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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
71

Single cell analysis reveals all-or-none G1 arrest decisions upon TGFβ stimulation

Wu, Guoyu 22 May 2019 (has links)
Der transformierende Wachstumsfaktor-β (TGFβ) übt verschiedene Wirkungen auf die Regulierung zahlreicher biologischer Prozesse aus. Insbesondere die zytostatische Wirkung von TGFβ ist wichtig, um die Homöostase in Geweben aufrechtzuerhalten und proliferative Störungen, wie in Krebs, zu verhindern. Frühere Studien zur Regulation des Zellzyklus mit TGFβ wurden auf Populationsebene, oft durch physikalische oder chemische Synchronisation durchgeführt. Dabei wird die Heterogenität auf zellulärer Ebene vernachlässigt und die Anfälligkeit gegen potenzielle Artefakte erhöht. Um zu verstehen, wie einzelne Zellen TGFβ-Signale entschlüsseln und diese in die Entscheidung zur Zellproliferation integrieren, wurden sowohl die Dynamik der TGFβ-Signale als auch die Zellzyklusprogression in asynchronen Zellen durch „Live Cell Imaging“ quantifiziert. In Kombination von experimentellen und theoretischen Studien wurde gezeigt, dass TGFβ einen „Alles-oder-Nichts-G1- Stillstand“ auslöst, der sowohl dosisabhängig als auch phasenabhängig ist. Wenn die Zellen während der S / G2 / M-Phase TGFβ ausgesetzt werden, erfahren sie in der darauf folgenden G1-Phase einen ererbten, verzögerten Stillstand. Zusätzlich sind die Zellen nach einem TGFβ-Stimulationsimpuls für weitere TGFβ-Behandlungen unempfindlich. In Anbetracht der Bedeutung von Einzelzellinformationen und den Herausforderungen bei der automatischen Zellverfolgung wurde ein Rahmenkonzept von „Population to Single Cell“ (P2S-Framework) erarbeitet, um von der Populationsdynamik auf die Abstammung einzelner Zellen zu schließen. Zusammengefasst bietet diese Arbeit neue Einblicke in Strategien zur Kontrolle der Zellproliferation durch Manipulation der TGFβ-Signalgebung. / The transforming growth factor-β (TGFβ) exerts diverse effects on regulating numerous biological processes. Especially, the cytostatic effect of TGFβ is important for maintaining tissue homeostasis and preventing proliferative disorders, like cancer. Previous studies on the regulation of cell cycle by TGFβ were conducted at the population level, and often through physical or chemical synchronization, which neglected cellular heterogeneity and might introduce artifacts. To understand how individual cells decode and integrate TGFβ signals into cell proliferation decisions, we quantitatively characterized both TGFβ signaling dynamics and cell cycle progression in asynchronous cells by live cell imaging. Combining experimental and theoretical studies, we demonstrated that TGFβ triggers all-or-none G1 arrest, which is both dose-dependent and phase- dependent. When exposed to TGFβ during S/G2/M phase, cells undergo an inherited, delayed arrest at the next G1 phase. In addition, after one pulse of TGFβ stimulation, cells are refractory to further TGFβ treatments. Considering the importance of single cell information and challenges in automatic cell tracking, we proposed a Population to Single cell framework (P2S framework) to infer single- cell lineages from population dynamics. Taken together, this work provides new insight into strategies to control cell proliferation by manipulating TGFβ signaling.
72

Biophysical properties of AMPA receptor complexes

Riva, Irene 11 May 2020 (has links)
Die exzitatorische Neurotransmission im gesamten Zentralnervensystem (ZNS) der Wirbeltiere wird weitgehend durch die α-Amino-3-hydroxy-5-methyl-4-isoxazolpropionsäure-Rezeptoren (AMPARs) vermittelt. AMPARs sind Glutamat-gesteuerte Ionenkanäle, die sich an der postsynaptischen Membran befinden, wo sie den Kern makromolekularer Komplexe mit einer Reihe von Hilfsproteinen bilden, die die Rezeptorfunktion konzertiert regulieren. Die bekanntesten dieser Proteine sind die transmembranen AMPA-Rezeptor-Regulierungsproteine (TARPs). TARPs zeigen eine verwirrende Reihe von Effekten auf den Handel, die synaptische Verankerung, die Gate-Kinetik und die Pharmakologie von AMPARs. Über die strukturellen Merkmale des AMPAR-TARP-Komplexes wurde zunehmendes Wissen gesammelt. Die molekularen Mechanismen, die der TARP-Modulation der AMPARs zugrunde liegen, sind jedoch noch nicht vollständig aufgeklärt. In der vorliegenden Studie wurden die AMPAR-TARP-Interaktionen mit Hilfe der Elektrophysiologie in 293 Zellen der menschlichen embryonalen Niere (HEK) untersucht. Die Rolle der extrazellulären TARP-Schleifen, Loop1 (L1) und Loop2 (L2), bei der Modulation der AMPAR-Ansteuerung wurde analysiert. Es wurde ein Modell für die TARP-Modulation vorgeschlagen, das auf vorhergesagten zustandsabhängigen Wechselwirkungen von TARP L1 und L2 mit dem AMPAR basiert. Da die nativen AMPARs im Gehirn hauptsächlich aus heterotetrameren Zusammensetzungen von vier verschiedenen Untereinheiten (GluA1-4) bestehen, wurden außerdem verschiedene Zusammensetzungen von AMPAR-Untereinheiten getestet. Es wurden sowohl gemeinsame als auch von den Untereinheiten abhängige Mechanismen der AMPAR-Modulation durch TARPs beobachtet. Zusammenfassend liefern diese Experimente den Nachweis, dass TARP L1 und L2 nicht an der Assoziation von AMPAR-TARP-Komplexen beteiligt sind und die Modulation der AMPAR-Ansteuerung durch TARPs vollständig erklären können. / Excitatory neurotransmission throughout the vertebrate central nervous system (CNS) is largely mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). AMPARs are glutamate-gated ion channels located at the postsynaptic membrane, where they compose the hub of macromolecular complexes with a number of auxiliary proteins that concertedly regulate the receptor function. Among these proteins the most known ones are the transmembrane AMPA receptor regulatory proteins (TARPs). TARPs show a bewildering array of effects on the trafficking, synaptic anchoring, gating kinetics and pharmacology of AMPARs. Growing knowledge has been gathered about the structural features of the AMPAR-TARP complex. However, the molecular mechanisms underlying TARP modulation of AMPARs have not been fully revealed yet. Given that higher brain functions rely upon AMPAR activity and dysregulation of AMPARs has been associated to life-threatening CNS disorders, big efforts are being made to unravel the molecular machinery behind AMPAR regulation and to identify AMPAR auxiliary proteins as potential pharmacological targets. In the present study, AMPAR-TARP interactions were investigated using electrophysiology in human embryonic kidney (HEK) 293 cells. The role of TARP extracellular loops, Loop1 (L1) and Loop2 (L2), in the modulation of AMPAR gating was analysed. A model for TARP modulation has been proposed, based on predicted state-dependent interactions of TARP L1 and L2 with the AMPAR. Moreover, considering that native AMPARs in the brain mainly consist of heterotetrameric assemblies of four distinct subunits (GluA1-4), different AMPAR subunit compositions were tested. Common as well as subunit-dependent mechanisms of AMPAR modulation by TARPs have been observed. In summary, these experiments provided evidence that TARP L1 and L2 are not involved in association of AMPAR-TARP complexes and can entirely account for the modulation of AMPAR gating by TARPs.
73

"Vi och dom" - ett pedagogiskt tillvägagångssätt? : En kvalitativ studie av lärares erfarenheter och åsikter kring kategoriseringen "vi och dom" inom religionsundervisningen / "We and them" - a pedagogically approach?

Gerdin, Elin, Ali, Shang January 2016 (has links)
To categorise people is by society viewed as a basic cognitive process. The process is described to occur frequently. The purpose of this study was to investigate teachers experience and views concerning the categorization "we and them", and its relationship to the education of religion. The study aims to explore how the categorisation is expressed and valued. The study also aims to investigate the relationship between the teaching and the student groups heterogeneity/homogeneity, but also the relationship between the categorisation and the teaching. The data was conducted true semi-structured interviews with experienced teachers. The results of the study showed that "we and them" exist in the education of religion. The results of the study did not show an unambiguous perception of how the categorisation is expressed and viewed. The result also showed that the heterogeneity, alternatively homogeneity, of the student groups affects the education. The result also showed that the categorisation is affected by the heterogeneity or homogeneity, of the student groups. / Att kategorisera människor betraktas i den samtida kontexten som en av människans grundläggande kognitiva processer. Kategoriseringen och därmed indelning av människor är en ständigt pågående process. Syftet med denna studie är där av att undersöka i vilken utsträckning kategoriseringen av ett "vi" tillika ett "dom" är påtaglig i dagens religionsundervisning. Studien ämnar att undersöka religionslärares erfarenheter och åsikter kring en eventuell kategorisering av "vi och dom " i religionsundervisningen. Studien syftar till att undersöka hur en eventuell kategorisering av "vi och dom" yttrar sig och hur kategoriseringen värderas. Tillika syftar studien till att undersöka hur religionsundervisningen påverkas om elevgruppen är heterogen alternativt homogen, samt vilken betydelse heterogena-/homogena elevgrupper spelar för den eventuella kategoriseringen. Empirin erhölls genom semistrukturerade intervjuer med erfarna religionslärare. Studiens resultat visade att kategoriseringen "vi och dom" existerar i religionsundervisningen. Resultatet visade inte på någon entydig uppfattning rörande hur kategoriseringen yttrar sig tillika värderas. Vidare visade resultatet att religionsundervisningen påverkas utifrån elevgruppens heterogenitet alternativt homogenitet. Resultatet visade tillika att kategoriseringen "vi och dom" yttrar sig på olika vis, beroende på om religionsundervisningen bedrivs i en heterogen- eller en homogen elevgrupp.
74

Myth in the Fiction of C. S. Lewis

Miller, Ruth Humble 08 1900 (has links)
In both his fiction and non-fiction, Lewis comments on myth, its characteristics and strengths, and its relation to Christian doctrine. His use of myth to examine and to illustrate Christian ideas is most important in the space trilogy, the Narnia series of children's books, and Till We Have Faces. These books are the primary sources for this thesis, and they will be examined in chronological order.
75

In the right mirror: we are all gods

Koehn, Aaron 25 April 2014 (has links)
I look to the common and mundane as sources for inspiration and imagination. In an attempt to evolve a veneer away from representing a coveted material, I have taken phenomenological events from my own personal experience and have searched for commonalities with them to create a new idea for veneering. My exploratory use of Google as a grammar-less machine deciphers the very nature of naming and its ambiguous attachment to an image. I am interested in the multiplicity of personal associations that become attached to images, and the subjectivity thus involved in the naming of an image.
76

“You are a political soldier” : the people’s war in N’wamitwa 1989-1994

Lundeberg, Faelan 30 August 2019 (has links)
In the waning days of apartheid, an operative of Umkhonto we Sizwe, the armed wing of South Africa’s most powerful dissident organization the African National Congress, returned to his home community of N’wamitwa after over a decade in exile. His mission was to spark a people’s war, an imported form of revolutionary warfare developed by Mao Zedong and perfected by the North Vietnamese in their revolutionary struggles. In this thesis I examine the political context in which the ANC chose to adopt the strategy and how it was imported into South Africa. The later chapters of this thesis use N’wamitwa as a case study examining how a people’s war is successfully implemented on the ground. I argue that one can see the three phases of a people’s war as articulated by Mao play out in N’wamitwa between the years 1989 to 1994 This piece was largely written and researched using oral testimony from nine former members of the MK in N’wamitwa and thus can also be seen as a collection of personal histories of the South African Freedom Struggle. / Graduate
77

Unfinished lives: The biographies of Nokuthula Simelane

Abrahams, Brent Nicholas January 2018 (has links)
Magister Artium - MA (History) / Nokuthula Simelane, born near Bethal in Mpumalanga, joined the ANC's armed-wing uMKhonto we Sizwe (MK) as a courier while studying at the University of Swaziland in the early 1980s. In 1983 she set out on a mission to South Africa on the pretext of purchasing clothing for her up-coming graduation. Simelane was however abducted, and has since not been heard from nor has her body been found. Her disappearance was one of those examined by the Truth and Reconciliation Commission (TRC) of South Africa. These are some facts about Simelane. This thesis seeks to explore how Simelane's biographies manifest themselves across multiple genres and in so doing determine their similarities and differences, with a view to understanding the difficulties of producing the biography of a missing person. The genres of biography I examine relation to Simelane are: the TRC's Amnesty Committee (AC) hearings, the Human Rights Violations Committee (HRVC) hearing, their transcripts and the TRC reports; a documentary film called Betrayal directed by Mark Kaplan; and a statue of Simelane located in Bethal sculpted by Ruhan Janse van Vuuren.
78

Det glorifierade Sverige : en kvalitativ studie om nationalism i två tidningars miljöjournalistik

Georgsson, Elin, Nord, Gustav January 2008 (has links)
<p><p>This study searches for hidden nationalism in two Swedish news papers’ environmental journalism. How it contributes to a national identity and creates “we” against “them”.</p><p>The purpose of this study is to show how important it is to be aware of what picture Swedish media gives of Sweden concerning environmental journalism to the readers.</p><p>The theories are based on nationalism, banal nationalism, medias and identities and “we” and “them”. The method used is critical discourse analysis where language and power is in focus.</p><p>We analysed 56 texts in two of the largest Swedish news papers.</p><p>We searched for signs proving that Swedish media glorifies Sweden within environmental journalism.</p><p>The most important result was that we so obviously could see signs of “we” and “them”. That contributed to signs of nationalism and Swedish identities.</p><p>We found that if you keep writing about Sweden when it is good and not write when it is bad you will give the readers a glorified picture. This picture can in turn cause the people to feel that the environmental issues are distant. Through constant writing about other countries failure, Sweden’s good performance and our Swedish children’s future the Swedish identity is strengthened.</p></p>
79

Companionate Lives and Consonant Voices in We Two Together: The 1950 Dual Autobiography of Irish and Indian Reformers Margaret and James Cousins

Copland, Jennifer D 26 November 2012 (has links)
This thesis explores We Two Together, the unique dual autobiography of the reformers Margaret and James Cousins. It places this rich text in the context of the first half of the twentieth century and demonstrates its value as a source for Irish, Indian, gender, and global history. It investigates how the Cousinses represent their efforts to create and maintain a companionate marriage over a lifetime, depict their work as activists for women’s suffrage, Indian nationalism, educational reform, and other causes, and recount the impact of cross-cultural encounters on their cosmopolitan lives. We Two Together provides insight into the lives of two extraordinary individuals as they witnessed and participated in several key social and political movements in Ireland and India. In bringing attention to this book, I hope that other historians will make use of it and that librarians will preserve the rare copies in their possession.
80

Det glorifierade Sverige : en kvalitativ studie om nationalism i två tidningars miljöjournalistik

Georgsson, Elin, Nord, Gustav January 2008 (has links)
This study searches for hidden nationalism in two Swedish news papers’ environmental journalism. How it contributes to a national identity and creates “we” against “them”. The purpose of this study is to show how important it is to be aware of what picture Swedish media gives of Sweden concerning environmental journalism to the readers. The theories are based on nationalism, banal nationalism, medias and identities and “we” and “them”. The method used is critical discourse analysis where language and power is in focus. We analysed 56 texts in two of the largest Swedish news papers. We searched for signs proving that Swedish media glorifies Sweden within environmental journalism. The most important result was that we so obviously could see signs of “we” and “them”. That contributed to signs of nationalism and Swedish identities. We found that if you keep writing about Sweden when it is good and not write when it is bad you will give the readers a glorified picture. This picture can in turn cause the people to feel that the environmental issues are distant. Through constant writing about other countries failure, Sweden’s good performance and our Swedish children’s future the Swedish identity is strengthened.

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