rättssäkerhet, skolinspektion
    Nationell ämneskategori
    Utbildningsvetenskap
    Forskningsämne
    Pedagogik
    Identifikatorer
    urn:nbn:se:uu:diva-300592 (URN)9789171734747 (ISBN)
    Tillgänglig från: 2016-08-09 Skapad: 2016-08-09 Senast uppdaterad: 2017-12-07
    2. Juridification of examination systems: extending state level authority over teacher assessments through regrading of national tests
    Öppna denna publikation i ny flik eller fönster >>Juridification of examination systems: extending state level authority over teacher assessments through regrading of national tests
    2017 (Engelska)Ingår i: Journal of education policy, ISSN 0268-0939, E-ISSN 1464-5106, Vol. 32, nr 5, 673-693 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Since 2009, the Swedish Government uses an ‘audit’ agency – the Swedish Schools Inspectorate – to monitor and assess the accuracy with which teachers grade student responses on national tests. This study explores the introduction and subsequent establishment of the Inspectorate’s regrading programme as an example of political management of the tensions between competition and equity inherent in neoliberal regulatory regimes. The programme is considered a case for examining contemporary policies and discourses on fairness and government actions undertaken to resolve issues of unfair assessment and safeguard students’ rights. Work of Carol Bacchi forms part of the theoretical background for the investigation of problem representations around and within the programme. The article demonstrates how discursive practices in the fields of government, audit and media have worked to frame teachers’ assessments as incorrect, unfair and as jeopardizing the credibility of the grading system, thus justifying increased central control and authority over teacher assessments. As such, the regrading programme contributed to increased mistrust in teacher professionalism. A legal discourse is identified, and we argue the examination system is being juridified where the abundance of control over knowledge risks turning into a deficit of that same knowledge.

    Nationell ämneskategori
    Utbildningsvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-320479 (URN)10.1080/02680939.2017.1318454 (DOI)000402988500008 ()
    Tillgänglig från: 2017-04-20 Skapad: 2017-04-20 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    3. Anpassningarnas för(e)ställning: Om Skolinspektionens tillsyn som en scen för förändring
    Öppna denna publikation i ny flik eller fönster >>Anpassningarnas för(e)ställning: Om Skolinspektionens tillsyn som en scen för förändring
    2014 (Svenska)Ingår i: Utbildning och Demokrati, ISSN 1102-6472, E-ISSN 2001-7316, Vol. 23, nr 1, 127-144 s.Artikel i tidskrift (Refereegranskat) Published
    Ort, förlag, år, upplaga, sidor
    Örebro: , 2014
    Nationell ämneskategori
    Utbildningsvetenskap
    Forskningsämne
    Pedagogik
    Identifikatorer
    urn:nbn:se:uu:diva-224684 (URN)
    Projekt
    Inspektion som styrning, Skolinspektion och utbildningsstyrning i Sverige, England och Skottland
    Anmärkning

    Tema: Skolinspektion som styrning

    Tillgänglig från: 2014-05-17 Skapad: 2014-05-17 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
  • Disputation: 2018-02-02 13:15 Brusewitzsalen, Uppsala
    Cronert, Axel
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Statsvetenskapliga institutionen. Uppsala Center for Labor Studies.
    All Interventionists Now?: On the Political Economy of Active Labor Market Policy as Micro-Interventionist Multi-Tools2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    As recent decades have seen a growing interest in reforming advanced welfare states to promote employment, active labor market policy (ALMP) has emerged as a major topic of inquiry among comparative political economists. Whereas the literature to date disagrees on, and mostly downplays, the role of partisan politics in the development of ALMP, this dissertation shows that political actors systematically use ALMP programs in different ways to achieve distinct political aims. Drawing mostly on a rich, new panel data set on approximately 1,000 programs across Europe, the dissertation draws attention to several politically salient dimensions of ALMP that need to be taken seriously to understand how partisan politics matter in advanced industrial democracies.

    Essay I reconciles the conflicting understandings of partisanship and ALMP in the ‘power resources’ and ‘insider/outsider’ schools by highlighting that ALMP programs may serve two overarching purposes. The essay shows that left-leaning governments are particularly inclined to expand programs designed primarily to reduce unemployment, whereas governments of all suits are equally supportive of programs that also, or instead, serve to increase labor supply.

    Essay II focuses on employment subsidies, documenting how these may be designed to tackle different labor market challenges among different target groups. Emphasizing institutional path dependency, the essay then shows that cross-national variation in employment subsidy design broadly reflects the varying institutional regimes in different parts of Europe.

    Essay III reconsiders the conventional view on the importance of employer involvement and corporatist institutions for ALMP by separating programs produced unilaterally by the state from programs, such as employment subsidies, produced jointly by the state and employers to the benefit of both. The essay finds that corporatist institutions primarily matter for ALMP by paving the way for governments—especially with business-friendly center-right parties—that favor joint over unilateral production.

    The introductory essay argues that ALMP forms part of a larger family of economic policies that are sufficiently versatile to be sustained and used by actors across the political spectrum. Reviewing long-term trends in economic policy in OECD countries, it shows that these policies, which are here labelled micro-interventionist multi-tools, have expanded considerably since the early 1980s.

    Delarbeten
    1. Unemployment reduction or labor force expansion? How partisanship matters for the design of active labor market policy in Europe
    Öppna denna publikation i ny flik eller fönster >>Unemployment reduction or labor force expansion? How partisanship matters for the design of active labor market policy in Europe
    2017 (Engelska)Ingår i: Socio-Economic Review, ISSN 1475-1461, E-ISSN 1475-147XArtikel i tidskrift (Refereegranskat) In press
    Abstract [en]

    Comparative scholars fundamentally disagree about the impact of partisan politics in modern welfare states, particularly in certain ‘new’ policy areas such as active labor market policy (ALMP). Using new data on 900 ALMP programs across Europe, this study attempts to reconcile a long-standing dispute between the traditional ‘power resources’ approach and the ‘insider/outsider’ approach pioneered by Rueda. The study argues that both left-wing and right-wing governments invest in ALMP but that politics still matter because parties’ preferences regarding unemployment differ. The left is more inclined to expand programs primarily designed to reduce unemployment, which exclusively target ‘core’ groups in, or at risk of, unemployment, and programs in which participants are no longer counted among the unemployed. In contrast, both sides are equally prone to expand programs that also—or instead—target people who are not yet participating in the labor market, which thus also—or instead—serve to increase labor supply.

    Ort, förlag, år, upplaga, sidor
    Oxford: Oxford University Press, 2017
    Nyckelord
    comparative politics, ideology, labor market institutions, labor supply, social policy; JEL Codes: H53 Government Expenditures and Welfare Programs, I38 Government Policy • Provision and Effects of Welfare Programs, J68 Public Policy
    Nationell ämneskategori
    Statsvetenskap (exklusive studier av offentlig förvaltning och globaliseringsstudier)
    Forskningsämne
    Statskunskap
    Identifikatorer
    urn:nbn:se:uu:diva-325740 (URN)10.1093/ser/mwx014 (DOI)
    Tillgänglig från: 2017-06-27 Skapad: 2017-06-27 Senast uppdaterad: 2018-01-13
    2. One tool, many applications: Employment subsidies, institutional regimes, and labor market segmentation
    Öppna denna publikation i ny flik eller fönster >>One tool, many applications: Employment subsidies, institutional regimes, and labor market segmentation
    (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Abstract [en]

    Employment subsidy programs have experienced considerable expansion across Europe in recent decades. To date, most studies analyzing this policy shift have assumed that these programs are largely equivalent in terms of their designs, effects, and explanations. In contrast, using new, detailed data from across Europe, this essay argues that employment subsidies are best understood as versatile multi-purpose tools that can be used as a means to rather different distributional ends. Importantly, while they may be designed to counteract insider/outsider divides in the labor market, they can also sustain these divides. This essay furthermore demonstrates that how employment subsidies are designed, financed and administered varies systematically across different parts of Europe, in ways broadly in line with the distinct logics associated with their long-standing institutional regimes. Employment subsidies are mostly used in a manner that 'reinvents' existing institutional regimes rather than replaces them with something profoundly new.

    Nyckelord
    Comparative politics, active labor market policy, ALMP, employment subsidies, institutional legacies, welfare regimes, insider/outsider theory
    Nationell ämneskategori
    Statsvetenskap (exklusive studier av offentlig förvaltning och globaliseringsstudier)
    Forskningsämne
    Statskunskap
    Identifikatorer
    urn:nbn:se:uu:diva-333931 (URN)
    Tillgänglig från: 2017-11-19 Skapad: 2017-11-19 Senast uppdaterad: 2018-01-13
    3. Accommodation or extraction? Employers, the state, and the joint production of active labor market policy
    Öppna denna publikation i ny flik eller fönster >>Accommodation or extraction? Employers, the state, and the joint production of active labor market policy
    (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Abstract [en]

    Conventional wisdom among comparative political economists maintains that employer participation in policy-making and policy implementation, fostered by corporatist arrangements, is crucial for successfully expanding active labor market policy (ALMP). This essay presents a theory that challenges the dominant view by arguing that corporatist arrangements do not affect the overall scope of ALMP but instead facilitate a particular type of ALMP programs; namely, those whose production requires joint participation by employers and the state, and that involves a transfer of public resources to employers. By facilitating such programs—which center-right parties tend to prefer over programs produced unilaterally by the state—the presence of corporatist arrangements also shift the focus of partisan conflict over ALMP, from the level to the structure of public expenditure. Evidence for these claims is provided from a set of time-series–cross-sectional analyses of 21 OECD countries since the mid-1980s.

    Nyckelord
    comparative politics, active labor market policy, ALMP, corporatism, employers, partisanship, partisan politics
    Nationell ämneskategori
    Statsvetenskap (exklusive studier av offentlig förvaltning och globaliseringsstudier)
    Forskningsämne
    Statskunskap
    Identifikatorer
    urn:nbn:se:uu:diva-333930 (URN)
    Tillgänglig från: 2017-11-19 Skapad: 2017-11-19 Senast uppdaterad: 2018-01-13
  • Disputation: 2018-02-02 13:15 ITC/2446, Uppsala
    Aronis, Stavros
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för datalogi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Datalogi.
    Effective Techniques for Stateless Model Checking2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Stateless model checking is a technique for testing and verifying concurrent programs, based on exploring the different ways in which operations executed by the processes of a concurrent program can be scheduled. The goal of the technique is to expose all behaviours that can be a result of scheduling non-determinism. As the number of possible schedulings is huge, however, techniques that reduce the number of schedulings that must be explored to achieve verification have been developed. Dynamic partial order reduction (DPOR) is a prominent such technique.

    This dissertation presents a number of improvements to dynamic partial order reduction that significantly increase the effectiveness of stateless model checking. Central among these improvements are the Source and Optimal DPOR algorithms (and the theoretical framework behind them) and a technique that allows the observability of the interference of operations to be used in dynamic partial order reduction. Each of these techniques can exponentially decrease the number of schedulings that need to be explored to verify a concurrent program. The dissertation also presents a simple bounding technique that is compatible with DPOR algorithms and effective for finding bugs in concurrent programs, if the number of schedulings is too big to make full verification possible in a reasonable amount of time, even when the improved algorithms are used.

    All improvements have been implemented in Concuerror, a tool for applying stateless model checking to Erlang programs. In order to increase the effectiveness of the tool, the interference of the high-level operations of the Erlang/OTP implementation is examined, classified and precisely characterized. Aspects of the implementation of the tool are also described. Finally, a use case is presented, showing how Concuerror was used to find bugs and verify key correctness properties in repair techniques for the CORFU chain replication protocol.

    Delarbeten
    1. Source Sets: A Foundation for Optimal Dynamic Partial Order Reduction
    Öppna denna publikation i ny flik eller fönster >>Source Sets: A Foundation for Optimal Dynamic Partial Order Reduction
    2017 (Engelska)Ingår i: Journal of the ACM, ISSN 0004-5411, E-ISSN 1557-735X, Vol. 64, nr 4, 25Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Stateless model checking is a powerful method for program verification that, however, suffers from an exponential growth in the number of explored executions. A successful technique for reducing this number, while still maintaining complete coverage, is Dynamic Partial Order Reduction (DPOR), an algorithm originally introduced by Flanagan and Godefroid in 2005 and since then not only used as a point of reference but also extended by various researchers. In this article, we present a new DPOR algorithm, which is the first to be provably optimal in that it always explores the minimal number of executions. It is based on a novel class of sets, called source sets, that replace the role of persistent sets in previous algorithms. We begin by showing how to modify the original DPOR algorithm to work with source sets, resulting in an efficient and simple-to-implement algorithm, called source-DPOR. Subsequently, we enhance this algorithm with a novel mechanism, called wakeup trees, that allows the resulting algorithm, called optimal-DPOR, to achieve optimality. Both algorithms are then extended to computational models where processes may disable each other, for example, via locks. Finally, we discuss tradeoffs of the source-and optimal-DPOR algorithm and present programs that illustrate significant time and space performance differences between them. We have implemented both algorithms in a publicly available stateless model checking tool for Erlang programs, while the source-DPOR algorithm is at the core of a publicly available stateless model checking tool for C/pthread programs running on machines with relaxed memory models. Experiments show that source sets significantly increase the performance of stateless model checking compared to using the original DPOR algorithm and that wakeup trees incur only a small overhead in both time and space in practice.

    Ort, förlag, år, upplaga, sidor
    Association for Computing Machinery (ACM), 2017
    Nationell ämneskategori
    Programvaruteknik
    Identifikatorer
    urn:nbn:se:uu:diva-331842 (URN)10.1145/3073408 (DOI)000410615900002 ()
    Projekt
    UPMARCRELEASE
    Forskningsfinansiär
    EU, FP7, Sjunde ramprogrammet, 287510Vetenskapsrådet
    Tillgänglig från: 2017-10-18 Skapad: 2017-10-18 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
    2. The shared-memory interferences of Erlang/OTP built-ins
    Öppna denna publikation i ny flik eller fönster >>The shared-memory interferences of Erlang/OTP built-ins
    2017 (Engelska)Ingår i: Proceedings of the 16th ACM SIGPLAN International Workshop on Erlang, New York: Association for Computing Machinery (ACM), 2017Konferensbidrag, Publicerat paper (Refereegranskat)
    Abstract [en]

    Erlang is a concurrent functional language based on the actor modelof concurrency. In the purest form of this model, actors are realizedby processes that do not share memory and communicate witheach other exclusively via message passing. Erlang comes quiteclose to this model, as message passing is the primary form of interprocesscommunication and each process has its own memoryarea that is managed by the process itself. For this reason, Erlangis often referred to as implementing “shared nothing” concurrency.Although this is a convenient abstraction, in reality Erlang’s mainimplementation, the Erlang/OTP system, comes with a large numberof built-in operations that access memory which is shared byprocesses. In this paper, we categorize these built-ins, and characterizethe interferences between them that can result in observabledifferences of program behaviour when these built-ins are usedin a concurrent setting. The paper is complemented by a publiclyavailable suite of more than one hundred small Erlang programsthat demonstrate the racing behaviour of these built-ins.

    Ort, förlag, år, upplaga, sidor
    New York: Association for Computing Machinery (ACM), 2017
    Nyckelord
    Actors, BEAM, Concuerror, Erlang, Scheduling nondeterminism
    Nationell ämneskategori
    Programvaruteknik
    Identifikatorer
    urn:nbn:se:uu:diva-331840 (URN)10.1145/3123569.3123573 (DOI)978-1-4503-5179-9 (ISBN)
    Konferens
    ERLANG 2017
    Projekt
    UPMARC
    Tillgänglig från: 2017-10-18 Skapad: 2017-10-18 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
    3. Testing And Verifying Chain Repair Methods For CORFU Using Stateless Model Checking
    Öppna denna publikation i ny flik eller fönster >>Testing And Verifying Chain Repair Methods For CORFU Using Stateless Model Checking
    2017 (Engelska)Konferensbidrag, Publicerat paper (Refereegranskat)
    Abstract [en]

    Corfu is a distributed shared log that is designed to be scalable and reliable in the presence of failures and asynchrony. Internally, Corfu is fully replicated for fault tolerance, without sharding data or sacrificing strong consistency. In this case study, we present the modeling approaches we followed to test and verify, using Concuerror, the correctness of repair methods for the Chain Replication protocol suitable for Corfu. In the first two methods we tried, Concuerror located bugs quite fast. In contrast, the tool did not manage to find bugs in the third method, but the time this took also motivated an improvement in the tool that reduces the number of traces explored. Besides more details about all the above, we present experiences and lessons learned from applying stateless model checking for verifying complex protocols suitable for distributed programming.

    Ort, förlag, år, upplaga, sidor
    Cham: Springer, 2017
    Serie
    Lecture Notes in Computer Science, 10510
    Nationell ämneskategori
    Datorsystem Programvaruteknik
    Identifikatorer
    urn:nbn:se:uu:diva-331836 (URN)10.1007/978-3-319-66845-1_15 (DOI)978-3-319-66844-4 (ISBN)978-3-319-66845-1 (ISBN)
    Konferens
    Integrated Formal Methods. IFM 2017
    Projekt
    UPMARC
    Tillgänglig från: 2017-10-18 Skapad: 2017-10-18 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
    4. Optimal Dynamic Partial Order Reduction with Observers
    Öppna denna publikation i ny flik eller fönster >>Optimal Dynamic Partial Order Reduction with Observers
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Datavetenskap (datalogi)
    Identifikatorer
    urn:nbn:se:uu:diva-333508 (URN)
    Projekt
    UPMARC
    Tillgänglig från: 2017-11-21 Skapad: 2017-11-21 Senast uppdaterad: 2018-01-13
  • Disputation: 2018-02-09 09:15 Sal IV, Universitetshuset, Uppsala
    Almblad, Ann-Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Early Detection and Treatment for Children: Experiences and outcome of implementation at a pediatric hospital2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Early recognition of severely ill children is necessary to prevent serious adverse events and unexpected death. To promote patient safety the Early Detection and Treatment Program for Children (EDT-C) was developed at a University Children’s Hospital in Sweden. This program consists of validated tools for communication and teamwork combined with the Pediatric Early Warning Score (PEWS) and guidelines for recommended actions. Ward specific guidelines were developed and EDT-C instructors were trained. The aims were to describe healthcare professionals’ experience of caring for acutely, severely ill children (Study I) and to evaluate the implementation of EDT-C (Study II, III, IV). The Promoting Action on Research Implementation in Health Services (PARiHS) framework guided both implementation and the research study.

    Before introducing the EDT-C, focus group interviews were performed to explore healthcare professionals’ experience of caring for acutely, severely ill children. A context assessment, using the Alberta Context Tool (ACT) was also conducted. After implementation, a retrospective review of the electronic patient records (EPR) to assess adherence to guidelines were carried out. Instructors’ and healthcare professionals’ experiences from the implementation of EDT-C were gathered through individual interviews. To evaluate the introduction of EDT-C in relation to admission and stay at intensive care a retrospective before-after study using EPR data was performed. Interviews were analyzed using qualitative content analysis and descriptive statistical methods were utilized for quantitative data.

    The caring for acutely severely ill children was described as being in a multifaceted area of tension with paradoxical elements where contradictory emotions emerged. According to documentation, children at a very high risk of clinical deterioration according to PEWS were identified. Adherence to actions prescribed in guidelines varied.

     Healthcare professionals and instructors described EDT-C as suitable for clinical practice and that it created a more structured way of working. It was furthermore described that PEWS measurement had become routine practice at the hospital.

    EDT-C can lead to increased knowledge about early detection of deterioration, strengthen the healthcare in their profession, optimize treatment and teamwork and thereby has potential to increase patient safety for children treated in hospitals.

    Delarbeten
    1. Caring for the Acutely, Severely Ill Child-A Multifaceted Situation with Paradoxical Elements: Swedish Healthcare Professionals' Experiences
    Öppna denna publikation i ny flik eller fönster >>Caring for the Acutely, Severely Ill Child-A Multifaceted Situation with Paradoxical Elements: Swedish Healthcare Professionals' Experiences
    2016 (Engelska)Ingår i: Journal of Pediatric Nursing: Nursing Care of Children and Families, ISSN 0882-5963, E-ISSN 1532-8449, Vol. 31, nr 5, E293-E300 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Purpose: The aim of this study was to describe healthcare professionals' experience of caring for acutely, severely ill children in hospital in Sweden.

    Design and Methods: Five focus group interviews were conducted with nurses, nurse assistants and physicians comprising a total of 20 participants. Data were analyzed using qualitative content analysis.

    Results: An overall theme emerged that describes healthcare professionals' experiences as: "being in a multifaceted area of tension with paradoxical elements". The theme is based on three categories: proficiency of the individuals and the team is the fundamental base; interactions are crucial in an area of tension; and wellbeing of the individual is a balance of contradictory emotions. With maintained focus on the ill child, proficiency is the fundamental base, interactions are crucial, and moreover contradictory emotions are described.

    Conclusions: The interplay based on proficiency may influence the assessments and treatments of acutely, severely ill children.

    Practice Implications: Recognizing the multifaceted area of tension with paradoxical elements, practical teamwork exercises, a structured approach, and assessment tools could be a possible way to develop interprofessional team collaboration to improve the care of acutely, severely ill children in order to increase patient safety.

    Nyckelord
    Content analysis, Interprofessional, Focus groups, Pediatric care, Healthcare professionals, Children
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-306761 (URN)10.1016/j.pedn.2016.05.001 (DOI)000384134300001 ()27237793 (PubMedID)
    Tillgänglig från: 2016-11-10 Skapad: 2016-11-03 Senast uppdaterad: 2017-12-20Bibliografiskt granskad
    2. Implementation of Pediatric Early Warning Score: Adherence to Guidelines and Influence of Context
    Öppna denna publikation i ny flik eller fönster >>Implementation of Pediatric Early Warning Score: Adherence to Guidelines and Influence of Context
    2018 (Engelska)Ingår i: Journal of Pediatric Nursing: Nursing Care of Children and Families, ISSN 0882-5963, E-ISSN 1532-8449, nr 38, 33-39 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    PURPOSE: To describe data of Pediatric Early Warning Score (PEWS) registrations and to evaluate the implementation of PEWS by examining adherence to clinical guidelines based on measured PEWS, and to relate findings to work context. DESIGN AND METHODS: PEWS, as a part of a concept called Early Detection and Treatment-Children (EDT-C) was implemented at three wards at a Children's Hospital in Sweden. Data were collected from the Electronic Patient Record (EPR) retrospectively to assess adherence to guidelines. The Alberta Context Tool (ACT) was used to assess work context among healthcare professionals (n=110) before implementation of EDT-C. RESULTS: The majority of PEWS registrations in EPR were low whereas 10% were moderate to high. Adherences to ward-specific guidelines at admission and for saturation in respiratory distress were high whereas adherence to pain assessment was low. There were significant differences in documented recommended actions between wards. Some differences in leadership and evaluation between wards were identified. CONCLUSIONS: Evaluation of PEWS implementation indicated frequent use of the tool despite most scores being low. High scores (5-9) occurred 28 times, which may indicate that patients with a high risk of clinical deterioration were identified. Documentation of the consequent recommended actions was however incomplete and there was a large variation in adherence to guidelines. Contextual factors may have an impact on adherence. PRACTICE IMPLICATIONS: EDT-C can lead to increased knowledge about early detection of deterioration, strengthen nurses as professionals, optimize treatment and teamwork and thereby increase patient safety for children treated in hospitals.

    Nyckelord
    Deterioration, Implementation, PARIHS, Pediatric, Pews
    Nationell ämneskategori
    Pediatrik
    Forskningsämne
    Pediatrik
    Identifikatorer
    urn:nbn:se:uu:diva-336550 (URN)10.1016/j.pedn.2017.09.002 (DOI)29167078 (PubMedID)
    Anmärkning

    Supplementary data to this article can be found online at https://doi. org/10.1016/j.pedn.2017.09.002

    Tillgänglig från: 2017-12-14 Skapad: 2017-12-14 Senast uppdaterad: 2017-12-20Bibliografiskt granskad
    3. Increased intensive care admission rate after introduction of Early Detection and Treatment program for Children and the establishment of a pediatric intensive care unit at a tertiary hospital in Sweden
    Öppna denna publikation i ny flik eller fönster >>Increased intensive care admission rate after introduction of Early Detection and Treatment program for Children and the establishment of a pediatric intensive care unit at a tertiary hospital in Sweden
    (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Abstract [en]

    Objective: To evaluate the introduction of an Early Detection and Treatment program- Children (EDT-C) including a paediatric early warning score (PEWS) in relation to admission and length of stay at intensive care unit (ICU). Design: Before-after study utilizing data from the Electronic Patient Record (EPR) system, comparing outcomes over a total time period of 60 months between April 2010 and September 2015. Setting: A Swedish tertiary hospital. Patients: A total of 16,283 paediatric patients were included over the study period. Interventions: EDT-C including PEWS Measurements and Main Results: The following variables were extracted from the EPR data: 1) Admissions to paediatric wards 2) Length of stay at paediatric wards 3) Admissions to intensive care units 4) Length of stay at intensive care unit 5) Diagnosis. Intensive care unit admission increased from 5.0% (440/8746) before to 10.2 % (772/7537) after the introduction of the EDT-C (p<0.01). Mean treatment time at ICU did not change (41.0 vs 48.3 hours, p=0.23). Conclusion: The introduction of EDT-C including PEWS, in conjunction with the establishment of a paediatric intensive care unit at the hospital, resulted in an increased intensive care admittance rate among paediatric in-patients.

    Nationell ämneskategori
    Klinisk medicin Pediatrik
    Forskningsämne
    Pediatrik
    Identifikatorer
    urn:nbn:se:uu:diva-336775 (URN)
    Tillgänglig från: 2017-12-17 Skapad: 2017-12-17 Senast uppdaterad: 2017-12-20
    4. From skepticism to assurance and control: implementation of a patient safety system at a pediatric hospital in Sweden
    Öppna denna publikation i ny flik eller fönster >>From skepticism to assurance and control: implementation of a patient safety system at a pediatric hospital in Sweden
    (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Nationell ämneskategori
    Pediatrik
    Forskningsämne
    Pediatrik
    Identifikatorer
    urn:nbn:se:uu:diva-336557 (URN)
    Tillgänglig från: 2017-12-14 Skapad: 2017-12-14 Senast uppdaterad: 2017-12-20Bibliografiskt granskad
  • Disputation: 2018-02-09 09:15 Rudbecksalen, Rudbecklaboratoriet, Uppsala
    Nikitidou, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Cellular responses to amyloid-beta protofibrils: Focus on astrocytes, extracellular vesicles and antibody treatment2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Knowledge about the cellular mechanisms behind the initiation and propagation of Alzheimer’s disease (AD) is limited. Decades of research have focused on neuronal abnormalities in AD, but recently more attention has been given to the glial cells. Being the most numerous glial cell type in the brain, astrocytes are important for many functions, but their role in AD is poorly understood. The aim with this thesis was to clarify the involvement of astrocytes in AD by using a co-culture system of primary neurons and glia. The co-cultures were exposed to soluble amyloid-beta (Aβ) aggregates, i.e. protofibrils that are known to be particularly harmful.

    In Paper I, the capacity of astrocytes to ingest and degrade Aβ protofibrils was investigated. We found that astrocytes effectively ingested Aβ, but were ineffective in degrading the material. The intracellular accumulation of Aβ in astrocytes resulted in lysosomal dysfunction, high intracellular load of partly N-terminally truncated Aβ and extracellular vesicle (EV) mediated neuronal cell death.

    Cells can communicate by releasing cargo into EVs, but the role of EVs in the spreading of Aβ pathology is unclear. In Paper II, the protein content of EVs released specifically following Aβ protofibril exposure was analyzed. We found markedly increased levels of apolipoprotein E (apoE) in EVs from Aβ protofibril exposed co-cultures, suggesting a role for intercellular transfer of apoE in Aβ pathology.

    Passive immunotherapy has been suggested as a promising therapeutic strategy for AD. In Paper III, we investigated if the Aβ protofibril-selective antibody mAb158 could affect Aβ clearance in the co-culture. The mAb158 treatment reduced Aβ accumulation in astrocytes and rescued neurons from Aβ-induced cell death.

    In Paper IV, we explored the effect of EVs, isolated from Aβ protofibril exposed co-cultures on cultured neurons. In addition to increased cell death, we found that such EVs had a strong negative impact on the synapses, dendrites and mitochondria of the neurons.

    Taken together, this thesis contributes with important knowledge about the role of astrocytes in Aβ pathology, the vesicle-mediated spreading of Aβ and the effects of anti-Aβ antibody treatment.

    Delarbeten
    1. Accumulation of amyloid-beta by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons
    Öppna denna publikation i ny flik eller fönster >>Accumulation of amyloid-beta by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons
    Visa övriga...
    2016 (Engelska)Ingår i: Molecular Neurodegeneration, ISSN 1750-1326, E-ISSN 1750-1326, Vol. 11, 38Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Despite the clear physical association between activated astrocytes and amyloid-beta (A beta) plaques, the importance of astrocytes and their therapeutic potential in Alzheimer's disease remain elusive. Soluble A beta aggregates, such as protofibrils, have been suggested to be responsible for the widespread neuronal cell death in Alzheimer's disease, but the mechanisms behind this remain unclear. Moreover, ineffective degradation is of great interest when it comes to the development and progression of neurodegeneration. Based on our previous results that astrocytes are extremely slow in degrading phagocytosed material, we hypothesized that astrocytes may be an important player in these processes. Hence, the aim of this study was to clarify the role of astrocytes in clearance, spreading and neuronal toxicity of A beta. Results: To examine the role of astrocytes in A beta pathology, we added A beta protofibrils to a co-culture system of primary neurons and glia. Our data demonstrates that astrocytes rapidly engulf large amounts of A beta protofibrils, but then store, rather than degrade the ingested material. The incomplete digestion results in a high intracellular load of toxic, partly N-terminally truncated A beta and severe lysosomal dysfunction. Moreover, secretion of microvesicles containing N-terminally truncated A beta, induce apoptosis of cortical neurons. Conclusions: Taken together, our results suggest that astrocytes play a central role in the progression of Alzheimer's disease, by accumulating and spreading toxic A beta species.

    Nyckelord
    Alzheimer's disease, Protofibrils, Glia, Phagocytosis, Degradation, Enlarged vacuole, Microvesicle
    Nationell ämneskategori
    Neurologi
    Identifikatorer
    urn:nbn:se:uu:diva-298408 (URN)10.1186/s13024-016-0098-z (DOI)000376366500001 ()27176225 (PubMedID)
    Tillgänglig från: 2016-07-04 Skapad: 2016-07-04 Senast uppdaterad: 2017-11-28Bibliografiskt granskad
    2. Increased Release of Apolipoprotein E in Extracellular Vesicles Following Amyloid-β Protofibril Exposure of Neuroglial Co-Cultures
    Öppna denna publikation i ny flik eller fönster >>Increased Release of Apolipoprotein E in Extracellular Vesicles Following Amyloid-β Protofibril Exposure of Neuroglial Co-Cultures
    Visa övriga...
    2017 (Engelska)Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 60, nr 1, 305-321 s.Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Extracellular vesicles (EVs), including exosomes and larger microvesicles, have been implicated to play a role in several conditions, including Alzheimer's disease (AD). Since the EV content mirrors the intracellular environment, it could contribute with important information about ongoing pathological processes and may be a useful source for biomarkers, reflecting the disease progression. The aim of the present study was to analyze the protein content of EVs specifically released from a mixed co-culture of primary astrocytes, neurons, and oligodendrocytes treated with synthetic amyloid-beta (A beta(42)) protofibrils. The EV isolation was performed by ultracentrifugation and validated by transmission electron microscopy. Mass spectrometry analysis of the EV content revealed a total of 807 unique proteins, of which five displayed altered levels in A beta(42) protofibril exposed cultures. The most prominent protein was apolipoprotein E (apoE), and by western blot analysis we could confirm a threefold increase of apoE in EVs from A beta(42) protofibril exposed cells, compared to unexposed cells. Moreover, immunoprecipitation studies demonstrated that apoE was primarily situated inside the EVs, whereas immunocytochemistry indicated that the EVs most likely derived from the astrocytes and the neurons in the culture. The identified A beta-induced sorting of apoE into EVs from cultured neuroglial cells suggests a possible role for intercellular transfer of apoE in AD pathology and encourage future studies to fully elucidate the clinical relevance of this event.

    Nyckelord
    Alzheimer’s disease, amyloid-beta, apolipoprotein E, astrocytes, exosomes, extracellular vesicles, mass spectrometry, neurons, shedding microvesicles
    Nationell ämneskategori
    Medicin och hälsovetenskap Neurovetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-331137 (URN)10.3233/JAD-170278 (DOI)000408582800025 ()
    Forskningsfinansiär
    VetenskapsrådetStiftelsen Gamla TjänarinnorÅke Wibergs Stiftelse
    Tillgänglig från: 2017-10-11 Skapad: 2017-10-11 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
    3. The Aβ protofibril selective antibody mAb158 prevents accumulation of Aβ in astrocytes and rescues neurons from Aβ-induced cell death.
    Öppna denna publikation i ny flik eller fönster >>The Aβ protofibril selective antibody mAb158 prevents accumulation of Aβ in astrocytes and rescues neurons from Aβ-induced cell death.
    Visa övriga...
    (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Nyckelord
    Alzheimer’s disease, amyloid-β, antibody, clearance, astrocyte, neuron
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Medicinsk vetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-264223 (URN)
    Tillgänglig från: 2015-10-15 Skapad: 2015-10-07 Senast uppdaterad: 2017-11-28
    4. Extracellular vesicle-mediated amyloid-β toxicity in cortical neurons
    Öppna denna publikation i ny flik eller fönster >>Extracellular vesicle-mediated amyloid-β toxicity in cortical neurons
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    Alzheimer’s disease, amyloid-β, extracellular vesicles, apoptosis, neurons, synapses, mitochondria
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Medicinsk vetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-334346 (URN)
    Tillgänglig från: 2017-11-22 Skapad: 2017-11-22 Senast uppdaterad: 2017-11-28
  • Disputation: 2018-02-09 09:15 Häggsalen, Uppsala
    Denisova, Aleksandra
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Hyperconjugation in Group 14 Organic Compounds: Design and Property Investigations2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Nowadays π-conjugated molecules are widely used as materials for devices in organic and molecular electronics. This is due to the ability of such molecules to conduct electricity. However, π-conjugation leads to molecular rigidness and associated lower solubility, which limits possible applications. Meanwhile, there are other types of conjugation that do not cause molecular rigidness but still provide conductivity. One of them is so called hyperconjugation. While π-conjugation involves only p atomic orbitals, hyperconjugation is characterized by interaction of π and σ orbitals. Hyperconjugation is normally weaker than π-conjugation, thus, in order to get strongly hyperconjugated molecules they should be enhanced in some way.

    In this thesis, I describe methods for design of strongly hyperconjugated molecules. It is possible to increase the strength of hyperconjugation by various methods and some of them are discussed. We performed quantum chemical calculations in order to investigate optical and geometric properties of the hyperconjugated molecules and evaluate the relative strength of hyperconjugation. In some cases, results of calculations were compared with experimental results aiming to confirm the relevance of the calculations. First, we have investigated how the change of group 14 elements in the 1,4-ditetrelocyclohexa-2,5-dienes influence the hyperconjugation strength. Next, the substituent effect was considered in fulvenes and their hyperconjugated analogs. We showed this effect from the perspective of the substituents influence on the aromatic properties of molecules in the ground and first electronically excited states. Further, the gradual shift when going from monomer to oligomers were investigated. For this hyperconjugated oligomers were constructed from 1,4-disilacyclohexa-2,5-diene and cyclobutadisilole fragments. Additionally we showed the influence of electron withdrawing and electron donating groups on hyperconjugation in siloles and 1,4-disilacyclohexa-2,5-dienes. Finally, hyperconjugation was investigated in a set of silicon-containing omni-hyperconjugated compounds.

    The results obtained from this research showed that hyperconjugation strength can be increased significantly up to levels comparable to purely π-conjugated molecules. We hope that these results will be useful in development of other hyperconjugated small molecules, oligomers, and polymers, which can be further used as material for electronic devices.

    Delarbeten
    1. Optimization of the Cyclic Cross-Hyperconjugation in 1,4-Ditetrelcyclohexa-2,5-dienes
    Öppna denna publikation i ny flik eller fönster >>Optimization of the Cyclic Cross-Hyperconjugation in 1,4-Ditetrelcyclohexa-2,5-dienes