Zugl.: Heidelberg, Univ., Diss., 2008

Zugleich: Diss. Heidelberg, 2008. / Register. Literaturverz.

Proefschrift--Letteren--Universiteit Leiden, 2005. / Contient un résumé en anglais. Bibliogr. p. 261-275.

Aortic stiffness underlies systolic hypertension, promotes heart failure and is associated with increased cardiovascular morbidity and mortality. It is regarded as a primary driver of left ventricular hypertrophy and aortic aneurysms and is linked to the pathogenesis of cognitive impairment, stroke and renal failure. Like most cardiovascular traits, aortic stiffness is a complex trait and is moderately heritable, yet the precise molecular mechanisms that underpin the stiffening process remain poorly defined. This study aimed to employ multiple approaches to further identify the genetic basis of aortic stiffness in a large repository of human donor aortas that had undergone ex vivo pulse wave velocity (PWV) phenotyping. The first part of this work sought to investigate the molecular basis of Loeys-Dietz type 4 syndrome in a pedigree with multiple cases of aortic aneurysms and dissections. A missense variant p.(Arg320Cys) was identified in a highly evolutionary conserved region of TGFB2. There was striking upregulation of TGFB1, TGFB2 and pSMAD2/3 on imunocytochemical straining and western blotting of the aortic tissue from the index case confirming the functional importance of the variant. This case highlighted the striking paradox of predicted loss-of-function mutations in TGFB2 causing enhanced TGFβ signalling in this emerging familial aortopathy and underscored the significance of TGFβ signalling in aortic extracellular matrix biology. The second part of this work attempted to characterise the biological basis for the susceptibility locus identified in the most recent genome wide analysis of carotid-femoral PWV. While the locus lies within the 14q32.2 gene desert, it contains regulatory elements, with the transcriptional regulator B-cell CLL/lymphoma 11B (BCL11B) and non-coding RNA DB129663 representing potential targets for these enhancers. The association of five lead SNPs from the genome-wide association studies (GWAS) meta-analysis was examined for ex vivo aortic stiffness and BCL11B and DB129663 aortic mRNA expression. Three of the five SNPs associated significantly with PWV and showed allele-specific differences in BCL11B mRNA. The risk alleles associated with lower BCL11B suggesting a protective role for BCL11B. Despite the strong association, BCL11B protein was not detected in the human aorta; however, qPCR for CD markers showed that BCL11B transcript correlated strongly with markers for activated lymphocytes. In contrast, DB129663 transcripts were detected in 55% of the samples, and of the five SNPs only one showed allele-specific differences in aortic DB129663 transcripts. No significant differences were observed in PWV between samples expressing or lack- ing DB129663, and therefore the implication of this lncRNA in aortic stiffness remains elusive. The BCL11B transcript detected in the human aorta may reflect lymphocyte infiltration, suggesting that immune mechanisms contribute to the observed association with PWV. For the final part of this work genetic associations with aortic stiffness were explored in a candidate gene-based study utilising tagging SNPs to effectively capture the genetic information from linkage disequilibrium blocks. Association analyses were performed in young, healthy ENIGMA study par- ticipants selected for high and low PWV values then validated in the remaining ENIGMA cohorts. The association of four lead SNPs was then examined for ex vivo aortic stiffness in human donor aortas. The tissue expression of these SNPs and their encoded proteins was also explored. Neither the aggrecan nor the fibulin-1 SNPs showed significant associations with ex vivo PWV in the donor aortas. The exonic aggrecan tagSNP rs2882676 displayed differential transcript abundance between homozygous allele carriers but this did not translate at the protein level. Both aggrecan and fibulin-1 were found in the aortic wall, but with marked differences in the distribution and glycosylation of aggrecan, reflecting loss of chondroitin-sulphate binding domains. These differences were age-dependent but the striking finding was the acceleration of this process in stiff versus elastic young aortas. These findings suggest that aggrecan and fibulin-1 have critical roles in determining the biomechanics of the aorta and their modification with age could underpin age-related aortic stiffening.

Bakgrund och syfte: Sociala mediers framväxt har lett till uppkomsten av en ny yrkesgrupp kallad influencer. Detta yrke innebär en betydande uppmärksamhet och ett visst ansvar gentemot både sin publik och samhället. För att undvika att skada förtroendet och riskera negativa konsekvenser för sin karriär är det viktigt att agera med eftertanke och vara medveten om konsekvenserna av ens handlingar och uttryck. Denna studie fokuserar på influencern Margaux Dietz, som hamnade i en kontrovers efter att ha publicerat en YouTube-video där hon filmar och dehumaniserar en medvetslös man. Syftet med studien är att undersöka hur en offentlig person använder kriskommunikation för att återupprätta sitt anseende efter en kris. Metod: Studien använder sig av en kvalitativ metod i form av en innehålls- och textanalys, samt de retoriska appellerna ethos, pathos och logos och den retoriska teorin/metoden apologia. Detta är för att undersöka hur hon försöker återupprätta sitt anseende med hjälp av retoriska strategier. Primärdatan består av en dokumentär, en YouTube-video och ett Instagram-inlägg. Resultat och Slutsats: Utifrån innehållsanalysen framgår det att de retoriska argumenten ethos, pathos, och logos är ofta förekommande i hennes argumentation. Samtidigt som hon delvis uppfyller kraven för en idealisk apologia genom dess strategier. Studien visar att Dietz använder sig frekvent av retoriska argumenteringar för att framföra ett meddelande som kan återställa hennes anseende. Däremot tyder studien på att hennes försök till att återupprätta sitt anseende inte lyckats utifrån de strategier hon har använt, eftersom det förekommer för många motsägelser som dementerar hennes ansats. / Background and Purpose: The emergence of social media has led to the rise of a new profession called influencers. This profession entails significant attention and a certain responsibility towards both their audience and society. To avoid damaging trust and risking negative consequences for their career, it is important to act thoughtfully and be aware of the consequences of one's actions and expressions. This study focuses on the influencer Margaux Dietz, who found herself in controversy after posting a YouTube video where she films and dehumanizes an unconscious man. The purpose of the study is to examine how a public figure uses crisis communication to restore their reputation after a crisis. Method: The study employs a qualitative method in the form of content and text analysis, as well as the rhetorical appeals of ethos, pathos, and logos, and the rhetorical theory/method of apologia. This is done to investigate how she attempts to restore her reputation using rhetorical strategies. The primary data consists of a documentary, a YouTube video, and an Instagram post. Results and Conclusion: Based on the content analysis, it is evident that the rhetorical arguments of ethos, pathos, and logos are frequently employed in her arguments. At the same time, she partially meets the requirements of an ideal apologia through its strategies. The study demonstrates that Dietz frequently uses rhetorical arguments to convey a message that can restore her reputation. However, the study suggests that her attempts to restore her reputation have not been successful based on the strategies she has employed, as there are too many contradictions that contradict her approach.

xx, 463 p. : ill., maps. Two print copies of this title are available through the UO Libraries under the call number: KNIGHT E61 .W72 1989 / Western Clovis and Western Stemmed cultural traditions, archaeologically indexed by fluted (Clovis) and stemmed projectile point complexes, represent the earliest human occupation documented in Far Western North America. The temporal closeness of Western Clovis, dated roughly from 11,500 to 11,000 B.P., to Western Stemmed complexes known as early as 11,140 to 10,800 B.P., has generated debate over the age and historical relationship of these cultures. The frequent co-occurrence of fluted and stemmed points along the lowest strandlines in pluvial lake basins has also led scholars to hypothesize an early development of the characteristically "Archaic" lake-marsh adaptations known from later periods. Geoarchaeological research in the northern Alkali Lake Basin of south-central Oregon has addressed these issues of cultural chronology and economy by seeking data to test a paleoecological model of human land use in the basin from 11,500 to 7,000 B.P. The model posits a late Pleistocene Western Clovis settlement oriented to a small, shallow lake or pond, followed by an early Holocene Western Stemmed occupation around a much larger lake and marsh fringe. Data gathered through basin-wide site survey, stratigraphic studies, and high-resolution mapping of lake features and artifacts, support the model as proposed, and reveal a settlement pattern indicative of a "tethered" focus on local lake-marsh habitats. Research also verifies the horizontal separation of fluted and stemmed artifacts on different, sequent shorelines, indicating that Western Clovis occupation precedes Western Stemmed, although the two are close in time. Data from Alkali Basin, and elsewhere, support the notion that Far Western cultures developed broad-spectrum adaptations much earlier than was once thought. This implies that the foundations of the Western Archaic were already in place by 11,000 B.P. In keeping with the adaptive flexibility embodied within the Desert Culture concept, environmental data further suggest that this "paleo-Archaic" lifeway developed quickly, not gradually, in response to punctuated climatic change and the emerging mosaic of regional habitats which characterized the Pleistocene-Holocene boundary, at a time when the desert as we know it was just coming into being. / Adviser: Aikens, C. Melvin

This thesis aims to investigate Swedish PR practitioners’ assessments of and proposed response strategies to the cancellation case of Swedish social media influencer Margaux Dietz. Multiple organisations cancelled their collaborations with Dietz in November 2022 following a criticized video scandal. Furthermore, the thesis aims to examine Swedish PR practitioners’ reasoning of risk in their work with influencer marketing, considering a present “cancel culture”. Two research questions are posed: RQ1: How do Swedish PR practitioners reflect on the cancellation of Swedish social media influencer Margaux Dietz in November 2022, and how would they have handled the situation? RQ2: In what ways do Swedish PR practitioners reflect on the risks of working with influencer marketing in relation to cancel culture? With a sample of nine participants, semi structured interviews were conducted with PR practitioners active in Stockholm, Sweden. The interviews were first analysed through a qualitative content analysis, and thereafter a theoretical framework, consisting of the notion cancel culture as defined by Clark (2020) and Ng (2020), as well as Benoit’s (2015) Image Repair Theory, was applied. Findings suggested that there were five themes present in the interviewees’ responses, (1) Risks of Influencer Marketing, (2) Cancel Culture as Positive, (3) Cancel Culture as Negative, (4) Managing Being Cancelled and (5) Uncertainty. The main conclusions indicated that there was a general uncertainty in practitioners concerning their opinions of the Dietz case. Interviewees both expressed an understanding for and questioned the organisations’ actions in the case, however most would consider cancelling collaborations during similar circumstances themselves due to a need to protect their brands. There was a common reasoning that cancel culture could be limiting and even harmful, and interviewees perceived risks in their work with influencer marketing relating to a loss of control, the human factor and cancel culture.

Studiens syfte är att undersöka vilka diskurser som representeras i dokumentärfilmen "Kan vi förlåta Margaux?” producerad av public service företaget SVT. Vidare undersöks den kritik som diverse nyhetsartiklar har presenterat i samband med dokumentärfilmens publicering. Kritiken som framförs innehåller bland annat uttalanden som berör public service-uppdrag i det svenska samhället och att innehållsvillkor som riktas mot filmproduktionen ej uppfylls. Ovanstående har analyserats och jämförts med innehållsvillkoren som regeringen ställt upp för public service. Studiens empiriska material består av dokumentärfilmen "Kan vi förlåta Margaux?", utvalda nyhetsartiklar som innehåller respons på filmen samt regeringens innehållsvillkor för public service. Metoden som studien använde är Norman Faircloughs tredimensionella modell som har sin grund i den kritiska diskursanalysen. Studiens teoretiska ramverk utgjordes av både teoretiska analysbegrepp från den tredimensionella modellen samt Westerståhls objektivitetsmodell. Resultaten visar vilka teman responsen till dokumentärfilmen berör samt de diskurser som representeras i dokumentärfilmen. Analysen av diskurserna visade bland annat att dokumentärfilmen förhåller sig till de krav och riktlinjer som public service ska följa då de diskurser som dokumentärfilmen skildrar är i linje med de krav om saklighet och opartiskhet som SVT har att förhålla sig till.

The complicated problem of efficient stimulation of elastic fiber production in already developed human tissues has not yet been solved. The present study introduces sodium ascorbate (SA) as a stimulator of elastogenesis in cultures of different cell types including fibroblasts isolated from patients with elastopathy genetic diseases. We then elucidated mechanisms of elastogenic action of SA. SA exercises its net elastogenic effect only after being actively transported into the cell interior through two separate mechanisms. These are the “fast effect,” which reflects the greater stability of intracellular tropoelastin, and the “late effect,” which reflects the true enhancement of the elastin gene expression occurring after SA-induced activation of c-src tyrosine kinase and the consecutive phosphorylation of IGF-1 receptor, which triggers the downstream signals leading to activation of the elastin gene expression. In conclusion, for the first time we have established that SA is a potent stimulator of elastic fiber production.

The complicated problem of efficient stimulation of elastic fiber production in already developed human tissues has not yet been solved. The present study introduces sodium ascorbate (SA) as a stimulator of elastogenesis in cultures of different cell types including fibroblasts isolated from patients with elastopathy genetic diseases. We then elucidated mechanisms of elastogenic action of SA. SA exercises its net elastogenic effect only after being actively transported into the cell interior through two separate mechanisms. These are the “fast effect,” which reflects the greater stability of intracellular tropoelastin, and the “late effect,” which reflects the true enhancement of the elastin gene expression occurring after SA-induced activation of c-src tyrosine kinase and the consecutive phosphorylation of IGF-1 receptor, which triggers the downstream signals leading to activation of the elastin gene expression. In conclusion, for the first time we have established that SA is a potent stimulator of elastic fiber production.