The United Kingdom published a legally binding document to reduce national greenhouse gas emissions by year 2020 up to 34% against the 1990 levels. This target also fulfils the Europe 2020 strategy of 20% carbon emission reductions by year 2020 (EC, 2010). Emissions due to space heating count for around 60% of the total domestic emissions (DCLG, 2012). The report “Rethinking Construction” published in 1998 emphasised the opportunities to improve the quality and efficiency of the UK construction sector (Egan, 1998). More recently, a framework has been published by the Government to tackle fuel poverty by building more energy efficient homes (DECC, 2015). In terms of energy performance, Passivhaus is recognised as one of the most energy efficient and researched construction standards which requires an exceptionally high-level of insulation and airtightness. Closed-panel timber frames are a relatively new system in UK with an opportunity for growth. These advanced panels are pre-fitted in the factory, reducing the on-site work. However, closed-panel systems present a more complex sole plate fixing detail which can have an undesirable long-term impact on the structural and thermal performance of the building. The work presented in this thesis investigates the structural considerations, racking performance, of timber frame closed panel systems for future building regulations. The thesis underlines the significance of structural stability, serviceability and detailing in relationship with long-term thermal efficiency and airtightness, according to Passivhaus standard. An experimental study was carried out to investigate the structural racking performance of advanced closed panel systems. A comparison was made between the behaviour of the timber frame panels and the analytical PD 6693-1. A set of different wall panel built-ups is presented for optimised Passivhaus design, including thermal bridge-free sole plate details. A timber frame racking software application was developed to optimise the structural design of shear walls. A parametric study was carried out with this tool to generate efficient timber frame wall design tables for different applied racking loads and U-values. The software application also allows for direct specification of robust sole plate base fixings and thermal bridge free details.

The long-term (>1 Ga) thermal histories of cratons are enigmatic, with geologic data providing only limited snapshots of their evolution. We use zircon (U-Th)/He (zircon He) thermochronology and age composition correlations to understand the Proterozoic-Phanerozoic thermal history of Archean Wyoming province rocks exposed in the northern Laramide ranges of western North America. Zircon He ages from the Wind River Range (54 dates) and Bighorn Mountains (32 dates) show negative correlations with effective uranium (eU), a proxy for radiation damage. Zircon dates from the Bighorns are between 960 Ma (low-eU) and 20 Ma (high-eU) whereas samples from the Wind Rivers are between 582 Ma (low-eU) and 33 Ma (high-eU). We applied forward modeling using the zircon radiation damage and annealing model ZrDAAM to understand this highly variable dataset. A long-term t-T path that is consistent with the available geologic constraints successfully reproduced age-eU correlations. The best fit to the Wind Rivers data involves two phases of rapid cooling at 1800-1600 Ma and 900-700 Ma followed by slower cooling until 525 Ma. During the Phanerozoic, these samples were heated to maximum temperatures between 160 and 125 degrees C prior to Laramide cooling to 50 degrees C between 60 and 40 Ma. Data from the Bighorn Mountains were successfully reproduced with a similar thermal history involving cooler Phanerozoic temperatures of similar to 115 degrees C and earlier Laramide cooling between 85 and 60 Ma. Our results indicate that age-eU correlations in zircon He datasets can be applied to extract long-term thermal histories that extend beyond the most recent cooling event. In addition, our results constrain the timing, magnitude and rates of cooling experienced by Archean Wyoming Province rocks between recognized deformation events, including the >1 Ga period represented by the regionally-extensive Great Unconformity.

The physical tumor microenvironment contributes significantly to carcinogenesis, cancer progression and metastatic dissemination. Two main components of the tumor microenvironment, hypoxia and acidosis, are present in nearly every solid tumor and act as powerful selection forces against the tumor. Hypoxia and acidosis promote tumor heterogeneity and contribute to chemotherapy and radiotherapy resistance. This dissertation interrogates methods to target the tumor microenvironment including two novel studies describing mechanisms of buffer therapy resistance and targeting tumor hypoxia with vasodilators to enhance the efficacy of a hypoxia activated prodrug, TH-302. In the first study, mechanisms of buffer therapy resistance were identified and detailed. Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of the buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, I confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit. In the second study, improving the efficacy of hypoxia activated prodrug, TH-302, through induction of hypoxia was investigated. Pancreatic ductal adenocarcinomas are desmoplastic and hypoxic tumors, both of which are associated with poor prognosis. Hypoxia activated prodrugs, such as TH-302, are specifically activated in hypoxic environments and are now in a Phase III clinical trial in pancreatic cancer. Using animal models, we show that tumor hypoxia can be exacerbated using a vasodilator, hydralazine, improving TH-302 efficacy. Hydralazine reduces tumor blood flow through the "Steal" phenomenon, where atonal immature tumor vasculature fails to dilate in coordination with normal vasculature. The current study shows that MiaPaCa-2 tumors exhibit a "Steal" effect in response to hydralazine, resulting in decreased tumor blood flow and subsequent tumor pH reduction. The effect is not observed in SU.86.86 tumors with mature tumor vasculature, as measured by CD31 and smooth muscle actin (SMA) immunohistochemistry staining. Combination therapy of hydralazine and TH-302 resulted in a reduction in MiaPaCa-2 tumor volume growth after 18 days of treatment. Further optimization of hypoxia-inducing agents and dosing regimens may lead to increased TH-302 activity, potentially improving clinical outcome. The data presented here demonstrate methods to effectively target the tumor microenvironment for therapeutic benefit. Further investigation into mechanisms of action and biomarkers for therapy response may have important implications on clinical treatment regimens for cancer patients.

The thesis looks at the question asking for the computability of the dot-depth of star-free regular languages. Here one has to determine for a given star-free regular language the minimal number of alternations between concatenation on one hand, and intersection, union, complement on the other hand. This question was first raised in 1971 (Brzozowski/Cohen) and besides the extended star-heights problem usually refered to as one of the most difficult open questions on regular languages. The dot-depth problem can be captured formally by hierarchies of classes of star-free regular languages B(0), B(1/2), B(1), B(3/2),... and L(0), L(1/2), L(1), L(3/2),.... which are defined via alternating the closure under concatenation and Boolean operations, beginning with single alphabet letters. Now the question of dot-depth is the question whether these hierarchy classes have decidable membership problems. The thesis makes progress on this question using the so-called forbidden pattern approach: Classes of regular languages are characterized in terms of patterns in finite automata (subgraphs in the transition graph) that are not allowed. Such a characterization immediately implies the decidability of the respective class, since the absence of a certain pattern in a given automaton can be effectively verified. Before this work, the decidability of B(0), B(1/2), B(1) and L(0), L(1/2), L(1), L(3/2) were known. Here a detailed study of these classes with help of forbidden patterns is given which leads to new insights into their inner structure. Furthermore, the decidability of B(3/2) is proven. Based on these results a theory of pattern iteration is developed which leads to the introduction of two new hierarchies of star-free regular languages. These hierarchies are decidable on one hand, on the other hand they are in close connection to the classes B(n) and L(n). It remains an open question here whether they may in fact coincide. Some evidence is given in favour of this conjecture which opens a new way to attack the dot-depth problem. Moreover, it is shown that the class L(5/2) is decidable in the restricted case of a two-letter alphabet. / Die Arbeit beschaeftigt sich mit der Frage nach der Berechenbarkeit der Punkttiefe sternfreier regulaerer Sprachen. Dabei handelt es sich um die Aufgabe, zu einer gegebenen sternfreien regulaeren Sprache die minimal moegliche Anzahl von Wechseln zwischen den Operationen Konkatenation einerseits und Durchschnitt, Vereinigung, Komplement andererseits in einem sternfreien regulaeren Ausdruck fuer die gegebene Sprache zu bestimmen. Diese Frage wurde 1971 erstmals aufgeworfen (Brzozowski/Cohen) und gilt neben dem Problem der erweiterten Sternhoehe als eine der schwierigsten offenen Fragen der Theorie der regulaeren Sprachen. Formal fassen laesst sich das Problem der Punkttiefe durch Hierarchien von Klassen sternfreier regulaerer Sprachen B(0), B(1/2), B(1), B(3/2),...sowie L(0), L(1/2), L(1), L(3/2),.... die - ausgehend von einzelnen Buchstaben - mittels Alternierung zwischen Konkatenation und Booleschen Operationen definiert sind. Die Frage nach der Punkttiefe wird hier zur Frage nach der Entscheidbarkeit der Hierarchieklassen. In der Arbeit werden neue Fortschritte mittels sogenannter Verbotsmuster erzielt. Bei diesem Ansatz werden Klassen regulaerer Sprachen dadurch charakterisiert, dass in den zugehoerigen endlichen Automaten bestimmte Muster (Teilgraphen des Ueberfuehrungsgraphen) verboten werden. Gelingt eine solche Charakterisierung, folgt unmittelbar die Entscheidbarkeit der Klasse, da das Nichtvorhandensein eines Musters in einem gegebenen endlichen Automaten effektiv geprueft werden kann. Bisher war die Entscheidbarkeit von B(0), B(1/2), B(1) und L(0), L(1/2), L(1), L(3/2) bekannt. Mit Hilfe von Verbotsmustern erfolgt eine genaue Untersuchung dieser Klassen, die zu neuen Erkenntnissen ueber ihre innere Struktur fuehrt. Darueberhinaus gelingt der Nachweis der Entscheidbarkeit von B(3/2). Basierend auf diesen Ergebnissen wird eine Theorie der Verbotsmusteriteration entwickelt, die zur Einfuehrung von zwei neuen Hierarchien sternfreier regulaerer Sprachen fuehrt. Diese neuen Hierarchien sind zum einen entscheidbar, zum anderen stehen sie in enger Beziehung zu den Klassen B(n) und L(n). Es bleibt an dieser Stelle eine offene Frage, ob sie eventuell sogar mit ihnen uebereinstimmen. Fuer diese Vermutung werden einige Indizien gesammelt und somit ein neuer Weg fuer eine moegliche Loesung des Problems der Punkttiefe aufgezeigt. In diesem Zusammenhang erfolgt auch erstmals der Nachweis der Entscheidbarkeit der Klasse L(5/2) im eingeschraenkten Fall eines zweielementigen Alphabets.

Dans cette th`ese, nous proposons l'´etude d'un nouveau syst`eme de trafic a´erien, caract´eris´e par un tr`es haut degr´e d'organisation. Dans ce syst`eme, les avions sont assujettis `a suivre des points mobiles fictifs durant leur trajet. Ces points mobiles sont organis´es et s´equenc´es de fa¸con `a ´eviter les conflits entre avions, notamment lorsque ces derniers convergent vers une mˆeme intersection. Cette th`ese propose la mod´elisation d'un probl`eme sous-jacent `a ce paradigme. Ce probl`eme peut ˆetre vu comme la recherche d'un stable dans un graphe infini sous certaines contraintes. Apr`es une ´etude th´eorique de ce probl`eme, nous proposons une heuristique de r´esolution, amenant `a pr´esenter un syst`eme global de trafic a´erien, puis nous exposons des r´esultats num´eriques.

<p>Avhandlingen söker svara på två förberedande frågor: hur man kan tolka Theodor W. Adornos kritiska teori idag? Samt hur en sådan tolkning kan göras relevant för aktuell teologisk problematik?</p>

Cette ��tude porte sur le mouvement dit de la "��Th��ologie de la lib��ration��" en Ha��ti. A partir d'une approche historique, elle retrace le parcours du mouvement de 1970 �� 2004, en mettant en ��vidence ses r��seaux et ses acteurs.Bien que l'apparition r��elle de ce mouvement soit tr��s r��cente dans la soci��t��, son d��veloppement a ��t��, n��anmoins, fulgurant. Il est perceptible �� travers de nombreuses structures de base comme��: les Communaut��s eccl��siales de base, commun��ment appel��es TKL (Ti Kominote Legliz), les groupements paysans et les centres de formation. Lieu de conscientisation, de fraternit�� et de solidarit��, ces structures ont jou�� un r��le tr��s important, dans les ann��es 80, non seulement dans la redynamisation de l'��glise catholique mais aussi dans la diffusion de la "��Th��ologie de la lib��ration��" en Ha��ti. Leur force a ��t�� d��montr��e sous la dictature tant par leurs prises de position que par leurs actions qui ont largement contribu�� �� la chute du r��gime.A leur t��te se trouvent des pr��tres, issus de milieux sociaux et de Congr��gations divers dont la dictature avait contraint un certain nombre �� l'exil. Si l'exil a ��t�� l'une des sanctions les plus courantes sous la dictature, il ne se r��v��le pas, n��anmoins, la plus efficace puisqu'il a permis le d��veloppement, par ces pr��tres, d'un puissant courant anti-duvali��riste fortement influenc�� par la "��Th��ologie de la lib��ration��", dont les journaux, les revues et les associations de base seront les principaux vecteurs et qui sera �� l'origine du d��part de Jean-Claude Duvalier, le 7 f��vrier 1986. Sa cons��cration est marqu��e par l'��lection, en 1990, de Jean-Bertrand Aristide, l'un d'entre eux. Qui sont ces acteurs��? En quoi consiste leur travail��? Quels sont les principaux r��seaux impliqu��s dans ce mouvement��? Existe-t-il une r��elle convergence de vues entre les id��es de la th��ologie de la lib��ration et celles d��fendues par ses acteurs en Ha��ti ? En quoi les id��es de Jean-Bertrand Aristide concordent-elles avec celles de la "��Th��ologie de la lib��ration��"��? Sa politique pr��sidentielle s'inscrit-elle, ou non, dans la continuit�� de la "��Th��ologie de la lib��ration��" ? Ce sont les principales questions auxquelles cette ��tude tentera de r��pondre.

Cette th��se de doctorat a pour objet l'��dition critique, la traduction et l'analyse de l'oeuvre th����trale compl��te de Fran��ois de Cort��te (1585-1667). Ce seigneur agenais a ��volu�� dans l'entourage d'Adrien de Monluc, m��c��ne et protecteur de nombreux auteurs de langue fran��aise et de langue occitane. Le th����tre de Cort��te, partiellement ��dit�� apr��s sa mort par ses fils, pr��sente deux pastorales qui se distinguent par un certain " souci de r��alit�� " dans la repr��sentation des bergers mis en sc��ne sur les terres dont il est le seigneur. La Miramondo explore les r��gles d'unit��s ; dans son Ramonnet Cort��te reprend l'��thnotype comique du matamore gascon dont il inverse le sens du ridicule en dessinant un des premiers portraits de francimand de la litt��rature en langue occitane ; Sancho al palays del Duc est une com��die, qui sur le mod��le de Gu��rin de Bouscal, adapte �� la sc��ne une dizaine de chapitres du second livre du Quichotte. A l'instar du po��te toulousain Pierre Godolin en po��sie, Cort��te exploite et illustre les ressources de la langue d'oc en produisant une oeuvre th����trale sur le mod��le des cr��ations contemporaines des ��lites europ��ennes. Ses trois pi��ces refl��tent la richesse et ladiversit�� de la production th����trale en France entre les ann��es 1630 et 1650 ainsi que les bouleversements qui la traversent. Cette ��dition, r��alis��e �� partir des manuscrits autographes, se veut aussi fid��le que possible au texte tout en veillant �� pr��server sa lisibilit��. Elle constitue aussi la premi��re traduction fran��aise du th����tre de Cort��te de Prades. Aucune indication de datation n'ayant ��t�� donn��e par l'auteur sur la chronologie de la composition de ses pi��ces et la bibliographie critique ��tant extr��mement r��duite, l'analyse donn��e en introduction aborde les trois pi��ces de mani��retransversale et tente de r��pondre �� cette probl��matique chronologique tout en pr��cisant et en explorant les principales questions qui d��finissent la singularit�� de cette oeuvre.

Avhandlingen söker svara på två förberedande frågor: hur man kan tolka Theodor W. Adornos kritiska teori idag? Samt hur en sådan tolkning kan göras relevant för aktuell teologisk problematik?

Flat plate systems are constructed with slabs directly supported on columns. Since there are no beams in the system, the behavior of connections between the slabs and columns play a crucial role. Due to the sudden and brittle nature of punching shear failures, slab-column connection design must be conducted with proper safety precautions. The first part of this study aims to evaluate the safety level of different design expressions in the codes. Fir this purpose, the ability of ACI 318-11, TS-500 and Eurocode-2 to estimate punching shear strength was examined in light of experimental results compiled from previous research. Interior and exterior connections were examined in the course of the study. In the second part of the study, beam and shell models were calibrated to simulate the load-deformation response of interior slab-column connections in light of experimental results. In the final part of this thesis, a typical floor plan of a flat plate system was analyzed to investigate the possibility of a progressivefailure mechanism after punching failure takes place at a slab-column connection. Minimum post-punching capacity required to avoid progressive punching failure in a floor was estimated. It is believed that, the results of this study can be helpful in guiding engineers in understanding the safety inherent in punching shear design expressions and to take necessary precautions against progressive collapse.