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  • Disputation: 2018-09-27 13:00 Gröjersalen, hus 3, Kräftriket, Stockholm
    Stendahl, Emma
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Företagsekonomiska institutionen.
    Headquarters' Involvement in Managing Subsidiaries2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Within contemporary research on the multinational corporation (MNC), the topic of headquarters' involvement has grown considerably in importance. As the central organisational unit in the MNC, headquarters has the potential to add value to the firm by performing an administrative and entrepreneurial role. While the administrative role concerns synergetic coordination and control activities, the entrepreneurial role pertains to developing and implementing new innovations such as management innovations at the corporate-wide level. 

    Existing literature has generated valuable insights into headquarters' administrative and entrepreneurial role and the potential to create value for the MNC. However, more research is needed on how headquarters can advantageously involve itself and integrate subsidiaries to ensure that their activities are aligned with the MNC strategy without impinging upon subsidiaries' autonomy and without incurring their resistance to headquarters' coordination, control, and innovation activities. 

    This thesis aims to advance our knowledge on headquarters' involvement in managing its subsidiaries. Within the administrative role, I examine coordination and control activities, and within the entrepreneurial role, I examine the process of developing and implementing management innovations and facilitating factors. The thesis draws on a single longitudinal case study of the development and implementation of a new performance management practice by a European MNC within the construction industry. During the fieldwork, I gathered empirical material from observations and interviews as well as secondary data. While this thesis has been carried out as a single case study, the outcome of the thesis is presented in four separate papers, exploring headquarters' involvement in coordination, control and innovation activities. 

    This thesis contributes to the literature on headquarters' involvement in managing subsidiaries by suggesting a collaborative approach to subsidiary engagement and participation that addresses 1) the issue of subsidiary demotivation by feeling degraded to an implementer, 2) the suitability issue by reducing the risk of mismatch between new headquarters integration and innovation activities and subsidiary contexts. Combining headquarters' and subsidiaries' stocks of perspectives and knowledge helps transcend the spatial, cultural, institutional and political boundaries between headquarters and subsidiaries.

  • Disputation: 2018-09-28 09:00 Nordenskiöldsalen, Geovetenskapens hus, Stockholm
    Barrett, Damon
    Stockholms universitet, Juridiska fakulteten, Juridiska institutionen.
    Drugs and the Convention on the Rights of the Child: Fragmentation, Contention and Structural Bias2018Doktorsavhandling, monografi (Övrigt vetenskapligt)
    Abstract [en]

    Responding to the harms caused by drug use and the drug trade is one of the most pressing and interdisciplinary challenges of our time, within which the protection of children has become central. But there has been relatively little academic attention to the international legal dimensions of drug policy, despite the existence of a dedicated international legal framework on the issue and a range of other treaties that include drugs in some way. This has begun to change in recent years as attention to human rights in drug policy has increased, and as calls for reform to the extant international legal regime of drug control have grown. This thesis adds by focusing on the only core UN human rights treaty to refer to drugs – the Convention on the Rights of the Child (CRC). Based on archival research, extensive document analysis, participant observation at UN forums, and semi-structured interviews, the thesis explores how the child’s right to protection from drugs under Article 33 of the CRC has been understood, and what the relationship has been between the CRC and the UN drug control conventions. Adopting a critical approach to child rights studies, it offers a number of additions to the growing literature on international law and drug control:

    • A detailed history of the parallel drafting of the international drug control and child rights legal regimes in the twentieth century, tracing their substantive detachment over time until their political convergence to the height of the ‘war on drugs’ in the late 1980s;
    • A discussion of the CRC and the UN drugs conventions set against the background of the fragmentation of international law, highlighting a degree of surface level coherence yet important inconsistencies of background theory and ethos;
    • An analysis of contemporary debates among scholars, activists, States and UN mechanisms on the relationship between human rights, child rights and drug control, demonstrating the potential for fragmentation playing out in real-world contentions;
    • A comprehensive review and critique of the periodic reporting process to the Committee on the Rights of the Child from 1993-2015 through the theoretical lens of ‘structural bias’, showing that while the CRC may offer an alternative legal lens through which to approach drug policy, the process has tended to lean in favour of a restrictive and often punitive status quo.
  • Disputation: 2018-09-28 10:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Schäfer, Jacob
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Wiring Components of the Respiratory Chain: Modulation of the Respiratory Chain in Yeast and Bacteria2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The enzyme complexes of the respiratory chain are organized in supramolecular assemblies, so-called respiratory supercomplexes. In the yeast Saccharomyces cerevisiae, these supercomplexes consist of two copies of complex III (bc1 complex) and one or two copies of complex IV (cytochrome c oxidase, CytcO). Several factors, including lipids and small proteins, have been identified to facilitate or stabilize this organization.

    Respiratory supercomplex factor (Rcf) 1 interacts with CytcO. In this work, we show that in the native S. cerevisiae mitochondrial membrane several forms of CytcO co-exist. Intact CytcO shows spectral and functional properties similar to those of CytcOs from other organisms characterized earlier. A second population displayed a lower midpoint potential of heme a3 as well as accelerated ligand binding, suggesting structural differences around the catalytic site. Severe structural changes of the catalytic site and the overall structure of the enzyme were found in a third population of CytcO. The fraction of the structurally altered CytcO increased upon removal of Rcf1. Here, a mechanism is proposed in which Rcf1 regulates function of the CytcO by altering the catalytic site so that electron transfer between heme a and heme a3 is slowed, resulting in a more exergonic O2-ligand binding. This scenario would in turn increase heat production on the expense of the proton electrochemical gradient.

    Rcf1 was further shown to facilitate electron transfer from the bc1 complex to CytcO in a supercomplex by interacting with the electron carrier cytochrome c (cyt. c).

    In addition, we purified and structurally and functionally characterized the supercomplex of Mycobacterium smegmatis, which contains a membrane-anchored cyt. c as a subunit of the bcc1 complex.

  • Disputation: 2018-09-28 10:00 De Geersalen, Geovetenskapens hus, Stockholm
    Ingre-Khans, Ellen
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi. Stockholm University.
    Transparency within REACH?: Regulatory risk assessment of industrial chemicals2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Chemicals provide us with many benefits but can also have adverse effects on human health and the environment. Concerns that previous European legislations were not providing adequate protection from chemical risks resulted in a new chemicals legislation – REACH – in 2007. According to REACH, the chemical industry must ensure that risks from chemicals they produce or import at or above one tonne per year can be adequately controlled. Data on the chemicals’ properties and uses, hazards and risks as well as instructions for safely handling the chemicals, must be provided by industry to the European Chemicals Agency (ECHA) before the chemicals are allowed on the European market. The information is used by ECHA and the competent authorities of the Member States to identify chemicals of concern that warrant regulation. Thus, the registered data need to be reliable and relevant as well as transparently reported to ensure that chemicals of concern can be identified. The aim of this thesis was to provide insights into the risk assessments carried out by industry under REACH to contribute to a safer use of chemicals.

    The results in this thesis show that information that is used for concluding on hazards and risks of chemicals as well as industry’s conclusions are reported in a semi-transparent manner and therefore difficult for third parties to fully scrutinise and evaluate (paper I). This was in part due to the protection of confidential information as laid down by law but also related to ECHA’s procedures for making information available to the public as well as industry’s reporting. Furthermore, industry is only required under REACH to summarise (eco)toxicity studies that are gathered for the risk assessment. Consequently, data based on industry studies that are not publicly available cannot be scrutinised and independently assessed by third parties. Thus, the system relies on studies being accurately summarised by the registrant although this was not always seen to be the case (paper IV). 

    Furthermore, the current framework for industry to evaluate (eco)toxicity studies and report data evaluations under REACH was found to be neither systematic nor transparent (paper II). Studies may not be evaluated based on their inherent scientific quality when the Klimisch method for evaluating data is used, which is the recommended data evaluation method under REACH. Using the Klimisch method may also result in giving less weight to non-standard studies, such as many academic research studies, than studies performed according to standardised test guidelines, although non-standard studies could contribute with important information to the risk assessment. The structure and transparency of data evaluations could be improved by using a framework that has clear criteria and guidance as well as a structured format for reporting data evaluations (paper III). This would support more harmonised and transparent data evaluations and encourage studies to be evaluated according to their inherent scientific quality rather than mere compliance with standardised test guidelines.

    The overall objective of this thesis is to contribute to the development of systematic and transparent risk assessments under REACH, which is critical for using chemicals safely.

  • Disputation: 2018-09-28 13:00 William-Olssonsalen, Geovetenskapens hus, Stockholm
    Wallsten, Barbara
    Stockholms universitet, Humanistiska fakulteten, Institutionen för slaviska och baltiska språk, finska, nederländska och tyska.
    Pädagogische Bildtexte: Kontrastive Analysen von Bild-Text-Beziehungen in deutschen und schwedischen Geschichtslehrbüchern2018Doktorsavhandling, monografi (Övrigt vetenskapligt)
    Abstract [en]

    The thesis examines captions in history textbooks. Captions can be described as short texts connected to images. They have a complex function involving highlighting information, and can be comments, interpretations or questions directly addressing the reader in terms of their nature. Captions in textbooks have a more or less enunciated didactic or educational aim. I call them educational captions

    By using a triangulation of methods and theories, such as multimodal text analysis, linguistic comparative discourse analysis and systemic-functional grammar, this thesis explores how meaning and knowledge are discursively represented and conveyed by captions in history textbooks. The corpus consists of German and Swedish history textbooks for upper secondary school pupils. A total of 26 examples have been selected, taking into account various considerations regarding qualitative research, and have been analysed in detail. For the detailed analyses, a flowchart for processing the categories has been designed: presentation of the caption with its image, location within the textbook, image description, image-text-arrangement, processes, agency and grammatical metaphor, construction of subjects, recontextualization and (re)presentation of the historical event. The examples represent three historical events: The Berlin Blockade, the Cuban Missile Crisis and the Fall of the Berlin Wall.

    The analyses show that the length of captions can differ a lot – they can consist of a name or be a longer text with a narrative character. The uses of history differ in German and Swedish textbooks. German captions treat the associated pictures like documents by using letters and numbers to describe them; moreover they provide information about time and place. In contrast, the Swedish ones are more narrative in nature. Subjects are constructed differently in the multimodal representations of the events, the most significant of which is the positive (re)presentation of the USA during the Cuban Missile Crisis and the Berlin Blockade. First and foremost, meaning and knowledge are discursively represented and expressed by the selection of the image. This choice influences how the captions are formed and meanings conveyed. Iconic pictures representing a celebrating crowd on the Berlin Wall in front of the Brandenburg Gate serve to construct national identity, together with national symbols, in German textbooks, and captions reinforce this meaning potential. The captions demonstrate that their meaning potential lies within their function of being an interface in the multimodal composition of the textbook, and captions also indicate the different uses of history in the two different educational systems. Finally, their potential in constructing and transforming discursive knowledge and meanings is demonstrated.

  • Disputation: 2018-09-28 13:00 Ahlmannsalen, Geovetenskapens hus, Stockholm
    Kielman, Ross
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för geologiska vetenskaper. Naturhistoriska riksmuseet.
    Assessing the reliability of detrital zircon in Early-Earth provenance studies2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Vår kunskap om jordens tidigaste historia och processerna som har format dess utveckling kommer företrädesvis från geokemiska och isotopkemiska signaturer hos ett fåtal zirkonpopulationer från olika delar av världen. Studier av spårelementsfördelning, Hf- och O-isotopsystematik samt kemidata från mineralinklusioner i detritiska zirkoner kan kombineras med U-Pb kronologi för att bestämma ursprungsbergarternas karaktär. Tidigare forskning har emellertid fäst uppmärksamhet på att primära geokemiska och isotopkemiska signaturer kan modifieras efter depositionen, förstärkt av interna strålningsskador och kristall-plastisk deformation. Ytterligare komplikationer uppstår när ett okänt antal ursprungsbergarter bidrar till detritiska sediment eller när ursprungsbergarterna saknas, vilket är fallet för hadeiska detritiska zirkoner.

    I denna avhandling har ett antal analysmetoder tillämpats på relativt outforskade detritiska zirkonpopulationer, tillsammans med systematiska undersökningar av titans, sällsynta jordartselements, U-Th-Pb, Lu-Hf och O-isotopers beteende i en magmatisk ursprungsbergart analog med sådana tidiga detritiska zirkonsviter. Tre lokaler har studerats: Mt. Alfred i Yilgarn-kratonen i västra Australien (detritisk studie); Saglek Block, den västligaste utlöparen av den nordatlantiska kratonen i norra Labrador (detritisk studie); och en lokal söder om Isua i sydvästra Grönland (jämförelsestudie). Vi har använt oss av en CAMECA ims 1280 jonmikrosond (SIMS) för dess höga rumsliga upplösning och goda förmåga att analysera små provvolymer, med undantag av Lu-Hf analyserna, vilka utfördes med laserablation (Laser Ablation Multicollector Inductively Coupled Mass Spectrometer, LA-MC-ICP-MS).

    De främsta resultaten från denna studie är följande tre: 1) Starkt diskordanta zirkonpopulationer av hög ålder fordrar omfattande datafiltrering för att generera data som är tillförlitliga för ålderskorrelation. Vidare, åldersuppskattningar av genomgripande blyförlust, även i metamikta, detritiska zirkoner, kan erhållas genom beräkning av diskordia-intercept-åldrar inom enskilda kristaller. När detta tillämpas i ett regionalt perspektiv framkommer det att detritiska zirkoner från Mt. Alfred, Western Australia har en distinkt provenans jämfört med andra metasedimentära enheter i Youanmi Terraine och uppvisar likheter med Mt. Narryer metasediment i Narryer Terraine. 2) Detritiska zirkoner från metasediment som utsatts för höggradig metamorfos i Saglek Block, norra Labrador ger företrädesvis mesoarkeiska ålderssignaturer, tillsammans med en mindre eoarkeisk komponent. Lu-Hf isotopdata från dessa zirkoner visar på upp till fem populationer med nära-kondritisk sammansättning. U-Pb-Hf data från två prover av metapelit (L1407 och L1408) tyder på att en tidigare omtolkning av depositionsåldern för denna enhet till >3.95 Ga är ogrundad, vilket undergräver senare studier baserade på denna tolkning. 3) Geokemisk komplexitet i zirkoner från en eoarkeisk metatonalit, ansedd som en motsvarighet beträffande ursprung till äldre detritiska zirkoner, ifrågasätter antaganden och tolkningar baserade på studier av detritiska zirkoner. Lu-Hf och O-isotopsystem uppvisar mestadels homogena sammansättningar, trots uppvisad U-Pb störning. Petrogenetiska spårelement proxies såsom REE och Ti ger heterogena resultat, även inom enskilda korn. Påvisande av magmatiska signaler från detritiska zirkonpopulationer kan därför, utan noggrann granskning, visa på konstgjort komplexa resultat som följaktligen kan leda till felaktiga tolkningar.

  • Disputation: 2018-10-05 13:00 Nordenskiöldsalen, Stockholm
    Letzter, Eva-Marie
    Stockholms universitet, Humanistiska fakulteten, Historiska institutionen.
    Med öga för publiken: Moralisk fostran genom heliga Birgittas och de svenska predikanternas exempelberättelser, cirka 1340-15002018Doktorsavhandling, monografi (Övrigt vetenskapligt)
    Abstract [en]

    This dissertation is a comparative and deconstructive study of the use of narrative exempla in the Revelations of Saint Birgitta (also known as Saint Bridget of Sweden) and in Swedish sermon collections from the Late Middle Ages. The purpose is to show how Birgitta during the 14th century and Swedish preachers during the 15th century morally educated their audiences through the inclusion of exemplary stories in their works. Furthermore, this dissertation discusses and analyses the ways in which these authors adapted their stories to suite their respective audience. It distinguishes between how Birgitta addressed the worldly and religious leaders of Europe and how the Swedish preachers addressed a socially stratified Swedish congregation by applying Jonathan Cohen’s theory of identification with media characters. This dissertation hereby contributes not only to research concerning the didactics of Christian exemplary literature, but also to the methodology in which audience adaptation in this literature can be evaluated.

    Among the results of this study one finds that the exemplary stories in the Revelations and Swedish sermon collections are often used to rhetorically reinforce doctrinal lessons concerning man’s reciprocal relationship with God. Many of the lessons deal with Christ’s justice, the devil’s evil nature and man’s proper faith and hope in God. However, Birgitta tends to use her stories as analytical explanations for theses lessons, while the Swedish preachers use theirs as simple arguments for them. In view of narrative structure and content, Birgitta tends to focus on describing protagonists’ thoughts and inner disposition in her stories, whereas the Swedish preachers focus on protagonists’ physical course of action in their stories. Moreover, both authors depict international characters, settings and complication motives. Still, Birgitta highlights those associated with the higher estates, while the Swedish preachers emphasize those associated with general church life and the lower laity.

    These results correlate well with strategies suggested in media research for enticing audience identification with characters. In particular, I find that the virtuous or sinful way of life, led by the protagonists in the exemplary stories, mimics that of Birgitta’s and the Swedish preachers’ different target groups. Yet even more strikingly, numerous protagonists are also found to possess attractive heroic ideals. They embody heroic role models, which the authors’ respective audience can be expected to have wished to emulate themselves, and which Birgitta and the Swedish preachers likewise wanted their audience to follow, though to different extents and in different manners. While Birgitta and the Swedish preachers both used exemplary stories to morally educate their recipients in accordance with the Christian exemplary tradition, I thus conclude that their teaching differed in several significant ways, supporting the premise that the authors knew what they wanted to convey, and that they had a good eye for their respective audience.

  • Disputation: 2018-10-08 13:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Baumgarten, Thomas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Protein production in the E. coli cell envelope2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Proteins fulfil essential functions in every cell and malfunctioning proteins are often the cause of diseases. On the other hand, proteins like antibody fragments or hormones can be used to treat diseases. Proteins are often produced in the bacterium Escherichia coli so that they can be studied to understand their (mal)function or so that they can be used to treat a disease. Unfortunately, producing proteins in the cell envelope of E. coli, like integral membrane proteins, which are important drug targets, and secretory proteins like antibody fragments and hormones, often results in unsatisfactory yields. Therefore, the objectives of this doctoral thesis were to identify bottlenecks that can limit the production of recombinant proteins in the cell envelope of E. coli and to try to overcome these bottlenecks. In the first study, we isolated and characterized the E. coli membrane protein production strain Mt56(DE3). This strain, in which the target gene expression intensity is strongly reduced, outcompetes the standard E. coli membrane protein production strains for most targets tested. In the second and third study we focused on the production of secretory proteins, i.e., proteins that are translocated across the inner membrane into the periplasm of E. coli. First, we investigated the impact of the targeting pathway used to direct a secretory protein to the translocation machinery on the cell physiology and protein production yields. We found that the co-translational targeting of a produced protein saturates the capacity of the translocation machinery resulting in heavily impaired biomass formation and low protein production yields. In contrast, post-translational targeting of a produced protein did not saturate the capacity of the protein translocation machinery resulting in hardly affected biomass formation and high protein production yields. In the third study we investigated how optimizing the production of a co-translationally targeted protein, by harmonizing its production rate with the capacity of the protein translocation machinery, affects the physiology of the cell. We found that, in stark contrast to the non-optimized condition, the optimized production did not affect the composition of the E. coli proteome. This surprising finding indicates that a protein can be produced efficiently in the periplasm of E. coli without compromising the physiology of the cell. In the last study we aimed at developing an outer membrane vesicle-based tuberculosis vaccine. To this end, an E. coli strain was created that produced outer membrane vesicles coated with different tuberculosis antigens. It was shown that a homogenous population of vesicles was produced, which will hopefully facilitate the isolation of these vesicles on an industrial scale.

  • Disputation: 2018-10-10 10:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Henriksson, Linda
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Structural and functional studies of a novel Botulinum neurotoxin and of MTH12018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    X-ray crystallography visualizes the three dimensional molecular structures of proteins at atomic resolution. Seeing the molecular structure of a biomedically interesting protein enables a higher understanding of its function. The process of producing pure protein from genetic material to generate crystals and determine the molecular structure can be a long and challenging process. My thesis involves structural and functional studies of two different proteins, which are both biomedically interesting and important to learn about. X-ray crystallography is the method which has been used to determine the majority of the protein structures that we know of today and is also the method used in the results presented in my thesis. 

    Today there are no cancer therapies defeating all types of cancers and they do not come without side effects. Battling cancer diseases often include long and painful treatments. Finding an anti-cancer drug targeting phenotypes characteristic of cancer cells is a compelling thought. MutT homolog-1 (MTH1) is an enzyme present in all proliferating cells. The enzyme seems to be crucial for cancer cell survival but not for the viability of normal cells. MTH1 cleans out oxidized and thereby damaged nucleotides from the free nucleotide pool and stops them from being used in DNA synthesis. This process is very important in fast proliferating cancer cells. The hypothesis is to inhibit MTH1 and thereby allow a limitless amount of DNA damage in the cancer cells. This action will eventually kill cancer cells while not affecting normal cells. The molecular structure of MTH1 with (PDB ID: 3ZR0) and without a product bound (PDB ID: 3ZR1) was determined and is presented in my thesis. These two structures aided in the synthesis of inhibitors. 

    Botulinum neurotoxins (BoNTs) are the most potent toxins known. As little as one gram of pure toxin could potentially kill one million people. Due to its potency BoNT is a potential  bioterrorism threat. The toxin is also a very potent drug used clinically to relieve the symptoms of an array of neuromuscular disorders. Most people know this neurotoxin by one of its commercial names: Botox™. Additionally BoNTs are the cause of botulism. BoNTs are neuro-specific enzymes that target neuromuscular signaling, inducing flaccid paralysis and potentially death. It is of importance to learn more about these toxins to enable the development of new countermeasures, vaccines or more efficient neuroparalytic drugs. BoNTs consist of three domains with different functions, all crucial for intoxication. The toxins are fragile and can easily be destroyed by harsh surroundings if not protected by non-toxic non-hemagglutinin (NTNH) proteins. The complex of some BoNT serotypes and their protective NTNH have proven to be pH-dependent. Parts of the intoxication process are not yet clear and their mechanisms are still puzzling researchers. Until recently seven BoNT serotypes were identified. We have now identified and characterized a novel serotype called BoNT/X. The molecular structure of the active domain is presented here (PDB ID: 6F47). The pH-dependent mechanism forming a complex as seen in other serotypes, is confirmed to be present in BoNT/X as well.

  • Disputation: 2018-10-11 10:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Dowaidar, Moataz
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Chimeric gene delivery vectors: Design, synthesis, and mechanisms from transcriptomics analysis2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Genterapi med hjälp av av oligonukleotider (ON) har en enorm potential för behandling av olika genetiska sjukdomar. För att ha terapeutisk effekt måste dock oligonukleotiderna nå in i cellen och detta försvåras på grund av deras negativa laddningar och snabba nedbrytning. Cellpenetrerande peptider (CPP), är korta katjoniska peptider, som kan användas för att förbättra det cellulära upptaget (transfektionen) av oligonukleotider. I denna avhandling undersöks nya strategier för hur CPP tillsammans med magnetiska nanopartiklar, såsom MNP och Fe3O4, eller grafenoxid (GO) nanopartiklar, kan möjliggöra effektivare transfektion av ON.  Vidare studeras även de möjliga cellulära signalvägar som reglerar CPP-medierat upptag.

    En så kallad ”fragment quantitative structure-activity relationship” (FQSAR) modell  användes för att förutsäga nya effektiva CPP för leverans av plasmider (ringformade DNA-molekyler med omkring 5000 nukleotidbaspar). De bäst prediktade peptiderna visade en signifikant ökad transfektionsförmåga jämfört med den tidigare använda peptiden PeptFect 14 (PF14). De nya peptiderna PF220, PF221, PF222, PF223 och PF224 som identifierades med FQSAR kunde dessutom bilda självmonterande komplex med MNP eller GO nanopartiklar. I cellulära försök uppvisade dessa nya hybridvektorer (CPP/MNP och CPP/GO) en klart förbättrad transfektionsförmåga av såväl plasmider, som splitsningskorrigerande oligonukleotider (SCO) och små interfererande RNA (siRNA), jämfört med PF14-nanopartikel hybridvektorer, såväl som den kommersiella lipidbaserade transfektionsvektorn Lipofectamine™ 2000. Den höga transfektionseffektiviteten hos dessa nya hybridvektorer beror troligen på deras låga cellulära toxicitet och en möjlig synergistisk effekt vid kombinationen av CPP och MNP/GO nanopartiklar. Förmågan hos en CPP/MNP hybridvektor att levera plasmider in vivo undersöktes också och transfektion av celler i såväl lunga och mjälte i behandlade djur kunde påvisas. Dessa nya hybridvektorer utgör således en ny lovande strategi för leverans av ON vid genterapi.

    För att kartlägga de signalvägar som kontrollerar upptaget av CPP-baserade vektorer analyserades  genuttrycket hos celler som transfekterats med PF14 eller PF14-ON, med hjälp av  RNA-sekvensering och qPCR-analys. Resultaten påvisade att en ökning i uttrycket av flera autofagirelaterade gener sker tidigt vid transfektionen. Konfokal- och transmissionselektronmikroskopi demonstrerade vidare en ökad initiering av autofagi och samlokalisering av ON med autofagosomer. Detta visar att CPP-medierad transfektion aktiverar signalvägar som stryr autofagi och öppnar nya möjligheter att använda autofagimodifierare för att förbättra genterapi.

  • Disputation: 2018-10-12 10:00 Ahlmannsalen, Geovetenskapens hus, Stockholm
    Borg, Ida
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Kulturgeografiska institutionen.
    Housing, poverty and the welfare state: Spatial distribution of tenure types and its effects on housing deprivation, unemployment and residualisation2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    An important question that has caused much academic debate is how to best organise the welfare state system to combat poverty and social exclusion. Much such research is focused on how to combat income poverty through core areas in the welfare state. This dissertation widens the perspective to include housing as a part of the welfare state and it represents an attempt to study poverty outcomes beyond income measures. In doing this, the dissertation uses power resource theory to understand welfare state change and the design of institutions in terms of housing tenures, and shows how this design might affect individual outcomes. Thus, the overall aim of this dissertation is to gain knowledge of the principles that underpin the design and organisation of the housing market in terms of tenure types and to understand the ways in which this design might affect the well-being of individuals and the society as a whole. The dissertation consists of an introductory essay and four papers. The introductory essay presents my theoretical approach and methodology. It also summarises the papers and discusses my main findings.

    Paper I analyses the extent to which the organisation of the rental sector may explain cross-national differences in the prevalence of housing deprivation. Using a multilevel framework on survey data covering 26 European countries, I find that a large and integrated rental sector significantly reduces the prevalence of housing deprivation across EU countries. The organisation of the rental sector appears to be crucial when it comes to reducing poverty and social exclusion in terms of housing insufficiencies.

    Paper II continues the quest to find explanations of the variations in the prevalence of housing deprivation in Europe. Our results develop the findings of Paper I. We find that a high proportion of outright owners is positively associated with housing deprivation. This is suggested to reflect the historical and political processes that affect the housing markets in eastern and southern European housing regimes.

    Paper III investigates a puzzle regarding the relationship between the extent of home-ownership and unemployment. At the macro level, more home-owners indicate higher unemployment rates, while home-owners in general are less unemployed. What can explain this? In this paper, we show that regions with high home-ownership also tend to be regions with small labour markets, which affects the efficiency of matching on the labour market.

    Paper IV turns to the process of residualisation, a process which can be described as when the public or social rental sectors become dominated by low-income households. For Sweden, this process is of key interest since the public housing sector aims to be universal and is not directed towards any specific income group. The results indicate a clear trend towards increasing residualisation. The trend is most pronounced in sparsely populated municipalities, while the public rental sector is quite mixed in larger cities and municipalities near larger cities.

    This dissertation offers a contribution to the field of housing by showing that power resource theory may be used to understand institutional design in terms of tenure types, and that this design also affects individual outcomes. Moreover, power resource theory is presented as a viable theory to understand geographical variation in institutional design across and within countries.

     

  • Disputation: 2018-10-12 13:00 Nordenskiöldsalen, Geovetenskapens hus, Stockholm
    Nedevska Törnqvist, Jasmina
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Statsvetenskapliga institutionen.
    Why Care About Future People's Environment?: Approaches to Non-Identity in Contractualism and Natural Law2018Doktorsavhandling, monografi (Övrigt vetenskapligt)
    Abstract [en]

    The dissertation analyses the capacity of contractualism and natural law to justify environmental intergenerational duties.

    For three decades, climate change has been a major political concern. As a fundamental threat to environmental sustainability, climate change is believed to threaten the long-term welfare of humankind. It thus seems imperative to affirm long-term duties regarding future people’s environment. Furthermore, contractualism and natural law are two important moral theories in contemporary political life. While the former seems influential among political liberals, natural law seems more appealing to political conservatives. It is thus of interest how both of these theories can be used to argue for environmental intergenerational duties. Yet, natural law has been particularly understudied in this regard.

    The point of departure of the study is the so-called non-identity problem, formulated by Derek Parfit. As concerns future generations, what we do not only affects the quality of people’s lives, but also who will come to exist. If future people come to exist as a consequence of how we live our lives, including the choice of living unsustainably, a degraded environment will be worse for no one. For so-called person-affecting theory, such as contractualism, non-identity seems to imply that there is nothing morally objectionable about leaving future people with an unsustainable environment.

    First, the dissertation demonstrates recent attempts in contractualism, in the vein of John Rawls and Thomas Scanlon, to solve the non-identity problem on person-affecting terms. It is shown that these attempts either fail to affirm environmental intergenerational duties or implicitly abandon a person-affecting view.

    Second, the dissertation explores a natural law approach to the non-identity problem, employing a recent account of natural law suggested by John Finnis. While natural law can be considered of import in contemporary political decision-making, it has hardly ever been used to ground environmental intergenerational duties. This dissertation shows how an impersonal application of natural law could be used in attempts to circumvent the non-identity problem, i.e. to affirm environmental intergenerational duties, and treats possible objections to such an account. It is argued that the requirement to consider so-called basic values, also in cases when no individual would be worse off by one’s act, should render it at least morally objectionable to leave future generations with an unsustainable environment.

    Third, a new kind of objection to environmental intergenerational duties is discussed in depth. The objection applies to theories that, although they may accept an impersonal view in morals, subscribe to a person-affecting restriction in politics. On some interpretations, this limited restriction can be ascribed to both contractualism and natural law. This may imply a specifically institutional non-identity problem. It conveys the possibly paralysing conclusion that, even if there are environmental intergenerational duties in a moral sense, we are not permitted to use political institutions to enforce them.

    Again, contractualism is used to demonstrate the possible difficulties in overcoming this kind of problem. With regard to natural law, the dissertation explores how the use of institutions could be justified impersonally by reference to the common good and the idea of intergenerational community. In this view, experiences that link us to previous generations justify institutional responsibility for the future.

  • Disputation: 2018-10-12 13:00 Lilla hörsalen, NOD-huset, Kista, Sweden
    Ibrahim, Osama
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Design and Investigation of a Decision Support System for Public Policy Formulation2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The ultimate aim of support for public policy decision making is to develop ways of facilitating policymaking that can create policies that are consistent with the preferences of policymakers and stakeholders (such as an increase in economic growth, the reduction of social inequalities, and improvements to the environment), and that are at the same time based on the available knowledge and evidential information.

    Using the design science research methodology, an iterative design process was followed to build and evaluate a research artefact in the form of an analytical method that is also operationalised as a decision support system (DSS) – in order to facilitate the problem analysis, the impact assessment and the decision evaluation activities carried out at the policy formulation stage of the policymaking process. The DSS provides a web-based, user-friendly interface for two main software modules: (i) a tool for modelling and simulation of policy scenarios; and (ii) a tool for multi-criteria evaluation of policy decisions. The target end-users of the DSS tools are policymakers, the support staff of politicians, policy analysts and researchers within governmental departments and parliaments at the various institutional levels of the European Union.

    The proposed model-based decision support approach integrates systems thinking, problem structuring methods and multi-criteria decision analysis, in what can be described as a ‘sense-making’ approach. A new policy-oriented quantitative problem structuring method is introduced in this research, the ‘labelled causal mapping’ method, which aims to reduce the cognitive overload involved in representing complex mental models using system dynamics simulation modelling in order to facilitate knowledge representation and system analysis. One contribution of this work is an object-oriented implementation of a prototype tool for systems modelling and simulation of policy decision situations based on the labelled causal mapping method. The method provides a basis for further computational decision analysis. We proposed criteria models and data formats for common (generic) policy appraisal, and a preference elicitation method for in-depth decision evaluation based on the results of scenario simulation and the preferences of decision makers and stakeholder groups.

    The artefact evaluation clarifies how well the proposed approach and the DSS tool prototype support a solution to the problem and the extent to which the outcomes in two policy analysis use cases are useful in terms of output analysis and knowledge synthesis.

    The contributions of this research to theory and practice were articulated based on the design knowledge obtained through an iterative design process, notably the emergence of the concepts of transparency and intelligibility in policymodelling, (i.e., the need for explicit and interpretable models that can provide justification of a specific decision).

  • Disputation: 2018-10-15 10:00 Aula Svea, Socialhögskolan, Stockholm
    von Braun, Therese
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för socialt arbete - Socialhögskolan. Högskolan i Gävle, Sverige.
    Theorizing the therapeutic process in substance use-related dependency treatment2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The aim of the thesis was to increase knowledge on how to understand the therapeutic process highlighting the importance of the therapeutic relationship as described by therapists and clients in substance use-related dependency treatment. The research questions were related to how the therapeutic process can contribute to a positive outcome considering the therapists’, the clients’ and close co-dependent relatives’ perspectives.

     

    The thesis followed a qualitative and narrative research design and consists of six studies (I-VI). Study I contributed a description of a multidimensional interactional model for the analysis of substance use-related dependency. The study revealed how a multidimensional interactional model can provide holistic and detailed knowledge about the complex processes involved in the use or misuse of alcohol and drugs. The interactional model was illustrated by a narrative analysis of qualitative empirical data. This model seemed to support a person-by-situation interactional analysis of substance use-related dependency. Study II revealed the possibilities and limitations of using a self-theoretical perspective in the analysis of the use or misuse of alcohol and drugs. The self-theoretical perspective was related to empirical case illustrations based on qualitative or narrative data. The implications of studies I and II were that a self-theoretical perspective can be integrated within a multidimensional model and can be a fruitful theoretical framework for the analysis of treatment processes of dependency. Study III presented conceptual contributions for understanding treatment of substance use-related dependency, focusing on the importance of the therapeutic process and the therapeutic relationship and the use of narrative methods. Study IV presented a structural perspective on clients’ narrative descriptions of different phases of the use or misuse of alcohol and drugs including phases of treatment. Study V contributed an in-depth analysis of three therapists’ narratives of therapeutic relationships in the treatment of drug-dependent clients. The analysis pointed out the multidimensional aspects of the treatment and focused on three phases of therapy; starting the therapeutic process and building a therapeutic relationship, the ongoing therapeutic process, and the closing phase of therapy. The study also presented an in-depth analysis of two narrative case histories on dependency treatment. Study VI focused on a qualitative in-depth analysis based on narrative data from a group of 10 clients that had undergone treatment for alcohol and drug use or misuse. The study also included qualitative and narrative data from four co-dependent clients and six therapists about their views on the treatment process and the therapeutic relationship. The results of the study described how to understand the experiential world of the clients and their cognitive, emotional and behavioral changes associated with the treatment process.

     

    The thesis’ contributions relate to an outline of a self-theoretical perspective integrated within a multidimensional interactional model for the analysis of the therapeutic process and the therapeutic relationship in substance use-related dependency treatment. The theoretical analysis sheds new light on the complexity of the treatment process and the clients’ struggle with their personal identity and sense of self, especially their drug self.

  • Disputation: 2018-10-16 10:00 sal FB54, AlbaNova universitetscentrum, Stockholm
    Rebrov, Oleksii
    Stockholms universitet, Naturvetenskapliga fakulteten, Fysikum.
    Interactions of chiral ions and molecules in gas phase: Towards an understanding of chiral recognition mechanism2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    This thesis comprises the research related to interactions of enantiopure amino acids with chiral and achiral molecules in gas phase. The investigation of the mechanism responsible for chiral discrimination is of the special interest in this work. An electrospray ion source platform (Stockholm University), quadrupole time-of-flight mass spectrometer (University of Oslo) and Fourier-transform ion cyclotron resonance mass spectrometer in combination with OPO laser (Centre Laser Infrarouge d'Orsay (CLIO), France)  have been used in our studies. Results of experiments on collisions of enantiopure amino acids, namely phenylalanine (Phe), tryptophan (Trp), and methionine (Met) with chiral and achiral targets in high and low energy regimes are presented. The fragmentation process is discussed in detail and compared with generally accepted models of amino acid fragmentation. Formation of proton bound diastereomeric adducts of amino acid and chiral alcohols (2-butanol and 1-phenylethanol) in single collisions is reported. The emphasis was given to reveal stereochemical effects in above mentioned reactions. The structure and vibrational properties of diastereomeric dimers of tryptophan studied using infrared multiphoton dissociation (IRMPD) spectrometry are presented. Structures and energies of most stable conformers obtained with quantum chemical calculations are described and compared to the experimental data. The stereo-dependent features are underlined and the chiral discrimination using IRMPD is addressed.

  • Disputation: 2018-10-26 10:00 David Magnussonsalen (U31), Stockholm
    Cornell Kärnekull, Stina
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen.
    Auditory and Olfactory Abilities in Blind and Sighted Individuals: More Similarities than Differences2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Blind individuals face various challenges in everyday life because of the lack of visual input. However, since they need to rely on the non-visual senses for everyday tasks, for instance, when navigating the environment, the question has been raised as to whether perceptual and cognitive abilities in these senses may be enhanced. This question has mainly been addressed for auditory and tactile abilities, whereas there is considerably less research into the chemical senses, such as olfaction. However, to determine whether blindness has general effects, different senses and types of tasks should be studied, preferably in one and the same study. Therefore, throughout this thesis, analogous auditory and olfactory tasks that varied in cognitive complexity were studied. In Study I, absolute thresholds, discrimination, identification, episodic recognition (i.e., after a short retention interval), metacognition, and self-reported imagery ability were assessed in early blind, late blind, and sighted participants. The only objective measure on which the blind and sighted clearly differed was the auditory episodic recognition task. The fact that early blind but not late blind participants displayed better memory than the sighted suggested that the onset age of blindness may be important for whether this ability becomes enhanced following blindness. Furthermore, the early blind participants rated their auditory imagery ability higher than the sighted, whereas both early and late blind participants rated their olfactory imagery ability higher than the sighted. In Study II, the participants from Study I were followed up after more than a year and retested on auditory and olfactory episodic recognition and identification. This time, the early blind displayed no advantage over the sighted, suggesting that the influence of blindness on auditory memory may be modulated by the length of the retention interval. Moreover, in line with Study I, identification of sounds and odors was similar in the three groups. In Study III, early blind and sighted participants were examined for potential differences in autobiographical memory as evoked by sounds and odors, respectively. Blindness did not influence the reminiscence bumps (i.e., memory peaks in certain age intervals) or have any clear impact on the number of retrieved sound- or odor-evoked memories. Taken together, the present findings indicate that blindness has no general influence across tasks or sensory modalities. Rather, specific auditory abilities, such as episodic memory, may be enhanced in blind individuals, although such effects may depend on both the onset age of blindness and the length of the retention interval. In conclusion, for most perceptual and cognitive abilities examined, performance seemed unaffected by blindness.