Reprogramming energy metabolism and inducing angiogenesis : co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas

Reprogramming energy metabolism and inducing angiogenesis: co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas.

Patente farmacêutica: especificidades e tutela

Dissertação de mestrado em Direito dos Contratos e da Empresa

Optimization of peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) for the detection of bacteria: the effect of pH, dextran sulfate and probe concentration

Fluorescence in situ hybridization (FISH) is a molecular technique widely used for the detection and characterization of microbial populations. FISH is affected by a wide variety of abiotic and biotic variables and the way they interact with each other. This is translated into a wide variability of FISH procedures found in the literature. The aim of this work is to systematically study the effects of pH, dextran sulfate and probe concentration in the FISH protocol, using a general peptide nucleic acid (PNA) probe for the Eubacteria domain. For this, response surface methodology was used to optimize these 3 PNA-FISH parameters for Gram-negative (Escherichia coli and Pseudomonas fluorescens) and Gram-positive species (Listeria innocua, Staphylococcus epidermidis and Bacillus cereus). The obtained results show that a probe concentration higher than 300 nM is favorable for both groups. Interestingly, a clear distinction between the two groups regarding the optimal pH and dextran sulfate concentration was found: a high pH (approx. 10), combined with lower dextran sulfate concentration (approx. 2% [w/v]) for Gram-negative species and near-neutral pH (approx. 8), together with higher dextran sulfate concentrations (approx. 10% [w/v]) for Gram-positive species. This behavior seems to result from an interplay between pH and dextran sulfate and their ability to influence probe concentration and diffusion towards the rRNA target. This study shows that, for an optimum hybridization protocol, dextran sulfate and pH should be adjusted according to the target bacteria.

Interpersonal and attitudinal factors in women's work role: Cross-cultural comparison

The last four decades have seen a dramatic increase in the number of women entering employment. This is particularly true in Europe and although more European women are working outside the home, the patterns of female employment have changed very little. An analysis of these patterns is presented. It was found that women continue to dominate specific fields, particularly teaching and service providing. An investigation of the interpersonal behavior differences among 117 American women from the southeastern United States in three work roles--homemakers, women in traditional occupations, and in nontraditional occupations--was conducted and the sex-role orientation, attitudes toward success, and demographic indicators were examined in order to consider the interplay of these variables with female occupational role and interpersonal behavior. A second focus of the study is on the cross-cultural comparison of the psychological and work variables in women of two different cultures: America and Portugal. Thirty-one Portuguese women were a preliminary comparison sample. The American results showed significant differences between groups in self-perceived interpersonal behaviors and the findings contradicted current stereotypes. The cross-cultural data, although preliminary, indicates differences between the countries in social desirability, aggressive and assertive behaviors, and in sex-role attitudes, which seem to reflect the different stages of economic development. (MKA)

Determination of the importance of iron acquisition for Staphylococcus epidermidis biofilm survival in human blood

Dissertação de mestrado em Bioengenharia

Careers, identities and professionalization. A study on doctors about their social representations related to the labor market today and its foreseeable future

This study is in line with the analyses of university and working career in their interaction in relation with conditioning factors. It comprises two central issues: the issue of identity bound to the issue of professionalization within the domain of training and employment. Nowadays, professionalization of the individuals, inside a troubled occupational world, demands the implementation of mechanisms favoring the development of both the individuals and the institution in which they work. All this has an impact at the local, regional and even national levels. Three levels of analysis interplay from a sui generis perspective: macro-meso-micro-macro (Aparicio, 2005; 2007a; 2007b, 2013a, 2014, 2015 b, d – See the Three- Dimensional Spiral of Sense Theory). The aim was to be aware of the doctors’ representations regarding the value of such degree under the present “degree devaluation”, and its impact on the professional future as well as on the core issues of the labor market which need urgent measures with a view to a belter interaction between the two systems. The methodology used was quanti-qualitative (semi-structured questionnaires, interviews, and hierarchical evocations). The population consisted of doctors (2005-2012) from the National University of Cuyo, in Argentina. The results helped us understand the nucleus of such representations and the peripheral aspects by career and institution, thus revealing professional and disciplinary identities. The professional identities show the situated needs in terms of professionalization within the different contexts and, particularly, within the labor market.

O trabalho coletivo do Departamento de Educação Física e a gestão da ecologia das aulas : a integração da agenda social dos alunos nas decisões de planeamento e ação dos professores

O estudo das condições que potenciam o ensino-aprendizagem em educação física precisa de considerar mais consistentemente e explicitamente as evidências do mesossistema estabelecido entre as ecologias do trabalho colaborativo do grupo disciplinar e as das suas aulas. Especificamente, incita-se à compreensão como a negociação integradora do sistema social dos alunos pode ser potenciada pelo grupo disciplinar. Para alcançar essa compreensão articularam-se os modelos das comunidades de aprendizagem profissional e da ecologia da aula, através da bioecologia do desenvolvimento humano. Conduziu-se um desenho de estudo de caso longitudinal integrado, triangulando métodos, fontes e dados de um grupo disciplinar de educação física com qualidade colaborativa. Simultaneamente, observaram-se duas ecologias de aulas de educação física, diferenciadas pelas disposições de negociação dos respetivos professores, detalhando paralelamente os perfis de agenda social dos alunos para essas ecologias. Os resultados permitem salientar a interação das propriedades Pessoa-Contexto-Processo-Tempo como condições mesossistémicas favorecedoras da integração do sistema social dos alunos, nomeadamente: as caraterísticas do grupo como comunidade de aprendizagem profissional focada na integração; a interação macrossistémica e a alternância intencional cíclica grupo-aula; e a articulação entre o desenvolvimento curricular colaborativo e a partilha e produção de conhecimento em espirais curriculares plurianuais e anuais. Estas condições refletiram-se nas ecologias das aulas como semelhanças tendencialmente integradoras do sistema social na instrução e na organização. Todavia, também emergiram particularidades em cada ecologia traduzidas numa congruência mais consistente entre os perfis de agenda social encontrados para o envolvimento integrador, por associação às diferenças de alinhamento instrucional na negociação pelos professores. Este estudo lança implicações para a investigação relacionadas com a verificação e aprofundamento das condições mesossistémicas identificadas. Paralelamente, a prática profissional de professores e de formadores de professores encontra implicações sobre a melhoria da qualidade colaborativa profissional para promover continuamente melhores experiências de ensino-aprendizagem da educação física nos microssistemas aqui analisados.

Defining habitat characteristics influencing the distribution, density and growth of Plaice (Pleuronectes Platessa) and Dab (Limanda Limanda) on west of Ireland nursery grounds

Plaice (Pleuronectes platessa, L.) and dab (Limanda limanda, L.) are among the most abundant flatfishes in the north-eastern Atlantic region and the dominant species in shallow coastal nursery grounds. With increasing pressures on commercial flatfish stocks in combination with changing coastal environments, better knowledge of population dynamics during all life stages is needed to evaluate variability in year-class strength and recruitment to the fishery. The aim of this research was to investigate the complex interplay of biotic and abiotic habitat components influencing the distribution, density and growth of plaice and dab during the vulnerable juvenile life stage and to gain insight in spatial and temporal differences in nursery habitat quality along the west coast of Ireland. Intraspecific variability in plaice diet was observed at different spatial scales and showed a link with condition, recent growth and morphology. This highlights the effect of food availability on habitat quality and the need to consider small scale variation when attempting to link habitat quality to feeding, growth and condition of juvenile flatfish. There was evidence of trophic, spatial and temporal resource partitioning between juvenile plaice and dab allowing the co-existence of morphologically similar species in nursery grounds. In the limited survey years there was no evidence that the carrying capacity of the studied nursery grounds was reached but spatial and interannual variations in fish growth indicated fluctuating environments in terms of food availability, predator densities, sediment features and physico-chemical conditions. Predation was the most important factor affecting habitat quality for juvenile plaice and dab with crab densities negatively correlated to fish condition whereas shrimp densities were negatively associated with densities of small-sized juveniles in spring. A comparison of proxies for fish growth showed the advantage of Fulton’s K for routine use whereas RNA:DNA ratios proved less powerful when short-term environmental fluctuations are lacking. This study illustrated how distinct sets of habitat features can drive spatial variation in density and condition of juvenile flatfish highlighting the value of studying both variables when modeling habitat requirements. The habitat models generated in this study also provide a powerful tool to predict potential climate and anthropogenic impacts on the distribution and condition of juveniles in flatfish nurseries. The need for effective coastal zone management was emphasized to ensure a sustainable use of coastal resources and successful flatfish recruitment to the fishery.

The challenges of establishing the electric vehicle in Ireland

This thesis investigates the challenges of establishing the electric vehicle (EV) in Ireland and how the Irish government and industry are trying to meet them. It further seeks to provide information on Irish consumers’ attitudes towards the electric vehicle and their willingness to purchase it. The review of the literature showed that the Irish government is investing significant funds in trying to establish the market for the electric vehicle and position itself as a world leader in adopting the electric vehicle. The EV will also have an important role to play in how Ireland meets its targets for CO2 reductions towards 2020. Climate change and use of fossil fuels are driving the need for increased use of renewable energy and increased energy independence while reducing the greenhouse gas emissions that are the leading cause of climate change. The transport sector is almost completely dependent on the use of fossil fuel and resultantly is one of the largest sources of these GHG emissions. These issues are leading to the design and production of more energy efficient and environmentally friendly vehicles. The ultimate goal is to achieve a zero emissions vehicle. The electric vehicle is presently the only vehicle being mass produced that has the potential to be zero emissions. There are however issues that customers may not be willing to overlook such as the lower range of the vehicle and the length of time it takes to recharge. Vehicle cost is also an important issue that customers may not overlook. Knowing what the consumer’s attitudes are towards the EV and their willingness to purchase them is important as these new vehicles begin to appear in the showrooms. The consumers will be vital to how successful this market becomes. Using an online questionnaire methodology, in a sample of 118 consumers, the major conclusion to be drawn from the research is that the vehicle price, the convenience to recharge and vehicle range were the three most essential issues for the consumers if they were purchasing an EV. The success of the electric vehicle market may depend on what measures are taken to overcome them.

Rational sabotage in cooperative production

In this paper we consider a model of cooperative production in which rational agents have the possibility to engage in sabotage activities that decrease output. It is shown that sabotage depends on the interplay between the degree of congestion, the technology of sabotage, the number of agents the degree of meritocracy and the form of the sharing rule. In particular it is shown that, ceteries paribus, meritocratic systems give more incentives to sabotage than egalitarian systems. We address two questions: The degree of meritocracy that is compatible with absence of sabotage and the existence of a Nash equilibrium with and without sabotage.

De l'economia a les mentalitats: reforma agrària, desenvolupament rural i identitat ètnica als Andes

Estudi elaborat a partir d’una estada a la Facultad Latinoamericana de Ciencias Sociales, Ecuador, entre setembre i desembre del 2006. El projecte té l'objectiu general d'elaborar una monografia, entre el treball d’arxiu i el de camp, capaç d’exemplificar els processos de consolidació dels sectors dirigents indígenes i de vincular-los amb les transformacions de la societat rural andina contemporània. L’estudi de cas és el d’una organització de segon grau molt representativa (la UNOCANC, parròquia de Toacazo, província de Cotopaxi, Equador), analitzant el que han significat aquest canvis des de la descomposició del règim d’hisenda fins a l’ascens d’una part de l’élite camperola local a les altes instàncies de la CONAIE (Confederación de Nacionalidades Indígenas del Ecuador).

Nuclear factor I-C links platelet-derived growth factor and transforming growth factor beta1 signaling to skin wound healing progression.

Transforming growth factor beta (TGF-beta) and platelet-derived growth factor A (PDGFAlpha) play a central role in tissue morphogenesis and repair, but their interplay remain poorly understood. The nuclear factor I C (NFI-C) transcription factor has been implicated in TGF-beta signaling, extracellular matrix deposition, and skin appendage pathologies, but a potential role in skin morphogenesis or healing had not been assessed. To evaluate this possibility, we performed a global gene expression analysis in NFI-C(-/-) and wild-type embryonic primary murine fibroblasts. This indicated that NFI-C acts mostly to repress gene expression in response to TGF-beta1. Misregulated genes were prominently overrepresented by regulators of connective tissue inflammation and repair. In vivo skin healing revealed a faster inflammatory stage and wound closure in NFI-C(-/-) mice. Expression of PDGFA and PDGF-receptor alpha were increased in wounds of NFI-C(-/-) mice, explaining the early recruitment of macrophages and fibroblasts. Differentiation of fibroblasts to contractile myofibroblasts was also elevated, providing a rationale for faster wound closure. Taken together with the role of TGF-beta in myofibroblast differentiation, our results imply a central role of NFI-C in the interplay of the two signaling pathways and in regulation of the progression of tissue regeneration.

Role of cytokines in secondary lymphoid organ development

Summary Secondary lymphoid organs are sites of antigen presentation, clonal expansion of B and lymphocytes, and affinity maturation of B lymphocytes. In the intestine, these immune functions occur mainly in Peyer's patches (PP). PP develop through the interplay of two main cell types, haematopoietic cells and meserichyrnal cells. One particular haematopoietic cell type was identified as the inductive cell type in the formation of both PP and lymph nodes and was therefore designated as lymphoid tissue inducer cell. For a successful PP organogenesis, the crucial molecular components involved in the crosstalk of inducer cells and their mesenchymal target cells are adhesion molecules, lymphotoxin (LT) family members, and cytokines. In particular, the interleukin 7 receptor (IL-7R) expressed on inducer cells is absolutely required. To investigate the contribution of the ligand for the IL-7R. the cytokine IL-7, in the process of PP formation, we analyzed double transgenic (TG) mice. These mice resulted from an interbreeding of an IL-7TG mouse strain where the transgene is under the control of the MHC class II promoter with a second transgenic mouse strain, which overexpresses a transactivator for MHC class II genes. Double TG offsprings revealed higher levels of IL-7 mRNA occuring earlier in embryogenesis. Consequently, double TG mice showed a striking phenotype with a 3- to 5-fold increase in PP numbers compared to single IL-7TG or control littermates. Analysis of embryonic double TG intestines demonstrated that the process of PP development was already elevated during development as early as the embryonic day 16.5. Importantly, inducer cells were significantly increased in numbers in these embryonic intestines. Furthermore, the expression of LT? mRNA, which at this early time point is exclusively expressed by inducer cells, was also increased in double TG animals. These data clearly indicate a direct influence of IL-7 on the expansion of lymphoid tissue inducer cells and on the availability of LT? leading to a higher frequency of developing PP in fetal life. Interestingly, in addition to an enhanced frequency of PP development, in double TG mice, three additional phenotypic differences were observed. i) Lymphocyte infiltration in various non-lymphoid organs, such as stomach, salivary gland, and liver. Subsequent analysis demonstrated that B lymphocytes were predominant within these tertiary lymphoid structures. ii) Ectopic lymph node-like structures containing both B and T lymphocytes were found near the inguinal lymph node. iii) Double TG mice had a severe bone resorption syndrome most likely as a consequence of the pro-osteoclastic effect of IL-7. Taken together, these results show that IL-7 plays a key role in the homeostasis of inducer cells, in the generation of PP in the gut, in the formation of ectopic lymphoid tissue, and in bone resorption. Résumé Les organes lymphoïdes secondaires sont les lieux de présentation des antigènes aux lymphocytes, permettant l'expansion des lymphocytes B et T et la maturation d'affinité des lymphocytes B. Dans l'intestin, ces fonctions immunitaires se déroulent dans les plaques de Peyer (PP). Ces plaques se développent grâce à l'interaction des cellules hématopoïétiques avec des cellules mésenchymales. Un type particulier de cellules hématopoïétiques a été identifié comme cellule inductrice dans la formation des PP et des ganglions lymphatiques et de ce fait a été désigné cellule inductrice des tissus lymphoïdes. Durant l'organogénèse des PP, les composants moléculaires cruciaux impliqués dans l'interaction des cellules inductrices et des cellules mésenchymales sont les molécules d'adhésion, les membres de la famille des lymphotoxines (LT) et les cytokines. En particulier, le récepteur de l'interleukine 7 (IL-7R) exprimé par les cellules inductrices est absolument nécessaire. Pour étudier le rôle du ligand de l'IL-7R, l'interleukine IL-7, dans la formation des PP, nous avons croisé une lignée de souris transgénique (TG) surexprimant IL-7 sous contrôle du promoteur MHC class Il avec une lignée de souris transgénique surexprimant un transactivateur des genes MHC class II. Les souris doubles TG présentent une concentration élevée d'ARNm de l'IL-7 durant l'embryogénèse, ce qui résulte en une augmentation du nombre de PP de 3 à 5 fois en comparaison aux souris ayant seul le transgène IL-7 et aux souris contrôles. L'analyse des intestins des souris doubles TG démontre que le processus de développement des PP était élevé dès le jour 16.5 du développement embryonnaire. L'augmentation du nombre des cellules inductrices dans ces intestins embryonnaires est signilicative. De plus l'expression de l'ARNm LT?, qui à ce stade précoce est exclusivement exprimé dans les cellules inductrices, est également augmenté dans les doubles TG. Ces résultats indiquent clairement une influence directe d'IL-7 sur l'expansion des cellules inductrices des tissues lymphoïdes et sur la synthèse de LT? induisant une augmentation des PP se développant durant la vie foetale. En plus du développement accru des PP dans les souris doubles TG, trois différences phénotypiques ont été observées. i) L'infiltration lymphocytaire dans différents organes non-lymphoïdes, comme l'estomac, les glandes salivaires et le foie. Des analyses complémentaires ont demontré que les lymphocytes B étaient prédominants dans ces structures lymphoïdes tertiaires. ii) Des structures de ganglions lymphatiques ectopiques contenant des lymphocytes B et T ont été trouvées près des ganglions lymphatiques inguinaux. iii) Les souris doubles TG présentent un syndrome de résorption osseuse sévère probablement dû à l'effet pro-osteoclaste d'IL-7. Globalement, ces résultats montrent que IL-7 joue un rôle clé dans l'homéostasie des cellules inductrices dans la génèse de PP de l'intestin, dans la formation des tissus lymphoïdes ectopiques et dans la résorption osseuse.

On the applicability of mathematics : philosophical and historical perspectives

The present thesis is a contribution to the debate on the applicability of mathematics; it examines the interplay between mathematics and the world, using historical case studies. The first part of the thesis consists of four small case studies. In chapter 1, I criticize "ante rem structuralism", proposed by Stewart Shapiro, by showing that his so-called "finite cardinal structures" are in conflict with mathematical practice. In chapter 2, I discuss Leonhard Euler's solution to the Königsberg bridges problem. I propose interpreting Euler's solution both as an explanation within mathematics and as a scientific explanation. I put the insights from the historical case to work against recent philosophical accounts of the Königsberg case. In chapter 3, I analyze the predator-prey model, proposed by Lotka and Volterra. I extract some interesting philosophical lessons from Volterra's original account of the model, such as: Volterra's remarks on mathematical methodology; the relation between mathematics and idealization in the construction of the model; some relevant details in the derivation of the Third Law, and; notions of intervention that are motivated by one of Volterra's main mathematical tools, phase spaces. In chapter 4, I discuss scientific and mathematical attempts to explain the structure of the bee's honeycomb. In the first part, I discuss a candidate explanation, based on the mathematical Honeycomb Conjecture, presented in Lyon and Colyvan (2008). I argue that this explanation is not scientifically adequate. In the second part, I discuss other mathematical, physical and biological studies that could contribute to an explanation of the bee's honeycomb. The upshot is that most of the relevant mathematics is not yet sufficiently understood, and there is also an ongoing debate as to the biological details of the construction of the bee's honeycomb. The second part of the thesis is a bigger case study from physics: the genesis of GR. Chapter 5 is a short introduction to the history, physics and mathematics that is relevant to the genesis of general relativity (GR). Chapter 6 discusses the historical question as to what Marcel Grossmann contributed to the genesis of GR. I will examine the so-called "Entwurf" paper, an important joint publication by Einstein and Grossmann, containing the first tensorial formulation of GR. By comparing Grossmann's part with the mathematical theories he used, we can gain a better understanding of what is involved in the first steps of assimilating a mathematical theory to a physical question. In chapter 7, I introduce, and discuss, a recent account of the applicability of mathematics to the world, the Inferential Conception (IC), proposed by Bueno and Colyvan (2011). I give a short exposition of the IC, offer some critical remarks on the account, discuss potential philosophical objections, and I propose some extensions of the IC. In chapter 8, I put the Inferential Conception (IC) to work in the historical case study: the genesis of GR. I analyze three historical episodes, using the conceptual apparatus provided by the IC. In episode one, I investigate how the starting point of the application process, the "assumed structure", is chosen. Then I analyze two small application cycles that led to revisions of the initial assumed structure. In episode two, I examine how the application of "new" mathematics - the application of the Absolute Differential Calculus (ADC) to gravitational theory - meshes with the IC. In episode three, I take a closer look at two of Einstein's failed attempts to find a suitable differential operator for the field equations, and apply the conceptual tools provided by the IC so as to better understand why he erroneously rejected both the Ricci tensor and the November tensor in the Zurich Notebook.

Association of N-acetylaspartate and cerebrospinal fluid Aβ42 in dementia.

The interplay of amyloid and mitochondrial function is considered crucial in the pathophysiology of Alzheimer's disease (AD). We tested the association of the putative marker of mitochondrial function N-acetylaspartate (NAA) as measured by proton magnetic resonance spectroscopy within the medial temporal lobe and cerebrospinal fluid amyoid-β42 (Aβ42), total Tau and pTau181. 109 patients were recruited in a multicenter study (40 mild AD patients, 14 non-AD dementia patients, 29 mild cognitive impairment (MCI) AD-type patients, 26 MCI of non-AD type patients). NAA correlated with Aβ42 within the AD group. Since the NAA concentration is coupled to neuronal mitochondrial function, the correlation between NAA and Aβ42 may reflect the interaction between disrupted mitochondrial pathways and amyloid production.