Challenges with in vitro and in vivo experimental models of urinary bladder cancer for novel drug discovery

Urinary bladder cancer (UBC) is the second most frequent malignancy of the urinary system and the ninth most common cancer worldwide, affecting individuals over the age of 65. Several investigations have embarked on advancing knowledge of the mechanisms underlying urothelial carcinogenesis, understanding the mechanisms of antineoplastic drugs resistance and discovering new antineoplastic drugs. In vitro and in vivo models are crucial for providing additional insights into the mechanisms of urothelial carcinogenesis. With these models, various molecular pathways involved in urothelial carcinogenesis have been discovered, allowing therapeutic manipulation.

Occurrence and abundance models of threatened plant species: Applications to mitigate the impact of hydroelectric power dams

Species occurrence and abundance models are important tools that can be used in biodiversity conservation, and can be applied to predict or plan actions needed to mitigate the environmental impacts of hydropower dams. In this study our objectives were: (i) to model the occurrence and abundance of threatened plant species, (ii) to verify the relationship between predicted occurrence and true abundance, and (iii) to assess whether models based on abundance are more effective in predicting species occurrence than those based on presence–absence data. Individual representatives of nine species were counted within 388 randomly georeferenced plots (10 m × 50 m) around the Barra Grande hydropower dam reservoir in southern Brazil. We modelled their relationship with 15 environmental variables using both occurrence (Generalised Linear Models) and abundance data (Hurdle and Zero-Inflated models). Overall, occurrence models were more accurate than abundance models. For all species, observed abundance was significantly, although not strongly, correlated with the probability of occurrence. This correlation lost significance when zero-abundance (absence) sites were excluded from analysis, but only when this entailed a substantial drop in sample size. The same occurred when analysing relationships between abundance and probability of occurrence from previously published studies on a range of different species, suggesting that future studies could potentially use probability of occurrence as an approximate indicator of abundance when the latter is not possible to obtain. This possibility might, however, depend on life history traits of the species in question, with some traits favouring a relationship between occurrence and abundance. Reconstructing species abundance patterns from occurrence could be an important tool for conservation planning and the management of threatened species, allowing scientists to indicate the best areas for collection and reintroduction of plant germplasm or choose conservation areas most likely to maintain viable populations.

Quantum integrability as a new method for exact results on N=2 supersymmetric gauge theories and black holes

In this thesis I show a triple new connection we found between quantum integrability, N=2 supersymmetric gauge theories and black holes perturbation theory. I use the approach of the ODE/IM correspondence between Ordinary Differential Equations (ODE) and Integrable Models (IM), first to connect basic integrability functions - the Baxter’s Q, T and Y functions - to the gauge theory periods. This fundamental identification allows several new results for both theories, for example: an exact non linear integral equation (Thermodynamic Bethe Ansatz, TBA) for the gauge periods; an interpretation of the integrability functional relations as new exact R-symmetry relations for the periods; new formulas for the local integrals of motion in terms of gauge periods. This I develop in all details at least for the SU(2) gauge theory with Nf=0,1,2 matter flavours. Still through to the ODE/IM correspondence, I connect the mathematically precise definition of quasinormal modes of black holes (having an important role in gravitational waves’ obervations) with quantization conditions on the Q, Y functions. In this way I also give a mathematical explanation of the recently found connection between quasinormal modes and N=2 supersymmetric gauge theories. Moreover, it follows a new simple and effective method to numerically compute the quasinormal modes - the TBA - which I compare with other standard methods. The spacetimes for which I show these in all details are in the simplest Nf=0 case the D3 brane in the Nf=1,2 case a generalization of extremal Reissner-Nordström (charged) black holes. Then I begin treating also the Nf=3,4 theories and argue on how our integrability-gauge-gravity correspondence can generalize to other types of black holes in either asymptotically flat (Nf=3) or Anti-de-Sitter (Nf=4) spacetime. Finally I begin to show the extension to a 4-fold correspondence with also Conformal Field Theory (CFT), through the renowned AdS/CFT correspondence.

Hidden Schrödinger symmetry in FLRW and Bianchi I minisuperspace models of cosmology and black holes Schwarzschild dynamics

A broad sector of literature focuses on the relationship between fluid dynamics and gravitational systems. This thesis presents results that suggest the existence of a new kind of fluid/gravity duality not based on the holographic principle. The goal is to provide tools that allow us to systematically unearth hidden symmetries for reduced models of cosmology. The focus is on the field space of these models, i.e. the superspace. In fact, conformal isometries of the supermetric leave geodesics in the field space unaltered; this leads to symmetries of the models. An innovative aspect is the use of the Eisenhart-Duval’s lift. Using this method, systems constrained by a potential can be treated as free ones. Moreover, charges explicitly dependent on time, i.e. dynamical, can be found. A detailed analysis is carried out on three basic models of homogenous cosmology: i) flat Friedmann-Lemaître-Robertson-Walker’s isotropic universe filled with a massless scalar field; ii) Schwarzschild’s black hole mechanics and its extension to vacuum (A)dS gravity; iii) Bianchi’s anisotropic type I universe with a massless scalar field. The results show the presence of a hidden Schrödinger’s symmetry which, being intrinsic to both Navier-Stokes’ and Schrödinger’s equations, indicates a correspondence between cosmology and hydrodynamics. Furthermore, the central extension of this algebra explicitly relates two concepts. The first is the number of particles coming from the fluid picture; while the second is the ratio between the IR and UV cutoffs that weighs how much a theory has of “classical” over “quantum”. This suggests a spacetime that emerges from an underlying world which is described by quantum building blocks. These quanta statistically conspire to appear as gravitational phenomena from a macroscopic point of view.

Redefining functional models of basal ganglia organisation: Role for the posteroventral pallidum in linguistic processing?

Traditionally the basal ganglia have been implicated in motor behavior, as they are involved in both the execution of automatic actions and the modification of ongoing actions in novel contexts. Corresponding to cognition, the role of the basal ganglia has not been defined as explicitly. Relative to linguistic processes, contemporary theories of subcortical participation in language have endorsed a role for the globus pallidus internus (GPi) in the control of lexical-semantic operations. However, attempts to empirically validate these postulates have been largely limited to neuropsychological investigations of verbal fluency abilities subsequent to pallidotomy. We evaluated the impact of bilateral posteroventral pallidotomy (BPVP) on language function across a range of general and high-level linguistic abilities, and validated/extended working theories of pallidal participation in language. Comprehensive linguistic profiles were compiled up to 1 month before and 3 months after BPVP in 6 subjects with Parkinson's disease (PD). Commensurate linguistic profiles were also gathered over a 3-month period for a nonsurgical control cohort of 16 subjects with PD and a group of 16 non-neurologically impaired controls (NC). Nonparametric between-groups comparisons were conducted and reliable change indices calculated, relative to baseline/3-month follow-up difference scores. Group-wise statistical comparisons between the three groups failed to reveal significant postoperative changes in language performance. Case-by-case data analysis relative to clinically consequential change indices revealed reliable alterations in performance across several language variables as a consequence of BPVP. These findings lend support to models of subcortical participation in language, which promote a role for the GPi in lexical-semantic manipulation mechanisms. Concomitant improvements and decrements in postoperative performance were interpreted within the context of additive and subtractive postlesional effects. Relative to parkinsonian cohorts, clinically reliable versus statistically significant changes on a case by case basis may provide the most accurate method of characterizing the way in which pathophysiologically divergent basal ganglia linguistic circuits respond to BPVP.

A light stop and electroweak baryogenesis

The possibility of creating baryon asymmetry at the electroweak phase transition in the minimal supersymmetric standard model is considered for the case when right-handed squarks are much lighter than left-handed ones. It is shown that the usual requirement upsilon(T-c)/T-c greater than or similar to 1 for baryogenesis can be satisfied in a range of the parameters of the model, consistent with present experimental bounds.

A behavioral analysis tool for models of software systems

Trabalho apresentado no âmbito do Mestrado em Engenharia Informática, como requisito parcial para obtenção do grau de Mestre em Engenharia Informática

Social Security in Theory and Practice (II): Efficiency Theories, Narrative Theories, and Implications for Reform

166 countries have some kind of public old age pension. What economic forces create and sustain old age Social Security as a public program? Mulligan and Sala-i-Martin (1999b) document several of the internationally and historically common features of social security programs, and explore "political" theories of Social Security. This paper discusses the "efficiency theories", which view creation of the SS program as a full of partial solution to some market failure. Efficiency explanations of social security include the "SS as welfare for the elderly" the "retirement increases productivity to optimally manage human capital externalities", "optimal retirement insurance", the "prodigal father problem", the "misguided Keynesian", the "optimal longevity insurance", the "government economizing transaction costs", and the "return on human capital investment". We also analyze four "narrative" theories of social security: the "chain letter theory", the "lump of labor theory", the "monopoly capitalism theory", and the "Sub-but-Nearly-Optimal policy response to private pensions theory". The political and efficiency explanations are compared with the international and historical facts and used to derive implications for replacing the typical pay-as-you-go system with a forced savings plan. Most of the explanations suggest that forced savings does not increase welfare, and may decrease it.

Social security in theory and practice (II): Efficiency theories, narrative theories and implications for reform

166 countries have some kind of public old age pension. What economic forcescreate and sustain old age Social Security as a public program? Mulligan and Sala-i-Martin (1999b) document several of the internationally and historically common features of social security programs, and explore "political" theories of Social Security. This paper discusses the "efficiency theories", which view creation of the SS program as a full of partial solution to some market failure. Efficiency explanations of social security include the "SS as welfare for the elderly" the "retirement increases productivity to optimally manage human capital externalities", "optimal retirement insurance", the "prodigal father problem", the "misguided Keynesian", the "optimal longevity insurance", the "governmenteconomizing transaction costs", and the "return on human capital investment". We also analyze four "narrative" theories of social security: the "chain letter theory", the "lump of labor theory", the "monopoly capitalism theory", and the "Sub-but-Nearly-Optimal policy response to private pensions theory".The political and efficiency explanations are compared with the international and historical facts and used to derive implications for replacing the typical pay-as-you-go system with a forced savings plan. Most of the explanations suggest that forced savings does not increase welfare, and may decrease it.

Influence of disorder strength on phase-field models of interfacial growth

We study the influence of disorder strength on the interface roughening process in a phase-field model with locally conserved dynamics. We consider two cases where the mobility coefficient multiplying the locally conserved current is either constant throughout the system (the two-sided model) or becomes zero in the phase into which the interface advances (one-sided model). In the limit of weak disorder, both models are completely equivalent and can reproduce the physical process of a fluid diffusively invading a porous media, where super-rough scaling of the interface fluctuations occurs. On the other hand, increasing disorder causes the scaling properties to change to intrinsic anomalous scaling. In the limit of strong disorder this behavior prevails for the one-sided model, whereas for the two-sided case, nucleation of domains in front of the invading front are observed.

Trauma and disorganized attachment in refugee children : integrating theories and exploring treatment options

Refugee families incur many different types of stressors in the course of the phases prior to flight, those of flight, and resettlement. Multiple and varied negative life events and traumas, such as those experienced by refugee families, may give rise to negative changes in attachment between children and their parents. However, such negative changes in attachment may be countered through the use of culturally appropriate counselling theories and their respective interventions. The integration of attachment theory with family systems, trauma systems, and cognitive behavioural theories and the use of cognitive behavioural caregiver support, filial therapy training, and play therapy interventions are discussed as a treamtent framework for promoting more positive and secure attachments between refugee children and their caregivers.

Supergravity models of (3+1)-dimensional QCD

The most general black M5-brane solution of eleven-dimensional supergravity (with a flat R4 spacetime in the brane and a regular horizon) is characterized by charge, mass and two angular momenta. We use this metric to construct general dual models of large-N QCD (at strong coupling) that depend on two free parameters. The mass spectrum of scalar particles is determined analytically (in the WKB approximation) and numerically in the whole two-dimensional parameter space. We compare the mass spectrum with analogous results from lattice calculations, and find that the supergravity predictions are close to the lattice results everywhere on the two dimensional parameter space except along a special line. We also examine the mass spectrum of the supergravity Kaluza-Klein (KK) modes and find that the KK modes along the compact D-brane coordinate decouple from the spectrum for large angular momenta. There are however KK modes charged under a U(1)×U(1) global symmetry which do not decouple anywhere on the parameter space. General formulas for the string tension and action are also given.

Institutionalism Theories and Hegemonic Practices in Global Polity Formation

Institutionalistische Theorien und hegemoniale Praktiken Globaler Politikgestaltung. Eine neue Beleuchtung der Prämissen Liberaler Demokratischer National-Staatlicher Ordnungen. Deutsche Zusammenfassung: Moderne Sozialwissenschaften, seien es Metatheorien der Internationalen Beziehungen, die Geschichte politischer Ökonomie oder Institutionentheorien, zeigen eine klare Dreiteilung von Weltanschauungen bzw. Paradigmen auf, die sich in allen „großen Debatten“ nachvollziehen lassen: Realismus, Liberalismus und Historischer Materialismus. Diese Grund legend unterschiedlichen Paradigmen lassen sich auch in aktuellen Ansätzen des Institutionalismus aufzeigen, liegen aber quer zu den von anderen Wissenschaftlern (Meyer, Rittberger, Hasenclever, Peters, Zangl) vorgenommenen Kategorisierungen der Institutionalismusschulen, die systemkritische Perspektiven in der Regel ignorieren oder vergleichsweise rudimentär diskutieren. Deshalb entwickelt diese Arbeit einen Vergleich von Institutionalismusschulen entlang der oben skizzierten Weltanschauungen. Das Ziel ist es, fundamentale Unterschiede zwischen den drei Paradigmen zu verdeutlichen und zu zeigen, wie ihre jeweiligen ontologischen und epistemologischen Prämissen die Forschungsdesigns und Methodologien der Institutionalismusschulen beeinflussen. In Teil I arbeite ich deshalb die Grund legenden Prämissen der jeweiligen Paradigmen heraus und entwickle in Teil II und III diesen Prämissen entsprechende Institutionalismus-Schulen, die Kooperation primär als Organisation von unüberwindbarer Rivalität, als Ergebnis zunehmender Konvergenz, oder als Ergebnis und Weiterentwicklung von Prozeduren der Interaktion versteht. Hier greife ich auf zeitgenössische Arbeiten anderer Autoren zurück und liefere damit einen Vergleich des aktuellen Forschungsstandes in allen drei Denktraditionen. Teil II diskutiert die zwei dominanten Institutionalismusschulen und Teil III entwickelt einen eigenen Gramscianischen Ansatz zur Erklärung von internationaler Kooperation und Institutionalisierung. Die übergeordnete These dieser Arbeit lautet, dass die Methodologien der dominanten Institutionalismusschulen teleologische Effekte haben, die aus dem Anspruch auf universell anwendbare, abstrahiert Konzepte resultieren und die Interpretation von Beobachtungen limitieren. Prämissen eines rational handelnden Individuums - entweder Konsequenzen kalkulierend oder Angemessenheit reflektierend – führen dazu, dass Kooperation und Institutionalisierung notwendiger Weise als die beste Lösung für alle Beteiligten in dieser Situation gelten müssen: Institutionen würden nicht bestehen, wenn sie nicht in der Summe allen Mitgliedern (egoistisch oder kooperativ motiviert) nützten. Durch diese interpretative „Brille“ finden wichtige strukturelle Gründe für die Verabschiedung internationaler Abkommen und Teile ihrer Effekte keine Berücksichtigung. Folglich können auch Abweichungen von erwarteten Ergebnissen nicht hinreichend erklärt werden. Meine entsprechende Hypothese lautet, dass systemkritische Kooperation konsistenter erklären können, da sie Akteure, Strukturen und die sie umgebenden Weltanschauungen selbst als analytische Kriterien berücksichtigen. Institutionalisierung wird dann als ein gradueller Prozess politischer Entscheidungsfindung, –umsetzung und –verankerung verstanden, der durch die vorherrschenden Institutionen und Interpretationen von „Realität“ beeinflusst wird. Jede politische Organisation wird als zeitlich-geographisch markierter Staatsraum (state space) verstanden, dessen Mandat die Festlegung von Prozeduren der Interaktion für gesellschaftliche Entwicklung ist. Politische Akteure handeln in Referenz auf diese offiziellen Prozeduren und reproduzieren und/oder verändern sie damit kontinuierlich. Institutionen werden damit als integraler Bestandteil gesellschaftlicher Entwicklungsprozesse verstanden und die Wirkungsmacht von Weltanschauungen – inklusive theoretischer Konzepte - berücksichtigt. Letztere leiten die Wahrnehmung und Interpretation von festgeschriebenen Regeln an und beeinflussen damit ihre empfundene Legitimation und Akzeptanz. Dieser Effekt wurde als „Staatsgeist“ („State Spirit“) von Montesquieu und Hegel diskutiert und von Antonio Gramsci in seiner Hegemonialtheorie aufgegriffen. Seine Berücksichtigung erlaubt eine konsistente Erklärung scheinbar irrationalen oder unangemessenen individuellen Entscheidens, sowie negativer Effekte konsensualer Abkommen. Zur Veranschaulichung der neu entwickelten Konzepte werden in Teil II existierende Fallstudien zur Welthandelsorganisation analysiert und herausgearbeitet, wie Weltanschauungen oder Paradigmen zu unterschiedlichen Erklärungen der Praxis führen. Während Teil II besonderes Augenmerk auf die nicht erklärten und innerhalb der dominanten Paradigmen nicht erklärbaren Beobachtungen legt, wendet Teil III die Gramscianischen Konzepte auf eben diese blinden Stellen an und liefert neue Einsichten. Im Ausblick wird problematisiert, dass scheinbar „neutrale“ wissenschaftliche Studien politische Positionen und Forderungen legitimieren und verdeutlicht im Sinne der gramscianischen Theorie, dass Wissenschaft selbst Teil politischer Auseinandersetzungen ist.