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  • Public defence: 2017-11-23 10:00 Gröjersalen, hus 3, Kräftriket, Stockholm
    von Schantz, Hanna
    Stockholm University, Faculty of Social Sciences, Stockholm Business School.
    Well, that makes sense!: Investigating opportunity development in a technology start-up2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Digital technologies have profoundly reshaped many industries in the past years and we are continuously witnessing the creation of new ventures designing and serving entirely new markets. At the heart of these initiatives lies decisions to act, take risk and pursue ideas in the form of entrepreneurial opportunities. Much of the research on the journey from ideas to market has advanced from the idea that entrepreneurial agency emerges at the nexus of individuals and opportunities. In most academic work, opportunities are either assumed to be exogenous to the individual or socially constructed. Despite many valuable contributions in the field, the construct as it has traditionally been used only accounts for and explains opportunities once they have been realized. Hence, the established perspectives fall short in informing our understanding of how individuals actually act and make decisions that lead up to the identification and exploitation of opportunities that lack tangible premises. The question is therefore, how do we define and understand entrepreneurial opportunities before they have been realized and how do we make the construct empirically operable? The present study challenges and extends the conventional views of entrepreneurial opportunities by investigating what they are and how they emerge and evolve over time. By drawing upon in-depth qualitative data from a longitudinal study of the new venture creation process of a digital TV and film production firm, the thesis provides a reconceptualization of the opportunity construct. External enablers, a new venture idea, a business model and opportunity confidence are suggested as components that clarify what aspiring entrepreneurs actually mean when they talk about opportunities. Departing from these components, the thesis provides a framework describing opportunity development as an iterative process evolving through modes of sensemaking, sensegiving and sensebreaking. This framework adds to entrepreneurial process studies by extending the individual-opportunity nexus to include the actions and interactions between the entrepreneurs and the external environment in which they operate. The results lay a foundation for future theorizing and empirical inquiry into the early stages of new venture creation.

  • Public defence: 2017-11-24 10:00 Högbomsalen, Geovetenskapens hus, Stockholm
    Krzywkowski, Tomasz
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    iLocks: a novel tool for RNA assays with improved specificity2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The Central Dogma of molecular biology describes a framework for how genetic information is transferred in cells, placing RNA as a messenger between DNA and translated proteins. During the last years, interest in RNA research has grown tremendously due to the increasing understanding and recognition of the importance of RNA in regulation of gene expression, biochemical catalysis, and genome integrity surveillance. Most importantly, RNA content, unlike DNA, changes constantly, fine-tuning the cellular response to match the environmental conditions. There is a clear potential for RNA biomarkers, reflecting both the natural and pathological conditions in vivo.

    Various methods have been developed to study RNA, of which the most common tools and techniques are described in this thesis. Since many of these gold standard methods are based on detecting RNA derivative (cDNA), there is a wide scope for efficient alternative tools directly targeting RNA. In Paper I, the spatiotemporal expression of human adenovirus-5 mRNA in epithelial and blood cells infected with the virus has been studied. For this, padlock probes and rolling circle amplification (RCA) were used to visualize, quantify and analyse both viral and host cell cDNAs in different infection scenarios, at single cell level. In Paper II, direct RNA detection fidelity has been evaluated using padlock probes. A novel type of probe (iLock) that is activated on RNA via invasive cleavage mechanism, prior to RCA was developed in this approach. Using iLocks, a substantial improvement of direct RNA sensing fidelity has been observed. In Paper III, RNA modifications were introduced in otherwise DNA iLock probes to enhance the probes’ efficiency on miRNAs. Using chimeric iLock probes, multiplexed differentiation of conserved miRNA family members were performed with next- generation sequencing-by-ligation readout. Efficient replication of chimeric probes used in Paper III implies that the Phi29 DNA polymerase readily accepts RNA-containing circles as amplification substrates. In Paper IV, real-time RCA monitoring for measurement of amplification rates and analysis of amplification patterns of various RNA-containing circles was achieved. Moreover, the RCA products were sequenced as a proof for the reverse-transcriptase activity of the Phi29 DNA polymerase.

    This thesis effectively contributes to a better understanding of mechanisms influencing RNA detection with, but not limited to, padlock probes. It expands the available RNA analyses toolkit with novel strategies and solutions, which can be potentially adapted for RNA-focused research, in general and molecular diagnostics, in particular.

  • Public defence: 2017-11-24 10:00 hörsal 8, hus D, Stockholm
    Geschwind, Britta Zetterström
    Stockholm University, Faculty of Humanities, Department of Ethnology, History of Religions and Gender Studies.
    Publika museirum: Materialiseringar av demokratiska ideal på Statens Historiska Museum 1943-20132017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    The aim of this dissertation is to investigate how public spaces in the Swedish History Museum in Stockholm have materialized in relation to cultural policy objectives and ideals of a democratic and inclusive museum. The investigated time period spans from 1943 to 2013. The Swedish History Museum is a state-run archaeological museum, where norms and values are expressed through various governmental policy- and control documents. Hence, entering the museum also means entering a symbolic national space. The fact that the museum has been politically regulated throughout the studied period makes it illustrative of changing democratic public ideals in the 20th century.

    Unlike other similar studies, the empirical focus is not on exhibitions, but on other public spaces that visitors encounter; the entrance, the shop, children’s spaces and the courtyard. These spaces are less invisible in the museum hierarchy. At the same time, they are often central spaces to visitors. The museum building is not as fixed as it might appear to be. Drawing on ideas from Bruno Latour and Doreen Massey – and their perspectives on space, materiality and power – I explore how the social and spatial changes of the museum affect each other. Efforts have continuously been made to alter these public spaces, and the outlines and uses have repeatedly changed.

    By combining archival materials, interviews and observations, I investigate how democratic ideals have been negotiated in material forms, and what kind of audiences/visitors these spaces have conceptualized over time. Linking different kinds of sources, that speak from various levels and positions, has been an analytically important method.

    The analysis describes the museum as a meaning producing network that materially embody different, and sometimes conflicting ideologies. The public spaces have been shaped by tensions; between education versus pleasure, collecting versus showing, and by the dichotomy between culture and commerce. What is communicated thorough various materialities and inscriptions in the shop, the entrance, and the spaces for children sometimes contradict perspectives produced in exhibitions and educational programmes. Hierarchies between professional positions and knowledges propagate as social extensions towards the visitors, and sometimes, reproduce structural hierarchies. Museum functions literally “takes place”, depending on how they are valued and assigned meaning. The museum has increasingly included children, while also becoming a space for commerce. Various, and sometimes incompatible ideals on equality and inclusion have been implemented, simultaneously. At the same time, the public spaces carry unique spatial qualities, which can benefit inclusion. Concluding, the dissertation stresses that the entrance, the shop, the children spaces and other public spaces perceived as “peripheral” need to be viewed as central, not as superficial services or add-ons to the “real” museum experience, i.e. the exhibition.

  • Public defence: 2017-11-24 13:00 Auditoriet, Humanistvillan, Stockholm
    Ek, Imelda Helena
    Stockholm University, Faculty of Humanities, Department of Culture and Aesthetics.
    Erotic Insanity: Sex and psychiatry at Vadstena asylum, Sweden 1849-18782017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    The early nineteenth century saw the emergence of institutional psychiatry across Europe. Aware that Sweden had fallen behind in this development, Parliament decreed in 1823 that a number of specialised institutions for the care of the insane were to be established. The Vadstena asylum, opened in 1826, was the first such institution in Sweden.  

    The aim of this study is to examine medical interpretation of and responses to erotic behaviour in psychiatric practice at the Vadstena asylum in the period 1849-1878.

    The book places the theme of the erotic, a topical subject in nineteenth-century public debate, in the context of psychiatry as an emerging specialty in Sweden. The book explores how erotic behaviour was conceptualised as disease, and the nature of therapeutic intervention in erotic cases, in order to present a more nuanced image of nineteenth-century medical attitudes to sexuality. By highlighting the superintendency of physician Ludvig Magnus Hjertstedt, and linking his account of an 1845 study tour through Europe to medical practice at Vadstena, the study situates responses to erotic patients in a period when psychiatry claims authority over human sexuality.

     

    In methodological terms, the study applies critical questions inspired by revisionist scholarship to a body of empirical source material. Focusing on a single institution, and conducting in-depth readings of case notes – with regard to language, form, and function – allows the study to highlight the everyday practice of the asylum physician in his encounters with male and female erotic patients, including the use, importance and diagnostic integrity of the concepts nymphomania, erotomania and masturbation. Hjertstedt’s travel journal provides insight into the physician’s medical philosophy, informing the analysis of diagnostic and interpretive procedures, while connecting medical practice at Vadstena to its European paragons.  

     

    The results indicate that while the use of specific diagnostic terms to describe erotic behaviour was infrequent, therapeutic and managerial intervention shows that sexual acts and expressions of desire were considered disturbing and dangerous symptoms in both male and female patients. The analysis thus makes visible a gap between psychiatric theory and asylum practice, emphasising uncertainties and complexities inherent in the latter. While erotic behaviour could be considered indicative of illness, it might also be interpreted as a lack of character or a result of insufficient moral instruction. The asylum’s regime of work and moral instruction was designed to restore health as well as sound values and appropriate behaviour in its patients, indicating a medical culture at Vadstena which was both curative and normalising.

     

  • Public defence: 2017-11-24 13:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Wang, Yunchen
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    3D Electron Diffraction: Application and Development towards High-quality Structure Determination2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Electron crystallography has been proven to be effective for structure determination of nano- and micron-sized crystals. In the past few years, 3D electron diffraction (3DED) techniques were used for the structure solution of various types of complex structures such as zeolites, metal-organic frameworks (MOF) and pharmaceutical compounds. However, unlike X-ray crystallography, electron diffraction has not yet become an independent technique for a complete structure determination due to relatively poorer diffraction intensities and often powder X-ray diffraction data are used for structure validation and refinement.

    Electron beam damage to the structures that are sensitive to high energy electrons and dynamical scattering are important factors to lead to the deviation of electron diffraction intensities from the squared amplitudes of the structure factors. In this thesis, we investigate various aspects around the 3D electron diffraction data quality and strategies for obtaining better data and structure models. We combined 3D electron diffraction methods and powder X-ray diffraction to determine the structure of an open-framework material and discussed the difficulties and limitations of electron diffraction for beam sensitive materials. Next, we illustrated the structure determination of a pharmaceutical compound, bismuth subgallate, using 3D electron diffraction. While severe beam damage and diffuse scattering were observed in the dataset collected with the conventional rotation electron diffraction (RED) method, the continuous rotation electron diffraction (cRED) method coupled with sample cooling significantly improved the data quality and made the structure solution possible. In order to better understand the potentials and limitations of the continuous rotation method, we collected multiple datasets from different crystals of a known structure and studied the data quality by evaluating the accuracy of the refined structure models. To tackle dynamical scattering in electron diffraction data, we explored a routine for structure refinement with dynamical intensity calculation using RED data from a known structure and discussed its potentials and limitations.

  • Public defence: 2017-11-24 13:15 sal FB42, Stockholm
    Kjellsson Lindblom, Tor
    Stockholm University, Faculty of Science, Department of Physics.
    Relativistic light-matter interaction2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    During the past decades, the development of laser technology has produced pulses with increasingly higher peak intensities. These can now be made such that their strength rivals, and even exceeds, the atomic potential at the typical distance of an electron from the nucleus. To understand the induced dynamics, one can not rely on perturbative methods and must instead try to get as close to the full machinery of quantum mechanics as practically possible. With increasing field strength, many exotic interactions such as magnetic, relativistic and higher order electric effects may start to play a significant role. To keep a problem tractable, only those effects that play a non-negligible role should be accounted for. In order to do this, a clear notion of their relative importance as a function of the pulse properties is needed. 

    In this thesis I study the interaction between atomic hydrogen and super-intense laser pulses, with the specific aim to contribute to the knowledge of the relative importance of different effects. I solve the time-dependent Schrödinger and Dirac equations, and compare the results to reveal relativistic effects. High order electromagnetic multipole effects are accounted for by including spatial variation in the laser pulse.

    The interaction is first described using minimal coupling. The spatial part of the pulse is accounted for by a series expansion of the vector potential and convergence with respect to the number of expansion terms is carefully checked. A significantly higher demand on the spatial description is found in the relativistic case, and its origin is explained. As a response to this demanding convergence behavior, an alternative interaction form for the relativistic case has been developed and presented.

    As a guide mark for relativistic effects, I use the classical concept of quiver velocity, vquiv, which is the peak velocity of a free electron in the polarization direction of a monochromatic electromagnetic plane wave that interacts with the electron. Relativistic effects are expected when vquiv reaches a substantial fraction of the speed of light c, and in this thesis I consider cases up to vquiv=0.19c. For the present cases, relativistic effects are found to emerge around vquiv=0.16c .

  • Public defence: 2017-11-25 10:00 hörsal 9, hus D, Stockholm
    Svensson, Harry R:son
    Stockholm University, Faculty of Humanities, Department of History.
    Fabian Philip, familjen Ruben och örlogsstaden: Entreprenörsfamiljen som grundade Mosaiska församlingen i Karlskrona 1780–19452017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    The purpose of the dissertation is to investigate Jewish integration in the naval city of Karlskrona in the period 1780–1945. This was done by the investigation of the economic, social and cultural strategies that the Jewish Philip/Ruben family used in their family business in Karlskrona during the 19th century. This has made it possible to understand how a Jewish family and congregation interacted with and became integrated in a Swedish naval-city environment. The study gives also new information about and a better understanding of the Swedish naval environment and naval production capacity. The study provides new knowledge on different fields of studies as Swedish Jewish history, urban history, naval history (the history of the Swedish Royal Navy), history of migration and integration, and the history of Karlskrona. The dissertation studies the history of the Philip/Ruben family in three distinct perspectives: economic, social and cultural. Moreover, the study pays attention to the process of the family’s integration and adaptation of different Jewish groups in Karlskrona.

    Fabian Philip obtained an exception from the Swedish legislation forbidding Jews to live in other towns than Stockholm, Göteborg and Norrköping, and settled in the naval city of Karlskrona. His family came to constitute the Jewish congregation in Karlskrona in the period 1782–1862. Karlskrona therefore became the fourth city in Sweden where Jews were allowed to settle. Fabian Philip and his family originated from Bützow in northern Germany. Fabian Philip’s establishment in Karlskrona depended upon his role as contractor, supplying sailcloth to the Swedish Royal Navy. After the Vienna Congress of 1815 Sweden adopted a Doctrine of Central defense and The Swedish Royal Navy lost its importance for the defense of Sweden. With a minimum of funding the Swedish Royal Navy went into a state of despair and so did Karlskrona’s local economy.

    By 1830 agriculture was the only viable economic niche in the economically neglected Karlskrona but Jews were prohibited to own landed property until 1860. Fabian Philip was able, with the help of Karlskrona’s officer staff, to circumnavigate the legislation and became a landowner of big Afvelsgärde estate. Of all the Jewish-owned estates in Sweden in the mid-century 10 percent were to be owned by the Philip/Ruben family. When Sweden was industrialized in 1870–1890, the local economy of Karlskrona managed to compensate for the decline in activities of the Swedish Royal Navy. The family succeeded to take part in the program of local modernization that was launched from the 1880s. The Philip/Ruben family contributed to the economic modernization of Karlskrona as bankers and factory owners. The family thrived in the city’s surprisingly open and cosmopolitan environment. Until now, no research has been undertaken about the Jewish congregation or the Jewish life in Karlskrona. The results of this dissertation contribute to the understanding of Jewish life in Sweden.

  • Public defence: 2017-11-28 13:00 De Geersalen, Geovetenskapens hus, Stockholm
    Thorslund, Josefin
    Stockholm University, Faculty of Science, Department of Physical Geography.
    Hydrological spreading of metal pollution and wetlands as nature-based solutions2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The quality of the Earth’s water resources have deteriorated due to human impacts. A key scientific challenge is to understand, quantify and predict the water-borne spreading of pollutants at relevant scales for freshwater management and water quality restoration programs. However, understanding the natural processes controlling large-scale hydrological transport of pollutants may be masked by river regulation schemes (in the form of dams and reservoirs), which are common in many large rivers. The main objective of this thesis is to increase the current knowledge regarding large-scale spreading of metals in hydrological systems. This objective is addressed through studying net impacts of mining (a main contributor to global metal pollution) on the spreading of metals in water systems and through investigating the mitigation opportunities of wetlands across the landscape. The main study region of this thesis is the Lake Baikal basin of Russia and Mongolia, which includes the large unregulated Selenga River and its delta-wetland areas. In addition, a set of global wetland sites are also studied. A multi-method approach is used in the four studies of this thesis. The methods include field-measurements, data synthesis, metal mass flow and water flow-path quantifications, as well as geochemical modelling. Results show that mining in the upstream part of the Lake Baikal basin is a significant contributor to riverine mass flows of several metals. The mass flows increased by an order of magnitude over the mining site. The observed speciation between dissolved (more bioavailable) and suspended (less bioavailable) phases could be well predicted for some metals (Fe, V, Pb and Zn) using a geochemical equilibrium model. However, the model failed to reproduce the speciation of other metals (Cr, Cu, Mn and Mo). In these cases, non-equilibrium processes may need to be considered, and adsorption databases may need to be developed, in order to make dependable predictions. Results also suggest that the concentration of dissolved organic carbon, which exhibits seasonal variability and long-term increasing trends due to climate change effects in the Arctic, can have a large impact on metal pollution transport. Further, observations showed that individual wetlands of the Selenga River delta locally retained between 77-99 % of incoming metal loads. However, a systematic analysis of current knowledge showed that large-scale net effects can differ considerably from the functions observed at individual wetlands on smaller scales. Along large-scale flow-paths, through which wetlands are connected with each other as well as with the larger landscape, key processes which can considerably contribute to such scale differences in function may occur. A survey of the current wetland research showed that relatively few studies have considered the larger scales at which key pollutant pressures and water quality changes take place. This thesis highlights the need for more research on large-scale wetland systems, which can aid in evaluating net pollution effects at landscape scales. This in turn can facilitate evaluations of how and when wetland systems may function as large-scale nature-based solutions.

  • Public defence: 2017-11-30 10:00 David Magnussonsalen (U31), Stockholm
    Forsström, David
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    The use and experience of responsible gambling tools: An explorative analysis of user behavior regarding a responsible gambling tool and the consequences of use2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Responsible gambling tools are an intervention that is designed to decrease gambling among individuals with an at-risk gambling behavior. Studies have indicated that responsible gambling tools can decrease gambling behavior, but little is known about how this intervention is used by gamblers. The aim of the present thesis was to explore different facets of the use, experience and functions of these tools. Study I used descriptive statistics and latent class analysis (LCA) combined with multinomial regression to explore the use of the responsible gambling tool Playscan among 9528 gamblers (regular and at-risk gamblers). The participants had volunteered to use the tool. The functions of the tool had a high rate of initial use but a low rate of repeated use. The LCA identified five user classes. Two of the classes (self-testers and multifunctional users) were defined as high users of the tool and had a higher risk of developing gambling problems according to multinomial regression. The multifunctional users were characterized by an extensive use of all the functions while the other high usage class had an extensive use of the self-test. The three other classes were as follows: those who did not use the tool, those who visited the tool but did not engage in any of the functions, and those who only used the tool’s advice on how to decrease their gambling. Participants’ reasons for use and non-use of the tool were attributed to their degree of need of the tool and its functions. The tool’s most widely used function was the self-test that investigated the level of negative consequences faced by a user due to his or her gambling. Study II was a qualitative study investigating participants’ views, experiences and their reasons for using the tool. The study was conducted by interviewing 20 volunteer users of the tool. These semi-structured interviews were analyzed by thematic analysis. The results showed that the users had a positive attitude towards the tool and understood its purpose. The self-test was the most widely used function in this sample as well. However, the participants’ positive attitude toward the tool did not effectively encourage them to use it; they displayed low use of the tool’s functions. This paradox was explained by lack of feedback and the fact that some participants did not understand that they had registered to use the tool. Providing more feedback and tailoring the feedback to individual users were seen as ways of bridging the paradox. Study II also found that participants used the gambling website (which Playscan was linked to) in an analogue way, preparing their bets before placing them online. This limited the time they spent on the site and inhibited their use of Playscan. Study III was motivated by the extensive use of the self-test among users in Study I and Study II. The aim of Study III was to investigate the psychometric properties of the self-test (known as GamTest) to better understand how it could be used with Playscan in the most efficient way. Two thousand two hundred and thirty four respondents answered the questionnaire, along with instruments measuring depression, anxiety and another instrument measuring problems due to gambling. Factor analysis, parallel analysis, Cronbach’s alpha, and correlations were used to establish the tool’s psychometric properties. The results yielded a three-factor model, excellent reliability, and high correlation with the Problem Gambling Severity Index (PGSI), endorsing the validity of the self-test. The results also indicated that the questionnaire could be effectively shortened. Overall, the studies show that the tool has an initial high use, low repeated use and that the self-test is the most used feature. In addition, the self-test had good psychometric properties. 

  • Public defence: 2017-12-01 10:00 Auditorium 215, Stockholm
    Miočević, Ljubica
    Stockholm University, Faculty of Humanities, Department of Culture and Aesthetics.
    Fantasiens morgonrodnad: En studie i Clas Livijns romaner2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This doctoral thesis investigates four novels of the Swedish Romantic author Clas Livijn (1781–1844). Livijns’s self-reflective prose is dense with allusions to contemporary literary works and political events, delivered in a style that abounds with metaphors and allegories, and characterized by satire, parody, and irony. One aim of this dissertation is to investigate some of the important themes in these four novels and explore the intertextual techniques utilized by means of a semiotics-based approach. My intent in this respect is to identify the intertexts that are actualized and the manner in which they are used.

    A second aim of the study is to explore how the dialogical and allusive elements in Livijn’s work are linked to the practices of collaborative writing and the writer’s own constant rewriting of his works, both of which negate the notion of the solitary “Romantic genius” as an artist who serves as a vessel for the outpouring of the imagination. Livijn’s work is also marked by its fragmented state: several of his novels were never finished, and one of the four books analyzed was not published during his lifetime. Not only did Livijn typically rewrite his works repeatedly, several times he stopped the printing of a given book precisely in order to rewrite it. The manuscript versions of his novels give an insight into the genesis of the works and Livijn’s creative process, including his relentless efforts to increase the density of the allusions.

    The imagination, as one of the key concepts of Romanticism, plays a prominent role in Livijn’s novels. However, the ambiguous relations that his heroes have with the imagination are symptomatic of the duality imbedded in Livijn’s own relation to Romantic stereotypes. Although he makes use of them in his novels, he also undermines them with irony (at times Romantic irony) and satire.

    There has been little previous research on Livijn’s work, and that which exists is mainly focused on only one of his novels, The Queen of Spades (1824). Consequently, a third aim of this thesis is to reveal the diversity of Livijn’s work: although the four novels share a certain number of qualities, including metafictional elements and a high degree of self-reflectivity, they differ substantially in respect to their genres, styles, and narrative techniques. Within a broader context, the thesis contributes to the historiography of the novel as a genre in Swedish Romanticism.

  • Public defence: 2017-12-01 10:00 Nordenskiöldsalen, Geovetenskapens hus, Stockholm
    Ignell, Caroline
    Stockholm University, Faculty of Social Sciences, Department of Education.
    Exploring changes of conceptions, values and beliefs concerning the environment: A longitudinal study of upper secondary school students in business and economics education2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis examines students’ understanding of economic aspects of global environmental problems. The first aim is to identify and characterise changes in business and economics students’ conceptions of negative environmental effects and pricing goods and services. The second aim is to identify and characterise changes in students’ values, beliefs and personal norms regarding effective solutions to climate change problems. Three studies were carried out with students in Swedish upper secondary schools. The first study used an open-ended questionnaire and is presented in Article I. The second and third studies drew on a longitudinal study, using both qualitative and quantitative research methods and results are presented in Article II and Article III.

    Article I shows that students’ awareness of environmental issues varies in relation to the type of good. Some goods are seen as more harmful to nature than others, for example, jeans were not perceived as environmentally negative while beef burgers and travel services were to some extent. This indicates that environmental references are often characterised through perceptible aspects of goods’ production i.e. being more expensive because of environmentally friendly production. Furthermore, some understanding of negative externalities was revealed. Interestingly, when value aspects of how prices should be set students more frequently refer to environmental impact.

    Article II describes changes in students’ price and environmental conceptions over the course of a year. It identifies the fragmentary nature of students’ every-day thinking in relation to productivity, consumer preference and negative externalities. Differences in conceptions of how prices are linked to negative impact is characterised in terms of basic, partial and complex understandings of productivity as well as basic and partial understandings of consumers’ influences. Partial conceptions are seen as students’ conceptions in a process of change towards a more scientific understanding of price and negative environmental impact. Most interestingly, the results show that more than one aspect of environmental impact and pricing are simultaneously relevant. This is highlighted by a change from views putting productivity at the centre for how prices are set to include consumers’ preferences when judgmentally describing how prices should be set. The results conclude that students show a broader content knowledge regarding pricing and the environment when including normative preferences.

    Article III explores changes in students’ value orientations, beliefs regarding efficient solutions to climate change and norms for pro-environmental actions. Small changes are observed regarding the three constructs. Value changes are reported in terms of a small average increase in importance of altruistic, biospheric and egoistic orientations while common individual changes are shown in shifts between weak and strong values. Beliefs regarding efficient climate change solutions are taxes and legislations while changes in market prices are perceived as being least effective. The findings show no direct relations between values and norms hence change in norms is associated with values through changes in beliefs.

  • Public defence: 2017-12-01 10:00 Vivi Täckholmssalen, NPQ-huset, Stockholm
    Kazemi, Baharan
    Stockholm University, Faculty of Science, Department of Zoology.
    Evolution of Mimicry and Aposematism Explained: Salient Traits and Predator Psychology2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aposematic species have evolved conspicuous warning signals, such as bright colors and striking patterns, to deter predators. Some edible and harmless species take advantage of this deterrent effect by mimicking their appearance. Mimicry is a great example of how natural selection produces remarkable adaptations. However, while some species evolve a very close similarity to their models to effectively avoid attacks, others are successful in doing so despite an incomplete similarity, i.e. imperfect mimicry. In some cases, it is surprising how such a crude disguise can fool predators. Why and how imperfect mimicry can persist has been much discussed and considered as a problem for the theory of natural selection. It is therefore of great interest to understand what makes it possible.

    Predator psychology is an important factor in the evolution of aposematism and mimicry. In the past decades it has been suggested that certain components of prey appearance are more important to predators than others during prey assessment. We developed this idea by incorporating concepts from associative learning, and presented a new approach to explain imperfect mimicry. Our general hypothesis is that prey traits have different salience to predators. Certain traits are perceived as highly salient and are thus used primarily in the discrimination and generalization of prey, while traits with low salience are overshadowed and not used in the assessment. The salience of a trait can depend on how conspicuous or discriminable it is in the particular context, and can vary due to for example previous predator experience.

    We tested our ideas with wild blue tits and domestic chickens as predators, and artificial and semi-natural prey stimuli. In paper I we found that the trait that was perceived as most salient (color) was the one used to discriminate and generalize between prey. Mimics of that specific trait were highly avoided, despite differences in the other traits. We also found that salience is relative and context dependent (paper II). In a context where two traits were perceived as similarly salient, mimicry of a single trait offered intermediate protection, while mimicry of both offered high protection. In another context, the traits were perceived differently salient, and mimicry of one trait was enough for high protection. In paper III we tested a proposed scenario for the initiation of mimicry evolution in the edible butterfly mimic Papilio polyxenes asterius to its noxious model Battus philenor. The results showed that a partial similarity with the model in the salient black wing color offered intermediate protection from attacks, despite a general dissimilarity.

    This thesis investigates the major questions of imperfect mimicry: the initial step of mimicry evolution, the persistence of imperfect mimicry, and variation in mimic-model similarity. We conclude that mimicry evolution can begin in a non-mimetic species that acquires similarity to a model species in a high-salience trait. When multiple traits have similar salience, multi-trait mimicry is needed for higher protection. Mimicry can remain imperfect if the differences are in traits with low salience, and therefore under low or no selection pressure to change.

    To complete the picture, we showed that predators can have a biased generalization toward a more pronounced version of a salient trait (paper IV). The evolution of aposematism could therefore be explained by gradual enhancement of salient traits.

  • Public defence: 2017-12-01 13:00 L50, NOD-huset, Kista
    Strååt, Björn
    Stockholm University, Faculty of Social Sciences, Department of Computer and Systems Sciences.
    Extending Game User Experience - Exploring Player Feedback and Satisfaction: The Birth of the Playsona2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Video games are experience-based products and user satisfaction is key for their popularity. To design for as strong an experience as possible, game developers incorporate evaluation methods that help to discover their users’ expectations and needs. Despite such efforts, problems still occur with the game design that lower the user experience. To counter these problems, the evaluation methods should be investigated and improved.

    To address this need, I have explored various design tools and user experience theories. Applying these in a game evaluation context, I have analyzed user-created game reviews and conducted longitudinal user interview- and game diary studies in connection to playing a newly released game, in other words different methods to take advantage of users' expectations, opinions, attitudes and experiences. One result of the analysis of the obtained data is a set of “slogans” that illustrate how and why users lose interest in a game. A second result is a method for extracting user attitudes from pre-produced user reviews and how this can be used in game development. Thirdly, I introduce an alternative model, aimed at game user experience development, the Playsona. The Playsona is a lightweight tool that introduces a variant of the Persona-method, specifically for video game design.

  • Public defence: 2017-12-01 13:00 William-Olssonsalen, Geovetenskapens hus, Stockholm
    Renner, Lena F.
    Stockholm University, Faculty of Humanities, Department of Linguistics.
    The magic of matching – speech production and perception in language acquisition2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This thesis investigates the relationship between speech production and speech perception in the early stages of phonological and lexical acquisition. Previous studies have mainly focused on independent investigations of speech production and perception abilities in language acquisition. This thesis connects the individual speech production capacities to the child's perception and is organized around three major studies: Study I explores methodological alternatives such as the combination of EEG and eye-tracking in different Swedish participant groups: adults, 17-month-olds, and 24-month-olds. Visual and auditory stimuli, as well as the connection between word production and word perception are explored. Study II investigates phonological capacities in terms of consonant inventory, percentage of correctly pronounced words, segmental errors, as well as phonological templates in relation to vocabulary size in a group of Swedish 18-month-olds. Study III studies the influence of the children's individual phonological and lexical capacities in speech production on their word recognition in a group of Swedish toddlers with a productive vocabulary size above 100 words.

    The general results show that children accept mispronounced word forms as appropriate word candidates when the word forms are related to their individual word production. The occurrence of segmental errors increases with vocabulary size, and phonological templates are more likely to be observed in children with a productive vocabulary size above 100 words. The results thus indicate an influence of the individual child's production on word recognition, and a relationship between phonological capacities and lexical knowledge. These insights contribute to theoretical debates in linguistics regarding the abstractness of phonological word form representations and reveal a closer relationship between production and perceptual abilities in toddlers than what has previously been shown.

  • Public defence: 2017-12-01 14:00 Magnélisalen, Stockholm
    Daver, Henrik
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Quantum Chemical Modeling of Phosphoesterase Mimics and Chemistry in Confined Spaces2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, density functional theory is employed in the study of two kinds of systems that can be considered to be biomimetic in their own ways. First, three binuclear metal complexes, synthesized by the group of Prof. Ebbe Nordlander, have been investigated. The complexes are designed to resemble the active sites of phosphatase enzymes and have been examined in complexes where either two Zn(II) ions or one Fe(III) and one Mn(II) ion are bound. These dinuclear compounds were studied as catalysts for the hydrolysis of bis(2,4-dinitrophenyl) phosphate and the transesterification of 2-hydroxypropyl p-nitrophenyl phosphate, which are model systems for the same reactions occurring in DNA or RNA. It was found that the two reactions take place in similar ways: a hydroxide ion that is terminally bound to one of the metal centers acts either as a nucleophile in the hydrolysis reaction or as a base in the transesterification. The leaving groups depart in an effectively concerted manner, and the formed catalyst-product complexes are predicted to be the resting states of the catalytic cycles. The rate-determining free energy barriers are identified from the catalyst-product complex in one catalytic cycle to the transition state of nucleophilic attack in the next.

    Another type of biomimetic modeling is made with an aim of imitating the conceptual features of selective binding of guests and screening them from solute-solvent interactions. Such features are found in so-called nanocontainers, and this thesis is concerned with studies of two capsules synthesized by the group of Prof. Julius Rebek, Jr. First, the cycloaddition of phenyl acetylene and phenyl azide has experimentally been observed to be accelerated in the presence of a capsule. Computational studies were herein performed on this system, and a previously unrecognized structure of the capsule is discovered. Two main factors are then identified as sources of the rate acceleration compared to the uncatalyzed reaction, namely the reduction of the entropic component and the selective destabilization of the reactant supercomplex over the transition state.

    In the second capsule study, the alkane binding trends of a water-soluble cavitand was studied. It is found that implicit solvation models fail severely in reproducing the experimental equilibrium observed between binding of n-decane by the cavitand monomer and encapsulation in the capsule dimer. A mixed explicit/implicit solvation protocol is developed to better quantify the effect of hydrating the cavitand, and a simple correction to the hydration free energy of a single water molecule is proposed to remedy this. The resulting scheme is used to predict new hydration free energies of the cavitand complexes, resulting in significant improvement vis-à-vis experiments.

    The computational results presented in this thesis show the usefulness of the quantum chemical calculations to develop understanding of experimental trends observed for substrate binding and catalysis. In particular, the methodology is shown to be versatile enough such that experimental observations can be reproduced for such diverse systems as studied herein.

  • Public defence: 2017-12-05 10:00 CCK lecture hall, building R8, Solna
    Kjellsson Lindblom, Emely
    Stockholm University, Faculty of Science, Department of Physics.
    Time, dose and fractionation: accounting for hypoxia in the search for optimal radiotherapy treatment parameters2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The search for the optimal choice of treatment time, dose and fractionation regimen is one of the major challenges in radiation therapy. Several aspects of the radiation response of tumours and normal tissues give different indications of how the parameters defining a fractionation schedule should be altered relative to each other which often results in contradictory conclusions. For example, the increased sensitivity to fractionation in late-reacting as opposed to early-reacting tissues indicates that a large number of fractions is beneficial, while the issue of accelerated repopulation of tumour cells starting at about three weeks into a radiotherapy treatment would suggest as short overall treatment time as possible. Another tumour-to-normal tissue differential relevant to the sensitivity as well as the fractionation and overall treatment time is the issue of tumour hypoxia and reoxygenation.

    The tumour oxygenation is one of the most influential factors impacting on the outcome of many types of treatment modalities. Hypoxic cells are up to three times as resistant to radiation as well-oxygenated cells, presenting a significant obstacle to overcome in radiotherapy as solid tumours often contain hypoxic areas as a result of their poorly functioning vasculature. Furthermore, the oxygenation is highly dynamic, with changes being observed both from fraction to  fraction and over a time period of weeks as a result of fast and slow reoxygenation of acute and chronic hypoxia. With an increasing number of patients treated with hypofractionated stereotactic body radiotherapy (SBRT), the clinical implications of a substantially reduced number of fractions and hence also treatment time thus have to be evaluated with respect to the oxygenation status of the tumour.

    One of the most promising tools available for the type of study aiming at determining the optimal radiotherapy approach with respect to fractionation is radiobiological modelling. With clinically validated in vitro-derived tissue-specific radiobiological parameters and well-established survival models, in silico modelling offers a wide range of opportunities to test various hypotheses with respect to time, dose, fractionation and details of the tumour microenvironment. Any type of radiobiological modelling study intended to provide a realistic representation of a clinical tumour should therefore take into account details of both the spatial and temporal tumour oxygenation.

    This thesis presents the results of three-dimensional radiobiological modelling of the response of tumours with heterogeneous oxygenation to various fractionation schemes, and oxygenation levels and dynamics using different survival models. The results of this work indicate that hypoxia and its dynamics play a major role in the outcome of radiotherapy, and that neglecting the oxygenation status of tumours treated with e.g. SBRT may compromise the treatment outcome substantially. Furthermore, the possibilities offered by incorporating modelling into the clinical routine are explored and demonstrated by the development of a new calibration function for converting the uptake of the hypoxia-PET tracer 18F-HX4 to oxygen partial pressure, and applying it for calculations of the doses needed to overcome hypoxia-induced radiation resistance. By hence demonstrating how the clinical impact of hypoxia on dose prescription and the choice of fractionation schedule can be investigated, this project will hopefully advance the evolution towards routinely incorporating functional imaging of hypoxia into treatment planning. This is ultimately expected to result in increased levels of local control with more patients being cured from their cancer.

  • Public defence: 2017-12-06 10:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Svengren, Henrik
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Water splitting by heterogeneous catalysis2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A sustainable solution for meeting the energy demands at our planet is by utilizing wind-, solar-, wave-, thermal-, biomass- and hydroelectric power. These renewable and CO2 emission-free energy sources are highly variable in terms of spatial and temporal availability over the Earth, introducing the need for an appropriate method of storing and carrying energy. Hydrogen has gained significant attention as an energy storage- and carrier media because of the high energy density that is exploited within the ‘power-to-gas’ process chain. A robust way of producing sustainable hydrogen is via electrochemical water splitting.

    In this work the search for new heterogeneous catalyst materials with the aim of increasing energy efficiency in water splitting has involved methods of both electrochemical water splitting and chemical water oxidation. Some 21 compounds including metal- oxides, oxofluorides, oxochlorides, hydroxide and metals have been evaluated as catalysts. Two of these were synthesized directly onto conductive backbones by hydrothermal methods. Dedicated electrochemical cells were constructed for appropriate analysis of reactions, with one cell simulating an upscale unit accounting for realistic large scale applications; in this cell gaseous products are quantified by use of mass spectrometry. Parameters such as real time faradaic efficiency, production of H2 and O2 in relation to power input or overpotentials, Tafel slopes, exchange current density and electrochemical active surface area as well as turnover numbers and turnover frequencies have been evaluated.

    Solubility, possible side reactions, the role of the oxidation state of catalytically active elements and the nature of the outermost active surface layer of the catalyst are discussed. It was concluded that metal oxides are less efficient than metal based catalysts, both in terms of energy efficiency and in terms of electrode preparation methods intended for long time operation. The most efficient material was Ni-Fe hydroxide electrodeposited onto Ni metal foam as conductive backbone. Among the other catalysts, Co3Sb4O6F6 was of particular interest because the compound incorporate a metalloid (Sb) and redox inert F and yet show pronounced catalytic performance.

    In addition, performance of materials in water splitting catalysis has been discussed on the basis of results from electron microscopy, solubility experiments and X-ray diffraction data.

  • Public defence: 2017-12-08 10:00 E306, Arrheniuslaboratorierna, Stockholm
    Kaimal, Jayasankar Mohanakrishnan
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Regulation of cellular Hsp70: Proteostasis and aggregate management2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Proteins have to be folded to their native structures to be functionally expressed. Misfolded proteins are proteotoxic and negatively impact on cellular fitness. To maintain the proteome functional proteins are under the constant surveillance of dedicated molecular chaperones that perform protein quality control (PQC). Using the model organism yeast Saccharomyces cerevisiae this thesis investigates the molecular mechanisms that cells employ to maintain protein homeostasis (proteostasis). In Study I the role of the molecular chaperone Hsp110 in the disentanglement and reactivation of aggregated proteins was investigated. We found that Hsp110 is essential for cellular protein disaggregation driven by the molecular chaperones Hsp40, Hsp70 and Hsp104 and characterized its involvement via regulation of Hsp70 ATPase activity as a nucleotide exchange factor. In Study II we found out that Hsp110 undergoes translational frameshifting during its expression resulting in a nuclear targeting. Nuclear Hsp110 interacts with Hsp70 and reprograms the proteostasis system to better deal with stress and to confer longevity. Study III describes regulation of Hsp70 function in PQC by the nucleotide exchange factor Fes1. We found that rare alternative splicing regulates Fes1 subcellular localization in the cytosol and nucleus and that the cytosolic isoform has a key role in PQC. In Study IV we have revealed the molecular mechanism that Fes1 employ in PQC. We show that Fes1 carries a specialized release domain (RD) that ensures the efficient release of protein substrates from Hsp70, explaining how Fes1 maintains the Hsp70-chaperone system clear of persistent misfolded proteins. In Study V we report on the use of a novel bioluminescent reporter (Nanoluc) for use in yeast to measure the gene expression and protein levels. In summary, this thesis contributes to the molecular understanding of chaperone-dependent PQC mechanisms both at the level of individual components as well as how they interact to ensure proteostasis.

  • Public defence: 2017-12-08 10:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Vijayaraghavan, Balaje
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Identification and characterization of protein-protein interactions in the nuclear envelope2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The nuclear envelope forms the interface between the nucleus and the cytoplasm. The nuclear envelope consists of the two concentric lipid membranes, the nuclear pores and the nuclear lamina. The inner nuclear membrane contains hundreds of unique transmembrane proteins showing high tissue diversity. Mutations of some proteins in the nuclear envelope give rise to a broad spectrum of diseases called envelopathies or laminopathies. In this thesis, I aimed to study the functional organization of the nuclear envelope by identifying and characterizing interactions between the nuclear envelope proteins. For this, we developed a novel method called the Membrane Protein Crosslink Immuno-Precipitation, which enable identification of protein-protein interactions in the nuclear envelope in live cells. We identified several novel interactions of the inner nuclear membrane protein, Samp1, and studied the interaction between the Samp1 and the nuclear GTPase, Ran in detail. Samp1 can bind to Ran and is thus the first known transmembrane Ran binding protein and Samp1 might provide a local binding site for Ran in the inner nuclear membrane. We found that Samp1 also binds to the inner nuclear membrane protein, Emerin and Ran can regulate the Samp1-Emerin interaction in the nuclear envelope. During mitosis, Samp1 distributes in the mitotic spindle. Therefore, we investigated a possible functional role of Samp1 in the mitotic machinery. Samp1 depletion resulted in aneuploid phenotypes, metaphase prolongation and decreased distribution of γ-tubulin and β-tubulin in the mitotic spindle. We found that Samp1 can bind to γ-tubulin, which is essential for the microtubule nucleation and hence for the spindle stability. The new interesting features of Samp1 provide insights on the unforeseen functions of the nuclear envelope proteins.

  • Public defence: 2017-12-12 10:00 Magnélisalen Kemiska övningslaboratoriet, Stockholm
    Muheim, Claudio
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Antibiotic uptake in Gram-negative bacteria2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The increasing emergence and spread of antibiotic-resistant bacteria is a serious threat to public health. Of particular concern are Gram-negative bacteria such as Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae or Pseudomonas aeruginosa. Some of these strains are resistant to a large number of antibiotics and thus our treatment options are rapidly declining. In addition to the increasing number of antibiotic-resistant bacteria, a major problem is that many of the antibiotics at our disposal are ineffective against Gram-negative bacteria. This is partly due to the properties of the outer membrane (OM) which prevents efficient uptake. The overarching goal of this thesis was to investigate how the OM of the Gram-negative bacterium E. coli could be weakened to improve the activity of antibiotics.

    In the first two papers of my thesis (paper I + II), I investigated the periplasmic chaperone network which consists of the two parallel pathways SurA and Skp/DegP. This network is essential for the integrity of the OM and strains lacking either SurA or Skp are defective in the assembly of the OM, which results in an increased sensitivity towards vancomycin and other antimicrobials. We identified a novel component of the periplasmic chaperone network, namely YfgM, and showed that it operates in the same network as Skp and SurA/DegP. In particular, we demonstrated that deletion of YfgM in strains with either a ΔsurA or Δskp background further compromised the integrity of the OM, as evidenced by an increased sensitivity towards vancomycin.

    In the remaining two papers of my thesis (paper III + IV), the goal was to characterize small molecules that permeabilize the OM and thus could be used to improve the activity of antibiotics. Towards this goal, we performed a high-throughput screen and identified an inhibitor of the periplasmic chaperone LolA, namely MAC-13243, and showed that it can be used to permeabilize the OM of E. coli (paper III). We further demonstrated that MAC-13243 can be used to potentiate the activity of antibiotics which are normally ineffective against E. coli. In the last paper of my thesis (paper IV), we undertook a more specific approach and wanted to identify an inhibitor against the glycosyltransferase WaaG. This enzyme is involved in the synthesis of LPS and genetic inactivation of WaaG results in a defect in the OM, which leads to an increased sensitivity to various antibiotics. In this paper, we identified a small molecular fragment (compound L1) and showed that it can be used to inhibit the activity of WaaG in vitro.

    To summarize, this thesis provides novel insights into how the OM of the Gram-negative bacterium E. coli can be weakened by using small molecules. We believe that the two identified small molecules represent important first steps towards the design of more potent inhibitors that could be used in clinics to enhance the activity of antibiotics.

  • Public defence: 2017-12-12 13:00 sal 14, hus 5, Kräftriket, Stockholm
    Fetisova, Ekaterina
    Stockholm University, Faculty of Science, Department of Mathematics.
    Towards a flexible statistical modelling by latent factors for evaluation of simulated responses to climate forcings2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, using the principles of confirmatory factor analysis (CFA) and the cause-effect concept associated with structural equation modelling (SEM), a new flexible statistical framework for evaluation of climate model simulations against observational data is suggested. The design of the framework also makes it possible to investigate the magnitude of the influence of different forcings on the temperature as well as to investigate a general causal latent structure of temperature data. In terms of the questions of interest, the framework suggested here can be viewed as a natural extension of the statistical approach of 'optimal fingerprinting', employed in many Detection and Attribution (D&A) studies. Its flexibility means that it can be applied under different circumstances concerning such aspects as the availability of simulated data, the number of forcings in question, the climate-relevant properties of these forcings, and the properties of the climate model under study, in particular, those concerning the reconstructions of forcings and their implementation. It should also be added that although the framework involves the near-surface temperature as a climate variable of interest and focuses on the time period covering approximately the last millennium prior to the industrialisation period, the statistical models, included in the framework, can in principle be generalised to any period in the geological past as soon as simulations and proxy data on any continuous climate variable are available.  Within the confines of this thesis, performance of some CFA- and SEM-models is evaluated in pseudo-proxy experiments, in which the true unobservable temperature series is replaced by temperature data from a selected climate model simulation. The results indicated that depending on the climate model and the region under consideration, the underlying latent structure of temperature data can be of varying complexity, thereby rendering our statistical framework, serving as a basis for a wide range of CFA- and SEM-models, a powerful and flexible tool. Thanks to these properties, its application ultimately may contribute to an increased confidence in the conclusions about the ability of the climate model in question to simulate observed climate changes.

  • Public defence: 2017-12-14 10:00 Vivi Täckholmsalen (Q-salen) NPQ-huset, Stockholm
    Garcia Lobato Tavares, Raquel
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Host cell responses to Helicobacter pylori secreted factors2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The infection of the human gastric mucosa by the bacterium Helicobacter pylori can lead to the development of gastritis, gastroduodenal ulcers, and cancer. The factors that determine disease development in a small percentage of infected individuals are still not fully understood.

    In this thesis, we aimed to identify and functionally characterize novel virulence factors of H. pylori and to understand their effect on host cell responses.

    In Paper I, we found that JHP0290, an uncharacterized secreted protein of H. pylori, induced macrophage apoptosis concomitant to the release of pro-inflammatory cytokine TNF via the regulation of the Src family of kinases and ERK MAPK pathways. In paper II, we demonstrated that JHP0290 exhibits both proliferative and anti-apoptotic activity, together with a faster progression of the cell cycle in gastric epithelial cells. During these responses, ERK MAPK and NF-κB pathways were activated. Paper III revealed a pro-apoptotic effect of another H. pylori-secreted protein HP1286 in macrophages via the TNF-independent and ERK-dependent pathways. No apoptosis was observed in HP1286-treated T cells or HL60 neutrophil-like cells, suggesting cell-type specific effect of HP1286. In Paper IV, we observed the pro-inflammatory activity of H. pylori secreted protein HP1173 in macrophages. The protein was found to induce TNF, IL-1β, and IL-8 in macrophages through MAPKs, NF-κB, and AP-1 signaling pathways. Furthermore, differential expression and release of JHP0290, HP1286, and HP1173 homologues was observed among H. pylori strains (papers II, III, IV). 

    Due to their ability to regulate multiple host cell responses, proteins JHP0290, HP1286, and HP1173 could play an important role in bacterial pathogenesis.

     

  • Public defence: 2017-12-14 13:00 Nordenskiöldsalen, Geovetenskapens hus, Stockholm
    Raúl Sitoe, Sandra
    Stockholm University, Faculty of Science, Department of Physical Geography.
    Environmental history in southern Mozambique: Reconstruction of flooding events, hydroclimate and sea-level dynamics since mid-Holocene2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis has been to reconstruct paleoenvironment, paleohydrology and paleoclimate in coastal southern Mozambique, with emphasis on tracing past flooding events on the lower Limpopo River floodplain. In order to extend flood chronologies beyond periods covered by instrumental data, sediments from lakes on the floodplain were studied (Lake Lungué, Coassane Oxbow, Lake Magandane and Lake Soane). Past sea-level variations and climate changes were deduced by analyzing sediments from coastal sites north of the floodplain area (Lake Chilau, Lake Nhauhache and Macassa Bay). To achieve the established objectives, a multi-proxy approach was applied on most of the retrieved sediment cores, involving analysis of mineral magnetic parameters, grain-size and organic carbon in combination with analysis of microfossils such as diatoms and/or phytoliths. Chronologies for the constructed time-series analysis were obtained by radiocarbon dating and age-depth modelling. The synthesized data from the sampled sites on the Limpopo River floodplain suggest that the area was affected by at least 16 flooding events of variable magnitudes during the studied period. These are dated to c. AD 940, 980, 1040, 1100, 1250, 1300, 1370, 1580, 1665, 1730, 1755, 1855, 1920, 1945, 1970 and 2000. In calibrated years BP these ages correspond to 1010, 970, 910, 850, 700, 650, 580, 370, 285, 220, 195, 95, 30, and 5 cal yrs BP. The two youngest are dated to 20 and 50 years AP (After Present being 1950). Proxy data further suggest that southern Africa was subject to two periods of sea-level highstands, at c. 5000–4200 BC (6950–6150 cal yrs BP) and AD 300–950 (1650–1000 cal yrs BP). The former represents the middle part of the postglacial climatic optimum. The wettest period in the Limpopo River floodplain was reported between AD 1360 and 1560 (590 and 390 cal yrs BP) in the Lake Lungué record, while Lake Chilau experienced wet conditions between AD 1200 and 1400 (750 and 550 cal yrs BP), then returning to drier conditions that prevailed until c. AD 1600. In Lake Nhauhache, however, drier conditions prevailed from c. AD 1200–1700 (750–250 cal yrs BP), shifting towards wetter at c. AD 1900 (50 cal yrs BP). The deviating signals between records can partly be explained by Lake Lungué basin being located on the Limpopo River floodplain, responding to flooding events associated with precipitation upstream the drainage area. Therefore, wet and dry periods in floodplain lakes (e.g. Lake Lungué) are not expected to correlate with precipitation changes on a local scale, as indicated by e.g. Lake Nhauhache. This is supported by a relatively weak agreement between Lake Lungué record and other nearby records (outside the floodplain), but a better correlation with records from the upper catchment, where a more regional climate signal is provided of the southern African summer rainfall region.