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Immunomodulation during human pregnancy : placental exosomes as vehicles of immune suppression.Stenqvist, Ann-Christin January 2014 (has links)
The mammalian pregnancy comprises a challenge to the maternal immune system since the fetus is semi-allogeneic and could thus be rejected. Pregnancy success is associated with the placenta that is not only essential for oxygen supply, nourishment and pregnancy hormones but also plays a role in the protection of the fetus against maternal immunologic attack. The aim of the current studies was to elucidate the role of human placenta as an immunomodulatory organ with a special focus on placental exosomes as vehicles for establishment of maternal tolerance to the fetus. We discovered that the syncytiotrophoblast in human normal pregnancy constitutively produces and secretes exosomes. Exosomes are 30-100 nanometer-sized membrane vesicles of endosomal origin that convey intercellular communication. Exosomes are produced and released through the endosomal compartment and reflect the type and the activation state of the cells that produce and secrete them. They carry cytosolic and membrane-bound proteins and nucleic acids and can influence and re-program recipient cells. Depending on their interactions with cells of the immune system they can be divided into immunostimulatory or immunosuppressive. We developed methods for isolation and culture of trophoblast and placental explants from human normal first trimester pregnancy and isolated exosomes from the culture supernatants. These exosomes were characterized biochemically and functionally regarding mechanisms with potential importance in the establishment of maternal tolerance towards the fetus. The following aspects were studied: 1) exosomal modulation of the NKG2D receptor-ligand system, a major cytotoxic pathway for NK- and cytotoxic T cells and thus potentially dangerous to the fetus; 2) placental exosome-mediated apoptosis of activated immune effector cells; and 3) Foxp3-expressing T regulatory cells in human pregnant uterine mucosa, the decidua. Using immuno electron microscopy we show that human early syncytiotrophoblast constitutively expresses the stress-inducible NKG2D ligands MICA/B and ULBP1-5, and the apoptosis inducing molecules FasL and TRAIL. While MICA/B were expressed both on the cell surface and intracellularly on the limiting membrane of multivesicular bodies (MVB) and on exosomes, the ULBP1-5, FasL and TRAIL were solely processed through the MVB of the endosomal compartment and secreted on exosomes. The NKG2D ligand-expressing placental exosomes were able to internalize the cognate receptor from the cell surface of activated NK- and T cells thus down regulating their cytotoxic function. In our studies of apoptosis we found that placental exosomes carry the proapoptotic ligands FasL and TRAIL in their active form as a hexameric complex of two homotrimeric molecules, required for triggering of the apoptotic signaling pathways. This finding was supported by the ability of isolated placental FasL/TRAIL expressing exosomes to induce apoptosis in activated peripheral blood mononuclear cells (PBMC) and Jurkat T cells. Additionally, we studied Foxp3-expressing T regulatory (Treg) cells in paired human decidual and blood samples from pregnant women compared to non-pregnant controls. The CD4+CD25+Foxp3+ Treg cells were 10 fold enriched in the decidual mucosa compared to peripheral blood of pregnant women and non-pregnant controls. We discovered a pool of Foxp3-expressing, CD4+CD25- cells in human decidua, a phenotype consistent with naïve/precursor Foxp3+ Treg cells. These results suggest local enrichment of Treg cells in decidua of normal pregnancy. Furthermore, we have results indicating that the exosomes, isolated from placental explant cultures, carry PD-L1 and TGFβ on their surface, molecules known to promote induction of Treg cells. Taken together, our results provide evidence that placental exosomes are immunosuppressive and underline their role in the maternal immune modulation during pregnancy. The constitutive production and secretion of immunosuppressive placental exosomes create a protective exosomal gradient in the blood surrounding the feto-placental unit. This “cloud of immunosuppressive exosomes” conveys immunologic privilege to the developing fetus and thus contributes to the solution of the immunological challenge of mammalian pregnancy.
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AWARENESS OF PRIVILEGE AND OPPRESSION SCALE-2: CONSTRUCTION AND INITIAL VALIDATIONMcClellan, Michael J 01 January 2014 (has links)
The purpose of this study was to revise the Awareness of Privilege and Oppression Scale (Montross, 2003) and to improve upon the psychometric properties of the original instrument. The APOS-2 is a diversity training outcome measure that is designed to measure the social justice-related construct awareness of privilege and oppression. I retained 26 items from the original APOS (Montross, 2003) and utilized an expert focus group to generate new test items for the APOS-2. Feedback from an expert rater group was solicited and then incorporated into the APOS-2 to help reduce the number of items, improve item content, and evaluate content validity. The newly revised scale was then administered to a combined sample of 484 undergraduate students at a large public university through an internet-based survey. Item-analysis procedures and an exploratory factor analysis (EFA) with direct oblim oblique rotation were utilized to further reduce the number of items and then determine the psychometric properties of the final solution. The EFA of the APOS-2 data provided support for the theoretical four-factor solution. The observed Cronbach alpha reliability estimates for the final 40-item total score and subscale scores were as follows: Total score (.92), Awareness of Heterosexism (.84), Awareness of Sexism (.73), Awareness of Classism (.84), and Awareness of Racism (.86). The APOS-2 correlated low and positively (r = .29) with a measure of openness to diversity and negatively and close to zero (r = -.10) with a social desirability measure. These collective data suggest the APOS-2 may be a viable alternative to the original APOS with a stronger initial effort to link item content to the extant literature, improved subscale reliability estimates, continued support for the use of the theoretically derived subscales, and a predictable relationship with measures of convergent and discriminant validity.
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Racializing Spaces: Harlem, Housing Discrimination, and African American Community Repression in the War on DrugsHershewe, Mary 01 January 2013 (has links)
This paper focuses on exploring how housing discrimination and the war on drugs affect the way communities are shaped and viewed. The area of focus is Harlem, but the paper explores these tensions in a general way as well. The paper draws on popular academic theories about racialization.
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Specification And Verification Of Confidentiality In Software ArchitecturesUlu, Cemil 01 March 2004 (has links) (PDF)
This dissertation addresses the confidentiality aspect of the information security problem from the viewpoint of the software architecture. It presents a new approach to secure system design in which the desired security properties, in particular, confidentiality, of the system are proven to hold at the architectural level. The architecture description language Wright is extended so that confidentiality authorizations can be specified. An architectural description in Wright/c, the extended language, assigns clearance to the ports of the components and treats security labels as a part of data type information. The security labels are declared along with clearance assignments in an access control lattice model, also expressed in Wright/c. This enables the static analysis of data flow over the architecture subject to confidentiality requirements as per Bell-LaPadula principles. An algorithm takes the Wright/c description and the lattice model as inputs, and checks if there is a potential violation of the Bell-LaPadula principles. The algorithm also detects excess privileges. A software tool, which features an XML-based front-end to the algorithm is constructed. Finally, the algorithm is analyzed for its soundness, completeness and computational complexity.
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Vit men inte svensk : Andra generationens sverigefinnar i den svenska vithetens marginalBeckman, Stellan January 2018 (has links)
The following thesis explores the racialisation of second generation sweden finns in contemporary Sweden. This is done by applying a theoretical framework from critical race and whiteness studies on 8 interviews with second generation sweden finns. Especially the concept of the margins of whiteness has been of importance for the following study, which allows the analysis to consider both marginality and privilege. The analysis focus on the intersection of the variables of ethnicity, class and race, which allows the racialised position of the 8 informants in the study to be outlined. While the themes of ethnicity and class have ocurred in previous research, the study of race and in particular whiteness, have yet to be applied on sweden finns. As will be revealed through the analysis, there are good reasons to consider Sweden finns as belonging within the margin of swedish whiteness. While there are signs that sweden finns have a position of marginality within swedish society the informants in this study can pass for swedes thanks to being racialised as white in everyday contexts. / Följande masteruppsats undersöker andra generationens sverigefinnars rasifierade position i den svenska vitheten. Detta görs genom att applicera ett teoretiskt ramverk grundat i kritiska ras och vithetsstudier på 8 intervjuer med andra generationens sverigefinnar. Särskilt begreppet vithetens marginal är av betydelse för studiens analys eftersom det har gett analysen möjlighet att analysera privilegier och marginalitet samtidigt. I analysen ligger främst fokus på tre variabler i form av etnicitet, klass och ras, vilket gör det möjligt att måla ut den rasifierade position som studiens 8 informanter har i den svenska vitheten. Emedan teman kring etnicitet och klass varit vanliga inom tidigare forskning kring sverigefinnar, har studiet av ras och med detta vithet, varit frånvarande inom forskningsfältet kring sverigefinnar. Som vi kommer att se i analysen finns det mycket som talar för att sverigefinnar befinner sig i den svenska vithetens marginal. Även om sverigefinnar kan sägas ha en marginell position i det svenska samhället, har de informanter som återfinns i följande studie möjlighet att passera som svenskar eftersom de rasifieras som vita i vardagssammanhang.
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Proceduralizing Privilege: Designing Shakespeare in Virtual Reality and the Problem with the CanonFrisch, David M. 25 March 2016 (has links)
This thesis focuses on the development of the first project for FIU’s ICAVE, The Globe Experience, presented as part of the “First Folio! The Book That Gave Us Shakespeare” exhibit during February, 2016. The thesis is divided into two parts. The first part is the project itself: a virtual reality recreation of going to The Globe Theater to see a play by William Shakespeare. The second part examines the digital project and outlines how Walter Benjamin and postcolonial theorists influenced the design of The Globe Experience, resulting in, what I call, a “temporally and spatially disjointed London.” From this examination, the thesis goes on to question the role of canonical literature in the humanities. I go on to make the argument that the design decisions made in recreating The Globe reveals the ways in which canonical literature can reinforce and support hierarchical ideologies which can impede student learning.
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Advisory Board: Derek SixUniversität Leipzig, University of Miami January 2017 (has links)
Biography and Derek Six''s big five ideas on compliance
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Advisory Board: Marcus TrautUniversität Leipzig, University of Miami January 2017 (has links)
Biography and Marcus Traut''s five supporting pillars of compliance
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Advisory Board: Kenneth TungUniversität Leipzig, University of Miami January 2017 (has links)
Biography and Kenneth Tung''s five big ideas in compliance management
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Mentors: Cheryl E. ZuckermanUniversität Leipzig, University of Miami January 2017 (has links)
Biography of Cheryl E. Zuckerman
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