The challenge of the just war theory in the post-modern era is compounded by technologic advances in warfare and the friction among state actors in a decentralized state system. The inquiry of this investigation on just war is the extent of its validity in an era that extols the sciences and human reason on the one hand and economic necessity on the other as the standard by which state actors regulate their political objectives. The thesis Just war; unjust consequences examines the longevity of the just war tradition, its moral necessity throughout history and its indispensable application in the nuclear age. Chapter 2 examines the moral foundations of the ‘two kingdoms’, which formulates the background of the just war theory, from the biblical account of the great controversy between good and evil to the formation of modern church/state relations. Within the ancient and contemporary setting, ecclesiastical and theological traditions have provided a public platform to establish moral parameters in regards to state actor intent and post-modern application, such as the U.S.-Iraq war. Chapter 3 investigates Augustine’s enduring contribution to the moral and historical formation and longevity of the just war theory. From its earliest development to its modern antecedent the just war theory has been an integral aspect of the philosophical and theological analysis distinguishing ‘why’ and ‘how’ wars are fought and the import of moral parameters to manage international conflict. Chapter 4 examines Reinhold Niebuhr’s contribution to the realist tradition and U.S. foreign policy in the 20th and 21st centuries. This section examines the impact of the modern state actor’s intent for war. The primary issue is that the classical formulation that identifies human nature as the catalyst of social disorder and war is superseded by the scientific method, which adheres to the viewpoint that war is complicated by numerous economic and political factors. Hans Morgenthau’s realist tradition of international relations theory, which advocates that humankind is the centric disruptive force by its abuse of power at all levels of human interaction especially among nations was eventually eclipsed by Kenneth Waltz’s neorealist school of thought, which shifted the culpability of war from the egocentricities of human nature to the disproportions of economic and military power among competing state actors in a decentralized state system. This shift in international relations theory within the framework of weapons of mass destruction contested the validity of the just war tradition in the nuclear age. Chapter 5 reasserts the Christian realist tradition’s viewpoint that the perpetrator for war is the individual actor within collective competitive self-interest, epitomized by the state actor. The classical model is reinstated as a plausible cause for war. It is within this framework that a contemporary adaptation of the just war moral theory is provided to contest the contemporary complexities of warfare in the 21st century. Chapter 6 investigates the practical challenges of modern warfare. The background of Operation Iraqi Freedom reveals the complications of state actor competition in international politics, and the necessity of moral parameters to thwart unwarranted state actor aggression. Finally, Chapter 7 reiterates, the prolonged necessity of the just war tradition in both the ancient and modern eras and, the import of moral parameters to thwart unwarranted state actor aggression and provides a reformulation of the just war moral theory to challenge the viewpoint that deems the utility of weapons of mass destruction as viable national security alternative and its tactical application in warfare. / Thesis (PhD)--University of Pretoria, 2014 / gm2015 / Practical Theology / PhD / Unrestricted

Mechanical tension is an important regulator of cell proliferation, differentiation, migration and cell death. It is involved in the control of tissue architecture and wound repair and its improper sensing can contribute to cancer. The Hippo tumor suppressor pathway was recently shown to be involved in regulating cell proliferation in response to mechanical tension. The core of the pathway consists of the kinases MST1/2 and LATS1/2, which regulate the target of the pathway, the transcription co-activator YAP/ TAZ (hereafter referred to as YAP). When the Hippo pathway is inactive, YAP remains in the nucleus and promotes cell proliferation and stem cell maintenance. When the Hippo signaling pathway is turned on, MST1/2 phosphorylate and activates LATS1/2. LATS1/2 phosphorylates and inactivates YAP in the cytoplasm which is sequestered and degraded, stopping cell proliferation and promoting differentiation of stem cells. Mechanical forces are transmitted across cells and tissues through the cell-cell junctions and the actin cytoskeleton. However, the factors that connect cell-cell junctions to the Hippo signaling pathway were not clearly known. We identified a LIM domain protein called TRIP6 that functions at the adherens junctions to regulate the Hippo signaling pathway in a tension-dependent manner. TRIP6 responds to mechanical tension at adherens junctions and regulates LATS1/2 activity. Under high mechanical tension, TRIP6 sequesters and inhibits LATS1/2 at adherens junctions to promote YAP activity. Conditions that reduce tension at adherens junctions by inhibition of actin stress fibers or disruption of cell-cell junctions reduce TRIP6-LATS1/2 binding, which activates LATS1/2 to inhibit YAP. Vinculin has been shown to act as part of a mechanosensory complex at adherens junctions. We show that vinculin promotes TRIP6 inhibition of LATS1/2 in response to mechanical tension. Furthermore, we show that TRIP6 competitively inhibits MOB1 (a known LATS1/2 activator) from binding and activating LATS1/2. Together these findings reveal TRIP6 responds to mechanical signals at adherens junctions to regulate the Hippo signaling pathway in mammalian cells.

In cancer, aberrant activation of developmental signaling pathways such as the Hippo Pathway has been shown to drive proliferation and invasion of cancer cells. Therefore, understanding the normal function of the Hippo Pathway during embryonic development can provide critical insight into how aberrant activity contributes to tumorigenesis. This dissertation explores the role of the Hippo Pathway members YAP and TAZ in gastrointestinal (GI) development and tumorigenesis. I use mouse genetics to systematically dissect the roles of YAP/TAZ in the endoderm-derived gastrointestinal epithelia and mesoderm-derived gastrointestinal mesenchyme during mammalian development. In the GI epithelium, I demonstrate that YAP/TAZ are dispensable for development and homeostasis. However, YAP/TAZ are required for Wnt pathway-driven tumorigenesis. I find that YAP/TAZ are direct transcriptional targets of Wnt/TCF4 signaling. In the GI mesenchyme, I describe a previously unknown requirement for YAP/TAZ activity during mammalian GI development. YAP/TAZ are involved in normal GI mesenchymal differentiation and function as transcriptional co-repressors in a progenitor cell population. In this way, YAP/TAZ act as molecular gatekeepers prior to Hedgehog-mediated differentiation into smooth muscle cells. This work unveils a previously unknown requirement for Hippo pathway signaling in the mammalian GI tract and a novel mechanism wherein YAP/TAZ function as transcriptional co-repressors to maintain a mesenchymal progenitor cell population.

Indiana University-Purdue University Indianapolis (IUPUI)

This study represents a work of practical narrative theology which originates in the notable prominence of an ancient form of catechesis in a modern document, the General Directory for Catechesis (GDC), issued in 1997 by the Sacred Congregation for the Clergy in the Vatican. The GDC first mentions narratio explicitly in number 39 in the form of an imperative: "Catechesis, for its part, transmits the words and deeds of Revelation; it is obliged to proclaim and narrate them and, at the same time, to make clear the profound mysteries that they contain." It is under the weight of that obligation that this study came to be. Narratio, or the narration of salvation history, which was a standard part of the catechesis of the Church of the fourth and fifth centuries gave way to the exigencies of a changing Church in which the catechetical focus turned from adults, who needed a Judeo-Christian worldview to replace a Greco-Roman one, to children who had grown up in communities shaped by a Christian vision. This doctoral thesis proceeds by, first, surveying Roman Catholic magisterial teaching immediately preceding the issuance of the GDC to trace the roots of this apparent innovation within an institution which is otherwise noted for its conservatism. After establishing the context and character of the GDCs call for revival of narratio, this thesis examines the historical setting, rhetorical structure, and function of narratio in Augustine of Hippo's De catechizandis rudibus, and then its scriptural precursors in the two Testaments in order to discover how this narration functioned in the Jewish and Christian communities which practiced haggadic and anamnetic recitals of God's saving works as a means to the formation and maintenance of communal identity. This study seeks to establish that a positive response to the GDC's call is as much warranted by the evidence provided in the biblical and post-biblical Jewish and Christian practice of ritual/covenantal remembrance as by the Catholic magisterial imperative in the GDC. In this, it may aid to inform and direct such a positive response to the GDC for the revival of the catechetical narratio. / Christian Spirituality, Church History and Missiology / D. Th. (Church History)

Toute maladie rénale chronique (MRC), et ce quelle qu’en soit la cause, aboutit à une réduction néphronique, c’est-à-dire à une diminution du nombre d’unités fonctionnelles qui assurent la fonction rénale. Celle-ci se caractérise initialement par une croissance compensatrice des néphrons sains restants. Néanmoins, elle aboutit, dans certaines circonstances, à une détérioration secondaire de ces néphrons, responsable du déclin progressif de la fonction rénale. L’étude du modèle murin de réduction néphronique par néphrectomie subtotale (Nx) a permis de souligner le rôle des facteurs génétiques dans la susceptibilité de développer une MRC. En particulier, les souris FVB/N (FVB) développent une MRC précoce et sévère après Nx, à la différence des souris C57Bl/6 (B6) qui préservent l’intégrité de leur parenchyme rénal. Mon travail de thèse avait pour objectif d’identifier de nouvelles voies moléculaires impliquées dans les processus d’adaptation et de progression des MRC en réponse à la réduction néphronique. Le projet s’est articulé autour de deux axes menés en parallèle: - une approche « globale » fondée sur l’analyse temporelle et différentielle du transcriptome rénal des souches « sensibles » (FVB) et « résistantes » (B6) après Nx ; - une approche « candidate » centrée sur l’étude du rôle de YAP/TAZ au cours de la réduction néphronique. Dans un premier travail, l’analyse du profil d’expression transcriptomique rénal des souris « résistantes » et « sensibles » a permis d’ identifier une signature Interféron (IFN) de type I uniquement chez les souris FVB pendant la phase de compensation rénale. Cette signature était corrélée à une expression plus importante : (i) de marqueurs des cellules dendritiques plasmacytoïdes, connues pour leur capacité à produire rapidement et en grande quantité de l’IFN de type I ; et (ii) de marqueurs de nécroptose, qui représente une mort cellulaire immunogène associée à la libération par les cellules endommagées de signaux « dangers » pouvant induire l’activation des cellules immunitaires. Nous avons également établi un parallélisme entre cette signature IFN et des perturbations de la prolifération des cellules tubulaires. En effet, il existe 2 jours après la Nx, une activation de p21 dans les cellules tubulaires et un probable blocage des cellules en prolifération à la transition G1/S. Nos résultats suggèrent que ce blocage retentit sur le taux de prolifération des cellules tubulaires et sous-tend une tendance à l’hypertrophie rénale chez les souris FVB au cours de la phase de compensation rénale. Ce premier travail a permis de souligner le lien potentiel entre des processus cellulaires et moléculaires survenant précocement après Nx, au cours de la phase de compensation rénale, et l’évolution ultérieure vers la MRC chez les souris FVB. Dans un second travail découlant de l’étude temporelle et différentielle de l’expression de YAP dans le modèle de Nx chez les souris FVB et B6, nous avons montré que l’expression nucléaire de YAP dans les podocytes était maintenue voire augmentée chez les souris « résistantes » et diminuait fortement chez les souris « sensibles » avec une corrélation entre cette expression et la sévérité des lésions glomérulaires. L’invalidation spécifique dans les podocytes de YAP, ou de son paralogue TAZ, chez des souris initialement « résistantes » a permis de mieux préciser leur rôle respectif dans l’adaptation des podocytes à la réduction néphronique. L’inactivation de YAP s’associe à : (i) l’apparition de lésions de hyalinose segmentaire et focale et de glomérulosclérose; (ii) une augmentation de l’apoptose glomérulaire ; (iii) une altération de l’architecture du cytosquelette des podocytes ; et (iv) une raréfaction podocytaire responsable d’une albuminurie et d’une détérioration de la fonction rénale. L’invalidation de TAZ n’induit pas de phénotype glomérulaire. A la différence de TAZ, YAP joue donc un rôle crucial dans l’adaptation podocytaire à la réduction néphronique. / Chronic kidney disease (CKD), irrespectively of the underlying cause, usually leads to nephron reduction, which is defined by a decrease in the number of the renal functional units. This is first characterized by a compensatory growth of the remaining nephrons, which in some circumstances, may result in the progressive deterioration of the initially healthy nephrons. The study of subtotal nephrectomy (Nx), a murine model of nephron reduction, has outlined the role of genetic factors in the susceptibility of developing CKD after nephron reduction. In particular, FVB/N mice (FVB) develop early and severe CKD after Nx, contrary to C57Bl/6 (B6) mice that are characterized by a preserved renal parenchyma. My work aimed at identifying new molecular pathways involved in the adaptation and progression processes in response to nephron reduction. The project was articulated around two main axes: - a "global" approach with the temporal and differential analysis of the renal transcriptome of "sensitive" (FVB) and "resistant" strains (B6) after Nx ; - a "candidate" approach centered on the study of the role of YAP/TAZ during nephron reduction. In the first work, the analysis of the renal transcriptomic expression profile of "resistant" and "sensitive" mice allowed to identify a type I interferon (IFN) signature only in the FVB mice during the renal compensation phase. This signature was correlated with a more important expression of markers of : (i) plasmacytoid dendritic cells, known for their ability to rapidly produce large amount of type I IFN; and (ii) necroptosis, an immunogenic cell death associated with the release of "danger" signals by the damaged cells that may induce activation of the immune cells. We have also established a parallelism between this IFN signature and alterations of tubular cells proliferation. Indeed, 2 days after Nx, we observed an activation of p21 in the tubular cells associated with a likely G1/S blockade of proliferating cells. Our results suggest that this cell cycle arrest affects the proliferation rate of tubular cells and underlies a trend for renal hypertrophy in FVB mice during the renal compensation phase. This first work pointed to a potential link between cellular and molecular processes occurring early after Nx, during the compensation phase, and the subsequent progression towards CKD in FVB mice. In a second work investigating the temporal and differential expression of YAP in the Nx model in FVB and B6 mice, we showed that the nuclear expression of YAP in podocytes was maintained and even increased in the “resistant” mice, and decreased significantly in "sensitive" mice with a correlation between this expression and the severity of glomerular lesions. The specific knockdown of YAP, or of its paralogous TAZ, in the podocytes of initially "resistant" mice allowed to better determine their respective role in the adaptation of these cells to nephron reduction. YAP podocyte-specific inactivation is associated with: (i) the development of focal and segmental glomerulosclerosis lesions; (ii) an increase of glomerular apoptosis; (iii) an alteration of the architecture of podocytes cytoskeleton; and (iv) podocyte rarefaction responsible for albuminuria and deterioration of renal function. Surprisingly, TAZ podocyte-specific inactivation was not associated with glomerular lesions. Contrary to TAZ, YAP plays a crucial role in podocyte adaptation to nephron reduction.

This thesis explicates teh rebellion theories of three reowned Christian political thinkers and evaluates the extent that each can communicate an intelligible rebellion theory to a non-Christian audience. Augustine of Hippo, at a dawn of the medieval ages, John Calvin of Geneva during the Reformation and John Adams of the USA in the midst of the Enlightenment are the three thinkers selected for consideration. These thinkers have produced ideas that have transcended time and geographical location. Rebellion is an issue of the utmost political importance as it reveals the limits, and the first principles of politics. The issues surrounding the involovement of religion in politics have created a place for confusion in minds of many people today. The issues surrounding religion and politics need further elucidation. The way these thinkers were able to translate the divine command from Romans 13:1, which decrees an absolute prohibition against rebellion, into an intelligible rebellion theory to non-Christians, is an important consideration in this thesis. / ix, 158 leaves ; 28 cm.

This study represents a work of practical narrative theology which originates in the notable prominence of an ancient form of catechesis in a modern document, the General Directory for Catechesis (GDC), issued in 1997 by the Sacred Congregation for the Clergy in the Vatican. The GDC first mentions narratio explicitly in number 39 in the form of an imperative: "Catechesis, for its part, transmits the words and deeds of Revelation; it is obliged to proclaim and narrate them and, at the same time, to make clear the profound mysteries that they contain." It is under the weight of that obligation that this study came to be. Narratio, or the narration of salvation history, which was a standard part of the catechesis of the Church of the fourth and fifth centuries gave way to the exigencies of a changing Church in which the catechetical focus turned from adults, who needed a Judeo-Christian worldview to replace a Greco-Roman one, to children who had grown up in communities shaped by a Christian vision. This doctoral thesis proceeds by, first, surveying Roman Catholic magisterial teaching immediately preceding the issuance of the GDC to trace the roots of this apparent innovation within an institution which is otherwise noted for its conservatism. After establishing the context and character of the GDCs call for revival of narratio, this thesis examines the historical setting, rhetorical structure, and function of narratio in Augustine of Hippo's De catechizandis rudibus, and then its scriptural precursors in the two Testaments in order to discover how this narration functioned in the Jewish and Christian communities which practiced haggadic and anamnetic recitals of God's saving works as a means to the formation and maintenance of communal identity. This study seeks to establish that a positive response to the GDC's call is as much warranted by the evidence provided in the biblical and post-biblical Jewish and Christian practice of ritual/covenantal remembrance as by the Catholic magisterial imperative in the GDC. In this, it may aid to inform and direct such a positive response to the GDC for the revival of the catechetical narratio. / Christian Spirituality, Church History and Missiology / D. Th. (Church History)

Thesis (MPhil)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: This thesis sets out to examine, as far as possible within the constraints of a limited study, the nature of the Christianity professed in the first centuries of the Common Era, by means of an historical examination of Egyptian Christianity. The thesis contends that the believers in Christ's teachings, in the first century, were predominantly Jewish, that "Christianity" did not exist as a developed separate religion until its first formal systematizations commenced in the second century, through the prolific writings of the Alexandrians, Clement and Origen. It is noted that the name "Christianity" itself was coined for the first time in the second century by Ignatius of Antioch; and that until the fourth century it is more accurate to speak of many Christianities in view of regional-cultural and interpretative differences where the religion took root. The study examines the main religions of the world in which the new religion began to establish itself, and against which it had to contend for its very survival. Many elements of these religions influenced the rituals and formulation of the new religion and are traced through ancient Egyptian religion, the Isis and Serapis cults, Judaism, Gnosticism and Hermeticism. Alexandria, as the intellectual matrix of the Graeco-Roman world, was the key centre in which the new religion was formally developed. The thesis argues, therefore, that despite the obscurity of earliest Christianity in view of the dearth of extant sources, the emergent religion was significantly Egyptian in formulation, legacy and influence in the world of Late Antiquity. It is argued, in conclusion, that the politics of the West in making Christianity the official religion of the empire, thus centring it henceforth in Rome, effectively effaced the Egyptian roots. In line with current major research into the earliest centuries of Christianity, the thesis contends that while Jerusalem was the spring of the new religion Alexandria, and Egypt as a whole, formed a vital tributary of the river of Christianity which was to flow through the whole world. It is argued that without the Egyptian branch, Christianity would have been a different phenomenon to what it later became. The legacy of Egyptian Christianity is not only of singular importance in the development of Christianity but, attracting as it does the continued interest of current researchers in the historical, papyrological and archaeological fields, it holds also considerable significance for the study of the history of religions in general, and Christianity in particular. / AFRIKAANSE OPSOMMING: Die proefskrif poog om, insover moontlik binne beperkte skopus, die aard van die vroeë Christendom gedurende die eerste eeue V.C. te ondersoek, deur middel van 'n historiese ondersoek van die Egiptiese Christendom. Die tesis voer aan dat die vroegste Christelike gelowiges in die eerste eeu N.C. grootendeels Joods was, en dat die Christendom as afsonderlike godsdiens nie ontstaan het nie voor die formele sistematiseringe wat deur die Aleksandryne Clemens en Origines aangebring is nie. Selfs die term Christendom is vir die eerste keer in die tweede eeu n.C. deur Ignatius van Antiochië versin; daar word verder opgemerk dat voor die vierde eeu dit meer akkuraat is om van veelvuldige Christelike groepe te praat. Die studie ondersoek die vernaamste godsdienste van die milieu waarin die nuwe godsdiens wortel geskied het, en waarteen dit om sy oorlewing moes stry. Baie invloede van die godsdienste is uitgeoefen op die rites en die daarstelling van die nuwe godsdiens, en kan herlei word na die antieke Egiptiese godsdiens, die kultusse van Isis en Serapis, Judaïsme, Gnostisisme en Hermetisme. Aleksandrië, die intellektuele matriks van die Grieks-Romeinse wêreld, was die hoof-sentrum waarin die nuwe godsdiens formeelontwikkel het. Die tesis toon daarom aan dat ten spyte van die onbekendheid van die vroegste Christendom, wat te wyte is aan die tekort aan bronne, die opkomende godsdiens in die Laat Antieke wêreld opvallend Egipties van aard was in formulering, invloed en erfenis. Ten slotte word daar aangevoer dat die politiek van die Weste wat die Christendom as amptelike godsdiens van die ryk gemaak het, en wat dit vervolgens dus in Rome laat konsentreer het, die Egiptiese oorspronge van die godsdiens feitlik uitgewis het. In samehang met kontemporêre belangrike navorsing op die gebied van die Christendom se vroegste eeue, argumenteer die tesis dat terwyl Jerusalem wel die bron van die nuwe godsdiens was, Aleksandrië, en Egipte as geheel, 'n deurslaggewende sytak was van die rivier van die Christendom wat uiteindelik deur die ganse wêreld sou vloei. Daar word aangetoon dat sonder die Egiptiese tak, die Christendom 'n heel ander verskynsel sou gewees het in vergelyking met sy latere formaat. Die erfenis van die Egiptiese Christendom is nie alleen van die grootste belang vir die ontwikkeling van die Christendom nie, maar 'n nalatenskap wat die voortgesette aandag van navorsers op historiese, papirologiese en argeologiese gebiede vra, en is daarom van groot belang vir die studie van die geskiedenis van godsdienste in die algemeen, en die Christendom in die besonder.

Le Liber contra collatorem est un traité composé par Prosper d’Aquitaine en 432-433, qui réfute les positions d’un certain « conférencier », c’est-à-dire l’auteur des Conférences, Jean Cassien. C’est dans cette œuvre que Prosper, défenseur de saint Augustin et de sa doctrine de la grâce, a pu fournir la critique la plus complète des théories propagées par les adversaires provençaux de l’évêque d’Hippone, en s’appuyant exclusivement sur des extraits tirés de la Conl. XIII « Sur la protection de Dieu ».En abordant, dans une première partie, les aspects les plus importants de l’œuvre (finalité du traité, modus operandi, genre littéraire, pratiques polémiques, enjeux théologiques), la présente thèse cherche à défendre l’hypothèse qu’en composant son Liber, Prosper a voulu constituer un dossier à charge suffisamment argumenté pour obtenir de l’évêque de Rome une condamnation officielle de ce que l’on a nommé le « semipélagianisme » et, par là, la reconnaissance de l’autorité de la doctrine augustinienne en matière de grâce. La seconde partie consiste en l’étude de l’ensemble de la tradition manuscrite du traité et des témoignages médiévaux le concernant, qui permet de mettre en évidence une histoire du texte aussi riche que complexe, qui justifie pleinement l’établissement d’une nouvelle édition – la première qui soit critique – de nature à corriger un textus receptus, datant de 1711, qui ne laisse pas d’être par endroits problématique. Cette édition est assortie d’une traduction française et d’une annotation destinée à éclairer les passages les plus importants ou les moins facilement compréhensibles du texte. / The Liber contra collatorem is a treatise written in 432-433 by Prosper of Aquitaine, who refutes the positions taken by a certain “lecturer”, by which John Cassian is meant, author of the Conferences. As an advocate of Augustine and of his doctrine of grace, Prosper has provided in this work most fully his criticism of the theories expressed by the bishop of Hippo’s Southern-French opponents. In order to do this, Prosper built only on excerpts from Conference nr. 13, “On the protection of God”. The first part of this thesis addresses the principal aspects of the work: the purpose of the treatise, the modus operandi, the literary genre, polemical practices, and theological issues. In doing so, this thesis defends the hypothesis that Prosper wrote his treatise in order to assemble a sufficiently argued file to obtain an official condemnation by the bishop of Rome of what has been called “Semipelagianism” and thus the recognition of the authority of the Augustinian doctrine of grace. The second part presents a study of the manuscript tradition of the treatise and of its medieval testimonies, which allows unraveling a rich and complex textual history. Hence, a new edition is justified, the first critical one, correcting and replacing the textus receptus dating from 1711, which is problematic at various points. The edition here presented is provided with a French translation and annotated in order to cast light on the most important or les easily comprehensible passages of the text.