Stroke is a major cause of disability and death worldwide. Although different clinical studies and trials used Magnetic Resonance Imaging (MRI) to examine patterns of change in different imaging modalities (eg: perfusion and diffusion), we still lack a clear and definite answer to the question: “How does an acute ischemic stroke lesion grow?” The inability to distinguish viable and dead tissue in abnormal MR regions in stroke patients weakens the evidence accumulated to answer this question, and relying on static snapshots of patient scans to fill in the spatio-temporal gaps by “thinking/guessing” make it even harder to tackle. Different opposing observations undermine our understanding of ischemic stroke evolution, especially at the acute stage: viable tissue transiting into dead tissue may be clear and intuitive, however, “visibly” dead tissue restoring to full recovery is still unclear. In this thesis, we search for potential answers to these raised questions from a novel dynamic modelling perspective that would fill in some of the missing gaps in the mechanisms of stroke evolution. We divided our thesis into five parts. In the first part, we give a clinical and imaging background on stroke and state the objectives of this thesis. In the second part, we summarize and review the literature in stroke and medical imaging. We specifically spot gaps in the literature mainly related to medical image analysis methods applied to acute-subacute ischemic stroke. We emphasize studies that progressed the field and point out what major problems remain. Noticeably, we have discovered that macroscopic (imaging-based) dynamic models that simulate how stroke lesion evolves in space and time were completely overlooked: an untapped potential that may alter and hone our understanding of stroke evolution. Progress in the dynamic simulation of stroke was absent –if not inexistent. In the third part, we answer this new call and apply a novel current-based dynamic model âpreviously applied to compare the evolution of facial characteristics between Chimpanzees and Bonobos [Durrleman 2010] – to ischemic stroke. This sets a robust numerical framework and provides us with mathematical tools to fill in the missing gaps between MR acquisition time points and estimate a four-dimensional evolution scenario of perfusion and diffusion lesion surfaces. We then detect two characteristics of patterns of abnormal tissue boundary change: spatial, describing the direction of change –outward as tissue boundary expands or inward as it contracts–; and kinetic, describing the intensity (norm) of the speed of contracting and expanding ischemic regions. Then, we compare intra- and inter-patients estimated patterns of change in diffusion and perfusion data. Nevertheless, topology change limits this approach: it cannot handle shapes with different parts that vary in number over time (eg: fragmented stroke lesions, especially in diffusion scans, which are common). In the fourth part, we suggest a new mathematical dynamic model to increase rigor in the imaging-based dynamic modeling field as a whole by overcoming the topology-change hurdle. Metamorphosis. It morphs one source image into a target one [Trouvé 2005]. In this manuscript, we extend it into dealing with more than two time-indexed images. We propose a novel extension of image-to-image metamorphosis into longitudinal metamorphosis for estimating an evolution scenario of both scattered and solitary ischemic lesions visible on serial MR. It is worth noting that the spatio-temporal metamorphosis we developed is a generic model that can be used to examine intensity and shape changes in time-series imaging and study different brain diseases or disorders. In the fifth part, we discuss our main findings and investigate future directions to explore to sharpen our understanding of ischemia evolution patterns.

O presente trabalho consiste na transcrição e estudo do manuscrito inédito e autógrafo de Cândido Lusitano, pseudônimo de Francisco José Freire, intitulado As Transformações de Publio Ovidio Nasam, que é tradução das Metamorfoses de Ovídio, datada de 1771. O estudo contempla a mudança de gênero poético a partir da organicidade do poema, que sofre alteração das Metamorfoses latinas às Transformações portuguesas, bem como a omissão de passagens obscenas, por decoro e impossibilidade de leitura moralizante, e a identificação da edição latina utilizada para a tradução (Burman, 1727). / The current work consists of a transcription and a study of the Cândido Lusitano\'s newly manuscript and autograph - whose pseudonym is Francisco José Freire - entitled As Transformações de Publio Ovidio Nasam, a translation of the Ovidian metamorphosis, dated from 1771. This study focuses on a shifting of poetical genre which has arisen from the poem organicity that suffers changes from the latin metamorphosis to the portuguese transformations, as well as the omission of some obscene passages for moral reasons, the impossibility of a moralistic reading, and the idenfitication of a Latin edition used for the translation (Burman, 1727).

A cutícula dos insetos é composta principalmente por uma variedade de proteínas que interagem com filamentos de quitina, um polímero de N-acetilglicosamina, para formar um envoltório rígido que protege e dá forma ao organismo. O crescimento dos insetos depende da renovação periódica da cutícula, que se desprende durante a apólise e é digerida enquanto a epiderme sintetiza uma nova cutícula substituta. Tal renovação caracteriza a muda e metamorfose e é coordenada por hormônios, com destaque para os ecdisteróides. O atual trabalho objetivou caracterizar a expressão diferencial de genes do tegumento (cutícula e epiderme subjacente), além de elucidar aspectos de regulação e função no contexto da muda e metamorfose, com foco nos genes codificadores de proteínas estruturais e enzimas cuticulares. Para este fim, utilizamos o tegumento de fases específicas da muda pupal-adulta, isto é, de pupas (Pw), de pupas em apólise (Pp) e de adultas faratas (Pbl) para análises de microarrays de cDNA. As análises dos microarrays mostraram 761 e 1173 genes diferencialmente expressos nos tegumentos de adultas faratas (Pbl) em comparação com pupas (Pw) ou pupas em apólise (Pp), respectivamente. A categorização destes genes, segundo os critérios do Gene Ontology, distinguiu totalmente o tegumento de adultas faratas (Pbl) dos tegumentos de pupas (Pw) ou pupas em apólise (Pp) tanto em relação ao critério Processo Biológico quanto em relação à Função molecular, evidenciando grande mudança na expressão gênica durante a construção do exoesqueleto definitivo nas adultas faratas (Pbl). Os microarrays mostraram aumento estatisticamente significante da expressão de 24 genes cuticulares no tegumento de adultas faratas. Este resultado foi validado por RT-PCR em tempo real (qRT-PCR) para 23 destes genes (AmelCPR3, AmelCPR4, AmelCPR6, AmelCPR14, AmelCPR15, AmelCPR17, AmelCPR23, AmelCPR24, AmelCPR25, AmelCPR28, AmelCPR29, AmelCPR30, apd-1, apd-2, apd-3, CPLCP1, Am-C, Am-D, AmelTwdl1, AmelTwdl2, GB12449, GB12811 e GB11550), e por RT-PCR semiquantitativa para o gene Amlac2. Além disto, a maior expressão de outros 2 genes cuticulares (AmelCPR1 e AmelCPR2) em adultas faratas foi demonstrada por qRT-PCR. Estes genes cuticulares positivamente regulados no tegumento de adultas faratas (Pbl) devem estar envolvidos com a formação e diferenciação do exoesqueleto definitivo. O aumento da expressão gênica neste período da muda (Pbl) é regulado pela variação do título de ecdisteróides e ocorre enquanto o título deste hormônio decai, após ter atingido o pico indutor da apólise na fase de desenvolvimento precedente (Pp). Ao contrário, as análises por qRT-PCR mostraram que 2 outros genes cuticulares (AmelCPF1 e AmelCPR1) são negativamente regulados no tegumento de adultas faratas em comparação com pupas, sugerindo que são específicos de cutícula pupal. Estes genes foram inibidos pelo aumento dos níveis de ecdisteróides, que induz a apólise. Vinte e um entre os 24 genes cuticulares diferencialmente expressos nos microarrays codificam proteínas pertencentes às famílias CPF, CPR, Apidermina, CPLCP, Análoga a peritrofina e Tweedle. Os outros 3 genes diferencialmente expressos (GB12449, GB12811, GB11550) não tinham sido ainda caracterizados como genes cuticulares. Dois deles, GB12449 e GB12811, foram sequenciados para validação da predição e para a caracterização das respectivas estruturas genômicas. Experimentos de hibridação in situ com sonda fluorescente (FISH) nos permitiram localizar altos níveis de transcritos destes genes no citoplasma de células da epiderme de adultas faratas, sugerindo fortemente sua natureza cuticular e envolvimento na construção do exoesqueleto definitivo. O presente estudo consiste na primeira análise global de expressão de genes do tegumento de uma espécie de himenóptero social. Os resultados apresentados levaram à identificação de genes com expressão associada à muda pupal-adulta e formação do exoesqueleto definitivo. Este trabalho contribui com novos dados moleculares para o aprofundamento do conhecimento da metamorfose de A. mellifera. / The insect cuticle is mainly composed of proteins that interact with chitin filaments to form a rigid structure that protects and shapes the organism. Insects grow through the periodic renewal of the cuticle, which is shed at each apolysis episode, and subsequently digested while the epidermis synthesizes the cuticle of the next stage. These molting events are coordinated by hormones, mainly ecdysteroids. The current work aimed to characterize differential gene expression in the integument (cuticle and underlying epidermis) during the ecdysteroid-regulated pupal-to-adult molt. Special attention was given to the structure and expression of genes encoding proteins and enzymes involved in cuticle formation and differentiation. To achieve these goals, we used thoracic integument of newly-ecdysed pupae (Pw), pupae in apolysis (Pp) and pharate adults (Pbl) in cDNA microarray analyses. The microarray analysis showed 761 and 1173 differentially expressed genes in the pharate adult integument (Pbl) in comparison to pupae (Pw) or pupae in apolysis (Pp), respectively. Gene Ontology terms for Biological Process and Molecular Function completely distinguished the integument of pharate adults (Pbl) from the integument of pupae (Pw) or pupae in apolysis (Pp). The microarray analysis discriminated 24 cuticular genes with a significant expression increase in the pharate adult integument. This was validated by real time RT-PCR analysis (qRT-PCR) for 23 of these genes (AmelCPR3, AmelCPR4, AmelCPR6, AmelCPR14, AmelCPR15, AmelCPR17, AmelCPR23, AmelCPR24, AmelCPR25, AmelCPR28, AmelCPR29, AmelCPR30, apd-1, apd-2, apd-3, CPLCP1, Am-C, Am-D, AmelTwdl1, AmelTwdl2, GB12449, GB12811 and GB11550), and by semiquantitative RT-PCR for Amlac2. In addition, the increased expression of other two cuticular genes (AmelCPR1 and AmelCPR2) was confirmed by qRT-PCR. These up-regulated cuticular genes in pharate adult integument apparently are involved in adult cuticle formation and differentiation, which occurs while the ecdysteroids titers decay, after reaching the peak that induces apolysis in the preceding phase (Pp). In contrast, two cuticular genes (AmelCPF1 e AmelCPR1) were confirmed by qRT-PCR analysis as negatively regulated in the integument of pharate adults compared to pupae, suggesting that they are specific to pupal cuticle. Therefore, these genes were inhibited by the increasing ecdysteroid levels that induce apolysis. Twenty one of the 24 cuticular genes differentially expressed in the microarrays encode proteins belonging to the CPF, CPR, Apidermin, CPLCP, Analogous to peritrofins and Tweedle families. The other three differentially expressed genes (GB12449, GB12811, GB11550) had not yet been assigned as cuticular genes. Two of them (GB12449 and GB12811) were sequenced, thus allowing prediction validation and gene structure characterization. In situ hybridization experiments using fluorescent probe (FISH) localized high expression of these genes in the pharate adult epidermis, strongly suggesting their involvement in the construction of the adult exoskeleton. This study is the first global gene expression analysis of the integument from a social hymenopteran species. The expression of genes in the integument was associated to the molting process and to the adult exoskeleton formation. This work contributes with new molecular data for a deeper understanding of A. mellifera metamorphosis.

Ce travail porte sur la réception d’Apulée (IIe siècle de notre ère) dans la littérature italienne du XXe siècle, et plus précisément sur le cas d’Alberto Savinio (1891-1952). L’étude de la relation entre les deux auteurs a été abordée selon une perspective interdisciplinaire ayant pour but de faire interagir le point de vue des études italiennes avec celui de la philologie latine. Cette recherche concerne la manière dont Alberto Savinio a lu et « réécrit » les Métamorphoses d’Apulée, roman aussi connu sous le titre de L’Âne d’or. Elle tâche de comprendre, d’une part, les raisons qui ont poussé plusieurs fois l’auteur italien vers ce texte ancien, d’autre part, les résultats esthétiques et philosophiques de sa réélaboration, laquelle s’étend sur une période de vingt ans environ, dès le début des années vingt jusqu’à la fin des années quarante. Par ailleurs, nous avons saisi de la réception savinienne d’Apulée tout un ensemble de problématiques et d’outils conceptuels qui ont permis de réaliser un approfondissement de l’analyse du texte des Métamorphoses. L’aspect le plus évident des réécritures réalisées par Alberto Savinio est, du point de vue formel, la réélaboration de la complexité des structures de l’énonciation propres à son modèle, ainsi que l’héritage de certaines pratiques métalittéraires. Nous avons de ce fait étudié le fonctionnement de la métalepse dans ce texte latin et, à l’aide de ce concept, nous avons élucidé certains passages du roman particulièrement difficiles, afin d’en améliorer la compréhension et de faciliter l’établissement critique du texte. / The object of this research concerns the reception of Apuleius’ Metamorphoses in the 20th century Italian literature and, more precisely, the relationship between Apuleius and the Italian writer Alberto Savinio (1891-1952). This topic has been considered from an interdisciplinary perspective, in order to integrate the point of view of Italian studies with that of Latin philology. On the one hand, this research explores the way in which Alberto Savinio has read and “rewritten” the text of Metamorphoses during a long period of his multifaceted literary career, from the middle of the nineteen-twenties until the end of the nineteen-forties. The aim of the analysis is to understand the reasons which led Savinio to reflect on important issues of his time, which concern, for instance, the problem of evil in its relationship with human nature, through his interpretation of Apuleius’ work, as well as the philosophical and aesthetical results of his elaboration.On the other hand, we have come to grips with Savinio’s reception of this ancient text together with a set of problematics and conceptual devices that permits a more thorough comprehension of the Apuleian work in itself. This research investigates the function of metalepsis – a concept first identified by Genette – in Metamorphoses’ novel, elucidating its pivotal role for the construction of meaning. Furthermore, it shows how this concept allows us to deal in a more attentive way with some issues of a text-critical nature, in particular concerning the prologue (with the problem of speaker’s identity) and the authorial sphragis at the end of the novel.

The series of two fossil species belonging to the order Palaeodictyoptera from the Late Carboniferous of Kuznetsk Basin in Russia were re-examined. The two species as Tchirkovaea guttata and Paimbia fenestrata were investigated with emphasis on the wing growth and development in comparison with the structure of developing wings in recent mayflies. This fossil material of T. guttata and P. fenestrata was long considered by previous authors as undisputed evidence for a unique type of wing development in the Palaeozoic insects. The idea was that the larvae of these insects possessed the wings, which became articulated and fully movable already earlier during the postembryonic development and that these gradually growing wings changed their position from longitudinal to perpendicular to the body axis. Moreover, the development was supposed to include two or more subimaginal instars, implying that the fully winged instars moulted several times during postembryonic development. After detailed study of the available fossils and subsequent comparison of the fossil evidence with the development of wings in the recent mayfly Cloeon dipterum it was discovered, that the alleged series of immature, subimaginal and imaginal wings of T. guttata and P. fenestrata do not provide clear evidence that would support...

[pt] Esta dissertação visa uma aproximação entre a produção científica e a escrita autobiográfica de Johann Wolfgang von Goethe (1749-1832). Na intenção de um desdobramento deste objetivo, empreende-se uma análise do ensaio A metamorfose das plantas (Die Metamorphose der Pflanzen) e de sua autobiografia mais conhecida, Memórias: poesia e verdade (Aus Meinem Leben. Dichtung und Wahrheit). Primeiramente, a partir da recuperação de textos nos quais o escritor rememora conceitos centrais desenvolvidos naquele ensaio sobre o processo de crescimento das plantas, publicado pela primeira vez em 1790, discute-se em que medida o recorrente empenho por um acesso ao passado representou a oportunidade de revisitar, explicar, corroborar e aperfeiçoar alguns desses conceitos, sobretudo, o de metamorfose. Compartilhando do argumento de que a recordação, em Goethe, atua sobre a experiência pretérita de maneira profícua, produtiva, redireciona-se a análise, então, para sua escrita autobiográfica. Após um exame inicial sobre o estatuto do gênero, chamando-se a atenção para sua maleabilidade discursiva, delineiam-se tanto as semelhanças quanto as especificidades do texto autobiográfico goethiano. Sendo assim, ao se lançar mão da articulação de uma série de conceitos mobilizados pelo escritor, torna-se possível acenar para a maneira singular pela qual Goethe redimensionou sua existência, no ato ulterior da escrita, possibilitando associar concepções particulares de ciência e de história na conformação de sua perspectiva autobiográfica. / [en] This dissertation aims at an approximation between the scientific production and the autobiographical writing of Johann Wolfgang von Goethe (1749-1832). In order to work on this objective, an analysis of the essay The Metamorphosis of Plants (Die Metamorphose der Pflanzen) and his best-known autobiography, From my life: poetry and truth (Aus Meinem Leben, Dichtung und Wahrheit) is developed. First, from the retrieval of texts in which the writer recalls central concepts developed in that essay about the process of plant growth, first published in 1790, it is discussed to what extent the recurrent commitment to an access to the past represented the opportunity of revisiting, explaining, corroborating and perfecting some of these concepts, above all, the one of metamorphosis. Sharing the argument that the recollection, in Goethe, acts over the past experience in a profitable, productive way, the analysis is, then, redirected to his autobiographical writing. After an initial examination of the status of the genre, drawing attention to its discursive malleability, both the similarities and specificities of the Goethian autobiographical text are highlighted. Thus, by using the articulation of a series of concepts mobilized by the writer, it becomes possible to emphasize the singular way in which Goethe redimensioned his existence, in the later act of writing, making it possible to associate particular conceptions of science and history in conformation of his autobiographical perspective.

Amphibians have been facing global declines over the last decades due to direct and indirect effects of anthropogenic activities. One of the leading causes is environmental contamination, particularly that of waterbodies which are used by many amphibian species for reproduction, development, and adult life. An important source of contamination comes from agricultural runoffs of pesticides such as neonicotinoids, which are known to alter anuran survival, behaviour, predation stress response, and development. However, few studies have investigated the possible interactions between neonicotinoids and natural environmental stressors which could alter the strength and direction of observed neonicotinoid effects. This study investigated how a concentration of imidacloprid (a neonicotinoid) measured in surface waters interacted with high population density, an important environmental stressor, to influence behaviour and development across metamorphosis in wood frogs (Lithobates sylvaticus) known to breed in agricultural landscapes. I reared tadpoles in a fully crossed design experiment, between two densities (0.33 and 1 tadpole/L) and clean vs contaminated water (10 µg/L imidacloprid). Behaviours were measured in the absence and presence of predation cues using open-field tests at three distinct developmental stages, up to the metamorph stage. I found that imidacloprid did not interact with population density or independently affect behaviours in the absence of predation cues. However, individuals raised at high density compared with low density were more active at an early developmental stage but less active at metamorphic climax. Furthermore, both density and imidacloprid independently decreased the natural behavioural response (i.e., “freezing”) of tadpoles to predation cues. Both treatments also slightly accelerated metamorphosis while only density altered final mass at metamorphosis. Finally, I found that distance travelled was weakly repeatable between aquatic stages but not repeatable across metamorphosis, a pattern that was not affected by treatments. This study provides novel insights on the ecotoxicology of imidacloprid in the presence of a natural stressor, highlighting the importance of including behavioural assays and stressors in studies of amphibian ecotoxicology.

Recent models argue that thermal environments are the major cause of ectotherm life-history clines. However, elevational clines in body size in the mountain dusky salamander Desmognathus ocoee (family Plethodontidae) shift from positive at hatching, to negative at metamorphosis to positive again as adults, and so are not consistent with this explanation. The clinal shift from hatching to metamorphosis was investigated by examining the clinal and seasonal feeding patterns of larval salamanders at high and low elevation sites in rockface and woodland habitats. Repeated cohort sampling was also used to examine clinal and seasonal patterns in body size and to estimate average growth rates. Larval growth in both rockface and woodland habitats was tightly correlated with feeding activity. Although temperature was found to vary between high and low elevation sites, the greatest growth occurred in a cold woodland habitat with a high elevation, and the lowest growth occurred in an adjacent rockface habitat. Because this difference in growth cannot be attributed to thermal differences, we conclude that local food resource levels are the predominant source of local differences in growth. These findings, clinal patterns of variation in other predatory salamanders, and experimental analyses in which both food and temperature are orthogonally manipulated, indicate that general models that single out temperature as the principle cause of ectotherm life-history clines should be viewed with caution.

<p>Perfluoroalkyl substances are synthetic organic chemicals of environmental concern because they have been associated with adverse effects in both human epidemiological studies and standard laboratory animals. In the environment, PFAS occur as mixtures, especially in areas with a history of PFAS application, such as aqueous film forming foam (AFFF) sites. Among the PFAS, perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) are the most common, and occur at the highest concentrations. Thus, amphibian populations at or near AFFF sites are at risk of exposure to known bioaccumulative and persistent chemicals, likely compromising the physiology and body condition of the animals. Here, we exposed northern leopard frogs to environmentally relevant concentrations of 0.5 and 1 ppb PFOS and PFHxS, alone or as a mixture comprised of 0.5 ppb PFOS and 0.5 ppb PFHxS. Univariate analyses showed that in the larval stages, tadpoles exposed to PFAS had significantly reduced scaled mass indexes (SMI’s) relative to the control, and only the organisms exposed to PFHxS 0.5 ppb were significantly larger. Sex did not significantly influence toxicity in the later stages (GS 42 & 46), indicating no sex-related effects. Altered body condition (i.e., fat stores) in the larval stages indicate potential effects to energy balance. There is a need to assess fitness-related effects as amphibians’ transition into the terrestrial environment, and include endpoints such as: reproductive, developmental, immunological, mating, feeding, competition, and survival. Early developmental effects in the larval stages also suggests that earlier developmental endpoints may be of interest. Establishing ecological risk assessments for PFAS are necessary, as they are toxic, persistent, and bioaccumulative.</p>

Museums in Sweden are found to be more and more mission-laden, as they gradually evolve from a custodian role to a visitor-focused socio-cultural institution. In their efforts to live up to their newly acquired role, more and more museums are prompted to inject entrepreneurial mindset and practices into their activity, leading to a nascent interest from the academic field in the possibility offered by entrepreneurship in the context of museums. We identify museums as a unique context motivated by the values and desires of the museum workers, whilst arguing that research on museum entrepreneurship has so far neglected the social aspect of these museum workers. Instead, the popular discourse has generally favored functionalism and positivism. As such, we propose to explore and potentialize an alternative view of entrepreneurship in museums that places the people, along with their values and desires, at its core. To that end, we conduct a case study with the Naval Museum, a governmental museum located in Karlskrona, Sweden. Through an iterative abductive approach inspired by grounded theory method, we shed light on several potentials and phenomena emerging from a combination of the museum workers’ values and the unique context of the Naval Museum. After performing a metamorphosis analysis inspired by Weiskopf and Steyaert, we give birth to child-museum-entrepreneurship, a concept unburdened of preconceptions. We then infuse it with Hjorth’s public entrepreneurship theory and discover a new form of becoming of museum entrepreneurship, potentializing its existence and power of re-creation and opening the door towards a human-centered museum entrepreneurship.