Da serra à costa: migração e modernização peruana na obra de Mario Vargas Llosa (1950-1960)

Pós-graduação em História - FCHS

Power Transient Analysis of Experimental Devices for Jules Horowitz Material Testing Reactor (JHR)

The objective of this thesis is the power transient analysis concerning experimental devices placed within the reflector of Jules Horowitz Reactor (JHR). Since JHR material testing facility is designed to achieve 100 MW core thermal power, a large reflector hosts fissile material samples that are irradiated up to total relevant power of 3 MW. MADISON devices are expected to attain 130 kW, conversely ADELINE nominal power is of some 60 kW. In addition, MOLFI test samples are envisaged to reach 360 kW for what concerns LEU configuration and up to 650 kW according to HEU frame. Safety issues concern shutdown transients and need particular verifications about thermal power decreasing of these fissile samples with respect to core kinetics, as far as single device reactivity determination is concerned. Calculation model is conceived and applied in order to properly account for different nuclear heating processes and relative time-dependent features of device transients. An innovative methodology is carried out since flux shape modification during control rod insertions is investigated regarding the impact on device power through core-reflector coupling coefficients. In fact, previous methods considering only nominal core-reflector parameters are then improved. Moreover, delayed emissions effect is evaluated about spatial impact on devices of a diffuse in-core delayed neutron source. Delayed gammas transport related to fission products concentration is taken into account through evolution calculations of different fuel compositions in equilibrium cycle. Provided accurate device reactivity control, power transients are then computed for every sample according to envisaged shutdown procedures. Results obtained in this study are aimed at design feedback and reactor management optimization by JHR project team. Moreover, Safety Report is intended to utilize present analysis for improved device characterization.

Absence of the calcium-binding protein calretinin, not of calbindin D-28k, causes a permanent impairment of murine adult hippocampal neurogenesis

Calretinin (CR) and calbindin D-28k (CB) are cytosolic EF-hand Ca(2+)-binding proteins and function as Ca(2+) buffers affecting the spatiotemporal aspects of Ca(2+) transients and possibly also as Ca(2+) sensors modulating signaling cascades. In the adult hippocampal circuitry, CR and CB are expressed in specific principal neurons and subsets of interneurons. In addition, CR is transiently expressed within the neurogenic dentate gyrus (DG) niche. CR and CB expression during adult neurogenesis mark critical transition stages, onset of differentiation for CR, and the switch to adult-like connectivity for CB. Absence of either protein during these stages in null-mutant mice may have functional consequences and contribute to some aspects of the identified phenotypes. We report the impact of CR- and CB-deficiency on the proliferation and differentiation of progenitor cells within the subgranular zone (SGZ) neurogenic niche of the DG. Effects were evaluated (1) two and four weeks postnatally, during the transition period of the proliferative matrix to the adult state, and (2) in adult animals (3 months) to trace possible permanent changes in adult neurogenesis. The absence of CB from differentiated DG granule cells has no retrograde effect on the proliferative activity of progenitor cells, nor affects survival or migration/differentiation of newborn neurons in the adult DG including the SGZ. On the contrary, lack of CR from immature early postmitotic granule cells causes an early loss in proliferative capacity of the SGZ that is maintained into adult age, when it has a further impact on the migration/survival of newborn granule cells. The transient CR expression at the onset of adult neurogenesis differentiation may thus have two functions: (1) to serve as a self-maintenance signal for the pool of cells at the same stage of neurogenesis contributing to their survival/differentiation, and (2) it may contribute to retrograde signaling required for maintenance of the progenitor pool.

Tyrosine kinase modulation of protein kinase C activity regulates G protein-linked Ca2+ signaling in leukemic hematopoietic cells

We have used a recombinant mouse pre-B cell line (TonB210.1, expressing Bcr/Abl under the control of an inducible promoter) and several human leukemia cell lines to study the effect of high tyrosine kinase activity on G protein-coupled receptor (GPCR) agonist-stimulated cellular Ca(2+) release and store-operated Ca(2+) entry (SOCE). After induction of Bcr/Abl expression, GPCR-linked SOCE increased. The effect was reverted in the presence of the specific Abl inhibitor imatinib (1microM) and the Src inhibitor PP2 (10microM). In leukemic cell lines constitutively expressing high tyrosine kinase activity, Ca(2+) transients were reduced by imatinib and/or PP2. Ca(2+) transients were enhanced by specific inhibitors of PKC subtypes and this effect was amplified by tyrosine kinase inhibition in Bcr/Abl expressing TonB210.1 and K562 cells. Under all conditions Ca(2+) transients were essentially blocked by the PKC activator PMA. In Bcr/Abl expressing (but not in native) TonB210.1 cells, tyrosine kinase inhibitors enhanced PKCalpha catalytic activity and PKCalpha co-immunoprecipitated with Bcr/Abl. Unlike native TonB210.1 cells, Bcr/Abl expressing cells showed a high rate of cell death if Ca(2+) influx was reduced by complexing extracellular Ca(2+) with BAPTA. Our data suggest that tonic inhibition of PKC represents a mechanism by which high tyrosine kinase activity can enhance cellular Ca(2+) transients and thus exert profound effects on the proliferation, apoptosis and chemotaxis of leukemic cells.

Apparent survival of the salamander

Background Understanding the demographic processes underlying population dynamics is a central theme in ecology. Populations decline if losses from the population (i.e., mortality and emigration) exceed gains (i.e., recruitment and immigration). Amphibians are thought to exhibit little movement even though local populations often fluctuate dramatically and are likely to go exinct if there is no rescue effect through immigration from nearby populations. Terrestrial salamanders are generally portrayed as amphibians with low migratory activity. Our study uses demographic analysis as a key to unravel whether emigration or mortality is the main cause of "losses" from the population. In particular, we use the analysis to challenge the common belief that terrestrial salamanders show low migratory activity. Results The mark-recapture analysis of adult salamanders showed that monthly survival was high (> 90%) without a seasonal pattern. These estimates, however, translate into rather low rates of local annual survival of only ~40% and suggest that emigration was important. The estimated probability of emigration was 49%. Conclusion Our analysis shows that terrestrial salamanders exhibit more migratory activity than commonly thought. This may be due either because the spatial extent of salamander populations is underestimated or because there is a substantial exchange of individuals between populations. Our current results are in line with several other studies that suggest high migratory activity in amphibians. In particular, many amphibian populations may be characterized by high proportions of transients and/or floaters.

Beta-caryophyllene is a dietary cannabinoid

The psychoactive cannabinoids from Cannabis sativa L. and the arachidonic acid-derived endocannabinoids are nonselective natural ligands for cannabinoid receptor type 1 (CB(1)) and CB(2) receptors. Although the CB(1) receptor is responsible for the psychomodulatory effects, activation of the CB(2) receptor is a potential therapeutic strategy for the treatment of inflammation, pain, atherosclerosis, and osteoporosis. Here, we report that the widespread plant volatile (E)-beta-caryophyllene [(E)-BCP] selectively binds to the CB(2) receptor (K(i) = 155 +/- 4 nM) and that it is a functional CB(2) agonist. Intriguingly, (E)-BCP is a common constituent of the essential oils of numerous spice and food plants and a major component in Cannabis. Molecular docking simulations have identified a putative binding site of (E)-BCP in the CB(2) receptor, showing ligand pi-pi stacking interactions with residues F117 and W258. Upon binding to the CB(2) receptor, (E)-BCP inhibits adenylate cylcase, leads to intracellular calcium transients and weakly activates the mitogen-activated kinases Erk1/2 and p38 in primary human monocytes. (E)-BCP (500 nM) inhibits lipopolysaccharide (LPS)-induced proinflammatory cytokine expression in peripheral blood and attenuates LPS-stimulated Erk1/2 and JNK1/2 phosphorylation in monocytes. Furthermore, peroral (E)-BCP at 5 mg/kg strongly reduces the carrageenan-induced inflammatory response in wild-type mice but not in mice lacking CB(2) receptors, providing evidence that this natural product exerts cannabimimetic effects in vivo. These results identify (E)-BCP as a functional nonpsychoactive CB(2) receptor ligand in foodstuff and as a macrocyclic antiinflammatory cannabinoid in Cannabis.

Psychosocial aspects on the treatment of HIV-infection

Psychological and social factors have a deep impact on the treatment of HIV-infection, from the readiness to start antiretroviral therapy to treatment adherence over time. Among psychological factors, anxiety may affect HIV-infected persons in all stages of disease, from the disclosure of HIV diagnosis to the decision to start and maintain treatment. This is a lifelong challenge for both patients and doctors. Psychiatric comorbidities (depression, addiction) may enhance negative psychological effects of HIV. Among social factors, stigma and discrimination may occur in families and at work, leading to a loss of social support resulting in isolation and poverty. This may prevent HIV-positive individuals from seeking medical care. These aspects are particularly important in some groups of patients as injecting drug users and migrants. Acknowledgment and consideration of psychosocial factors are therefore essential for the long term success of antiretroviral therapy.

Efficient algorithms for dynamic probabilistic safety assessment. An application to convex damage domain.

The design of nuclear power plant has to follow a number of regulations aimed at limiting the risks inherent in this type of installation. The goal is to prevent and to limit the consequences of any possible incident that might threaten the public or the environment. To verify that the safety requirements are met a safety assessment process is followed. Safety analysis is as key component of a safety assessment, which incorporates both probabilistic and deterministic approaches. The deterministic approach attempts to ensure that the various situations, and in particular accidents, that are considered to be plausible, have been taken into account, and that the monitoring systems and engineered safety and safeguard systems will be capable of ensuring the safety goals. On the other hand, probabilistic safety analysis tries to demonstrate that the safety requirements are met for potential accidents both within and beyond the design basis, thus identifying vulnerabilities not necessarily accessible through deterministic safety analysis alone. Probabilistic safety assessment (PSA) methodology is widely used in the nuclear industry and is especially effective in comprehensive assessment of the measures needed to prevent accidents with small probability but severe consequences. Still, the trend towards a risk informed regulation (RIR) demanded a more extended use of risk assessment techniques with a significant need to further extend PSA’s scope and quality. Here is where the theory of stimulated dynamics (TSD) intervenes, as it is the mathematical foundation of the integrated safety assessment (ISA) methodology developed by the CSN(Consejo de Seguridad Nuclear) branch of Modelling and Simulation (MOSI). Such methodology attempts to extend classical PSA including accident dynamic analysis, an assessment of the damage associated to the transients and a computation of the damage frequency. The application of this ISA methodology requires a computational framework called SCAIS (Simulation Code System for Integrated Safety Assessment). SCAIS provides accident dynamic analysis support through simulation of nuclear accident sequences and operating procedures. Furthermore, it includes probabilistic quantification of fault trees and sequences; and integration and statistic treatment of risk metrics. SCAIS comprehensively implies an intensive use of code coupling techniques to join typical thermal hydraulic analysis, severe accident and probability calculation codes. The integration of accident simulation in the risk assessment process and thus requiring the use of complex nuclear plant models is what makes it so powerful, yet at the cost of an enormous increase in complexity. As the complexity of the process is primarily focused on such accident simulation codes, the question of whether it is possible to reduce the number of required simulation arises, which will be the focus of the present work. This document presents the work done on the investigation of more efficient techniques applied to the process of risk assessment inside the mentioned ISA methodology. Therefore such techniques will have the primary goal of decreasing the number of simulation needed for an adequate estimation of the damage probability. As the methodology and tools are relatively recent, there is not much work done inside this line of investigation, making it a quite difficult but necessary task, and because of time limitations the scope of the work had to be reduced. Therefore, some assumptions were made to work in simplified scenarios best suited for an initial approximation to the problem. The following section tries to explain in detail the process followed to design and test the developed techniques. Then, the next section introduces the general concepts and formulae of the TSD theory which are at the core of the risk assessment process. Afterwards a description of the simulation framework requirements and design is given. Followed by an introduction to the developed techniques, giving full detail of its mathematical background and its procedures. Later, the test case used is described and result from the application of the techniques is shown. Finally the conclusions are presented and future lines of work are exposed.

Modulação da diferenciação neural de células troco embrionárias por transientes de cálcio intracelulares: papéis dos receptores purinérgicos e de canais de cálcio voltagem-dependentes

Receptores purinérgicos e canais de cálcio voltagem-dependentes estão envolvidos em diversos processos biológicos como na gastrulação, durante o desenvolvimento embrionário, e na diferenciação neural. Quando ativados, canais de cálcio voltagem-dependentes e receptores purinérgicos do tipo P2, ativados por nucleotídeos, desencadeiam transientes de cálcio intracelulares controlando diversos processos biológicos. Neste trabalho, nós estudamos a participação de canais de cálcio voltagem-dependentes e receptores do tipo P2 na geração de transientes de cálcio espontâneos e sua regulação na expressão de fatores de transcrição relacionados com a neurogênese utilizando como modelo células tronco (CTE) induzidas à diferenciação em células tronco neurais (NSC) com ácido retinóico. Descrevemos que CTE indiferenciadas podem ter a proliferação acelerada pela ativação de receptores P2X7, enquanto que a expressão e a atividade desse receptor precisam ser inibidas para o progresso da diferenciação em neuroblasto. Além disso, ao longo da diferenciação neural, por análise em tempo real dos níveis de cálcio intracelular livre identificamos 3 padrões de oscilações espontâneas de cálcio (onda, pico e unique), e mostramos que ondas e picos tiveram a frequência e amplitude aumentadas conforme o andamento da diferenciação. Células tratadas com o inibidor do receptor de inositol 1,4,5-trifosfato (IP3R), Xestospongin C, apresentaram picos mas não ondas, indicando que ondas dependem exclusivamente de cálcio oriundo do retículo endoplasmático pela ativação de IP3R. NSC de telencéfalo de embrião de camundongos transgênicos ou pré-diferenciadas de CTE tratadas com Bz-ATP, o agonista do receptor P2X7, e com 2SUTP, agonista de P2Y2 e P2Y4, aumentaram a frequência e a amplitude das oscilações espontâneas de cálcio do tipo pico. Dados, obtidos por microscopia de luminescência, da expressão em tempo real de gene repórter luciferase fusionado à Mash1 e Ngn2 revelou que a ativação dos receptores P2Y2/P2Y4 aumentou a expressão estável de Mash1 enquanto que ativação do receptor P2X7 levou ao aumento de Ngn2. Além disso, células na presença do quelante de cálcio extracelular (EGTA) ou do depletor dos estoques intracelulares de cálcio do retículo endoplasmático (thapsigargin) apresentaram redução na expressão de Mash1 e Ngn2, indicando que ambos são regulados pela sinalização de cálcio. A investigação dos canais de cálcio voltagem-dependentes demonstrou que o influxo de cálcio gerado por despolarização da membrana de NSC diferenciadas de CTE é decorrente da ativação de canais de cálcio voltagem-dependentes do tipo L. Além disso, esse influxo pode controlar o destino celular por estabilizar expressão de Mash1 e induzir a diferenciação neuronal por fosforilação e translocação do fator de transcrição CREB. Esses dados sugerem que os receptores P2X7, P2Y2, P2Y4 e canais de cálcio voltagem-dependentes do tipo L podem modular as oscilações espontâneas de cálcio durante a diferenciação neural e consequentemente alteram o padrão de expressão de Mash1 e Ngn2 favorecendo a decisão do destino celular neuronal.

Aplicação de mapas auto-organizáveis na classificação de padrões de escoamento bifásico

O escoamento bifásico de gás-líquido é encontrado em muitos circuitos fechados que utilizam circulação natural para fins de resfriamento. O fenômeno da circulação natural é importante nos recentes projetos de centrais nucleares para a remoção de calor. O circuito de circulação natural (Circuito de Circulação Natural - CCN), instalado no Instituto de Pesquisas Energéticas e Nucleares, IPEN / CNEN, é um circuito experimento concebido para fornecer dados termo-hidráulicos relacionados com escoamento monofásico ou bifásico em condições de circulação natural. A estimativa de transferência de calor tem sido melhorada com base em modelos que requerem uma previsão precisa de transições de padrão de escoamento. Este trabalho apresenta testes experimentais desenvolvidos no CCN para a visualização dos fenômenos de instabilidade em ciclos de circulação natural básica e classificar os padrões de escoamento bifásico associados aos transientes e instabilidades estáticas de escoamento. As imagens são comparadas e agrupadas utilizando mapas auto-organizáveis de Kohonen (SOM), aplicados em diferentes características da imagem digital. Coeficientes da Transformada Discreta de Cossenos de Quadro Completo (FFDCT) foram utilizados como entrada para a tarefa de classificação, levando a bons resultados. Os protótipos de FFDCT obtidos podem ser associados a cada padrão de escoamento possibilitando uma melhor compreensão da instabilidade observada. Uma metodologia sistemática foi utilizada para verificar a robustez do método.

EU enlargement to the Balkans: will the leopard change its spots? EPC Commentary, 29 September 2014

As the leadership of the European Union hands over the baton to a new management this autumn, will the winds of change blow also through the cobwebs of the EU’s enlargement agenda? Jean-Claude Juncker – the incoming President of the European Commission – has already promised to put the gearbox of further EU widening in neutral for the next five years of his mandate, and has designated the Austrian Johannes Hahn as Commissioner for the re-baptised portfolio of now European Neighbourhood Policy and Enlargement Negotiations, instructing him to focus on the Union’s political and economic ties with Southern and Eastern Europe, and in particular with the Balkans. Such an approach in the field of enlargement – once crowned the jewel of EU foreign policy – has all the appeal of a damp rag but does not necessarily depart from the festina lente strategy of the recent past. Inside the Union, political appetite and public support for expansion have been fizzling since Bulgaria and Romania joined in 2007, and were then severely curbed in the context of the on-going crisis by growing fears of importing organised crime and migrants from the Balkans. Juncker’s logic of consolidation sounds depressingly similar to what it supposedly replaces and incidentally, it also fits neatly with the unambitious and inward-looking mantra favoured at present in discussions at all levels on the future of European integration, more generally. With the 28-member block determined to catch its breath in the immediate time period, and given that even the forerunner countries in the Balkans – that is, Montenegro and Serbia – will realistically need more than five years to complete their accession talks, what priorities should guide Commissioner Hahn, soon to be Directorate-General for Neighbourhood and Enlargement Negotiations – when they get down to business on 1 November?

The Migration Crisis: A Stress Test for European Values. European Policy Brief No. 38, September 2015

Confronted by the current refugee crisis, most Member States are turning inwards. But migration will continue to rise in the future. Given that migration is an unstoppable trend, the EU has everything to win from turning this crisis into an opportunity for its own citizens and economy, for the refugees and migrants it hosts and for their countries of origin. The manner in which the EU addresses this challenge will truly prove if it can live up to its founding principles of human dignity, solidarity, freedom, democracy and equality. This policy brief summarises European measures taken in the last few months and proposes four key actions to create a well-framed European migration policy: effectively implementing the principle of solidarity and fair-sharing of responsibility between Member States; creating more legal entry and integration channels; addressing the root causes of migration; and broadcasting a constructive and positive narrative on migration.

An examination of the determinants of entrepreneurship at the regional level:the case of East Midlands region

Despite the importance of new firms to the economy, determinants of start-ups have mainly been examined at a country level and discussion of regional entrepreneurial activity has received less attention. Since there are significant variations in entrepreneurship rates across and within countries, such an investigation at a regional level would help in gaining an in depth understanding of the impact of the individual level resource endowments and neighbourhood characteristics on an individual’s decision to engage in entrepreneurial activity. The main aim of the thesis is to explore various theories of entrepreneurship and develop integrated frameworks for examining the determinants of entrepreneurial activity at a neighbourhood level in the East Midlands region in England. The specific objectives of the thesis are to examine how the individual level resources and the neighbourhood characteristics: (i) combine to influence an individual to engage in the different stages of the entrepreneurial process, (ii) influence natives and migrants to engage in start up activity and (iii) influence women and men to become self-employed and ambitious entrepreneurs. In terms of the methodology, the empirical analysis is based on two databases combined: 2006 to 2009 GEM East Midlands region and the English Index of Multiple Deprivation dataset. Based on the critical review of the literature on entrepreneurship the thesis develop theoretical frameworks which led to formulate hypotheses related to the differentiated impact of both individual and neighbourhood level factors on the propensity of an individual to be involved in entrepreneurial activity. The findings indicate that the determinants of entrepreneurial activity vary with human, financial and the local environment factors affecting the entrepreneurial process. Finally, the thesis calls for caution when developing and applying generic and specific policy measures aimed at promoting entry into entrepreneurship.

Central American refugees in Costa Rica

The conflicts of the past decade in Central America have produced substantial refugee movements into neighboring nations. Costa Rica has had to cope with an influx of refugees and migrants as large as 10 percent of its population. This work presents a case study of the situation in Costa Rica, focusing on the issue of refugee integration into the host society. It draws on qualitative field research conducted in that country during 1986. The study discusses the evolution of the Costa Rican state's response to the refugee crisis and analyzes the characteristics and impact of policies undertaken by various state bureaucracies. It also describes the assistance efforts of the United Nations High Commissioner for Refugees and private voluntary organizations, along with their interaction with the Costa Rican state. The study concludes that the government's need to maintain firm control of refugee programs has overshadowed its commitment to refugee integration. In so doing, the humanitarian purpose of refugee assistance has been compromised.

Rethinking Care Through Social Reproduction: Articulating Circuits of Migration

Care has come to dominate much feminist research on globalized migrations and the transfer of labor from the South to the North, while the older concept of reproduction had been pushed into the background but is now becoming the subject of debates on the commodification of care in the household and changes in welfare state policies. This article argues that we could achieve a better understanding of the different modalities and trajectories of care in the reproduction of individuals, families, and communities, both of migrant and nonmigrant populations by articulating the diverse circuits of migration, in particular that of labor and the family. In doing this, I go back to the earlier North American writing on racialized minorities and migrants and stratified social reproduction. I also explore insights from current Asian studies of gendered circuits of migration connecting labor and marriage migrations as well as the notion of global householding that highlights the gender politics of social reproduction operating within and beyond households in institutional and welfare architectures. In contrast to Asia, there has relatively been little exploration in European studies of the articulation of labor and family migrations through the lens of social reproduction. However, connecting the different types of migration enables us to achieve a more complex understanding of care trajectories and their contribution to social reproduction.