Till följd av skiftet i svensk migrationspolitik efter ökningen av antalet flyktingar som kom till Sverige som skedde under 2015 blev det svenska civilsamhället tvunget att mobilisera både praktiskt och politiskt. Praktiskt skedde mobilisering genom olika former av direkt solidaritetsaktioner. Politiskt skedde mobiliseringen genom att debattera för att förkasta den nya hårdare svenska flyktingpolitiken. Det är i det politiska förändringsarbetet som den här uppsatsen gör sitt nedslag, med fokus på de diskurser som organisationer i det svenska civilsamhället kommit att bruka till stöd för de människor som flytt till Sverige. Metoden uppsatsen använt för att kartlägga och diskutera dessa politiska diskurser, både i förhållande till varandra och hegemoniska diskurser, är kritisk diskursanalys. Uppsatsen syfte är att genom en sådan språklig analys skapa kunskapsmässiga verktyg som den svenska flyktingsolidaritetsrörelsen kan använda för att skydda kortsiktigt och långsiktigt fungerande väg framåt.

Introdução: A modulação da resposta imune em muitas situações clínicas persiste como um dos problemas mais desafiadores em imunologia. Citocinas são fundamentais para esta regulação e são amplamente estudadas. Após a ligação com receptores específicos na superfície das células alvo, uma das principais vias de sinalização é o sistema JAKs/STATs. No entanto, em contraste com as citocinas, não existem estudos detalhados sobre a cinética expressão intracelulares de STAT in vitro. Objetivo: Determinar por citometria de fluxo, a cinética expressão de proteínas STAT 1, 3, 4, 5 e 6 fosforiladas, a produção de citocinas associadas e expressão de seus receptores em PBMC humanas estimuladas in vitro com fito-hemaglutinina (PHA) e antígeno de citomegalovírus (CMV). Metodologia: Foram avaliados CMNs de 23 doadores saudáveis em relação à cinética de expressão STATs (12 doadores estimulados com PHA e 11 estimulados com CMV), secreção de citocinas e expressão de seus receptores. Resultados: Em células estimulada com PHA e CMV, pSTAT1 e 6 tiveram sua expressão aumentada precocemente (4h e três dias, respectivamente). pSTAT3 teve sua expressão aumentada em momentos posteriores (respectivamente 36h e 6 dias). A indução de expressão de pSTAT4 e 5 foi observada nos tempos mais tardios da cinética em células estimuladas com PHA (24-36h), enquanto observamos constante baixo nível de expressão em todos os tempos analisados em células estimuladas com CMV. No que diz respeito á secreção de citocinas em células estimuladas com PHA, níveis maiores de IL-6, IL-10 e IL-4 foram detectados a partir de 12h, enquanto aumento da secreção de IFN-y e IL-2 ocorreu a partir de 24h. Com CMV, apenas IL-6 mostrou um aumento da secreção nos dias 4 e 6. Os receptores de citocinas CD119 (IFN-g), CD126 (IL-6), CD210 (IL-10), CD212 (IL-12), CD25 (IL -2) e CD124 (IL-4) tiveram um aumento da expressão após 24-36h de estimulação com PHA. Com estímulo de CMV, CD126, CD212, CD25, também aumentaram a expressão em tempos tardios (5-6 dias), enquanto os outros receptores mantiveram níveis baixos de expressão em todos os momentos estudados. Discussão: Houve uma correlação entre a cinética de expressão de pSTAT3 e 5, e a cinética das citocinas associadas e de seus receptores (IL-6 / CD126, IL-10 / CD210 e IL-2 / CD25). A cinética de expressão de pSTAT4 se correlacionou com a expressão de CD212. (IL-12p70 não foi detectada no presente estudo). Entretanto a expressão de pSTAT1 e 6 precedeu à de IFN-y / CD119 e IL-4 / CD124. Conclusão: A determinação da cinética de expressão pSTAT in vitro pode contribuir para a compreensão da regulação da resposta imune a patógenos distintos e, potencialmente, ajudar no desenvolvimento de novos alvos terapêuticos bem como de novas estratégias destinadas a modular as vias de sinalização em diversas condições clínicas associadas à desregulação imunológica / Introduction: Modulation of immune responses in many clinical situations persists as one of the most challenging issues in immunology. Cytokines are fundamental to this regulation and have already been extensively studied. After binding with its specific receptors on the surface of the target cells, the main signaling pathway is the JAKs/STATs system. However, in contrast to cytokines, there are no detailed studies on the in vitro intracellular expression kinetics of STATs. Objective: To determine by flow cytometry the kinetics of phosphorylated STAT1, 3, 4, 5 and 6 proteins expression in human PBMCs in vitro stimulated with phytohemagglutinin (PHA) and cytomegalovirus antigen (CMV), and the associated cytokine production and cytokine receptors expression. Methodology: We evaluated PBMCs from 23 healthy donors regarding the kinetics of STATs expression (12 donors stimulated with PHA and 11 stimulated with CMV), cytokine secretion and respective receptors expression. Results: In PHA and CMV stimulated cells, pSTAT 1 and 6 expression increased early, 4h and 3days respectively). pSTAT3 expression augmented at later times (respectively 36h and 6 days). pSTAT4 and 5 expression were observed late in PHA stimulated cells (24-36h), while there was a constantly low level of expression in all times analyzed. Regarding cytokine release In PHA stimulated cells, IL-6, IL10 and IL-4 secretion started to increase at 12h while IFN-y and IL-2 increased at 24h. With CMV, only IL-6 showed increased expression at days 4 and 6. The cytokines receptors CD119 (IFN-g), CD126 (IL-6), CD210 (IL-10), CD212 (IL-12), CD25 (IL-2) and CD124 (IL-4) had increased expression at 24-36h with PHA stimulation. With CMV stimulation, CD126, CD212, CD25 also had increased expression at late times (5-6 days) while the other receptors maintained low expression levels at all times. Discussion: There was a correlation in between the pSTAT3 and 5 expression kinetics and the associated cytokines and cytokine receptors kinetics (IL-6/CD126, IL-10/CD210 and IL-2/CD25. pSTAT4 expression kinetics correlated with that of CD212 expression (IL-12p70 was not detected in the present study). The higher pSTAT1 and 6 expressions preceded that of IFN-y/CD119 and IL-4/CD124, respectively. Conclusion: Determination of pSTAT expression kinetics in vitro can contribute to the understanding of the regulation of immune responses to distinct pathogens and potentially help in the design of new therapeutic targets as well as new strategies aimed at modulating signaling pathways

Drug resistant strains of Clostridium difficile are a major health concern with over 3 million cases costing over 1 billion $ per year in the United-States. The diseases associated with these bacteria (CDAD) are toxin-mediated which offers a mean of treating and lessening the severity of CDAD symptoms. Toxin inactivation via antibodies therapy can drastically reduce CDAD morbidity and this project was aiming at investigating the large-scale production and recovery of a novel llama single domain antibody (pSJF2H-ToxA5.1) in recombinant Escherichia coli TG1 targeting C. difficile enterotoxin A (TcdA). In order to achieve these objectives, the project was divided into four segments: 1) ToxA5.1 being an intracellular recombinant protein, obtaining a high biomass production was the first step towards large-scale production. To achieve HCDC, effects of initial glucose concentration and pH-stat feeding strategy were studied; 2) Upon achieving HCDC, effects of parameters such as temperature, induction timing and media supplementation with complex nitrogen sources were investigated; 3) Once large-scale production of ToxA5.1 was obtained, the recombinant protein needed to be recovered and a selective cell lysis scheme where synergistic lysis effects of Triton X-100 and temperature were studied. And finally 4) Single-step purification using nickel nanoparticles (NNP) synthesized via a modified polyol method was studied. Combining the HCDC strategy with a temperature shift and yeast extract addition at the time of induction, ToxA5.1 concentration of 127 mg/L was obtained. Synergistic and selective cell lysis using Triton X-100 and temperature was achieved where 95% of the available ToxA5.1 was recovered and still functional while ToxA5.1 fraction in the resulting lysate increased to 27% in the cell lysate. Single-step purification was achieved using the synthesized NNP which proved to be highly selective and could be used up to five times. Diameter of the NNP synthesized was controlled by using various concentration of ranging from 131 ± 80 nm to 47 ± 20 nm. Using experimental data from binding isotherm, the ToxA5.1-NNP system was modeled.

Lebanon is seen as a failed state by the international community and this study aims to look at the causes that have made Lebanon dysfunctional. The study uses Andrej Lijpharts consociational power sharing model and the international relations theory realism to analyse the internal and external causes that have made Lebanon a failed state. The study is based on interviews from the three major sects in Lebanon and a text analysis. The study shows that Lebanon is suffering from a corrupt elite that uses the state institutions to benefit their own families. The elite uses clientelism by manipulating consociational power sharing to make the ethnoreligious groups dependant on the elite’s own success. Different regional and international powers use Lebanon in their struggle for power and dominance over the Middle East. The external actors support different ethnic and religious groups by financing and arming them. That in turn deepens the divide between the sectarian groups and hinders the political progress.

The purpose and aim of this study is to offer a hitherto lacking perspective on the Sulu Archipelago’s history during the early years of American colonial rule – that of the native Sulu Sultan. Existing research, albeit new, tends to favour a U.S centred view. With concurrences as a theoretical framework and a theoretical understanding of the social and political power dynamics in the Sultanate, this study aims to challenge that perspective by examining the last Sultan of Sulu, Jamalul Kiram II’s agency and room for manoeuvre in relation to the bilateral Kiram-Bates treaty between the Sultanate of Sulu in the southern Philippines and the United States, represented by Colonel John C. Bates. Through a qualitative analysis of letters, official documents and a memoire originating from, or regarding, the time period, this study indicates that the Sultan’s agency and room for manoeuvre in relation to the Kiram-Bates treaty has been overlooked by scholars, and his position somewhat poorly understood. The Sultan did not simply sign the treaty according to American wishes. He negotiated terms, and influenced the outcome of above all the signing, and he at least reacted to and navigated the abrogation of the agreement in a way that has not been sufficiently described before. These findings prompt further research from a concurrences perspective to more thoroughly understand the history, and perhaps even the contemporary state, of the Sulu Archipelago and the Sulu Sultanate.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第22508号 / 農博第2412号 / 新制||農||1078(附属図書館) / 学位論文||R2||N5288(農学部図書室) / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 加納 健司, 教授 三芳 秀人, 教授 宮川 恒 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

PhD (Microbiology) / Department of Microbiology / Background Conversion of Cholesterol to 25-HydroxyCholesterol (25HC) by Cholesterol 25-hydroxylase (CH25H) has been shown to exert broad antiviral properties. Given its antiviral activities, CH25H is part of an increasingly appreciated connection between type I interferon (IFN-I) and lipid metabolism. Moreover, the details of this connection appear to differ in mouse and human cells. Nevertheless, the molecular basis for the induction of CH25H in humans is not known. Objective Elucidation of signaling and transcriptional events for induction of CH25H expression is critical to design therapeutic antiviral agents. Materials and methods: Wildtype THP-1 monocytic cell-line or THP-1 MyD88 Knockout cell-line were treated with PMA for 72 hours for differentiation into macrophages. Differentiated macrophages or Microglial cells were stimulated with either TLR-agonists, pro-inflammatory cytokine, or interferons, and CH25H mRNAs expression levels were measured by qPCR. Results In this study, we show that CH25H is induced by Zika virus infection or TLR stimulation. Interestingly, CH25H is induced by pro-inflammatory cytokines including 1L- 1, TNF-, and IL-6, and this induction depends on STAT-1 transcription factor. Additionally, we have observed that ATF3 weakly binds to the CH25H promoter, suggesting co-operation with STAT-1. However, ZIKV induced CH25H was independent of type I interferon. Conclusion This study has demonstrated for the first time that pro-inflammatory cytokines such as 1L-1, TNF-, and IL-6 induce CH25H expression. Moreover, this provides further understanding to the connection between innate immunity and sterol metabolism and encourages the exploration of cytokines in antiviral immunity. / NRF

Hållbar planering är idag ett allmänt vedertaget koncept inom samhällsplaneringen och den offentliga förvaltningen. Kommuner, regioner och statliga verk fokuserar alltmer sina strategiska inriktningar kring planeringsåtgärder som är tänkta att främja hållbarhet. Genom nationella miljömål och planeringsmässiga inriktningar som syftar till att möjliggöra för ett mer energisnålt samhälle ska samhällsplaneringen dra sitt strå till den gemensamma samhälleliga staken i kampen mot att reducera utsläppen. Samtidigt höjs kritiska röster mot vad hållbarhet egentligen betyder och innebär för planeringen. Vissa menar att konceptet i sig är fuzzy eller vagt med mångtydiga definitioner och betydelser. Kan då olika planeringsnivåer med olika särintressen att bevaka enas om gemensamma inriktningar för planeringen på både en konceptuell nivå och i den faktiska verkligheten. Med hjälp av en enfallsstudie kommer denna studie att jämföra de konceptuella inriktningarna för tre olika planeringsnivåer inom den svenska förvaltningen (region, stat och kommun). Till grund för studien ligger ett analytiskt ramverk förankrat i teoribildning kring policyintegrering. Genom det analytiska ramverket har det empiriska materialet, beståendes av olika dokument kopplat till hållbar planering och samverkan, bearbetats för att kunna analysera hur pass väl olika planeringsnivåers policys matchar och vilka genomslag de får i praktiken. Fallet utgår från en kommunal kontext, nämligen Höganäs kommuns översiktsplaneprocess. Det utmärkande draget för denna är att en central planeringsfråga för kommunen rör en statlig väg som, enligt kommunen, klyver flertalet tätorter. Hållbar planering, i en samhällsbyggnads kontext, kretsar i mångt och mycket kring frågor som förtätning och transportplanering. Detta göra att studiens fall skapar ett spänningsfält mellan policy och särintresse vilket gör det särskilt intressant att studera.  Studien visar att på ett övergripande konceptuellt plan finns det stor samsyn för vad hållbar planering är rent konkret. De gemensamma nationella målen hjälper till att skärpa ett visst fokus för de konkreta planeringsinriktningarna. Det konstateras också att samsynen delvis splittras när konceptet möter kontexten då de specifika särintressena tar över. Samtidigt går det även att konstatera att samtliga aktörer kan motivera sina olika inriktningar utifrån hållbar planering, vilket förstärker synen på hållbarhet som ett fuzzy concept.

Since roughly the 1990s, Sweden's labor market has consisted of comparatively few labor conflicts and a good real wage trend. Mediation has been highlighted as an important conflict resolution mechanism, and in relation to other Nordic countries' mediation authorities, Sweden's has historically been the weakest with the least power. In 2000, however, Sweden got a new mediation authority – The Swedish National Mediation Office (Medlingsinstitutet) – with a broader mandate than its predecessor. Today, Medlingsinstitutet must not only mediate in labor disputes, but also to promote an efficient wage formation process and be responsible for wage statistics. The purpose of this essay has been to study, through a text analysis and from an organizational perspective, how Medlingsinstitutet organizes the Swedish labor market. It has been carried out based on the premise that previous research, but without mentioning Medlingsinstitutet, believes that the Swedish state, through market-active authorities, has a central function to play in the organization of the markets today. The results show that Medlingsinstitutet appears to influence and organize the Swedish labor market, more or less and with varying severity, based on all of the methods considered in this study: information, different forms of analysis, rules, membership, hierarchy, monitoring and sanctions. The methods seem to be primarily directed at certain specific market elements: buyers and sellers, the exchange, and the price. The survey shows a pattern that Medlingsinstitutet is involved in organizing how the labor market can, should and will function. Thus, I argue that the Swedish state is not only an important market organizer in a free market society, but also in the labor market where the principle of freedom from state intervention has been pervasive. However, there is nothing that gives the impression that the labor market is now only controlled by organization, or only by the market itself, but rather with the help of both systems – the invisible and the visible hand.

Pulmonary arterial hypertension (PAH) is a rare, devastating disease with no cure. Current treatment consists of a cocktail of vasodilators which relieve symptoms of PAH but do not treat the cause. Thus, there is a need for novel drugs that target the underlying pathological causes of PAH. PAH is a multi-factorial, but one key contributor is the pro-inflammatory cytokine IL-6 which stimulates pro-inflammatory and pro-angiogenic signalling mediated by the JAK/STAT pathway. One way in which IL-6 signalling via JAK/STAT is inhibited is via SOCS3 in a type of negative feedback loop whereby IL-6 induces transcription of SOCS3, which then attenuates further JAK/STAT signalling. SOCS3 can also be induced by cAMP. This is interesting as prostanoids, a type of drug used in the treatment of PAH due to its vasodilator effects and the only type to show any efficacy improving the life expectancy of PAH patients, acts by mobilising cAMP. Thus, prostanoid stimulation of cAMP could potentially limit IL-6 signalling via the induction of SOCS3. This is a novel mechanism of prostanoids which has not previously been considered. This study investigated the capability of prostanoids to limit the pro-inflammatory/pro-angiogenic effects of IL-6 that enable PAH to develop. Initial experiments confirmed that vascular endothelial cells responded to prostanoids which increased SOCS3 and limited IL-6 signalling activity. Further experiments utilising SOCS3 KO endothelial cell models demonstrated prostanoid inhibition of IL-6 signalling was due in part to SOCS3. In conclusion, this project has confirmed that prostanoids do limit the pro-inflammatory effects induced by IL-6 and that this is in part due to SOCS3. Although the exact mechanism is yet to be discovered, it will be beneficial in the treatment of PAH as it provides currently unexploited drug targets which can be considered for future PAH therapies. / British Heart Foundation