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  • Disputas: 2019-11-15 10:00 William-Olssonsalen, Geovetenskapens hus, Stockholm
    Ul Hassan, Mahmood
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
    Achievement tests and optimal design for pretesting of questions2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Achievement tests are used to measure the students' proficiency in a particular knowledge. Computerized achievement tests (e.g. GRE and SAT) are usually based on questions available in an item bank to measure the proficiency of students. An item bank is a large collection of items with known characteristics (e.g. difficulty). Item banks are continuously updated and revised with new items in place of obsolete, overexposed or flawed items over time. This thesis is devoted to updating and maintaining the item bank with high-quality questions and better estimations of item parameters (item calibration). 

    The thesis contains four manuscripts. One paper investigates the impact of student ability dimensionality on the estimated parameters and the other three deal with item calibration.

    In the first paper, we investigate how the ability dimensionality influences the estimates of the item-parameters. By a case and simulation study, we found that a multidimensional model better discriminates among the students.

    The second paper describes a method for optimal item calibration by efficiently selecting the examinees based on their ability levels. We develop an algorithm which selects intervals for the students' ability levels for optimal calibration of the items. We also develop an equivalence theorem for item calibration to verify the optimal design.  

    The algorithm developed in Paper II becomes complicated with the increase of number of calibrated items. So, in Paper III we develop a new exchange algorithm based on the equivalence theorem developed in Paper II.

    Finally, the fourth paper generalizes the exchange algorithm described in Paper III by assuming that the students have multidimensional abilities to answer the questions.

  • Disputas: 2019-11-15 10:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Srinivas, Vivek
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    To metal, or not to metal: Diverse mechanisms of O2-activation and radical storage in the ferritin superfamily2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Proteins in the Ferritin-like superfamily are characterized by a four alpha-helical structural motif. These proteins are distributed across all three kingdoms of life and perform a wide range of functions. Several members in this protein superfamily can activate dioxygen using a di-metal active site coordinated by four carboxylate and two histidine amino acid residues. The resulting diverse set of dioxygen activated intermediates is used in nature to perform complex redox chemical reaction in cells. The R2 subunit of class I Ribonucleotide reductase and soluble Methane monooxygenase are the most well-characterized groups of proteins in this superfamily. Upon oxygen (or reduced-oxygen) activation of the di-metal site, the R2 subunit can generate a catalytic radical required for the conversion of ribonucleotides to deoxyribonucleotides, while soluble Methane monooxygenase can oxidize methane to methanol in an alternative form of carbon assimilation.

    The work presented in this thesis aims to better understand metal selectivity, working and the regulation of substrate specificity in various proteins of the Ferritin-like superfamily, and the development of a novel method to study radiation-sensitive intermediates. The papers discussed in this thesis present crystallographic and spectroscopic studies of several Ferritin-like superfamily proteins.

    In paper I, the assembly mechanisms of the heterodinuclear manganese-iron cofactor in a class Ic R2 protein and an R2-like ligand-binding oxidase are compared. Paper II presents the discovery of a novel radical-generating subunit subclass of Ribonucleotide reductase in Mollicutes, including mycoplasma pathogens, that breaks the paradigm of metal requirement for radical translocation and catalysis. This new subclass, denoted class Ie, is shown to instead use an unprecedented modified tyrosine DOPA residue in its four-helix bundle for radical translocation and storage. Paper III presents a new X-ray free-electron laser sample delivery system that combines acoustic droplet ejection with a drop-on-tape setup, allowing simultaneous multimodal X-ray diffraction and X-ray emission data collection. This setup is also shown to support photochemical and chemical activation of catalysis in crystals, allowing the study of radiation-sensitive transient reaction intermediates. We used this setup in paper IV to solve the first radiation damage-free crystallographic structures of the soluble methane monooxygenase hydroxylase and its regulatory subunit complex from Methylosinus trichosporium OB3b. The high-resolution crystal structures of the complex, in both di-ferrous and di-ferric oxidation states, illustrate the structural reorganization in the hydroxylase subunit upon binding to the regulatory subunit.

    These results illustrate the functional range and flexibility in the Ferritin-like protein superfamily. Including the distinctive metal discrimination in heterodinuclear metalloproteins, influencing substrate specificity in sMMO, and using a novel metal-free DOPA radical to catalyze ribonucleotide reduction in the class Ie R2 subclass. Experiments using the novel ADE-DOT setup also showed promising progress towards determining the highly sought-after structures of di-metal oxygen activated intermediates such as X and Q in subclass Ia R2 and sMMO, respectively.

  • Disputas: 2019-11-15 10:00 De Geersalen, Geovetenskapens hus, Stockholm
    H. Britton, Thérèse
    Stockholms universitet, Humanistiska fakulteten, Institutionen för de humanistiska och samhällsvetenskapliga ämnenas didaktik.
    Att möta det levda: Möjligheter och hinder för förståelse av levd religion i en studiebesöksorienterad religionskunskapsundervisning2019Doktoravhandling, monografi (Annet vitenskapelig)
    Abstract [en]

    The general aim of this study is to develop knowledge about how field visit-oriented religious teaching can contribute to students’ understanding of lived religion, in terms of inner diversity, religious practice and experiential dimensions. Previous research about Religious education (RE) shows that the Swedish non-confessional school subject “Religion” mainly deals with history, dogmas and concepts. Few students are concerned with the subject-matter itself in RE. "Secular" students talk about religion as something old-fashioned that concerns "the others". On the other hand, students who identify themselves religiously do not recognize what is being taught in school about their own tradition, since they miss perspectives concerning religion as part of everyday life, i.e., lived religion. A growing interest in individuals’ lived religion has also been identified in the field of religious studies. These circumstances related to field of RE serve as motivational ground for the present doctoral thesis.

    This thesis investigates designed RE-teaching in lower secondary school (year nine). The teaching design draws on findings reported in the licentiate thesis (Britton 2014).  Three theoretical approaches are used and integrated in a theoretical framework. The approaches applied to define and operationalize students’ understanding of lived religion are selected parts of Michail Bachtin's (1997) dialogue theory, Robert Jackson's (2002) interpretive approach of Religious education, and Meredith McGuire's (2008) religion sociology theories about lived religion.

    The empirical data were produced from selected parts of an enacted teaching design about Buddhism, including a field visit to a Tibetan-Buddhist congregation. The data consist of grade nine students' oral and written utterances from a lesson sequence, including lesson recordings, student journals, lesson exercises, assignments, group discussions and an examination. In addition, follow-up interviews were conducted with students, the teacher and the temple representative. Data were analysed using the integrated theoretical-analytical framework, in order to provide knowledge about what opportunities and obstacles in religious teaching that contribute to students’ understandings of lived religion.

    Three main results emerged. First, students' personal perspectives and values ​​of religion in general, and of the religious tradition studied (Buddhism) in particular, are important parts of students' understanding of lived religion. From students’ responses, some perspectives that interfered with their understanding of lived (Buddhist) religion were identified: student understandings that touch upon the links between individual freedom and religion; the relation between belief and religious practice and experiences; and ‘Western Buddhism’ in relation to Buddhism outside the West. Second, three didactical tools were constructed, aiming to develop RE teaching to further facilitate students’ understanding of lived religion: individual perspective, a diversity model and self-reflection. Didactical questions about representation, safe space and self-reflexivity came up. Third, there is support for arguing that lived religion as a perspective in the Swedish school subject of religion can be a goal as well as means to create a more inclusive religious education.

  • Disputas: 2019-11-15 13:00 Lilla Hörsalen, Naturhistoriska riksmuseet, Stockholm
    Jønland Højsgaard, Trine
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för pedagogik och didaktik.
    Reframed Identity: Red Cross nurses' identity formation between 1945 and 19772019Doktoravhandling, monografi (Annet vitenskapelig)
    Abstract [en]

    The overall aim is to explore the construction of nurse identity at the Red Cross Nursing School (RCNS) in Sweden, between 1945 and 1977, when nursing became part of the system of higher education in Sweden. Occupational identity is understood as a construct both of social learning and of a self-image. The empirical data consist of documents from the Red Cross Archive concerning the training of nurses and of interviews with nurses trained during the studied period. A hermeneutical interpretative method has been used. The result showed that the period studied was divided into two different phases. The first phase between 1945 and the end of the 1960s, is called the post war phase. The following phase, from the 1960s until 1977, is called the reform friendly phase. RCNS was in the post war phase a kind of total institution, based on a particular belonging to a very special and highly respected social community, reinforced by the student nurses being dressed in the same uniform and living under the same strong authority in a quite homogeneous group. The training was an introduction to a life-long membership in the total Red Cross Nurse community. This community was in the reform friendly phase challenged by diverse external changes in society. Within a period of approximately ten years, much came to be questioned, and many previously important customs and habits were abandoned. The total community started to dilute, and the lives of students changed gradually passing to a social arrangement where they slept, lived and worked in different places with different people under different authorities. The total community was impossible to modernise, built as it was on pre-modern values and hierarchies. This led to a breakdown of the traditional Red Cross nurse identity based on honour, where they were first of all Red Cross sisters. While the uniform occupational identity was challenged, more and more nurses combined family and work. This meant that their self-identities became more multidimensional. The key to our understanding of the Red Cross nursing education and the shift that took place in the late 1960s is thus to be found in the transformation of the internal collective, where nurses no longer lived and 2 learnt the traditional Red Cross codes of honour and conduct. Gradually, nurse training was integrated into higher education. This was a major reframing of the occupational identity formation, from specially selected Red Cross nurse students being trained into a total community of experienced Red Cross nurses, to an academic education of professional nurses.

  • Disputas: 2019-11-15 13:00 Nordenskiöldsalen, Stockholm
    Nystrand von Unge, Elin
    Stockholms universitet, Humanistiska fakulteten, Institutionen för etnologi, religionshistoria och genusvetenskap.
    Samla samtid: Insamlingspraktiker och temporalitet på kulturhistoriska museer i Sverige2019Doktoravhandling, monografi (Annet vitenskapelig)
    Abstract [en]

    This thesis is a study of contemporary collecting practices at museums of cultural history in Sweden. The study takes off from two questions: How is this practice of collecting understood at museums of cultural history today, and how are these modes of collecting effected when museums explicitly collect the “present” rather than the “past”? The aim is to examine how the present day has been collected, what modes of ordering were activated, as well as what relational effects contemporary collecting has had on the knowledge-building processes within the practice.

    The overall theoretical framework of the study primarily stands on sociologist John Law’s understanding of actor network theory. The actor network model is used as a theoretical tool to understand how agency and processes of knowledge production work. In addition, theoretical concepts from memory studies, as well as theories on knowledge building processes, are applied.The empirical material is collected through a combination of interviews and participant observations. Furthermore, archival studies were executed at the Nordiska museet archive.

    Through four chapters, the modes of ordering the Time, the Collectors, the Objects, and the Ideas are examined. The material analysed shows that the cultural historical “hinterland” that shaped the modern museum have had lasting effects on museum-collecting at large, but also on contemporary collecting practices. However, the reversed is also true: Contemporary collecting often acts as an important tool to make the self-evident position of traditional collecting visible. As the act of collecting activates fundamental ethical and moral questions concerning time, place, and social conditions, the practice has had constant effects on museum work in general. Therefore, without an active and conscious collecting, the content of museum work is in risk of stagnating. It is not only through exhibitions and outreach work that museums should have a contemporary societal awareness, but the collecting practices also deserve a mental presence in public space. Stating this, a continued expansive collecting at museums of cultural history is a necessity, by which the general museum-work is pushed forward and expanded. To collect and record expressions of the same contemporary perspectives is here seen as an active way of dealing with the blinding effects of being in the present.

  • Disputas: 2019-11-21 13:00 Hörsal 8, hus D, Stockholm
    Pettersson, Jimmy
    Stockholms universitet, Humanistiska fakulteten, Institutionen för kultur och estetik.
    Film på konstmuseum: Nationalmuseums möten med filmmediet 1945–19502019Doktoravhandling, monografi (Annet vitenskapelig)
    Abstract [en]

    This dissertation presents a number of previously-forgotten practices and ‘expected opportunities’ which surrounded film at the Swedish National Museum of Fine Arts (Nationalmuseum), between 1945 and 1950. The dissertation is structured around three projects and each project has its own chapter. The three projects are: (1) the educational film production entitled Möte med konsten which took place in connection with the exhibition entitled God konst i hem och samlingslokaler; the exhibition entitled Viking Eggeling 1880–1925 which included (2) showings of Viking Eggeling’s abstract film called Diagonalsymfonin (Diagonal Symphony) in the exhibition and (3) the related film series called 30 år experimentfilm (30 years of experimental film) which included films by Maya Deren, Man Ray, Fernand Léger, Jean Cocteau, Hans Richter and Viking Eggeling. The purpose of this dissertation is primarily to investigate the areas of use and ‘expected opportunities’ associated with film in these film projects as well as the prerequisites and implementation of working with film at the museum.

    Because media technologies are closely interwoven with human life, a number of individuals have been identified as important figures with respect to the curation and exhibition of film at Nationalmuseum between 1945 and 1950. The analysis of these figures’ speculations, their administration, and ‘expected opportunities’ has resulted in the creation of new knowledge with respect to the museum’s operations in post-war Sweden.

    In summary, the present dissertation highlights the medium of film’s role and importance for those individuals inside Nationalmuseum who, in response to contemporary needs (but also with an eye to the future) worked towards developing the museum. Film was seen as an answer to the question of how an art museum such as Nationalmuseum might be able to revitalise its operations and remain relevant to a new generation’s tastes and habits with respect to the consumption of art- and culture. In their work with film, they opened up the museum’s art division to working with modern abstract art in non-conventional forms, attempted to reach new sectors of the public and reinforced the contemporary relevance of the museum in a local cultural context. This dissertation thus does not only present new knowledge about the history of film at the art museum, of which it is an obvious part of today, but also new knowledge about Nationalmuseum. From a broader perspective, this dissertation also demonstrates how it is possible take the field of art museum research in a somewhat different and relatively unexplored direction, namely, in the direction of media history.

  • Disputas: 2019-11-22 09:00 CCK Lecture Hall, Solna
    Ödén, Jakob
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum. RaySearch Laboratories AB, Stockholm, Sweden.
    Relative biological effectiveness in proton therapy: accounting for variability and uncertainties2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Radiation therapy is widely used for treatments of malignant diseases. The search for the optimal radiation treatment approach for a specific case is a complex task, ultimately seeking to maximise the tumour control probability (TCP) while minimising the normal tissue complication probability (NTCP). Conventionally, standard curative treatments have been delivered with photons in daily fractions of 2 Gy over a period of approximately three to eight weeks. However, the interest in hypofractionated treatments and proton therapy have rapidly increased during the last decades. Given the same TCP for a photon and a proton plan, the proton plan selection could be made purely based on the reduction in NTCP. Such a plan selection system is clean and elegant but is not flawless. The nominal plans are typically optimised on a single three-dimensional scan of the patient trying to account for the treatment related uncertainties such as particle ranges, patient setup, breathing and organ motion. The comparison also relies on the relative biological effectiveness (RBE), which relates the doses required by photons and protons to achieve the same biological effect. The clinical standard of using a constant proton RBE of 1.1 does not reflect the complex nature of the RBE, which varies with parameters such as linear energy transfer (LET), fractionation dose, tissue type and biological endpoint.

    These aspects of proton therapy planning have been investigated in this thesis through five individual studies. Paper I investigated the impact of including models accounting for the variability of the RBE into the plan comparison between proton and photon prostate plans for various fractionation schedules. In paper II, a method of incorporating RBE uncertainties into the robustness evaluation was proposed. Paper III evaluated the impact of variable RBE models and breathing motion for breast cancer treatments using photons and protons. In Paper IV, a novel optimisation method was proposed, where the number of protons stopping in critical structures is reduced in order to control the enhanced LET and the related RBE. Paper V presented a retrospective analysis with alternative treatment plans for intracranial cases with suspected radiation-induced toxicities.

    The results indicate that the inclusion of variable RBE models and their uncertainties into the proton plan evaluation could lead to differences from the nominal plans made under the assumption of a constant RBE of 1.1 for both target and normal tissue doses. The RBE-weighted dose (DRBE) for high α/β targets (e.g. head and neck (H&N) tumours) was predicted to be slightly lower, whereas the opposite was predicted for low α/β targets (e.g. breast and prostate) in comparison to the nominal DRBE. For most normal tissues, the predicted DRBE were often substantially higher, resulting in higher NTCP estimates for several organs and clinical endpoints. By combining uncertainties in patient setup, range and breathing motion with RBE uncertainties, comprehensive robustness evaluations could be performed. Such evaluations could be included in the plan selection process in order to mitigate potential adverse effects caused by an enhanced RBE. Furthermore, objectives penalising protons stopping in risk organ were proven able to reduce LET, RBE and NTCP for H&N and intracranial tumours. Such approach might be a future optimisation tool in order to further reduce toxicity risks and maximise the benefit of proton therapy.

  • Disputas: 2019-11-22 10:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Nilsson, Tobias
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Protein and lipid interactions within the respiratory chain: Studies using membrane-mimetic systems2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Energy conversion from nutrients to ATP is a vital process in cells. The process, called oxidative phosphorylation (OXPHOS) is performed by a combination of membrane-bound proteins. These proteins have been studied in great detail in the past, however much is still unknown about how they interact with each other. Studying the OXPHOS proteins in their native environment can be difficult due to the complexity of living cells. By isolating parts of the OXPHOS system and inserting them into membrane-mimetic systems it is possible to investigate their functions in a controlled environment.

    In the work presented here, we co-reconstituted several of these proteins into liposomes made from synthetic lipids. We demonstrated production of ATP at steady-state conditions with the ATP synthase, driven by proton pumping by cytochrome bo3. Introduction of anionic lipids decreased the coupled activity and we could correlate this effect to weaker interactions between ATP synthase and cytochrome bo3 in the membrane. We also reconstituted cytochrome c oxidase (CytcO) from Saccharomyces cerevisiae with Respiratory supercomplex factor 1 (Rcf1) into liposomes and submitochondrial particles (SMPs). Loss of Rcf1 has previously been found to result in a lower CytcO activity. We found that activity could be restored upon co-reconstitution of CytcO with Rcf1, but only after unfolding and re-folding of the latter, which shows that Rcf1 can adopt two configurations in the membrane.

  • Disputas: 2019-11-22 10:00 De Geersalen, Geovetenskapens hus, Stockholm
    Nordklint, Caroline
    Stockholms universitet, Juridiska fakulteten, Juridiska institutionen.
    Bevisrättens tillämpning i skatteprocessen2019Doktoravhandling, monografi (Annet vitenskapelig)
    Abstract [en]

    The Swedish law of evidence is based on the principle of the free evaluation of evidence, meaning that the courts, as a main rule, should not be bound by any legal rules in its evaluation process of the evidence. Swedish tax law is, contrary to the law of evidence, based on the principle of legality. According to the principle of legality, tax shall follow from the law and this also applies to the tax procedure, whereby the Swedish Tax Agency and the courts need constitutional support for their executive and judicial activities. In addition, the Swedish tax procedure is characterized by high standards on the rule of law. The rule of law concerns the requirement that tax law should be predictable and foreseeable. These two branches of law, with different purposes and views, should be combined in the same tax procedure. Conflicts are unavoidable and this evokes the question if there is need for a more regulated Swedish law of evidence as it is applicable and interpreted in procedural tax law.

    The overall purpose of the thesis is to investigate and analyze the application of the law of evidence in the Swedish tax procedure, specifically concerning the evaluation of evidence in tax cases. Firstly, the thesis aims to examine and analyze the main rules for the law of evidence in the tax procedure, as well as identifying some established exemptions to these rules. These exemptions are further analyzed in order to investigate if there is need for such exemptions, and if there are any problems when these exemptions should be applied in a case. Secondly, the thesis aims to explore if there is need for additional exemptions from the main evidential rules in the tax procedure. As part of this objective, certain norms with regards to the rule of law and the tax procedure are analyzed in order to investigate in what way those norms have an impact on the application of the evidential rules and principles in the tax procedure. As a result of the analysis, the examination will present proposals for measures to promote improvements with regards to the application of the law of evidence in the tax procedure. 

    In the thesis, several arguments for more regulations in relation to the evidential issues in the tax procedure are presented. One argument is based on the conflict with the principle of legality and the importance of a predictable and foreseeable tax procedure. Sometimes the best alternative to avoid such conflicts is to introduce a norm in the law, which states how certain evidence should be evaluated, so-called instruction on the evaluation of evidence. However, this could cause conflict with the principle of the free evaluation of evidence. Therefore, it is argued that as a first alternative one should investigate if a similar evidential effect could be met by adjusting the evidential rules in relation to the application of law and the issue of law. Two examples of such an adjustment is to develop a presumption of evidence or to introduce an alleviation of evidentiary burden.

  • Disputas: 2019-11-22 13:00 sal FA32, AlbaNova universitetscentrum, Stockholm
    Liu, Chang
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Le Fantôme de l’Opéra - Studies on Atoms and Electrons Beneath2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The carbon dioxide reduction reaction is a promising candidate to tackle ecological challenges of our age. This is due to its capability of reducing carbon dioxide emission generated from the combustion of fossil fuels by converting carbon dioxide into valuable hydrocarbons. Oxide-derived metal nanostructures have been found to exhibit unique catalytic characteristics for facilitating the carbon dioxide reduction reaction. In this thesis work, the stability, influence, and effects of subsurface oxygen atoms are investigated by theoretical computations with various levels of theory and models. It is found that subsurface oxygen atoms are stable and that their presence increases the CO adsorption strength and coverage on oxide-derived Cu surface. This is explained by a reduced σ-repulsion and leads to the breaking of scaling relations. Although it does not directly reduce the CO dimerization barrier, the adsorption of H atoms is inhibited thus steering the selectivity. The presence of subsurface oxygen atoms is also concluded from a joint work with experimental and theoretical efforts of X-ray photoelectron spectroscopy. The precursor region of CO desorption from Ru(0001) is studied with the transition potential method. In contrast, for the simulation of the X-ray spectroscopy results on p4g C/Ni(100), which is a surface reconstruction when carbon atoms adsorb on Ni(100), vibrational effects are also needed for understanding the experimental data.

  • Disputas: 2019-11-25 09:30 Air & Fire, SciLifeLab, Solna
    Qian, Xiaoyan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Towards comprehensive cellular atlases: High-throughput cell mapping by in situ sequencing2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    With recent technological advancements in single-cell biology, many aspects of individual cells are characterized with unprecedented resolution and details. Cell types in human and model organisms are redefined, and multiple organ-wide atlases are proposed to integrate different types of data to provide a comprehensive view of biological systems at cellular resolution. Incorporating location information of cells in such atlases is crucial to understanding the structure and functions. Several spatially resolved transcriptomics technologies may serve this purpose, and in situ sequencing (ISS) is among the most powerful ones.

    ISS detects the expression of tens to hundreds of genes in situ, i.e. inside preserved cells and tissues. ISS is a targeted approach, using probes designed to identify specific transcripts. Its key advantages, as compared to other spatially resolved gene expression analysis methods, are high throughput, cellular resolution and tissue compatibility, making it a tool ideally suited for spatial cell mapping. The work included in this thesis aims to develop tools and methods for this application.

    In paper I, a network analysis tool was developed to analyze ISS and other spatially resolved data. The tool enables smooth visualization of large datasets and generates networks based on colocalization. It also includes functions to test statistical significance and resolve tissue heterogeneity.

    In paper II, we studied spatio-temporal patterns of immune response in tuberculosis granuloma by targeting immune markers with ISS. Using the tool developed in paper I together with other methods, we established an immune response time course at the granuloma sites and found histologically different granulomas based on transcriptional information. The paper demonstrated that ISS can robustly detect transcripts in formalin-fixed paraffin-embedded tissues across biological samples and reveal biologically relevant structures.

    In paper III, we developed probabilistic cell typing by in situ sequencing (pciSeq), a method to spatially map cell types defined by single-cell RNA-sequencing. pciSeq is an integrated pipeline that includes gene selection, image analysis, barcode calling and cell type calling. We mapped closely related interneuron cell types of the mouse hippocampal CA1 region in 14 coronal sections and validated the results against ground truth.

    In paper IV, we investigated the quantification bias of ISS resulting from the probe target selection. We developed a method to sequence in situ synthesized cDNA and found that the read coverage of in situ cDNA library reflected ISS counts more closely than conventional RNA sequencing, making it possible, to some extent, to predict a probe’s performance and guide the probe design.

    Taken together, the developments described in this thesis comprise several tools that make ISS suitable for building cellular atlases via large-scale spatial mapping.

  • Disputas: 2019-11-28 10:00 Vivi Täckholm-salen (Q-salen), Stockholm
    Wassing, Gabriela
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Bacteria-host cell interactions: Studies on initial colonization, antimicrobial peptides, and biofilms2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The obligate human pathogen Neisseria meningitidis asymptomatically colonizes the upper respiratory tract, but crossing of the epithelial barrier can cause life-threatening meningitis and/or sepsis. N. meningitidis encounters numerous environmental challenges during colonization in the host, and has evolved different evasion strategies and virulence factors to ensure its survival. In contrast, Lactobacillus species are part of the human microbiota and their commensal colonization confers many benefits to the host, including the inhibition of pathogens.

    The first cell type encountered by invading bacteria are epithelial cells and immune cells, which can effectively sense and respond to the presence of bacteria by alerting the immune system or by release of antimicrobial peptides. Antimicrobial peptides are small peptides that are able to directly kill bacteria, but also play a role in modulation of immune responses.  

    This thesis focuses on the interaction between the human host and bacteria. Paper I shows that epithelial colonization by different bacterial species induces the transcription factor early growth response protein 1 (EGR1). Induction of EGR1 is mediated primarily by signaling through EGFR and ERK1/2 pathway. In paper II the ability of N. meningitidis and Lactobacillus to modulate expression of antimicrobial peptide human beta-defensin 2 (hBD2) in epithelial cells is compared. Expression of hBD2 is upregulated by lactobacilli. In contrast, N. meningitidis dampens this effect, likely mediated by induction of the host molecule A20, a negative regulator of NF-κB. Since N. meningitidis is susceptible to hBD2-mediated killing, exploitation of A20 may be an immune evasion mechanism. In paper III we demonstrate that hBD2 is able to kill N. meningitidis without causing membrane permeabilization. N. meningitidis DNA can bind hBD2 and thereby inhibit hBD2-mediated killing, presenting a possible evasion mechanism. Finally, paper IV shows that the absence of D-lactate dehydrogenase LdhA in N. meningitidis promotes aggregation and biofilm formation through increased autolysis-mediated release of extracellular DNA.

  • Disputas: 2019-11-28 13:00 sal 14, hus 5, Kräftriket, Stockholm
    Hansson, Disa
    Stockholms universitet, Naturvetenskapliga fakulteten, Matematiska institutionen.
    Modelling Sexual Interactions: Sexual behaviour and the spread of sexually transmitted infections on dynamic networks2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In this thesis we develop statistical and mathematical models to study different factors of relevance for the spread of sexually transmitted infections (STIs). Two special interest groups for STI interventions are considered: sexually active youths and men who have sex with men (MSM). The statistical models developed make it possible to estimate individuals’ dispositions towards sexual behaviours related to the spread of STIs: condom use and anal sex. To study the spread of an infection in a population we use mathematical models. The mathematical models in this thesis give insights into the transmission process of HIV among MSM in Sweden—a population at high risk for HIV infection.

    The focus of the first paper is on mechanisms giving rise to observed sexual behaviour, such as condom use, among sexually active youths in Sweden. We study the sexual dispositions of individuals and how these interact and generate the observed sexual outcomes.

    The second paper concerns the sexual behaviour of MSM in Sweden and the transmission process of HIV within this population. The population is modelled by a stochastic dynamic network model that incorporates both steady partnerships and casual contacts. We model the spread of an infection where individuals are susceptible, infectious or diagnosed (unable to transmit) and derive the basic reproduction number R0, the probability of a major outbreak, and the endemic prevalence.

    The third paper further develops the dynamic network model of the second paper. The model now takes into account that individuals may be sexually high-active or sexually low-active. The division into two activity groups makes it possible to study a preventive intervention against HIV that is only targeted to sexually high-active. The intervention studied is pre-exposure prophylaxis for HIV (PrEP), i.e. that the antiviral drugs tenofovir-emtricitabine are taken by individuals with negative HIV serostatus to prevent getting infected by HIV. We study the PrEP coverage needed to reduce the observed HIV prevalence of 5% to a value close to 0%.

    In the fourth and final paper we focus on condom dispositions among MSM. The disposition models from the first paper are extended to better fit an MSM population and are additionally extended to be used for more types of sexual behaviour data.

  • Disputas: 2019-11-29 09:00 Vivi Täckholmsalen (Q-salen), NPQ-huset, Stockholm
    Mata Forsberg, Manuel
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Bacterial Regulation of Peripheral Immunity: Mechanistic insights from lactobacilli and Staphylococcus aureus2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    There is a constant cross-talk between our immune system and the colonizing microbiota. The gut resident bacteria produce a broad range of molecules with regulatory activities in both local and distal tissues. Staphylococcus (S.) aureus is a commensal bacterium with high pathogenic potential due to production of several potent virulence factors including staphylococcal enterotoxins (SEs). These SEs are known to induce overwhelming T cell responses, which can result in a serious condition known as toxic shock syndrome. In contrast, several species of bacteria from the genus Lactobacillus exhibit probiotic features and promote beneficial physiological and immunological effects in its host. The underlying mechanisms behind bacterial activation and regulation of peripheral lymphocytes remain elusive. In this thesis, we explored how secreted factors present in the cell free supernatants (CFS) of cultured S. aureus and lactobacilli mechanistically impact the activation of different types of T cells and NK cells. In paper I, we investigated the influence of S. aureus-CFS and SEA on regulatory T cells and found that despite de novo induction of FOXP3 expression, TREG cells also produced pro-inflammatory cytokines, which associated with CD161-expression. In paper II, we could show that S. aureus-CFS and SEA induce proliferation, cytotoxicity and cytokine production in conventional and unconventional T- and NK cells. Moreover, we also showed that the lactobacilli-CFS were able to dampen immune cell activation, which was partly linked to lactobacilli-derived lactate. In paper III, we continued to investigate the mechanism behind Lactobacillus-mediated dampening of induced lymphocyte responses and identified extracellular membrane vesicles to be one of the main components involved in Lactobacillus-mediated regulation of cytokine responses. Other observations made in paper II brought about several questions regarding the ability of SEs to activate unconventional T- and NK cells, which lacks certain receptors known to be required for SE-mediated activation of conventional T cells. In paper IV, we therefore investigated the mechanism behind SE-mediated activation of γδ T-, MAIT- and NK cells and found that SEs indirectly activated γδ T- and NK cells, which required the presence of conventional αβ T cells. In summary, this thesis presents novel insights into how soluble components from bacteria modulate immune cell responses and extends the general understanding of bacterial influence on peripheral immunity. 

  • Disputas: 2019-11-29 10:00 Högbomsalen, Geovetenskapens hus, Stockholm
    Wang, Tongmei
    Stockholms universitet, Naturvetenskapliga fakulteten, Meteorologiska institutionen (MISU).
    Seasonality and variability of stratospheric water vapour2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Stratospheric water vapour (SWV) plays a critical role in the climate system by modulating the radiation budget and influencing the stratospheric chemistry. Studying changes of SWV on global scale is helpful for our understanding of climate change. This thesis aims to gain an improved understanding of the stratospheric processes and dynamic mechanisms that determine the seasonality and variability of SWV. 

    Water vapour is characterized by its compound, which leaves an isotopic fingerprint in relevant atmospheric and hydrologic processes. The thesis starts with analyzing the global features of three stable water isotopes (SWIs) in the stratosphere by using satellite retrievals from Odin/SMR. The spatial pattern of SWI indicates clear effects of methane oxidation in the upper stratosphere, dehydration at the tropopause and stratospheric transport via the Brewer-Dobson circulation (BDC). In addition to the tropical tape recorder in the lower stratosphere, a pronounced downward propagation of the seasonal signal from the upper to the lower stratosphere is observed in high-latitudes. These observed features are further compared to model outputs to identify possible causes of model deficiencies in reproducing the distribution of SWV.

    The downward propagation signal of zonal wind has been demonstrated in the high-latitude stratosphere in spring seasonal transition in the Southern Hemisphere, but not in the Northern Hemisphere. This inter-hemispheric difference is due to the stronger stratospheric planetary wave activity in austral spring than in boreal spring. With strong wave activity in spring, the transition is inclined to occur first at the stratopause followed by a downward propagation to the lower stratosphere. In particular, the stronger the upward propagation of planetary waves in high-latitudes in spring the earlier the stratospheric seasonal transition. 

    The new generation reanalysis ERA5 represents climatological distribution and seasonal cycle of SWV better than its predecessor ERA-Interim by assimilating more satellite observations. The variability of SWV in ERA5 is highly consistent with SDI MIM observation. The interannual variability of water vapour in the lower stratosphere is found to be closely linked to the tropical Quasi-Biennial Oscillation (QBO) and QBO-induced residual circulation. On decadal scale, the deficit of SWV in boreal winter is associated with a warm sea surface temperature (SST) anomaly in the North Atlantic, which leads to stronger upward propagation of planetary waves, resulting in a warmer pole in the lower stratosphere, colder tropical tropopause and stronger BDC, hence less water vapour enters the stratosphere through the tropopause and the anomaly extends to the entire stratosphere. 

    Sensitivity experiments for a CO2 doubling scenario are performed with the model WACCM to investigate the SWV response to climate change. The response of SWV is dominated by the warm SST, which is induced by CO2 doubling in a coupled ocean-atmosphere system. The enhanced SST leads to a moist troposphere and warmer tropical and subtropical tropopause, resulting in more water vapour entering the stratosphere from below. A large increase of SWV in the lower stratosphere, in turn, affects stratospheric temperature. It results in a warming in the tropical and subtropical lower stratosphere, offsetting the cooling caused by CO2 doubling in general.

  • Disputas: 2019-11-29 13:00 sal FB54, AlbaNova universitetscentrum, Stockholm
    Wallängen, Veronica
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Performance Improvements for Particle Tracking Detectors in Extreme Rate and Radiation Environments2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In order to increase its discovery potential, the Large Hadron Collider (LHC) at CERN is being transformed into a higher luminosity machine expected to be operational around 2026. The number of particle collisions will increase by a factor of 10 beyond the current design value, which means that the detectors installed around the LHC are facing various new challenges. The most demanding challenges include handling the enormous data quantities that will be transferred from the front-end readout modules at significantly higher rates than previously, as well as the radiation effects that arise as a consequence of the intense particle flow and that cause damage to sensor elements and electronics.

    At the ATLAS experiment, a multipurpose detector operating at the LHC, the impact of the luminosity increase is especially severe for the silicon pixel tracking detector, being the central subsystem located closest to the particle interaction point and therefore exposed to the highest radiation dose and hit density. The extreme radiation doses that the pixel modules will be subject to will cause deformation of the sensor material structure and thus loss of the signals, which after subsequent digitization by the pixel readout chip must be transferred over relatively long distances through a low-mass data link, causing further signal distortion.

    The work presented here addresses both major challenges described and outlines solutions for the upcoming upgrade of the ATLAS pixel detector system with regards to these. Firstly, it is demonstrated how improved accuracy of detector simulations and reconstruction of particle trajectories through the detector can be achieved as higher particle fluences are approached, by modeling radiation damage effects that occur in the pixel sensors. Secondly, it is shown how a receiver integrated circuit utilizing an industry standard technique novel within high-energy physics applications has been designed as an integral part of a high-speed transmission link to efficiently restore the signal quality in order to achieve adequate data readout rates.

  • Disputas: 2019-12-02 10:00 Vivi Täckholmsalen (Q-salen), NPQ-huset, Stockholm
    Dou, Dan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Influenza A Virus: Spatial analysis of influenza genome trafficking and the evolution of the neuraminidase protein2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Influenza A viruses (IAVs) are a common infectious agent that seasonally circulates within the human population that causes mild to severe acute respiratory infections. The severity of the infection is often related to how the virus has evolved with respect to the pre-existing immunity in the population. For IAVs, the most common mechanisms to avoid the immune response are to vary the surface antigens, hemagglutinin (HA) and neuraminidase (NA), by processes known as antigenic drift and shift.

    Antigenic drift refers to point mutations that accumulate in HA and NA as a result of the antibody-mediated selection pressure that exists in the population. The majority of the changes attributed to antigenic drift localize to HA and NA surface exposed regions, however this does not exclude that drift can also result in the selection of residues that are not exposed. One region where non-exposed residues have potentially been selected for is the NA transmembrane domain (TMD) of human H1N1 IAVs, where a temporal bias exists for the accumulation of polar residues. By examining these sequence changes in the NA TMD, we found that the polar residues contribute to the amphipathic characteristic of the NA TMD, which mediates the oligomerization of the N-terminus. As more polar residues became incorporated, the strength of the TMD-TMD interaction increased, presumably to benefit the NA head domain assembly into a functional tetramer. We determined that the amphiphilic drift in the NA TMD is able to bypass the strict hydrophobicity required for membrane insertion at the endoplasmic reticulum because it can utilize the co-translational translocation process to facilitate the insertion and inversion of its non-ideal TMD. The contribution of the TMD to proper NA assembly was traced to the formation of the Ca2+ binding pocket that is located at the center of the tetrameric assembly, as this pocket lies above the stalk linker regions and must be occupied for NA to function.

    In addition to antigenic drift, NA and HA can also undergo antigenic shift. Antigenic shift occurs when either of the gene segments encoding NA or HA are exchanged with ones from another IAV encoding another subtype of NA or HA. Different from antigenic drift, antigenic shift can only occur when a cell is co-infected and most investigations on the process of reassortment have been made at the protein level due to the methodological issues for labeling the RNA genome in situ. To overcome these technical limitations, we developed an in situ RNA labeling approach that provides highly specific spatial resolution of the IAV genome throughout the infection process. By applying this approach to temporally analyze the co-infection process, we found that the entry of a second IAV is stalled in the cytoplasm if another IAV has begun to replicate. Together, these results provide insight into the low frequency of antigenic shift in nature and provide evidence that non-exposed residues may make an underappreciated contribution to NA antigenic drift in human H1N1 viruses.

  • Disputas: 2019-12-04 10:00 sal 14, hus 5, Stockholm
    Wahl, Felix
    Stockholms universitet, Naturvetenskapliga fakulteten, Matematiska institutionen.
    Micro-level claims reserving in non-life insurance2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Actuarial reserving deals with the problem of predicting outstanding claims payments on policies issued up to today to find an appropriate amount of capital, the claims reserve or technical provisions, to set aside in order to be able to meet obligations to policyholders. Historically, and commonly still today, this has been approached using purely algorithmic and deterministic methods, not based in any statistical models. This thesis contains five individual papers, mainly concerned with statistical models for use in the area of reserving in non-life insurance.

    Paper I sets out all the components needed for the valuation of aggregate non-life insurance liability cash flows based on data in the form of claims triangles. The paper contains all necessary ingredients for use in practice, including the estimation of model parameters and a bias correction of the plug-in estimator of the valuation formula. The valuation framework that the paper takes as its starting point is compatible with the view of the Solvency IIdirective on how to compute the value of the technical provisions, i.e. that the value should equal the amount which a so-called reference undertaking would demand in order to take over and handle the run-off of the liability cash flow.

    Paper II deals with the problem of estimating the conditional mean squared error of prediction(MSEP), conditional on the observed data. The paper presents an approach that yields analytically computable estimators for a wide range of different models — otherwise readily computable using simple numerical methods — and, moreover, it shows that the approach reproduces the famous MSEP formula for the distribution-free chain ladder model given by Mack in 1993. The approach is particularly useful when considering run-off triangles since itis then not feasible to perform a prediction assessment based on out-of-sample performance.

    Paper III is concerned with properties of the variance of the variance parameter estimator ina general linear model, mainly in the form of finite sample size bounds that are independent of the covariates and that are such that, asymptotically, the lower and upper bounds are the same. As opposed to the other papers of this thesis, this paper is purely theoretical without an immediate insurance context — except for a small example.

    Paper IV introduces a discrete-time micro-model called the collective reserving model (CRM). The model is highly accessible since, even though it is a micro-model, it is modelled on the aggregate level using two triangles, one for the number of reported claims and one for the claims payments. The paper shows, among other things, how the model gives predictors of outstanding claims payments separately for incurred but not reported and reported but not settled claims, and, interestingly, shows that the chain ladder technique is a large exposure (e.g. the number of contracts) approximation of the CRM.

    Paper V is chiefly concerned with deriving closed-form expressions for moments in a class of continuous-time micro-models. It is the first paper to accomplish this task, hopefully making continuous-time micro-models accessible to a broader audience.

  • Disputas: 2019-12-06 10:00 Vivi Täckholmsalen (Q-salen), NPQ-huset, Stockholm
    Johansson, Erik
    Stockholms universitet, Naturvetenskapliga fakulteten, Meteorologiska institutionen (MISU). SMHI - Sveriges meteorologiska och hydrologiska institut.
    Improving the understanding of cloud radiative heating2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Clouds play an essential role in regulating Earth’s radiation budget by reflecting and absorbing energy at different spectra. As they interact with radiation, they can radiatively heat or cool the adjacent atmosphere and the surface. This heating effect can have a strong implication for the circulation and can change the surface properties by, for example, melting sea ice. The lack of high-resolution global observations has previously been a limitation for our understanding of the vertical structure of cloud radiative heating, and for evaluating the cloud radiative effect in climate models. In this thesis, we will investigate and document cloud radiative heating derived from space-based observations. We will focus on two regions, the Arctic and the Tropics, where cloud radiative heating plays an important, but fundamentally different role.

    In the Tropics, radiative heating at high altitudes influences the large scale circulation. Stratiform, deep convective, and cirrus clouds have a strong radiative impact in the upper troposphere. We found while investigating the Indian monsoon, that thick stratiform clouds will radiatively heat the upper troposphere by more than 0.2 K/day when the monsoon is most intense during June, July and August. Deep convective clouds cause considerable heating in the middle troposphere and at the same time, cool the tropical tropopause layer (TTL). These two thick cloud types will also cool the surface during the monsoon, weakening the temperature gradient between land and ocean. During these months, cirrus clouds are frequently located inside the TTL. We further find that in the Tropics, the climate model, EC-Earth, can capture the seasonal variations in cloud radiative heating seen in the satellite observations. However, the model overestimates the radiative heating in the upper region  and underestimates them in the middle region of the troposphere. This dissimilarity is caused by unrealistic longwave heating and low cloud fraction in the upper and middle of the troposphere, respectively.

    Radiative heating from cirrus, located inside the TTL, is considered to play an important role in the mass transport from the troposphere to the stratosphere. This heating generates enough buoyancy so that the air can pass the barrier of zero net radiative heating. We find that high thin single-layer clouds can heat the upper troposphere by 0.07 K/day. If a thick cloud layer is present underneath, they will radiatively suppress the high cloud, causing it to cool the adjacent air instead. The optical depth and cloud top height of the underlying cloud are two crucial factors that radiatively impact the high cloud above.

    Warm moist air is regularly transported from the mid-latitudes into the Arctic by low- and high-pressure systems. As the moist air enters the Arctic, it increases the cloudiness and warms the surface. This surface heating has the potential to affect the ice cover months after the intrusion. We find that during extreme moist intrusions, the surface temperature in the Arctic can rise by more than 5 K during the winter months with an increase in cloudiness by up to 30% downstream from the intrusion. These extra clouds radiatively heat the lower part of the atmosphere and cool the middle part, affecting the stability of the Arctic atmosphere.

  • Disputas: 2019-12-06 10:00 Aula Svea, Socialhögskolan, Stockholm
    Forsman, Hilma
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för socialt arbete - Socialhögskolan.
    Addressing poor educational outcomes among children with out-of-home care experience: Studies on impact, pathways, and interventions2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Children with out-of-home care (OHC; foster family/residential care) experience is a high-risk group for future adverse outcomes. With an ambition of supporting the design of effective preventive child welfare measures targeting children in OHC, the overall aim of this thesis is to examine education as a possible intervention path for improving their development and overall life chances.

    The thesis consists of four interrelated empirical studies that address different aspects of poor educational outcomes among children with OHC experience by means of analyses of longitudinal survey and register data, and evaluations of two interventions aimed at improving their basic academic skills.

    Study I examined the hypothesized causal effect of poor school performance on adverse outcomes in young adulthood among children with OHC experience. The results showed that poor school performance has an impact on later psychosocial problems net of observed and unobserved factors, suggesting that the estimated effects allow for causal interpretations.

    Study II explored educational outcomes at different stages in the educational career, and pathways to varied educational outcomes for children with OHC experience and their peers. The results showed that the OHC group had lower educational outcomes across the life course. Yet, by large, their educational pathways did not differ significantly from their peers – cognitive ability and previous school performance had the largest associations with the outcomes in both groups. However, the influence of these factors were weaker in the OHC group whilst the influence of the birth family’s attitude towards higher education was stronger.

    Study III aimed at furthering our understanding of the book-gifting program the Letterbox Club’s potential impact on foster family children’s reading skills. The results showed that participation in the program was associated with small improvements. In general, the program was well received by children and carers, and could result in increased reading. The study furthermore suggested that promotion of carer involvement may improve its potential impact.

    Study IV explored the process of conducting a structured paired reading intervention involving foster family children and their carers. Findings showed that it is possible to engage carers in interventions targeting the education of children in OHC, but that this is no automatic process – carers need a rationale for getting involved, and support in delivering the intervention.

    In sum, this thesis shows that improving the educational outcomes of children in OHC may be a viable intervention path in supporting their life course development, a path that historically has been overlooked. The thesis furthermore shows examples of promising interventions which may improve the basic academic skills of children in OHC. The results also point out that the child welfare system should provide early and continuous educational support, and highlight the importance of addressing adults’ attitudes, expectations, and involvement in these children’s education.

  • Disputas: 2019-12-06 10:00 Ahlmansalen, Geovetenskapens hus, Stockholm
    Arvidsson, Klara
    Stockholms universitet, Humanistiska fakulteten, Romanska och klassiska institutionen.
    « C'est ça, en fait. » Développer l'idiomaticité dans une L2 pendant un séjour linguistique: Trois études sur le rôle des différences individuelles2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis deals with the development of idiomaticity in French as a second language (L2). Idiomaticity in this context refers to knowledge and use of multiword expressions (MWEs), such as for example c'est ça and en fait. Developing idiomaticity is an important yet challenging aspect of L2 learning, and requires substantial exposure to the target language (TL). This makes the study abroad learning context ideal. However, research shows that learners vary considerably with respect to their linguistic development during their stay abroad. The aim of this thesis is to investigate what factors promote the development of idiomaticity in L2 French during a semester abroad. The thesis comprises three studies which are informed by usage-based approaches to language learning and individual difference research, and which include a total of 43 participants. Study I quantitatively investigates the role of quantity of TL contact for the learning of MWEs used in informal conversations. The results show that quantity of TL contact during the stay abroad did not predict the development of MWE knowledge. Study II qualitatively explores what kind of TL contact and what psychological orientation (a constellation of psychological factors) might promote MWE learning by focusing on contrasting cases of learners from Study I. The findings suggest that a relatively varied contact with the TL in combination with a favorable psychological orientation promoted MWE learning, including a self-reported tendency to notice language forms, a strong L2 motivation, a sense of self-efficacy and self-regulatory capabilities. Study III explores the role of social networks for the development of idiomaticity in spoken L2 French. It is found that the learner's repertoire of MWEs was promoted by a social network including several relationships sustained in the TL. Overall, the findings suggest that a relatively varied TL contact in combination with a favorable psychological orientation and/or a social network including TL speakers promote the development of L2 idiomaticity during the semester abroad. In other words, mere exposure to the TL does not seem to be enough to develop idiomaticity. This thesis contributes to SA research on L2 learning and can hopefully be of use to future SA participants who want to develop their knowledge and use of MWEs which are key to successful communication in an L2.

  • Disputas: 2019-12-06 10:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Martinez-Erro, Samuel
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Catalytic Methods to Convert Allylic Substrates through Hydride and Proton Shifts: Transition Metal-Catalyzed and Organocatalyzed Approaches2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The present thesis describes the development of new catalytic protocols to transform allylic substrates into a wide variety of versatile carbonyl and vinyl organic compounds. All procedures that are described in this work have in common the existence of one or more hydrogen shifts as key steps in the mechanism of the reactions. The thesis is divided into two mayor sections depending on the strategy employed, metal catalysis or organocatalysis. 

    The introductory chapter (Chapter 1) starts with an overview of the different types of catalysis and the importance of allylic substrates in organic chemistry. The chapter continues with an extensive description of the isomerization of allylic alcohols and finishes with a short introduction about hypervalent iodine chemistry. The goals of the thesis are also depicted at the end of this chapter.

    Chapters 2, 3 and 4 embody the use of iridium catalysis as an effective tool to synthesize α-functionalized carbonyl compounds selectively as single constitutional isomers from allylic alcohols. The first two chapters of this section describe the employment of several electrophiles to trap enolate derivatives formed from the corresponding allylic alcohols. Chapter 2 shows the development of two new protocols for the preparation of challenging α-iodinated carbonyl compounds. In chapter 3, the synthesis of α-aminooxy and α-hydroxyketones is investigated by employing an N-oxoammonium salt as electrophilic agent. Chapter 4 describes the development of an umpolung strategy that allows the synthesis of α-functionalized carbonyls through the reaction of two formal nucleophiles: enolate derivatives and alcohols. Mechanistic investigations performed in this section point to the presence of an iridium-catalyzed hydride shift operating in the reaction pathways.

    The last three chapters (5, 6 and 7) describe the development of metal-free methods for the conversion of allylic substrates into valuable products by means of base catalysis. Chapter 5 and 6 depict the stereospecific isomerization of a large scope of allylic alcohols, ethers and halides. A simple guanidine-type base, TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene), is an effective catalyst to isomerize allylic substrates with excellent levels of transfer of chirality. The mechanism of this transformation is studied in detail experimentally and computationally and it is suggested to involve a [1,3]-proton shift through the formation of a tight ion-pair. Chapter 7 shows that base-catalysis allows the isomerization of conjugated polyenyl alcohols and ethers which has been proved to be challenging with metal–catalysis. Experimental and computational investigations in this last chapter suggests that the mechanism may proceed through a series of iterative [1,3]-proton shifts or “base-walk”. 

    Fulltekst tilgjengelig fra 2020-08-01 09:00
  • Disputas: 2019-12-06 13:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Dawitz, Hannah
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Mechanistic Insights in the Biogenesis and Function of the Respiratory Chain2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Mitochondria fulfill a plethora of functions, including harboring metabolic pathways and converting energy stored in metabolites into ATP, the common energy source of the cell. This last function is performed by the oxidative phosphorylation system, consisting of the respiratory chain and the ATP synthase. Electrons are channeled through the complexes of the respiratory chain, while protons are translocated across the inner mitochondrial membrane. This process establishes an electrochemical gradient, which is used by the ATP synthase to generate ATP. The subunits of two of the respiratory chain complexes, the bc1 complex and the cytochrome c oxidase, are encoded by two genetic origins, the nuclear and the mitochondrial genome. Therefore, the assembly of these complexes needs to be coordinated and highly regulated.

    Several proteins are involved in the biogenesis of the bc1 complex. Amongst these proteins, the Cbp3-Cbp6 complex was shown to regulate translation and assembly of the bc1 complex subunit cytochrome b. In this work, we established a homology model of yeast Cbp3. Using a site-specific crosslink approach, we identified binding sites of Cbp3 to its obligate binding partner Cbp6 and its client, cytochrome b, enabling a deeper insight in the molecular mechanisms of bc1 complex biogenesis. 

    The bc1 complex and the cytochrome c oxidase form macromolecular structures, called supercomplexes. The detailed assembly mechanisms and functions of these structures remain to be solved. Two proteins, Rcf1 and Rcf2, were identified associating with supercomplexes in the yeast Saccharomyces cerevisiae. Our studies demonstrate that, while Rcf1 has a minor effect on supercomplex assembly, its main function is to modulate cytochrome c oxidase activity. We show that cytochrome c oxidase is present in three structurally different populations. Rcf1 is needed to maintain the dominant population in a functionally active state. In absence of Rcf1, the abundance of a population with an altered active site is increased. We propose that Rcf1 is needed, especially under a high work load of the respiratory chain, to maintain the function of cytochrome c oxidase.

    This thesis aims to unravel molecular mechanisms of proteins involved in biogenesis and functionality of respiratory chain complexes to enable a deeper understanding. Dysfunctional respiratory chain complexes lead to severe disease, emphasizing the importance of this work.

  • Disputas: 2019-12-06 13:00 hörsal 8, hus D, Stockholm
    Hermansson, Klara
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Kriminologiska institutionen.
    Symbols and emotions in Swedish crime policy discourse2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The general public has assumed an increasingly prominent position in crime policy discourse, both in Sweden and internationally. Nowadays crime policy initiatives often acknowledge and respond to the presumed concerns of the general public, for instance through the promise of safety. This thesis analyses how political parties encourage the public to engage emotionally in crime policy matters. Since public involvement is crucial in elections, the election campaigns of political parties have served as the empirical basis of my studies. The three articles included in the thesis together examine the election campaigns in Sweden from 2006 to 2018.

    In this body of work, it is assumed that the emotional address of the political parties can be analysed by paying specific attention to the political use of symbols and the discursive organisation of emotions. The thesis illustrates how the welfare context influences the ways in which crime policy is communicated and legitimised in Sweden. Values and ideals associated with the welfare state and with the related notion of a ‘Nordic exceptionalism’ – such as equality, benevolence, social cohesion, trust and safety – permeate the Swedish crime policy discourse. By interpreting these values and ideals as a system of symbols, I stress the need to explore them in relation to the general public and with regards to the emotional appeal these symbols might have.

    In my work, I emphasise variation and contradiction regarding emotional tones and I explore the norms circumscribing emotional expressions in crime policy discourse. I have treated emotions as being present in all political communication. This suggests that emotions are not only being encouraged in the ‘hot’ emotional climate, but also in the more emotionally restrained discourse and when politicians allude to the utility of political measures. The results point towards the need to distinguish between emotions and to the exploration of the relationship between them since different emotions are associated with their distinct consequences and they influence how we are encouraged to perceive and feel for different crime policy measures.

    The thesis concludes that the political use of symbols and emotions should be understood as having a reassuring function. It is further suggested that symbols and emotions can be used politically both in order to limit and to promote change with regards to Swedish crime policy discourse.

  • Disputas: 2019-12-09 13:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Valencia, Luis
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Cellulose Nanofibril-based Hybrid Materials: Eco-friendly design towards separation and packaging applications2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Nanocellulose has been lately considered as the “Holy-Grail” in the design of sustainable materials due to its bio-origin and an unprecedented combination of prominent features, including good mechanical properties, anisotropy and versatile surface chemistry. In addition, nanocellulose in the form of cellulose nanofibrils, can adopt variable structures and morphologies depending on the processing technique, such as aerogels, films and monoliths.

    However, there are limitations that hinder the implementation of cellulose nanofibrils in “real-life applications”, such as inherent interaction with bacteria and proteins, thus leading to surface-fouling; and loss of integrity due to water-induced swelling. A way to overcome these challenges, and provide further functionality, is through hybridization strategies, at which the multiple components act synergistically towards specific properties and applications. In this thesis, the aim is to present multiple strategies for the synthesis of novel cellulose nanofibril-based hybrid materials, in the form of 2D-films and 3D-foams, towards their employment for separation applications or active food packaging.

    A novel strategy to surface-functionalize cellulose nanofibril-membranes is proposed via grafting zwitterionic polymer brushes of poly (cysteine methacrylate). The modification can suppress the absorption of proteins in an 85%, as well as decreasing the adhesion of bacteria in an 87%, while introducing antimicrobial properties, as demonstrated against S. aureus.

    The spontaneous formation of functional metal oxide nanoparticles occurring in situ on cellulose nanofibrils-films during the adsorption of metal ions from water is investigated, which occurs without the additional use of chemicals or temperature. Notably, this process not only enables the upcycling of materials through multi-stage applications, but also provides a cost-effective method to prepare multifunctional hybrid materials with enhanced dye-removal/antimicrobial activity.

    The processing of functional composite films from cellulose nanofibril-stabilized Pickering emulsions and their suitability to be used as active edible barriers was demonstrated. The presence of oil in the films fine-tuned the properties of the films, as well as acted as the medium to encapsulate bio-active hydrophobic compounds, providing further functionality such as antioxidant and antimicrobial properties.

    Anisotropic porous hybrid foams with ultra-high loading capacity of sorbents (e.g., zeolites and metal-organic frameworks) were produced via unidirectional freeze-casting method using cellulose nanofibrils/gelatin as template material. The foams indeed exhibited ultra-high loading capacity of sorbent nanomaterials, a linear relationship between sorbent content and CO2 adsorption capacity, and high CO2/N2 selectivity.