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Die vorliegende Arbeit beinhaltet umfangreiche histologische Untersuchungen an verschiedenen Tumoren bezüglich ihrer Infiltration durch Makrophagen-Subpopulationen, Granulozyten und Lymphozyten. Hierfür wurden 18 Gewebe-Mikroarrays mit jeweils 200 - 300 Tumorstanzen aus insgesamt 27 Organen des Gastrointestinaltraktes, des Urogenitaltraktes, des Respirationssystems und des endokrinen Systems angefertigt. Da alle Proben mit derselben Technik (Gewebe-Mikroarrays, Immunhiostochemie) ausgewertet wurden, bestand nun erstmalig die Möglichkeit eines direkten Vergleiches zwischen den verschiedenen Tumoren unterschiedlicher Organe. Für die immunhistochemischen Untersuchungen wurden fünf verschiedene Antikörper (anti-KP1, anti-PG-M1, anti-MRP8, anti-MRP14, anti-MRP8/14) eingesetzt. Die Antikörper gegen die Epitope PG-M1 und KP1 gelten als Pan-Makrophagen-Marker. Die Antikörper anti-MRP8, anti-MRP14 und anti-MRP8/14 gelten als Marker für entzündlich aktivierte Makrophagen. Diese Makrophagen wurden in einen aktiven inflammatorischen Typ (MRP14+, MRP8/14+), der proinflammatorische Zytokine wie TNF-a und Sauerstoffradikale bildet, und in einen chronisch inflammatorischen Typ (MRP8+) eingeteilt. Die Formation des MRP8/14-Heterodimers korreliert mit der zellulären Aktivierung wie z. B. mit der Aktivierung der NADPH-Oxidase. Es wurde beschrieben, dass diese Makrophagen auf Grund ihrer Eigenschaften eventuell die Tumorzellproliferation inhibieren und zytotoxische Wirkungen auf Tumorzellen ausüben können. Für die verschiedenen Tumorgewebe wurden höhere Makrophagendichten im Vergleich zum Normalgewebe und eine vergleichsweise geringe Dichte an MRP+ Makrophagen sowie signifikante Korrelationen zwischen den verschiedenen Makrophagen-Subpopulationen festgestellt. Die Dichte der Lymphozyten korrelierte negativ mit steigendem Tumorzellanteil und mit fortgeschrittenem Tumorstadium. Die Abnahme der Lymphozyten (Gastrointestinal- und Respirationstrakt) im Tumorgewebe im Vergleich zum tumorfreien Gewebe sowie die geringe Anzahl der potenziell tumoriziden MRP8/14+ Makrophagen lässt vermuten, dass die Immunantwort gegen den Tumor unterdrückt wird. Die positive Assoziation zwischen Makrophagen und Lymphozyten weist jedoch darauf hin, dass Makrophagen nicht am Rückgang der Lymphozyten beteiligt sind . Eine Korrelation der Makrophagen mit klinisch relevanten Parametern (pT-Stadium, UICC-Stadium, Lymphknotenmetastasen) zeigten ein voneinander abweichendes Infiltrationsmuster der CD68+ und MRP+ Makrophagen, was auf unterschiedliche Funktionen hinweist. Ferner liegen zahlreichen funktionelle Untersuchungsergebnisse anderer Arbeitsgruppen vor, welche darauf hinweisen, dass Makrophagen durch Hypoxie angezogen werden und im hypoxischen Tumorgewebe schließlich an der Neubildung von Blut- und Lymphgefäßen beteiligt sind. Um einen möglichen Zusammenhang zu zeigen, wurde mit den Antikörpern anti-CD31 und anti-CD34 die Gefäßdichte in Tumoren untersucht. Es zeigten sich zahlreiche positive Korrelationen zwischen Gefäßen und Makrophagen, jedoch konnte in den tumorfreien Geweben kein Zusammenhang zwischen beiden Größen gefunden werden. Das Vorkommen größerer Makrophagendichten in Tumoren mit wenig Nekrose als in Tumoren ohne Nekrose, die positive Korrelation zwischen der Anzahl der Gefäße und der Zahl der Makrophagen in Tumoren und die Unabhängigkeit von Makrophagen und Gefäßen im tumorfreien Gewebe legt die Vermutung nahe, dass TAM die Angiogenese begünstigen. Trotz vieler ähnlicher Charakteristika zwischen den Tumoren unterschiedlichen Ursprungsgewebes wurden auch Unterschiede festgestellt, die besonders die Anzahl der Makrophagen-Subpopulationen betreffen. Weitere Studien zur Aufklärung der Funktion unterschiedlicher Makrophagen-Subpopulationen (z. B. Immunsuppression, Neoangiogenese) sind notwendig, um deren Relevanz für das Tumorwachstum und die Tumorprogression aufzuklären.

Russian entrepreneurs have long faced considerable difficulties. While much is known about what these difficulties are, less is known about how entrepreneurs respond to them, what it is like to be an entrepreneur under these circumstances and why they bother in the first place. In this thesis I address these questions by conducting a multi-sited ethnography within three small Siberian enterprises, observing the directors as they conduct their everyday business. I find that these entrepreneurs all resent their vulnerable position in the political economy but that they have developed a capacity to survive or thrive in spite of the obstacles and threats they encounter. This capacity, I argue, is less a consequence of their commercial acumen than their understanding of what can be achieved given their particular circumstances, their knowledge that business-state relations take an informal, personalised form, and their preparedness to resist predatory outsiders. This leads me to reconsider the meaning of entrepreneurship in the Russian context. Furthermore, my informants’ agency presents a challenge to the idea in predominant political economic theories that the Russian state dominates the private sector. I therefore reconceptualise business-state relations using Douglass C. North et al’s Limited Access Order theory in combination with my empirical materials. This provides a more accurate theory that accepts the pre-eminent role of the state in the political economy while accommodating the agency displayed by my informants.

The Late Cretaceous–early Paleogene is the most recent period of Earth history with a dynamic carbon cycle that experienced sustained global greenhouse warmth and can offer a valuable insight into our anthropogenically-warmer future world. Yet, knowledge of ambient climate conditions and evolution of the carbon cycle at this time, along with their relation to forcing mechanisms, are still poorly constrained. In this thesis, I examine marine sediments recovered from the South Atlantic Walvis Ridge (ODP Site 1262) and Indian Ocean Ninetyeast Ridge (IODP Site U1443 and ODP Site 758), to shed new light on the evolution of the climate and carbon cycle from the Late Maastrichtian through to the Early Eocene (~67.10–52.35 Ma). The overarching aims of this thesis are: 1) to identify the long-term trends and principle forcing mechanisms driving the climate and carbon cycle during this time period, through construction of 14.75 million-year-long, orbital-resolution (~1.5–4 kyr), stratigraphically complete, benthic stable carbon (δ13Cbenthic) and oxygen (δ18Obenthic) isotope records; 2) to investigate in more detail the climatic and carbon-cycle perturbations of the Early–Middle Paleocene (e.g., the Dan-C2 event, Latest Danian Event and the Danian/Selandian Transition Event) and place these in their proper (orbital) temporal context; 3) to investigate the Late Maastrichtian warming event and its relationship to the eruption of the Deccan Traps Large Igneous Province, as well as its role (if any) in the subsequent Cretaceous/Paleogene (K/Pg) mass extinction; 4) to provide the first orbital-resolution estimates of temperature and carbonate chemistry variability from the low latitude Indian Ocean spanning the Late Paleocene–Early Eocene, through analysis of trace element and stable isotope data from multiple foraminiferal species. Taken together, the results presented in this thesis provide a critical new insight into the dynamic evolution of the climate and carbon cycle during the greenhouse world of the early Paleogene, and shed light on the potential forcing mechanisms driving the climate and carbon cycle during this time.

Lancé le 11 juin 2008 par la NASA, le satellite \textit{Fermi}, avec à son bord le LAT (Large Area Telescope), ouvre une nouvelle fenêtre sur le ciel gamma. Grâce à aux capacités de détection du LAT des photons dans la gamme en énergie 200 MeV-300 GeV, il devient possible d'étudier les Noyaux Actifs de Galaxie (NAG en anglais). En particulier, on s'intéressera à la classe des blazars et les plus énergétiques d'entres-eux les High frequency peaked BL Lac (HBL). Les blazars sont des NAG possédant un jet qui pointe dans la direction de la Terre. Cette thèse présente une étude systématique des blazars détectés par les observatoires Tcherenkov au dessus de 200 GeV, faite avec 5.5 mois de données prisent par le LAT. La comparaison entre les deux gammes en énergie permet d'étudier la distribution des particules émettrices ainsi que des effets de propagation des photons de la source jusqu'à l'observateur. Un modèle d'émission électromagnétique des jets de plasma dit synchrotron self-Compton (SSC) est décrit et utilisé pour rendre compte de l'émission sur tout le spectre des HBL PKS 2155-305 et PG 1553+113. Les résultats indiquent que les effets Klein-Nishina de réduction de la section efficace de diffusion Compton inverse jouent un rôle majeur dans ces objets. Une étude sur le long terme (environ 1 an) de PKS 2155-305 en rayons X et en rayons gamma est aussi décrite. Menée avec le satellite RXTE (rayons X) et le LAT, c'est la campagne d'observation conjointe la plus longue à ce jour. Les propriétés spectrales et temporelles sont décrites avec un modèle SSC dépendant du temps.

Made available in DSpace on 2014-07-29T15:08:21Z (GMT). No. of bitstreams: 1 Dissertacao_Marcos_Carneiro2.pdf: 1611954 bytes, checksum: 3a2f117c1f5e722726a65bedea74ac76 (MD5) Previous issue date: 2009-05-29 / This research proposes the application of an artificial intelligence technique called genetic programming (GP) to make easier the programming of programmable logical devices (PLC) by the automatic generation of Ladder and Instruction List programs. The system data input can be done by not-specialized people using scenarios composed by time lines. These time lines demonstrate graphically the sequencing details of the PLC input and output permitting the programming of systems that uses memory like inter-locking contacts and the use of timers. Since GP is great dependent of its initial simulation parameters, thousand of simulations have been done to determine the better kind of configuration of cross-over and mutation / Essa pesquisa propõe a aplicação da técnica de inteligência artificial programação genética (PG) para facilitar o trabalho de programação de controladores lógico programáveis (CLP) através da geração automática de programas Ladder e Instruction List. A entrada de dados do sistema de automação é feita de forma leiga a partir de cenários compostos por linhas do tempo. Essas linhas do tempo demonstram graficamente os detalhes do seqüenciamento dos acionamentos das entradas e saídas do CLP permitindo a programação de sistemas que utilizam memória como os inter-travamentos e o uso de temporizadores. Como a PG é altamente dependente dos parâmetros iniciais de simulação, foram feitas milhares de simulações para determinação das melhores formas de configuração dos parâmetros de reprodução por cross-over (cruzamento) e mutação

Electromagnetic flow meters are simple, rugged, non-invasive flow measuring instruments, which are extensively employed in many applications. In particular, they are ideally suited for the flow rate measurement of liquid metals, which serve as coolants in fast breeder reactors. In such applications, theoretical evaluation of the sensitivity turns out to be the best possible choice. Invariably, an evaluation of the associated electromagnetic fields forms the first step. However, due to the complexity of the problem, only numerical field computational approach would be feasible. In the pertinent literature, couple of e orts could be found which employ the well-known Galerkin Finite Element Method (GFEM) for the required task. However, GFEM is known to suffer from the numerical stability problem even at moderate flow rates. This problem is quite common in fluid dynamics area and several stabilization schemes have been suggested as a remedial measure. Among such schemes, the Streamline Upwinding Petrov Galerkin (SU/PG) method is a simple and widely employed approach. The same has been adopted in some of the moving conductor literatures for obtaining a stable solution. Nevertheless, in fluid dynamics literature, it has been shown that the SU/PG solution can suffer from distortion/peaking at the boundary. The remedial measures proposed are nonlinear in nature and hence are computationally demanding. Also, even the SU/PG scheme by itself requires significant additional computation for quadratic and higher order elements. Further, the value of stabilization parameter is not accurately known for 2D and 3D problems. The present work is basically an attempt to address the above problem for flow meter and other rectilinearly moving conductor problems. More specifically, but for the requirement of (graded) structured mesh along the flow direction, it basically aims to address a more general class of problems not just limited to the flow meter. Following the classical approach employed in fluid dynamics literature, first the problem is studied in its 1D form. It was observed that a relatively better performance of GFEM over FDM scheme is basically due to the difference in their Right Hand Side (RHS) terms, which represents the applied magnetic field. Taking clue from this, it was envisaged that a better insight to the numerical problem can be obtained by using the control system theory's transfer function approach. An application of FDM or GFEM to the 1D form of the governing equation, leads to flalge-braic equations with space variable in discrete form. Hence, a Z-transform based approach is employed to relate the applied magnetic field to the vector potential of the resulting reaction magnetic field. It is then shown that the presence of a pole at Z = -1 is basically responsible for the oscillations in the numerical solution. It is then proposed that by using the control systems pole-zero cancellation principle, stability can be brought into the numerical solution. This requires suitable modification of RHS terms in the discretised equations and accordingly, two novel schemes have been proposed which works within the framework of GFEM. In author's considered opinion, the use of Z-transform for analysing the stability of the numerical schemes and the idea of employing pole-zero cancellation to bring in stability, are first of its kind. In the first of the proposed schemes, the pole-zero cancellation is achieved by simply restating the input magnetic field in terms its vector potential. Solving the difference equations given by the application of FDM or GFEM to 1D version of the governing equation, it is analytically shown that the proposed scheme is absolutely stable at high flow rates. However, at midrange of flow rates there is a small error, which is analytically quantified. Then the scheme is applied to the original flow meter problem which has only axially varying applied field and the stability is demonstrated for an extensive range of flow rates. Note that the discretisation along the flow direction was restricted in the above exercise to graded regular mesh, which can readily be realised for problems involving rectilinearly moving conductors. In order to cater for more general cases in which the applied field varies in both axial and transverse directions, a second scheme is developed. Here the RHS term representing the input magnetic field is considered in a generic weighted average form. The required weights are evaluated by imposing apart from the need for an essential zero yielding term, the flux preservation and other symmetry conditions. The stability of this scheme is proven analytically for both 1D and 2D version of the problem using respectively, the 1D and 2D Z-transform based approaches. The analytical inferences are adequately validated with numerical exercises. Also, the small error present for the midrange of flow rates is analytically quantified. Then the second scheme is applied to the actual flow meter with a general magnetic field pro le. The proposed scheme is shown to be very stable and accurate even at very high flow rates. As before, the discretisation was restricted to graded regular mesh along the flow direction. By solving for the standard TEAM No. 9 benchmark problem, applicability of the second scheme for other rectilinearly moving conductor problem has been adequately demonstrated. Even though the problems considered in this work readily permits the use of a graded regular mesh along the flow direction, for the sake of completeness, discretisation with arbitrary quadrilateral and triangular mesh is also considered. The performance of the proposed schemes for such cases even though found to deteriorate, is still shown to be considerably better than the GFEM. In summary, this work has successfully proposed two novel, computationally effcient and stable GFEM schemes for the simulation of electromagnetic flow meters and other rectilin early moving conductor problems.

In den letzten Jahrzehnten hat sich in Lateinamerika ein neuer Kontext für die Durchsetzung von Menschenrechten herausgebildet. Die organisatorische Entwicklung des Interamerikanischen Menschenrechtsschutzsystems (IAS), die Verabschiedung neuer Verfassungen durch die nationalen Gesetzgeber und die Anwendung innovativer Verfassungsauslegungen durch die maßgeblichen Gerichte in der Region haben zur Entstehung eines kosmopolitischen lateinamerikanischen Konstitutionalismus geführt. In diesem neuen Kontext hat der Interamerikanische Gerichtshof für Menschenrechte (IACtHR) damit begonnen, die gerichtliche Überprüfung innerstaatlicher Gesetze zu praktizieren, d.h. er hat bei mehreren Gelegenheiten nationale Behörden angewiesen, innerstaatliche Gesetze wegen ihrer Unvereinbarkeit mit der Amerikanischen Menschenrechtskonvention (ACHR) für ungültig zu erklären. Angesichts der zunehmenden Konflikte zwischen nationalen und internationalen Menschenrechtsautoritäten zielt diese Studie darauf ab, den legitimsten und effektivsten Ansatz für die Praxis der interamerikanischen Konventionskontrolle zu finden. Ausgehend von der Debatte über die innerstaatliche richterliche Normenkontrolle werden zunächst die Gründe für die Praxis einer starken internationalen Normenkontrolle untersucht. Anschließend adressiert diese Studie Theorien, die versucht haben, die interamerikanische Konventionskontrolle zu schwächen. Diese Theorien haben sich häufig für die Übernahme des nationalen Ermessensspielraums auf der Grundlage der Rechtsprechung des Europäischen Gerichtshofes für Menschenrechte ausgesprochen. Schließlich plädiert die vorliegende Studie für eine kontextbasierte Theorie der interamerikanischen gerichtlichen Überprüfung und versucht, den nationalen Ermessensspielraum mit dem kosmopolitischen Konstitutionalismus Lateinamerikas in Einklang zu bringen. / In recent decades, a new human rights enforcement context has emerged in Latin America. The organizational evolution of the Inter-American System for Human Rights Protection (IAS), the adoption of new constitutions by national legislatures, and the adoption of innovative constitutional interpretations by the most authoritative courts in the region have led to the emergence of Latin American cosmopolitan constitutionalism. Within this new context, the Inter-American Court of Human Rights (IACtHR) has started practicing the judicial review of domestic laws, i.e., on several occasions, it has ordered national authorities to invalidate domestic laws due to their incompatibility with the American Convention on Human Rights (ACHR). By reviewing domestic laws, the IACtHR has placed itself in the middle of a dialogue between legislatures and courts that was long seen as an exclusively domestic conversation within Latin American constitutionalism. This strong form of international jurisprudence has made the normative questions relating to judicial review much more complex to address. Given the increasing conflicts between domestic and inter-American human rights authorities, this study aims to find the most legitimate and effective approach to the practice of inter-American judicial review. In line with this, and drawing on the debate about domestic judicial review, it first assesses the reasons behind the practice of strong international judicial review. In order to offer a better form of inter-institutional interaction within the IAS, this study later addresses theories that have sought to weaken the practice of inter-American judicial review based on the principle of subsidiarity. These theories have often advocated for the adoption of the national margin of appreciation based on the European experience with this concept of deference to national authorities. Finally, this study advocates for a context-based theory of inter-American judicial review and tries to reconcile the national margin of appreciation with Latin American cosmopolitan constitutionalism.

As part of the wider European GTS Next project, I propose new constraints on the ages of the Late Cretaceous, derived from a multitude of geochronological techniques, and successful stratigraphic interpretations from Canada and Japan. In the Western Canada Sedimentary Basin, we propose a new constraint on the age of the K/Pg boundary in the Red Deer River section (Alberta, Canada). We were able to cyclostratigraphically tune sediments in a non-marine, fluvial environment utilising high-resolution proxy records suggesting a 11-12 precession related cyclicity. Assuming the 40Ar/39Ar method is inter-calibrated with the cyclostratigraphy, the apparent age for C29r suggests that the K/Pg boundary falls between eccentricity maxima and minima, yielding an age of the C29r between 65.89 ± 0.08 and 66.30 ± 0.08 Ma. Assuming that the bundle containing the coal horizon represents a precession cycle, the K/Pg boundary is within the analytical uncertainty of the youngest zircon population achieving a revised age for the K/Pg boundary as 65.75 ± 0.06 Ma. The Campanian - Maastrichtian boundary is preserved in the sedimentary succession of the Horseshoe Canyon Formation and has been placed ~8 m below Coal nr. 10. Cyclostratigraphic studies show that the formation of these depositional sequences (alternations) of all scales are influenced directly by sea-level changes due to precession but more dominated by eccentricity cycles proved in the cyclostratigraphic framework and is mainly controlled by sand horizons, which have been related by autocyclicity in a dynamic sedimentary setting. Our work shows that the Campanian - Maastrichtian boundary in the Western Canada Sedimentary Basin coincides with ~2.5 eccentricity cycles above the youngest zircon age population at the bottom of the section and ~4.9 Myr before the Cretaceous - Palaeogene boundary (K/Pg), and thus corresponds to an absolute age of 70.65 ± 0.09 Ma producing an ~1.4 Myr younger age than recent published ages. Finally, using advances with terrestrial carbon isotope and planktonic foraminifera records within central Hokkaido, Northwest Pacific, sections from the Cretaceous Yezo group were correlated to that of European and North American counterparts. Datable ash layers throughout the Kotanbetsu and Shumarinai section were analysed using both 40Ar/39Ar and U-Pb methods. We successfully dated two ash tuff layers falling either side of the Turonian - Coniacian boundary, yielding an age range for the boundary between 89.31 ± 0.11 Ma and 89.57 ± 0.11 Ma or a boundary age of 89.44 ± 0.24 Ma. Combining these U-Pb ages with recent published ages we are able to reduce the age limit once more and propose an age for the Turonian - Coniacian boundary as 89.62 ± 0.04 Ma.

<p>The development of a novel charge inversion ion/ion reaction in conjunction with a mass spectrometry technique (collisional induced dissociation (CID)) to induce fragmentation of selected ions species in the gas-phase. The utility of this experiment allows identification of varying saturated and unsaturated classes of glycerophospholipids (GPLs) in a biological matrix. In this work, we are able to characterize GPLs species at the subclass, headgroup, fatty acyl sum compositional levels,  leaving the location(s) of carbon-carbon single bond (C-C), carbon-carbon double bond (C=C), cyclopropane moiety, branching site and differentiate isomeric species. </p> <p><br></p> <p>All data were collected on modified a Sciex QTRAP4000 hybrid triple quadrupole/linear ion trap mass spectrometer. Briefly, alternately, pulsed nano-electrospray ionization (nESI) was used for ion generation. Deprotonated lipid anions were generated via negative ion mode nESI, mass selected during transit through Q1, and transferred to q2 for storage. Next, the charge inversion (IIRXN) reagent doubly charged magnesium complex cations, were generated via positive ion mode nESI. To facilitate the ion/ion reaction, magnesium complex dictations and lipid anions were simultaneously stored in q2, resulting in the formation of charge-inverted lipid cations. Ion-trap CID of charge-inverted isomers resulted in distinctive fragmentation, facilitating differentiation of isomeric and localization of unsaturation sites in acyl chain constituents. </p>