Bumble bees (bombus spp.) are significant pollinators of many plants, and are particularly attracted to mass-flowering crops such as Oilseed Rape (Brassica Napus), which they cross-pollinate. B. napus is both wind and insect-pollinated, and whilst it has been found that wind is its most significant pollen vector, the influence of bumble bee pollination could be non-trivial when bee densities are large. Therefore, the assessment of pollinator-mediated cross-pollination events could be important when considering containment strategies of genetically modified (GM) crops, such as GM varieties of B. napus, but requires a landscape-scale understanding of pollinator movements, which is currently unknown for bumble bees. I developed an in silico model, entitled HARVEST, which simulates the foraging and consequential inter-patch movements of bumble bees. The model is based on principles from Reinforcement Learning and Individual Based Modelling, and uses a Linear Operator Learning Rule to guide agent learning. The model incoproates one or more agents, or bees, that learn by ‘trial-and-error’, with a gradual preference shown for patch choice actions that provide increased rewards. To validate the model, I verified its ability to replicate certain iconic patterns of bee-mediated gene flow, and assessed its accuracy in predicting the flower visits and inter-patch movement frequencies of real bees in a small-scale system. The model successfully replicated the iconic patterns, but failed to accurately predict outputs from the real system. It did, however, qualitatively replicate the high levels of inter-patch traffic found in the real small-scale system, and its quantitative discrepancies could likely be explained by inaccurate parameterisations. I also found that HARVEST bees are extremely efficient foragers, which agrees with evidence of powerful learning capabilities and risk-aversion in real bumble bees. When applying the model to the landscape-scale, HARVEST predicts that overall levels of bee-mediated gene flow are extremely low. Nonetheless, I identified an effective containment strategy in which a ‘shield’ comprised of sacrificed crops is placed between GM and conventional crop populations. This strategy could be useful for scenarios in which the tolerance for GM seed set is exceptionally low.

Doctor of Philosophy / Department of Agricultural Economics / Tian Xia / This dissertation presents the development of a new approach to include the interaction of vertically differentiated products, a subject that has been largely ignored in previous studies, to analyze the market power of exporters and importers in the world markets of agricultural commodities. Three theoretical models, a residual demand elasticity (RDE) model, a residual supply elasticity (RSE) model, and a two-country partial equilibrium trade model, are developed, and the corresponding empirical models are specified for U.S.-Japan soybean trade. Genetically modified (GM) and non-genetically modified (non-GM) soybeans are vertically differentiated products in the sense that GM soybeans are largely defined as an inferior substitute to non-GM soybeans. I compare two versions of these models: a new approach in which the interaction between non-GM and GM soybeans is taken into account and the traditional approach in which the interaction is ignored. In each of the three models (the RDE model, the RSE model, and the partial equilibrium trade model), the traditional approach overestimates the market margin of U.S. non-GM soybean exporters and that of Japanese non-GM soybean importers. By considering the interaction between non-GM and GM soybeans, the new approach greatly reduces the estimates of the corresponding market margins of U.S. exporters and Japanese importers to improve the accuracy of such estimates. The statistical significance of the coefficient estimate of the interaction term, the U.S. GM soybean price or the Japanese GM soybean price, in all three models suggests that the new approach, which includes the interaction between non-GM and GM soybeans, is necessary and preferred. The partial equilibrium trade model includes both an RDE equation and an RSE equation in a system to address the possible contemporaneous cross-equation correlation. Thus, the estimation results of the partial equilibrium trade model are further improved, compared to those of the RDE model and the RSE model. Using the traditional approach to estimate the partial equilibrium trade model, I find that the U.S. non-GM soybean exporters’ market margin is 56.5% and the Japanese non-GM soybean importers’ market margin is 16.1%. However, the results obtained by using the new approach show that the market margins of U.S. exporters and Japanese importers are 33.2% and 6%, respectively. By taking into account the interaction between non-GM and GM soybeans, the new approach improves the accuracy of the estimates of market margins of soybean exporters and importers. U.S. non-GM soybean exporters do have a significant market margin in international markets, but it is not as large as the one suggested by the traditional approach. Although Japanese non-GM soybean importers enjoy some market margin, it is relatively small. The theoretical and empirical models and results in this dissertation provide new and more accurate estimates of residual demand and supply elasticities and market power and improve the understanding on world soybean markets. These results can be useful for industry participants in international soybean markets, academic researchers, and policy makers.

La caractérisation des paléoenvironnements et paléoclimats des milieux continentaux du Néogène africain est un enjeu majeur pour comprendre l’émergence du rameau humain. La première partie du travail présente un état des lieux des connaissances dans ce domaine, mais aussi des avantages et des points faibles des marqueurs paléoenvironnementaux habituellement utilisés. Elle met ainsi en exergue la nécessité de développer de nouveaux marqueurs afin de documenter les paléoclimats, et plus particulièrement la paléosaisonnalité. Les marques de croissance squelettiques (MCS) des vertébrés ectothermes (poissons et tortues) sont présentées comme nouveau marqueur potentiel. D’une part, le but de ce travail est de déterminer la significativité du signal déposé par les MCS au sein d’un organisme et la capacité de ces structures à enregistrer un signal environnemental. D’autre part il vise à évaluer leur conservation dans les restes fréquents des dépôts du Néogène africains et à proposer des critères pour une meilleure exploitation de ce matériel. Ainsi, dans la deuxième partie, un large spectre de pièces squelettiques d’un spécimen de Polypterus bichir est analysé pour évaluer l’homogénéité intra-individuelle du signal enregistré par les MCS. La troisième partie présente la mise en place et le déroulement d’une étude expérimentale menée en conditions de température, photopériode et alimentation contrôlées. Elle a pour but de tester l’impact de ces facteurs dans le contrôle de la croissance de deux actinoptérigyens (Polypterus senegalus et Auchenoglanis occidentalis) et d’un chélonien pleurodire (Pelusios castaneus). La dernière partie présente une étude de restes fossiles de siluriformes, de Polypterus sp., de Lates sp. et de Pelusios sp. provenant des affleurements Mio-Pliocène du Tchad. Outre les conseils d’échantillonnage et de préparation de ces restes, de premières pistes d’interprétation des signaux observés sont proposées. / The paleoenvironmental and paleoclimatic characterization of continental environments from the Neogene of Africa is a major concern for the understanding of the emergence of the human lineage. The first part of this work presents a state of art of the knowledge on this field, and of the advantages and drawbacks of the paleoenvironmental proxies commonly used. It highlights the need to develop new proxies to document paleoclimates, and especially paleoseasonality. Ectothermic vertebrates (fish and turtles) growth marks (GM) are presented hereafter as a potential new proxy. On one hand, this work aims at ascertaining the significance of the signal left by GM within an organism and their efficiency in recording an environmental signal. On the other hand, it aims at evaluating their preservation in remains frequently found in African Neogene outcrops and at proposing criteria for their optimal use. Thus, in the second part, a wide array of skeletal pieces from one specimen of Polypterus bichir is analyzed to assess intra-individual homogeneity of GM signal. The third part introduces the set up and the progress of an experimental study led in controlled conditions of temperature, photoperiod and feeding. It aims at testing the impact of each factor on growth control in two Actinopterygii (Polypterus senegalus and Auchenoglanis occidentalis) and one pleurodiran Chelonii (Pelusios castaneus). The last part of this work presents a study of fossil remains of catfishes, Polypterus sp., Lates sp. and Pelusios sp. from Chadian Mio-Pliocene outcrops. Besides sampling and preparation advices, prelimininary paleoenvironmental and paleoclimatic interpretations are proposed.

A presente tese investiga como o Ambiente Institucional influencia o modo de governança de direitos de propriedade e a estratégia das firmas. O estudo divide-se em duas partes. A primeira parte empreende uma investigação teórica que se constitui em três etapas. Primeiro, examina-se o modelo de direitos de propriedade de Barzel (1994, 1997, 2003). Segundo, analisa-se uma abordagem de estratégia competitiva baseada em direitos de propriedade (Property Rights Perspective; Foss e Foss, 2001). Especificamente, argumenta-se que tal abordagem representa uma extensão do modelo de Barzel e demonstra-se que os conceitos introduzidos na etapa anterior possibilitam uma formulação mais geral da Property Rights Perspective, conduzindo a uma definição de estratégia competitiva que concilia as noções de strategizing e economizing (Williamson, 1991). A terceira etapa, por fim, examina particularmente o estabelecimento de estratégias de proteção de direitos de propriedade. Um modelo heurístico baseado em Williamson (1996) é proposto e com base nele três formas básicas de proteção são definidas em função da qualidade do Ambiente Institucional: estratégia centrada no sistema legal, no estabelecimento de mecanismos privados e no abandono de atributos valiosos. A segunda parte da pesquisa busca evidências empíricas que suportem o modelo teórico. O estudo examina três casos de proteção de direitos de propriedade sobre a tecnologia transgênica em sementes de soja: EUA, Brasil e Argentina. Cada um dos casos representa, respectivamente, uma forma de proteção de direitos como definido pelo modelo heurístico. A pesquisa examina também evidências econométricas que consolidam a análise empírica. De forma geral, o presente estudo desenvolve uma abordagem para o exame da apropriação de valor, colocando-se na interface entre a Economia de Direitos de Propriedade, o estudo da Estratégia e a análise do Ambiente Institucional. / The current thesis investigates how the Institutional Environment influences the mode of governance of property rights and the strategy of firms. The study is divided into two parts. The first part undertakes a theoretical investigation consisting of three steps. In the first step, the author examines the model of property rights developed by Barzel (1994, 1997, 2003). In the second step, an approach to competitive strategy based on property rights (Property Rights Perspective, Foss and Foss, 2001) is analyzed. Specifically, the author states that this approach represents an extension of Barzels model and demonstrates that the concepts introduced in the previous step allow a more general formulation of the Property Rights Perspective, leading to a definition of competitive strategy that reconciles the notions of strategizing and economizing (Williamson, 1991). The last step examines particularly the establishment of strategies for protection of property rights. A heuristic model based on Williamson (1996) is proposed and three strategies for protection of property rights are defined in terms of the quality of the Institutional Environment: strategy based on the legal system, on the establishment of private mechanisms, and on the abandon of valuable attributes. The second part of the research seeks empirical evidence to support the theoretical model. The study examines three cases of protection of property rights on genetically modified (GM) technology in soybean seeds: the US, Brazil, and Argentina. Each case represents, respectively, a strategy as defined by the heuristic model. The research also examines econometric evidence that consolidate the empirical analysis. Overall, the current study develops an approach for examining the appropriation of value, placing itself in the interface between the Property Rights Economics, the study of Strategy, and the assessment of the Institutional Environment.

Beim ersten Teil der Studie handelt es sich um eine Exposition der Symboltheorie Nelson Goodmans, deren Rezeption in der kognitivistischen Analyse der modernen Kunst an Bedeutung gewinnt. Goodmans ÄsthetikKonzeption geht von der philosophischen Problemstellung und vom Beschreiben und Lösen der Ästhetik als Erkenntnistheorie aus, deren kognitive Potentiale auf dem nominalistisch ausgerichteten Standpunkt vor dem Hintergrund seiner Symboltheorie dargestellt werden. Hauptthemen seiner philosophischen Untersuchungen sind die Revision der induktiven Logik und die Theorie der Welterzeugung an vorherrschenden Weltordnungen und pluralistischen Weltauffassungen. Insbesondere wird Goodmans Versuch „Kunstauffassung als ein Symbolsystem“ auf der Basis unserer erkenntnistheoretischen Aktivitäten seinem ästhetischen Anspruch „Erzeugung der Welten durch Kunstwerke“ gerecht, wobei Symbolsysteme ohne Weltbezüge, keineswegs aber Weltbezüge ohne Symbolsysteme behauptet werden. Ziel im zweiten Teil soll der Versuch sein, den abweichenden Sprachgebrauch der Dadaisten zu erläutern und als einen Kunstfaktor hinsichtlich seiner dargebotenen Metapher und ihrer ironischen Züge zu legitimieren. Die Dada-Nonsensprodukte kreieren sich aus skandalösen Vorstellungen von der (literarischen) Kunst, vor allem mit ihrem propagierten Unsinn zu einem signifikanten Bestandteil der Kunst. Der ambivalente Ausdruck „Unsinn“ muss nicht buchstäblich als „unsinnig“ aufgefasst werden; bewusst pocht der Unsinn auf den dadaistischen Status und will sich damit von anderer Kunst absetzen. Für dadaistische Kunstauffassungen gibt es zwei Grundannahmen: Entweder soll Kunst nur anhand des bloß Dargebotenen begriffen werden, unabhängig von allen Begleitumständen, oder, ganz im Gegenteil, Kunst könne nur aus den jeweiligen kontextuellen Gegebenheiten heraus verstanden werden, deren kognitives Potential sie dann wäre. Bei DadaProdukten wird deutlich, dass sie außerhalb ihrer textuell, bildlich oder aktionistisch dargestellten kognitiven Faktoren Bezug nehmen. Unter Bezugnahme auf die Autorität des Dadaismus gerät diese Gestaltung zum Ausbruchsversuch aus herrschenden Denk- und Rezeptionsmustern. So ist der Dada-Nonsens auch als eine Überwindung konventioneller Normierungen zu verstehen, die einen festen Bestandteil jeder Exemplifikation bildet. / The first part of the study is an exposition of the Nelson Goodman’s symbol theory, whose reception in the cognitivistic analysis of the modern art has gained importance. Goodman’s aesthetics conception proceeds with the philosophical problem presentation and from description and release of the aesthetics as an epistemology, whose cognitive potentials on the nominalistic aligned point of view in the context of its symbol theory are represented. Main topics of its philosophical researches are the revision of the inductive logic and the theory of the worldmaking at prevailing world orders and plural views of world. In particular Goodman’s attempt "view of art as a symbol-system" on the basis of our epistemological activities its aesthetic requirement "construction of the worlds by works of art" becomes fairly, whereby symbol-systems without world relations are not maintained by any means, however world relations without symbol-systems. A goal in the second part should be the attempt of describing and of legitimizing as an art factor, regarding its act metaphor and its ironical courses, the deviating linguistic usage of the Dadaists. The products of Dada create themselves from scandalous conceptions of the art, particularly with its publicised nonsense to a significant component of the (literary) art. The ambivalent expression "nonsense" does not have to be understood literally as "nonsensical"; consciously nonsense pounds on the dadaistic status and wants to set off thereby from other art. For dadaistic views of art there are two basic assumptions: Either art is to be understood only on the basis, only the act, independently of all attendant circumstances, or, completely the opposite, art can be understood only from the respective contextual conditions, whose cognitive potential would be it then. With products of Dada, it becomes clear that they can’t be taken out of their textually, pictorially or actionisticly represented cognitive factors. Referring to the authority of the Dadaism this arrangement turns out to the attempt to break through from dominant thinking- and reception-samples. So the Dada-nonsense is to be understood also as an overcoming of conventional standardisations that makes a firm component of each exemplification.

This dissertation reports a high-speed wideband wireless transmission solution for the tight power constraints of cortical interface application. The proposed system deploysImpulse Radio Ultra-wideband (IR-UWB) technique to achieve very high-rate communication. However, impulse radio signals suffer from significant attenuation within the body,and power limitations force the use of very low-power receiver circuits which introduce additional noise and jitter. Moreover, the coils’ self-resonance has to be suppressed to minimize the pulse distortion and inter-symbol interference, adding significant attenuation. To compensate these losses, an Error correction code (ECC) layer is added for functioning reliably to the system. The performance evaluation is made by modeling a pair of physically fabricated coils, and the results show that the ECC is essential to obtain the system’s reliability. Furthermore, the gm/ID methodology, which is based on the complete exploration ofall inversion regions that the transistors are biased, is studied and explored for optimizingthe system at the circuit-level. Specific focuses are on the RF blocks: the low noise am-plifier (LNA) and the injection-locked voltage controlled oscillator (IL-VCO). Through the analytical deduction of the circuit’s features as the function of the gm/ID for each transistor, it is possible to select the optimum operating region for the circuit to achieve the target specification. Other circuit blocks, including the phase shifter, frequency divider,mixer, etc. are also described and analyzed. The prototype is fabricated in a 65-nm CMOS(Complementary Metal-Oxide-Semiconductor) process.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multipotent cytokine involved in the production and function of hematopoietic cells, and GM-CSF plays in particular a major role in responses to infection and physiological and pathological inflammatory processes. GM-CSF is produced in many cell types, and increases in the intracellular Ca2+ concentration are, like in many other systems, of major importance in the intracellular signaling that determines GM-CSF expression after receptor stimulation of the cells. Previous studies have shown that the Ca2+/calmodulin-dependent phosphatase calcineurin (CN) mediates stimulation of GM-CSF transcription in response to Ca2+. This thesis shows that Ca2+ signaling also regulates GM-CSF transcription negatively through Ca2+/calmodulin-dependent kinase II (CaMK II) phosphorylation of serines in the autoinhibitory domain for DNA binding of the transcription factor Ets1. Mutation of the CaMK II target serines increased transactivation of the GM-CSF promoter/enhancer and decreased the sensitivity to inhibition by increased Ca2+ or constitutively active CaMK II. The Ca2+-dependent phosphorylation of Ets1 was also shown to reduce the binding of Ets1 to the GM-CSF promoter in vivo. RUNX1, also known as acute myeloid leukemia 1 (AML1), is one of three mammalian RUNX transcription factors and has many essential functions in hematopoiesis. RUNX1 has also many important roles in the immune system, and RUNX1 is the most frequent target for chromosomal translocation of genes in acute human leukemias. This thesis shows that RUNX1 directly interacts with both subunits of CN and that the strongest interaction is localised to the regulatory CN subunit and the DNA binding domain of the RUNX protein. Constitutively active CN was shown to activate the promoter/enhancer of GM-CSF synergistically with RUNX1, RUNX2 or RUNX3, and the Ets1 binding site of the promoter was shown to be essential for the synergy between RUNX1 and CN in Jurkat T cells. The analysis suggests that Ets1 phosphorylated by the protein kinase glycogen synthase kinase-3β is the target of RUNX1-recruited CN phosphatase at the GM-CSF promoter. Transforming growth factor-β (TGF-β) is another multipotent cytokine that often has a role opposite to that of GM-CSF in inflammatory responses since it is a potent suppressor of immune cells and therefore is anti-inflammatory. This thesis shows that TGF-β can decrease transcription from a GM-CSF promoter/enhancer. Certain constitutively active TGF-β receptors and the TGF-β activated transcription factor Smad3 could also repress GM-CSF transcription, whereas several other Smad proteins did not have this inhibitory effect. The inhibition required intact DNA binding ability of Smad3, and the 125 bp upstream of the transcription initiation site, which was sufficient for the inhibition, contains several weak Smad binding sites near the TATA box next to an Ets1 site of the promoter. Smad3 was able to bind to the promoter DNA together with Ets1 and could also be in complex with Ets1 in the absence of DNA. Surface plasmon resonance analysis revealed that Ets1 interacted with the DNA binding domain of Smad3, and the binding constant of this interaction was about 1 µM. The results identify a negative regulation of the GM-CSF promoter by TGF-β signaling through direct Smad3 binding and indicate that the mechanism is by Smad3 interaction with Ets1 and perhaps other proteins around the TATA box of the promoter. This thesis also identifies a novel transactivation domain in the N-terminal of RUNX1 including the N-terminal α-helix in the DNA binding domain. The domain was also required for RUNX2 and RUNX3 transactivation. Despite this, the N-terminal domain of RUNX1 was not essential for RUNX1 function in megakaryocytopoiesis in vitro from mouse embryonic stem cells.

This dissertation presents design and implementation of continuous time analog filters for two specific applications: wideband analog systems such as disk drive channel and low-power wireless applications. Specific focus has been techniques that reduce the power requirements of the overall system either through improvement in architecture or efficiency of the analog building blocks. The first problem that this dissertation addresses is the implementation of wideband filters with high equalization gain. An efficient architecture that realizes equalization zeros by combining available transfer functions associated with a biquadratic cell is proposed. A 330MHz, 5th order Gm-C lowpass Butterworth filter with 24dB boost is designed using the proposed architecture. The prototype fabricated in standard 0.35um CMOS process shows -41dB of IM3 for 250mV peak to peak swing with 8.6mW/pole of power dissipation. Also, an LC prototype implemented using similar architecture is discussed in brief. It is shown that, for practical range of frequency and SNR, LC based design is more power efficient than a Gm-C one, though at the cost of much larger area. Secondly, a complementary current mirror based building block is proposed, which pushes the limits imposed by conventional transconductors on the powerefficiency of Gm-C filters. Signal processing through complementary devices provides good linearity and Gm/Id efficiency and is shown to improve power efficiency by nearly 7 times. A current-mode 4th order Butterworth filter is designed, in 0.13um UMC technology, using the proposed building. It provides 54.2dB IM3 and 55dB SNR in 1.3GHz bandwidth while consuming as low as 24mW of power. All CMOS filter realization occupies a relatively small area and is well suited for integration in deep submicron technologies. Thirdly, a 20MHz, 68dB dynamic range active RC filter is presented. This filter is designed for a ten bit continuous time sigma delta ADC architecture developed specifically for fine-line CMOS technologies. Inverter based amplification and a common mode feedback for such amplifiers are discussed. The filter consumes 5mW of power and occupies an area of 0.07 mm2.

Systemic lupus erythematosus (SLE) is an autoimmune, inflammatory disease characterized by autoantibody production and an activated type I interferon system. Cardiovascular disease (CVD) is as a major cause of morbidity and mortality. The aim of this thesis was to identify genetic risk factors for CVD in SLE. The role of T cells in regulation of the interferon-α (IFNα) production by plasmacytoid dendritic cells (pDCs) was also investigated.    In paper I, a thicker intima, thinner media and increased intima/media ratio was found in young premenopausal women with SLE compared to healthy controls indicating increased cardiovascular risk. As traditional ultrasound assessment of the common carotid intima-media thickness (CCA-IMT) in SLE has given conflicting results separate measurement of the intima and media can be a useful tool to identify SLE patients at increased risk of CVD.    In paper II, an association was demonstrated in SLE between a STAT4 risk allele and ischemic cerebrovascular disease and presence of anti-phospholipid antibodies (aPL). The association remained after adjustment for traditional CVD risk factors. A possible mechanism for this association is that the risk allele leads to increased production of aPL, which promotes thromboembolism.    In paper III, a genetic locus in IRF8 was identified to be associated to coronary heart disease (CHD) in SLE. The association remained after adjustment of other CHD risk factors.  Patients with the IRF8 risk variant had increased CCA-IMT, more carotid plaques and reduced frequency of circulating B cells. Weaker binding of nuclear protein to the risk allele was demonstrated, suggesting a regulatory function of the IRF8 risk variant.    In paper IV, activated T cells were found to strongly enhance the IFNα production by pDC stimulated with RNA-containing immune complexes via GM-CSF and IL-3. Activated SLE T cells enhanced the IFNα production to the same extent as T cells from healthy controls. This finding together with previous observations in SLE of increased levels of GM-CSF and IL-3 suggests that T cells contribute to the activated type I interferon system in SLE.    In conclusion, this thesis demonstrates that genetic predisposition is important for CVD in SLE and describes a new role for T cells in the pathogenesis of SLE.

Dendritic cells (DC) are antigen-presenting cells that are critical for the initiation and regulation of the immune response. Several DC subtypes within mouse spleen have previously been characterised and these include the plasmacytoid (pDC), and conventional DC (cDC) of the CD8+ and CD8- subtypes. Each subtype appears to have a specialised role in the various arms of immunity and tolerance. Less clear is the process by which these DC develop from haematopoietic precursors, of the precursor stages and branch points from bone marrow (BM) stem cells to each of the peripheral DC subtypes. The research described herein had the aim of identifying and isolating some of the intermediate precursors of DC, downstream of stem cells, and determining whether these differed in the steady-state versus inflammation. Particular was given to DC of the spleen. Experiments that sought the identity of such precursors involved both i) transfer of cell fractions that contained DC precursors into steady-state or inflamed recipient mice to assess their in vivo development at later times, and ii) analysis of an in vitro culture system to question whether it reflected development of the steady-state DC subtypes.