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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
91

Os planos diretores e as ações de preservação de patrimônio edificado em Novo Hamburgo

Oliveira, Suzana Vielitz de January 2009 (has links)
Através de uma análise histórica, este trabalho busca constatar o quanto a legislação e as ações políticas influenciaram e controlaram as ações de preservação do patrimônio edificado na cidade de Novo Hamburgo. Ao desvelar os reais objetivos e as conseqüências dos Planos Diretores na cidade estudada e compará-los com a realidade encontrada, verificou-se que, mesmo havendo leis especificas de preservação, foi pouca a influência destas, assim como dos próprios Planos Diretores, nas ações de preservação de patrimônio e na conformação urbana de Novo Hamburgo. A existência de um patrimônio preservado no Centro Histórico de Hamburgo Velho se deu primeiramente devido a ação de alguns interessados que foram apoiados somente mais tarde por ações políticas. / While using historical analysis, this work seeks to find out, how legislation and public actions influenced and controlled actions of preservation of constructed cultural heritage in the city of Novo Hamburgo. Discovering the real objectives and consequences of the Urban Laws and comparing them with the actual situation, it was discovered that the existing cultural heritage laws, as well as the Urban Laws itself have little influence on the preservation of cultural heritage and the urban development of Novo Hamburgo. The existence of protected cultural heritage in the Historical Center of Hamburgo Velho was primarily given due to the action of a few engaged people, who were later supported by political actions.
92

Une analyse histopathologique et génomique d'une interaction in vitro entre Ulmus americana et Ophiostoma novo-ulmi

Aoun, Mirella 16 April 2018 (has links)
Les interactions entre les plantes et les agents pathogènes fongiques conduisent habituellement à la mise en place par l’hôte de différents mécanismes de défense. Des exemples de ces mécanismes sont le renforcement de la paroi cellulaire par la subérine, la lignine et les composés phénoliques pariétaux, ainsi que l’accumulation de protéines PR et la production de phytoalexines qui peuvent être toxiques pour l’agent pathogène. Chez les plantes susceptibles, ces mécanismes ne réussissent pas à empêcher le développement de la maladie. La maladie hollandaise de l’orme est une maladie à caractère épidémique qui a causé la mort de millions d’ormes en Europe et en Amérique du Nord. Les bases moléculaires de cette maladie sont encore peu connues. Afin d’identifier des gènes impliqués dans l’interaction entre l’espèce susceptible Ulmus americana L. et son champignon pathogène Ophiostoma novo-ulmi Brasier, un système in vitro a été mis au point, celui-ci utilisant des cultures de cals auxquelles des cellules levuriformes du champignon ont été inoculées. Afin de valider son utilisation pour l’analyse génomique, ce système a d’abord fait l’objet d’une analyse histopathologique en microscopie photonique et électronique. Le développement du champignon dans les cals et les réactions de défenses de ces derniers face à la présence du champignon ont été observés à 4, 24 48, 72 et 96 heures post-inoculation (hpi). Le champignon a été détecté sous forme de réseau d’hyphes dans toutes les parties du cal à partir de 48 hpi. Les tests histochimiques ont montré l’importance de certaines réactions telles que l’accumulation de phénols, de lignine et de subérine dans les cellules des cals. Le pourcentage de cellules subérisées était 4,6 fois plus élevé à 96 hpi dans les cals infectés que dans les cals témoins. Une banque d’ADN complémentaire a été construite à partir de cals infectés (72 hpi) en utilisant la technique des hybridations suppressives et soustractives (SSH). Un total de 535 étiquettes de séquences exprimées (EST) a été obtenu et déposé dans la banque de données Genbank suite au séquençage partiel des clones. Ces étiquettes ont été regroupées en 314 uniséquences dont la majorité correspondait à des gènes d’orme identifiés durant l’interaction. Cinquante-trois uniséquences représentant des gènes impliqués dans différentes voies métaboliques associées à la défense ont été sélectionnées par un criblage différentiel et considérées comme étant induites durant l’interaction. Les profils d’expression à différents temps après inoculation ont été établis par PCR quantitative chez 18 uniséquences provenant de cals infectés ainsi que de cals traités à l’eau stérile. Ils confirment l’induction ou l’expression constitutive des gènes correspondants durant le processus de l’infection. Cette étude fournit pour la première fois une ressource génomique pour l’orme et révèle des mécanismes moléculaires impliqués dans l’interaction entre l’orme américain et l’agent pathogène responsable de la maladie hollandaise de l’orme. / Interactions between plants and fungal pathogens usually lead to the induction of different host defense mechanisms. Some of these mechanisms are the reinforcement of the plant cell wall by suberin, lignin and wall bound-phenolics, the accumulation of pathogenesis-related proteins, and the production of phytoalexins that could be toxic to the pathogen. Yet in susceptible plants, these mechanisms are not effective to produce resistance and disease develops. Dutch elm disease (DED) is a pandemic tree disease that killed millions of elm trees, especially in North America and Europe. The molecular bases of this disease are still poorly understood. With the objective of identifying genes involved in the interaction between the susceptible Ulmus americana L. and the pathogen Ophiostoma novo-ulmi Brasier, an in vitro system was developed using callus cultures inoculated with budding cells of the fungus. In order to validate the use of this system for genomic analyses of the interaction, a histopathological analysis was carried out using light and electron microscopy. Fungal colonization of the callus tissue and reactions of callus cells to the presence of the pathogen were observed at 4, 24, 48, 72 and 96 hours post-inoculation (hpi). The fungus was seen in its hyphal form by 48 hpi in all parts of the callus. Histochemical tests showed the importance of host reactions such as the accumulation of phenols, lignin, and suberin. The percentage of suberized cells was 4.6 times higher at 96 hpi in infected calli than in mock-inoculated control calli. A cDNA library using suppression subtractive hybridization (SSH) was constructed from infected elm callus tissue harvested at 72 hpi. A total of 535 expressed sequence tags were generated through partial sequencing and submitted to Genbank. These were grouped into 314 unisequences, the majority corresponding to elm genes identified during the interaction. Fifty-three unisequences representing genes involved in different pathways associated with plant defense were selected by differential screening and considered upregulated in the infected tissues. The expression profiles in mock and infected elm callus cultures of a subset of 18 elm genes were analyzed in more detail by quantitative reverse transcriptase polymerase chain reaction. These confirmed upregulation and constitutive expression of selected genes during the infection process. This study provides, for the first time, a genome-wide resource for the elm, and furthermore identifies molecular mechanisms likely involved during the interaction between U. americana and the DED pathogen.
93

Experimental and Theoretical Models to Probe Mechanisms of Biological Charge Flow

Polizzi, Nicholas Francis January 2016 (has links)
<p>Nature is challenged to move charge efficiently over many length scales. From sub-nm to μm distances, electron-transfer proteins orchestrate energy conversion, storage, and release both inside and outside the cell. Uncovering the detailed mechanisms of biological electron-transfer reactions, which are often coupled to bond-breaking and bond-making events, is essential to designing durable, artificial energy conversion systems that mimic the specificity and efficiency of their natural counterparts. Here, we use theoretical modeling of long-distance charge hopping (Chapter 3), synthetic donor-bridge-acceptor molecules (Chapters 4, 5, and 6), and de novo protein design (Chapters 5 and 6) to investigate general principles that govern light-driven and electrochemically driven electron-transfer reactions in biology. We show that fast, μm-distance charge hopping along bacterial nanowires requires closely packed charge carriers with low reorganization energies (Chapter 3); singlet excited-state electronic polarization of supermolecular electron donors can attenuate intersystem crossing yields to lower-energy, oppositely polarized, donor triplet states (Chapter 4); the effective static dielectric constant of a small (~100 residue) de novo designed 4-helical protein bundle can change upon phototriggering an electron transfer event in the protein interior, providing a means to slow the charge-recombination reaction (Chapter 5); and a tightly-packed de novo designed 4-helix protein bundle can drastically alter charge-transfer driving forces of photo-induced amino acid radical formation in the bundle interior, effectively turning off a light-driven oxidation reaction that occurs in organic solvent (Chapter 6). This work leverages unique insights gleaned from proteins designed from scratch that bind synthetic donor-bridge-acceptor molecules that can also be studied in organic solvents, opening new avenues of exploration into the factors critical for protein control of charge flow in biology.</p> / Dissertation
94

Carnaval belenense em tempos de Estado Novo (1938-1946)

Teixeira, Tatiane do Socorro Correa 23 June 2013 (has links)
Made available in DSpace on 2016-04-27T19:30:47Z (GMT). No. of bitstreams: 1 Tatiane do Socorro Correa Teixeira.pdf: 4278157 bytes, checksum: 4ccb538dc84bd81adf13d03268c8c7d3 (MD5) Previous issue date: 2013-06-23 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / This study, Belenense Carnival in Times New State (1938-1946), aims to understand the belenense carnival mid-1938 to 1946 in a time when the Estado Novo regime will act on demonstrations across the country carnival. Aims to present a carnival beyond the control focusing on grassroots resistance when they sought numerous ordinances restrict their spontaneity in the days of carnival revelry. It proposes to submit like the Departamento Estadual de Imprensa e Propaganda do Pará (DEIP) acted changing the face belenense Carnival, with its rules and regulations established by the regime in an attempt to control over the carnival groups that disagreed its purposes. Objective know Rancho Não Posso me Amofiná throughout its history, memory and resistance in the belenense carnival. Thus, this thesis proposes techniques from oral history and the intersection with written sources, composing a framework of analysis and interpretation that enables the understanding belenense carnival in the context of the Estado Novo Regime in Belém / O presente estudo tem como objetivo compreender o carnaval belenense de meados de 1938 a 1946, momento de vigência do regime do Estado Novo, atuante sobre as manifestações carnavalescas pelo país. Visamos apresentar um carnaval para além do controle, enfocando resistências das camadas populares no momento em que inúmeras portarias buscavam restringir sua espontaneidade nos dias de folia carnavalesca. Propomos, com isso, apresentar como o Departamento Estadual de Imprensa e Propaganda do Pará (DEIP) atuou, mudando a fisionomia do carnaval belenense, com suas normas e regras estabelecidas pelo regime, na tentativa de domínio sobre grupos carnavalescos que destoassem dos seus propósitos. Objetivamos conhecer o Rancho Não Posso me Amofiná através de sua história, memória e resistência no carnaval belenense. Assim, esta dissertação busca, a partir de técnicas da história oral e do cruzamento com fontes escritas, compor um quadro de análise e interpretação que possibilite a compreensão acerca do carnaval no contexto do Estado Novo em Belém
95

Characterization of genome-wide deviations from Mendelian inheritance in bivalve species

Peñaloza Navarro, Carolina Soledad January 2018 (has links)
Marine bivalves are a group of species composed of clams, mussels and oysters. Bivalves are keystone species in coastal ecosystems and represent an increasingly important segment of the global aquaculture industry. Domestication of shellfish species is in the early stages, with few organized breeding programmes and a heavy reliance on wild seed. Consequently, the development and use of genomic markers may significantly assist shellfish aquaculture breeding and production. However, molecular genetic markers typically exhibit unusual patterns of segregation in bivalve species, which result in deviations from Mendelian expectations, and could potentially limit their use in parental assignment, mapping of quantitative trait loci and genomic prediction. Previous studies have suggested that segregation distortions originate at the larval stage, as a result of the linkage of markers to deleterious mutations. This high genetic load has been associated with the high fecundity of bivalve species. However, no direct evidence of a high incidence of de novo mutations has been provided. The aim of this thesis is to gain further insight into segregation distortions in bivalve species by studying the phenomenon at a genome-wide scale, using modern high-throughput sequencing technology. The studies presented in this thesis derive from experiments involving genotyping of parents and offspring from pair-crosses of three different bivalve species (the Pacific oyster Crassostrea gigas, the Blue mussel Mytilus edulis, and the GreenshellTM mussel Perna canaliculus) using high throughput sequencing and SNP arrays. The parent and offspring genotype data were used to characterize patterns of segregation distortion at a genome-wide level, followed by exploratory analyses to test hypotheses related to possible causes of this distortion. Three main findings resulted from the genome-wide analysis of segregation patterns. First, by using Restriction site Associated DNA sequencing (RAD-Seq) we observe that technical artefacts are more widespread than previously considered, contributing to apparent distortions via unreliable genotype calls. By analysing read depth data from RAD-Seq, we suggest that apparent homozygous genotype calls may actually be hemizygous, suggesting a very high frequency of null alleles which contribute to distorted segregation patterns. Bioinformatic pipelines to improve RAD-Seq locus assembly and marker genotyping for bivalve species are presented. Second, by using a high-density SNP array and RAD-Seq in pair crosses of Pacific oyster and aligning to the reference genome assembly, we find that segregation distortions cover extensive regions of the genome, and that certain genomic regions are consistently distorted in different families. Finally, following previous suggestions that the reproductive strategies of bivalve species may favour a high mutation rate, we provide preliminary evidence of a high incidence of de novo mutations that appear spontaneously (i) during male and female gamete formation and (ii) post-zygotically, during larval development. This putative high de novo mutation rate is likely to also contribute to deviations from Mendelian inheritance patterns in these species. New genomic technologies have allowed us to gain substantial insight into the intriguing yet poorly understood phenomena related to inheritance in bivalve species. The results have both fundamental and practical implications for genetic analysis interpretation and selective breeding for aquaculture in this large and highly diverse group of species.
96

Desenvolvimento de marcadores microssatélites para Ololygon centralis (Anura: Hylidae) por sequenciamento de segunda geração com baixa cobertura / Development of microsatellite markers for Ololygon centralis (Anura: Hylidae) using second generation sequencing with low coverage

Castro, Andrezza Arantes 12 March 2018 (has links)
Submitted by Franciele Moreira (francielemoreyra@gmail.com) on 2018-04-16T17:42:56Z No. of bitstreams: 2 Dissertação - Andrezza Arantes Castro - 2018.pdf: 2625041 bytes, checksum: 5c588cc8e4644fe3bfa34ba8e1dd05a9 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-04-17T10:54:33Z (GMT) No. of bitstreams: 2 Dissertação - Andrezza Arantes Castro - 2018.pdf: 2625041 bytes, checksum: 5c588cc8e4644fe3bfa34ba8e1dd05a9 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-04-17T10:54:33Z (GMT). No. of bitstreams: 2 Dissertação - Andrezza Arantes Castro - 2018.pdf: 2625041 bytes, checksum: 5c588cc8e4644fe3bfa34ba8e1dd05a9 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-03-12 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / The ease access to Next Generation Sequence methodologies has improved the development of several projects, once it makes possible the de novo assembly of DNA sequences, creating a great amount of data and giving access to unknown genomes of different organisms. The anuran species Ololygon centralis belong to Hylidae family. It is considered as endemic of Cerrado Biome and little is known about its genomics. The aim of this work was to realize a draft of the genome of O. centralis in order to identify, to characterize, to quantify repetitive elements and to predict possible genes. Also, we aimed to develop microsatellite markers for the species. The genome draft assembled in 13989 scaffolds, which correspond to 4926069 bp with N50 = 336. The repetitive elements found in the O. centralis genome (1795 transposons, 957, microsatellite, one satellite DNA and 25 small nuclear RNAs) comprised 531337 bp. Between the retrotransposons, the LINE element (49,83%) was the most abundant, followed by LTR (48,66%) and SINE (1,56%). It was possible to identify coding genes for the 5S, 18S and 28S subunits of ribosomes. Also, 18 types of coding regions for tRNA and 26 putative genes were found in the O. centralis genome. From the microsatellite regions, it was possible to design 87 pairs of primers for the flanking sites. There were found 47 regions composed of tetranucleotides, 39 dinucleotides and on trinucleotide on the microsatellite sites. From them, 31 pairs of primers were selected for amplification and 18 showed good results. The annealing temperatures varied from 50° e 60° C. Seven markers showed polymorphism. From them, only 5 markers (PCE05, OCE11, PCE20, OCE21, OCE26) were used to characterize the genotype of 30 individuals. The medium number of alleles was 10, the allelic amplitude varied from 148 bp (OCE20) to 318 bp (OCE21). The Expected Heterozygosity was 0,7 and the observed was 0,5. The probability of parentage exclusion (Q) was 0,993 and the probability of combined identity (I) was 1,13x10-6. The global value of the fixation index (FST) was significant and equal to 0,2 (p<0.05). The data obtained from the NGS Illumina platform represent one important step for the knowledge of genomics of this species and of the anuran in general. / A facilidade para o acesso às metodologias de Sequenciamento de Segunda Geração (Next Generation Sequence) tem impulsionado o desenvolvimento de diversos projetos, uma vez que possibilita a montagem de novo de sequências, gerando uma grande quantidade de dados e permitindo o acesso a genomas de diversos organismos ainda pouco conhecidos. A espécie de anuro Ololygon centralis (Pombal e Bastos 1996) pertence à família Hylidae, considerada endêmica do Bioma Cerrado e que ainda não dispõe de nenhuma informação genômica. O objetivo desse trabalho foi realizar uma montagem parcial do genoma de Ololygon centralis a fim de identificar, caracterizar, quantificar elementos repetitivos e predizer genes nas sequências genômicas, além de desenvolver marcadores microssatélites para a espécie. O genoma parcial montado resultou em 13.989 scaffolds, que correspondem a 4.926.069 pb com N50 de 336. Os elementos repetitivos encontrados no genoma de O. centralis (1.795 elementos transponíveis, 957 microssatélites, um DNA satélite e 25 pequenos RNAs nucleares) totalizaram 531.337 pb. Entre os retrotransposons, o elemento LINE (49,83%) foi o mais abundante, seguido do LTR (48,66%) e SINE (1,56%). Foram identificados os genes que codificam as subunidades 5S, 18S e 28S de ribossomos, 18 tipos de tRNAs no genoma e 26 genes. A partir das sequências foi possível desenhar 87 pares de primers flanqueando regiões microssatélites. Dentre elas, 47 foram regiões compostas de tetranucleotídeos, 39 dinucleotídeos, e um trinucleotídeo. Deste total, 31 pares de primers foram selecionados para padronização em gel de poliacrilamida (6%) e 18 deles apresentaram produto de amplificação adequado. Durante a padronização, as temperaturas de anelamento variaram entre 50° e 60° C e sete marcadores apresentaram polimorfismo. Dos sete, apenas cinco marcadores (OCE05, OCE11, OCE20, OCE21, OCE26) foram padronizados e utilizados para caracterização em 30 indivíduos de O. centralis no analisador automático ABI3500. O número médio de alelos foi igual a 10, a amplitude alélica variou entre 148pb (OCE 20) a 318 pb (OCE 21). A Heterozigosidade média esperada foi 0,7 e a observada igual a 0,5. A probabilidade de exclusão de paternidade (Q) foi igual a 0,993 e a probabilidade combinada de identidade (I) igual a 1,13x10-6. O valor global para o índice de fixação (FST) foi significativo e igual a 0,2 (p <0,05). Os dados obtidos a partir do NGS plataforma Illumina representam um importante passo para o conhecimento genômico dessa espécie e dos anfíbios em geral, o desenvolvimento de primers contribuirá para o estudos genéticos-populacionais de Ololygon centralis e espécies correlacionadas por meio da transferibilidade.
97

Validação estrutural de um novo conceito de base de patim para iniciação à patinagem

Sousa, Emanuel Soares de January 2012 (has links)
Tese de mestrado integrado. Engenharia Mecânica. Faculdade de Engenharia. Universidade do Porto. 2012
98

A geopolítica na história e no ensino da geografia portuguesa : 1910-1960

Teles, Pedro Francisco Figueiredo Cabral January 2000 (has links)
A evolução epistemológica e conceptual da Geografia Política e da Geopolítica segundo investigadores das diversas Escolas de Geografia Política da europa. O enquadramento histórico das Escolas de Geografia Política de Lisboa e coimbra. A Escola de Geografia de Lisboa, projecção nacional e internacional. Análise das concepções de Geografia Política em Silva Telles, L. Schwalbach (análise biobibliográfica deste autor) e Orlando Ribeiro. A Escola de Geografia de Coimbra, projecção nacional e internacional dos trabalhos de Geografia Política desenvolvidos por A. Amorim Girão. Influência dos geógrafos estrangeiros na Geografia Política Portuguesa.
99

Representações do Oriente em O Mundo Português : (1937-1947)

Couto, Marcos Miguel Oliveira do January 2011 (has links)
O presente trabalho debruça-se sobre as representações do Oriente na revista de propaganda colonial do Estado Novo O Mundo Português, publicada entre 1934 e 1947. De facto, procura-se demonstrar a forma como o Orientalismo se revelou um “instrumento” de grande utilidade para o regime, pela forma como “construiu” o Oriente de maneira a que este lhe legitimasse uma identidade e um destino imperial que se iria repercutir em África, assim como toda uma ideologia racista e preconceituosa, que “ficcionou” o oriental, foi veiculada de forma a ser demonstrada a superioridade civilizacional e cultural de Portugal face aos habitantes das suas colónias. Com efeito, se no primeiro capítulo se procura contextualizar e problematizar a questão do Orientalismo, procurando demonstrar que o conceito, para lá de instrumento de poder, definiu todo um estilo artístico e cultural – criando um “renascimento” no seio da sociedade europeia de finais de século XVIII. Porém, todo este “fascínio” oriental acabou em “desencanto” quando as grandes potências coloniais assumiram um imperialismo agressivo e expansivo, juntamente com uma ideologia racista. Em Portugal, como se procurou demonstrar, todo este fenómeno de ideias proveniente da descoberta das culturas orientais produziu um impacto menor no meio intelectual. No segundo capítulo trata-se de se demonstrar todo o antecedente místico que reveste o Oriente desde o momento da sua “perda”, como também se traçam as linhas gerais da ideologia e política salazarista. Perceber a dimensão do significado do Oriente enquanto “memória”, possibilitou uma melhor compreensão do porquê do seu “resgate” da História por parte do Estado Novo. [...]
100

Using de novo design proteins to explore tyrosine radicals and cation-π interactions

Berry, Bruce W. January 2014 (has links)
Redox cofactors and amino-acid free radicals play important roles in biology. Although many of the same cofactors and amino acids that form these radicals are found across a broad range of biological systems, identical cofactors can have different reduction potentials. The local environment plays a role in defining these redox potentials. An understanding of this local-environment effect can shed more light on how redox chemistry works in nature. Our laboratory has developed a library of model proteins that are well suited to study amino-acid radicals. a3X is a de novo designed protein that is composed of 67 residues. It forms a three-helix bundle connected by two glycine loops. The radical site is located at position 32 on the central a-helix. The a3X protein is designed to be well-folded and thermodynamically stable across a broad pH range. Paper 1 describes the structural and electrochemical characterization of a3Y, a tyrosine variant of a3X. We were able to obtain a unique Faradaic response from Y32 at both low and high pH, using differential pulse voltammetry. In addition, we successfully redesigned α3Y by introducing a histidine in close proximity to Y32, creating a tyrosine/histidine pair. Our goal in creating this pair was to study proton-coupled electron transfer (PCET) in a well-structured and solvent-sequestered protein environment.  In paper 2 we illustrated the redox reversibility of Y32 and produced the first ever Pourbaix diagram for a tyrosine radical in a protein. The formal potential of the Y32-OŸ/Y32-OH redox couple was determined to be 918 ± 2 mV vs. the normal hydrogen electrode (NHE) at pH 8.40.  While at pH 5.52, the formal potential of the Y32-OŸ/Y32-OH redox couple was recorded at 1.07 V. Papers 3 and 4 utilize a3W to study cation-π interactions. In paper 3, we showed how solvation can affect the strength of these interactions by -0.9 kcal/mol. In Paper 4, we were able to monitor the disruption of the cation-π interaction with the use of high-pressure fluorescence and were able to calculate the interaction energy for a solvent exposed cation-π. The aim of the work described in this thesis was to use model proteins to study tyrosine radicals to gain a broader perspective and better understanding of the versatility of biological electron transfer and to measure cation-π interactions and how they behave in different environments. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.</p>

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