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Orientador: Celso Dal Ré Carneiro Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Geociências Resumo: Nas últimas décadas, o ensino de Geociências passou por grandes transformações. Em princípio, abandonando concepções tradicionais de ensino por transmissão-recepção; em seguida, adotando metodologias voltadas para a redescoberta científica e abordagens interdisciplinares baseadas em discussões dialéticas e na transversalidade temática. Neste trabalho, pesquisou-se o modo pelo qual controvérsias e problematizações podem compor uma epistemologia transdisciplinar para o ensino de Geociências. Para tal, construiu-se um material didático a partir das demandas dos estudantes, que possibilitou a edificação de saberes científicos por meio de uma abordagem transdisciplinar de viés poscolonialista. Assim, discutiu-se o incentivo à reflexão e à alfabetização científica dos educandos, bem como o posicionamento do professor ao interferir e mediar a construção do conhecimento científico. Esta pesquisa mostrou que controvérsias e problematizações ¿ referentes à complexidade presente aos diversos níveis de realidade ¿ incentivam educadores e educandos a pensar e construir seus conhecimentos, relacionando-os aos modos de produção, utilização e as devidas consequências destes. Desse modo, as reflexões envolvendo controvérsias e problematizações tornam-se importantes estratégias para ressignificar e/ou edificar os saberes dos envolvidos no processo de ensino/aprendizagem e a criar uma massa crítica de professores e pesquisadores, que auxiliem na construção da cidadania Abstract: In recent decades, Geoscience teaching has undergone major transformations. First, by abandoning traditional teaching conceptions of transmission-reception; then when adopting methodologies aimed at scientific rediscovery and interdisciplinary approaches based on dialectical discussions and transversal themes. This study investigated the way in which controversies and problematizations can compose a transdisciplinary epistemology for teaching geosciences. To this end, we have built a courseware from the students' demands, which enabled the construction of scientific knowledge through a transdisciplinary approach with a postcolonialist bias. We have discussed the incentive to students' reflection and scientific literacy, as well as the teacher's posture to intervene and mediate the construction of scientific knowledge. This research has shown that controversies and problematizations - referring to the various levels of this complex reality - encourage teachers and students to think and build their knowledge, by relating it to the modes of production, use and its appropriate consequences. Thus, the reflections involving disputes and problematizations become important strategies to reframe and / or build the knowledge of those involved in the teaching / learning process and to create a critical mass of teachers and researchers, to assist in the construction of citizenship Doutorado Ensino e Historia de Ciencias da Terra Doutor em Ciências

It is argued that, in order to understand how life might have been originated under abiotic conditions, it is necessary to describe the appearance of both primitive cells and self-replicating sets of molecules. It is observed that, under quite general assumptions, the fluctuations in the internal composition of small protocells may be an important factor, which allows self-replication to take place by limiting the number of different types of molecular species and of reactions. The notion of a shadow biosphere is also briefly discussed.

Nos dias atuais, os estudantes estão a viver em um mundo repleto de imagens e sentem falta de atividades educativas práticas e lúdicas na escola. A maioria dos currículos escolares não prevê formas de ensino que permitam que os alunos compreendam imagens e reflitam sobre a importância destas. Esse artigo visa mostrar que uma pergunta, formulada por um estudante durante uma atividade prática, pode funcionar como um estopim para deflagrar um processo de construção do conhecimento, cuja base foi um estudo analítico prévio do meio.

Três dimensões compõem a construção do pensamento complexo: a heteroformação, a ecoformação e a autoformação. Esta última impacta um indivíduo adulto quando, em um círculo virtuoso de ação-reflexão-ação, ele toma as rédeas de seu amadurecimento. Autoformação requer autonomia e tempo. Evolui para aprendizagem permanente, ao se associar à transdisciplinaridade, uma perspectiva pluralista do conhecimento que transcende as fronteiras do saber e articula diferentes formas de compreensão do mundo. Identificam-se campos privilegiados para autoformação no grande campo interdisciplinar das Ciências Ambientais e, em especial, das Geociências. Este artigo descreve e analisa a oportunidade de uma proposta de autoformação em Geociências, baseada em situações polêmicas e conflituosas da interferência humana com os ecossistemas naturais, cujas consequências podem ser evidentes, dissimuladas ou até mesmo imprevisíveis. Um dos resultados esperados do processo é permitir que cada pessoa exerça, ao longo da vida, uma cidadania responsável e consequente.

Quantos sao os medos? No neolitico, os grandes animais causavam medo; utilizando artefatos rochosos, aprendemos a nos defender deles e a caca-los. Com o passar do tempo e o avanco da Ciencia, aprendemos que microrganismos podiam provocar doencas, as vezes fatais. Vacinas e remedios passaram entao a desempenhar a mesma funcao dos artefatos pre-historicos. Nos dias atuais, sabe-se que moleculas de poluentes, com dimensoes ainda menores que microrganismos, podem ser letais, a depender da quantidade e da toxicidade apresentada por determinado organismo. Esse artigo articula fatos e tenta revelar quao importante e estarmos preparados para enfrentar os agentes causadores de doencas agudas ou cronicas, e entendermos o papel dos contaminantes emergentes no mundo atual e futuro, visando implementar estrategias para remove-los ou – idealmente – elimina-los do ambiente. A partir da analise de casos historicos, propoe-se uma nova atitude frente aos desafios impostos no mundo atual, ao sugerir estrategias de curto, medio e longo prazo para evitar a contaminacao de importantes recursos hidricos e possibilitar melhores condicoes de vida as pessoas

Accessible and real-time genotyping for diagnostic, prognostic, or treatment purposes is increasingly impelling in diffuse large B-cell lymphoma (DLBCL). Cell-free DNA (cfDNA) is shed into the blood by tumor cells undergoing apoptosis and can be used as source of tumor DNA for the identification of DLBCL mutations, clonal evolution, and genetic mechanisms of resistance. In this study, we aimed at tracking the basal DLBCL genetic profile and its modification upon treatment using plasma cfDNA. Ultra-deep targeted next generation sequencing of pretreatment plasma cfDNA from DLBCL patients correctly discovered DLBCL-associated mutations that were represented in >20% of the alleles of the tumor biopsy with >90% sensitivity and ∼100% specificity. Plasma cfDNA genotyping also allowed for the recovery of mutations that were undetectable in the tissue biopsy, conceivably because, due to spatial tumor heterogeneity, they were restricted to clones that were anatomically distant from the biopsy site. Longitudinal analysis of plasma samples collected under rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) chemotherapy showed a rapid clearance of DLBCL mutations from cfDNA among responding patients. Conversely, among patients who were resistant to R-CHOP, basal DLBCL mutations did not disappear from cfDNA. In addition, among treatment-resistant patients, new mutations were acquired in cfDNA that marked resistant clones selected during the clonal evolution. These results demonstrate that cfDNA genotyping of DLBCL is as accurate as genotyping of the diagnostic biopsy to detect clonally represented somatic tumor mutations and is a real-time and noninvasive approach to tracking clonal evolution and the emergence of treatment-resistant clones.

Random Boolean networks are a widely acknowledged model for cell dynamics. Previous studies have shown the possibility of achieving Boolean Networks (BN) with given characteristics by means of evolutionary techniques. In this work we show that it is possible to evolve BNs exhibiting more positive than negative reactions to knock-out stresses. It is also interesting to observe that in the observed runs (i) the evolutionary processes can guide the BNs toward different dynamic regimes, depending on their internal structure and that (ii) the BNs forced to evolve by maintaining a critical dynamical regime achieve better results than those that do not have this characteristic; this observation supports the idea that criticality may be beneficial to an evolving population of dynamical systems.

Living beings share several common features at the molecular level, but there are very few large-scale &ldquo, operating principles&rdquo, which hold for all (or almost all) organisms. However, biology is subject to a deluge of data, and as such, general concepts such as this would be extremely valuable. One interesting candidate is the &ldquo, criticality&rdquo, principle, which claims that biological evolution favors those dynamical regimes that are intermediaries between ordered and disordered states (i.e., &ldquo, at the edge of chaos&rdquo, ). The reasons why this should be the case and experimental evidence are briefly discussed, observing that gene regulatory networks are indeed often found on, or close to, the critical boundaries. Therefore, assuming that criticality provides an edge, it is important to ascertain whether systems that are critical can further evolve while remaining critical. In order to explore the possibility of achieving such &ldquo, always-critical&rdquo, evolution, we resort to simulated evolution, by suitably modifying a genetic algorithm in such a way that the newly-generated individuals are constrained to be critical. It is then shown that these modified genetic algorithms can actually develop critical gene regulatory networks with two interesting (and quite different) features of biological significance, involving, in one case, the average gene activation values and, in the other case, the response to perturbations. These two cases suggest that it is often possible to evolve networks with interesting properties without losing the advantages of criticality. The evolved networks also show some interesting features which are discussed.

Orientadores: Cassiana Carolina Montagner Raimundo, Gildo Girotto Júnior Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química Resumo: Nos últimos tempos, o interesse de professores dos mais diversos componentes curriculares por cursos de formação continuada tem aumentado, tanto em busca do desenvolvimento de competências e habilidades, quanto da construção de conhecimentos sobre novas perspectivas didáticas. Dentro destas perspectivas, escolhi os contaminantes emergentes e a Química verde como motivação para a construção de um material didático contextualizado, de inspiração transdisciplinar e pautado pela lógica do desenvolvimento humano, voltado a um curso de formação continuada de professores de ciências. Na primeira fase da pesquisa, estruturou-se o curso e se redigiu o material instrucional voltado aos educadores e problematizado junto aos orientadores. Na segunda fase, a abordagem transdisciplinar foi contextualizada e apresentada aos educadores presentes ao curso de formação, anotando-se suas narrativas sobre o material didático e sobre suas problematizações; na terceira fase, os docentes propuseram atividades temáticas aos seus estudantes e recolheram dados para construírem, na quarta e última fase, um trabalho de análise das atividades temáticas, principalmente dos resultados sobre os debates mediados e das propostas de intervenção em âmbito escolar (ou comunitário) por meio de projetos de trabalho. Construí a metodologia de pesquisa tomando por base dois cenários de pesquisa: no primeiro deles ¿ durante o curso de formação ¿ abarquei as três fases da autoformação transdisciplinar junto aos professores, questionando e problematizando seus posicionamentos no que tange à heteroformação, à ecoformação e à autoformação, recolhendo dados em um caderno de campo; no segundo cenário, analisei narrativas e posicionamentos dos docentes, baseando-me nas análises e nos resultados obtidos de atividades temáticas e dos projetos de trabalho, mediados pelos professores, e desenvolvidos por seus estudantes, que constam de trabalhos finais do curso de formação. A análise e discussão dos dados, obtidos nas quatro fases, apontaram que, embora as estratégias utilizadas pelos professores fossem semelhantes, os resultados acabaram sendo bastante diversos, revelando que os docentes que fizeram uso da abordagem transdisciplinar, conseguiram construir, junto com seus estudantes, conceitos mais conformes ao pensamento complexo. Em conclusão é possível afirmar que, do ponto de vista: (1) pedagógico, a maior parte dos estudantes obteve sucesso, mesmo que parcial, ao construir (ou reconstruir) conceitos enfocados pelas atividades temáticas; (2) da autoformação, os resultados mais relevantes foram oferecidos pelos alunos que interferiram positivamente no processo, associados aos professores que se concentraram em mediar o processo de ensino/aprendizagem, e não em conduzi-lo; (3) social, construíram-se projetos de trabalho que, potencialmente, acarretarão ganhos à sociedade como um todo. Em conclusão, parece haver uma relação direta entre os resultados obtidos pelos educandos, o processo de autoformação e a utilização da abordagem transdisciplinar pelos educadores, notadamente auxiliarem na formação do pensamento complexo e na religação dos saberes Abstract: In recent times, the interest of teachers from different disciplines for continuing education courses has increased, both in search of the development of competences and skills, and in the construction of knowledge about new didactic perspectives. Within these perspectives, I chose the emerging contaminants and green Chemistry as the motivation for the construction of a contextualized didactic material, of transdisciplinary inspiration and guided by the logic of human development, aimed at a continuing education course for science teachers. In the first phase of the research, the course was structured and the instructional material aimed at the educators and discussed with the advisors was written. In the second phase, the transdisciplinary approach was contextualized and presented to the educators present at the training course, taking notes of their narratives about the didactic material and about their problematizations; in the third phase, the teachers proposed thematic activities to their students and collected data to build, in the fourth and last phase, a work of analysis of the thematic activities, mainly of the results on the mediated debates and the intervention proposals at school (or community level) ) through work projects. Constructed the research methodology based on two research scenarios: in the first one - during the training course - I covered the three phases of transdisciplinary self-training with teachers, questioning and questioning their positions regarding hetero-training, eco-training and self-training , collecting data in a field notebook; in the second scenario, I analyzed the teachers' narratives and positions, based on the analysis and results obtained from thematic activities and work projects, mediated by the teachers, and developed by their students, which are part of the final works of the training course. The analysis and discussion of the data, obtained in the four phases, showed that, although the strategies used by the teachers were similar, the results ended up being quite different, revealing that the teachers who used the transdisciplinary approach, managed to build, together with their students, concepts more in line with complex thinking. In conclusion, it is possible to state that: (1) from the pedagogical level, most students were successful, even if partial, in building (or reconstructing) concepts focused on the thematic activities; (2) from the scope of self-training, the most relevant results were offered by students who positively interfered in the process, associated with teachers who focused on mediating the teaching / learning process, rather than conducting it; (3) in the social sphere, work projects were built that, potentially, will bring gains to society as a whole. In conclusion, there seems to be a direct relationship between the results obtained by students, the process of self-training and the use of the transdisciplinary approach by educators, notably assisting in the formation of complex thought and the reconnection of knowledge Doutorado Química Analítica Doutor em Ciências

A well-known hypothesis, with far-reaching implications, is that biological evolution should preferentially lead to critical dynamic regimes. Useful information about the dynamical regime of gene regulatory networks can be obtained by studying their responses to small perturbations. The interpretation of these data requires the use of suitable models, where it is usually assumed that the system is homogeneous. On the other hand, it is widely acknowledged that biological networks display some degree of modularity, so it is interesting to ascertain how modularity can affect the estimation of their dynamical properties. In this study we introduce a well-defined degree of modularity and we study how it influences the network dynamics. In particular, we show how the estimate of the Derrida parameter from “avalanche” data may be affected by strong modularity.

Cellular types of multicellular organisms are the stable results of complex intertwined processes that occur in biological cells. Among the many others, chromatin dynamics significantly contributes...

Random Boolean networks are a widely acknowledged model for cell dynamics. Previous studies have shown the possibility of achieving Boolean networks with given characteristics by means of evolutionary techniques. In this work we make a further step towards more biologically plausible models by aiming at evolving networks with a given fraction of active nodes along the attractors, while constraining the evolutionary process to move across critical networks. Results show that this path along criticality does not impede to climb the mount of improbable, yet biologically realistic requirements.

The Relevance Index has been introduced to detect key features of the organisation of complex dynamical systems. It is based upon Shannon entropies and can be used to identify groups of variables that change in a coordinated fashion, while they are less integrated with the rest of the system. In previous work, we have shown that the average Relevance Index attains its maximum at the phase transition in both Ising model and random Boolean networks. In this contribution we present a further study on the Ising model, showing that the relevance index is maximised for large groups of variables at criticality. These results provide further evidence to the hypothesis that this index is a powerful measure for capturing criticality.

There are few data on clinical relevance of adrenal dysfunction and its relationship with occult microbial DNA in noninfected haemodynamically stable cirrhotic patients with ascites.The aim of this study was to evaluate prognostic role of adrenal dysfunction, microbial DNA, and their relationship.Adrenal function was assessed in 93 consecutive patients following a corticotropin stimulation test. Adrenal dysfunction was defined as: basal cortisol10 μg/dl, delta cortisol9 μg/dl, or peak cortisol18 μg/dl. Microbial DNA was assessed in blood and ascites of 54 consecutive patients. Patients were followed up until liver transplantation or death.Adrenal dysfunction was not significantly associated with mortality, while the risk of death rose significantly with an increase in basal cortisol values (HR 1.13 per 1-μl/dl increase; 95% CI 1.01-1.26). Microbial DNA was independently associated with reduced survival (HR 8.05, 95% CI 1.57-41.2). In microbial DNA-positive patients a significant correlation was found between Model for End-Stage Liver Disease (MELD) score and basal cortisol values (Pearson's r=0.5107; p=0.018).Microbial DNA and MELD score, but not adrenal function, were the best independent predictors of mortality in noninfected cirrhotic patients with ascites. High serum cortisol levels may be a systemic reaction to microbial translocation, increasing in parallel with deterioration of liver function.

The detection of critical states is a task of utmost importance in complex systems; to this aim, measures to identify such conditions are required. In general, the term criticality concerns the exi...

Recently a cell differentiation model based on noisy random Boolean networks has been proposed. This mathematical model is able to describe in an elegant way the most relevant features of cell differentiation. Noise plays a key role in this model; the different stages of the differentiation process are emergent dynamical configurations deriving from the control of the intracellular noise level. In this work we compare two approaches to this cell differentiation framework: the first one (already present in the literature) is focused on a network analysis representing the average wandering of the system among its attractors, whereas the second (new) approach takes into consideration the dynamical stories of thousands of individual cells. Results showed that under a particular noise condition the two approaches produce comparable results. Therefore both can be used to model the cell differentiation process in an integrative and complementary manner.

A well-known hypothesis, with far-reaching implications, is that biological evolution should preferentially lead to states that are dynamically critical. In previous papers, we showed that a well-known model of genetic regulatory networks, namely, that of random Boolean networks, allows one to study in depth the relationship between the dynamical regime of a living being’s gene network and its response to permanent perturbations. In this paper, we analyze a huge set of new experimental data on single gene knockouts in S. cerevisiae, laying down a statistical framework to determine its dynamical regime. We find that the S. cerevisiae network appears to be slightly ordered, but close to the critical region. Since our analysis relies on dichotomizing continuous data, we carefully consider the issue of an optimal threshold choice.

A major limitation of the classical random Boolean network model of gene regulatory networks is its synchronous updating, which implies that all the proteins decay at the same rate. Here a model is discussed, where the network is composed of two different sets of nodes, labelled G and P with reference to “genes” and “proteins”. Each gene corresponds to a protein (the one it codes for), while several proteins can simultaneously affect the expression of a gene. Both kinds of nodes take Boolean values. If we look at the genes only, it is like adding some memory terms, so the new state of the gene subnetwork network does no longer depend upon its previous state only.

In the previous chapters we have discussed some protocell models and we have analysed their behaviour in depth, so now it is time to consider what we have learnt, which questions have been at least partially answered, which questions are still open and which new questions have arisen. In this final chapter we will therefore take the liberty of revisiting and repeating some arguments that have already been dealt with in the previous chapters.

Let us now consider the contributions that a complex systems approach can provide to the research on protocells.

Models are of great importance for protocell research, not only for the usual reasons why models matter, but also because real protocells are not yet available in the lab. There are indeed some cases where one or a few duplications have been achieved (Hanczyc and Szostak 2004; Luisi et al. 2004; Luisi 2006; Stano et al. 2006; Schrum et al. 2010; Stano and Luisi 2010a) but so far, to the best of our knowledge, a sustained growth of a population of protocells has never been observed.

In the last two chapters we have shown several interesting results, which will now be brought together in a quite complete (albeit abstract) protocell model. In Chap. 3 we have studied how the presence of genetic memory molecules (GMMs) can affect the growth and fission rate of their lipid container, leading under quite broad assumptions to the important phenomenon of emergent synchronization, i.e. to a condition where protocell fission and duplication of its genetic material take place at the same pace. In that chapter, chemical kinetics has been described with deterministic differential equations (it has also been mentioned that synchronization is somewhat robust even if small fluctuations are considered).