Master of Science / Department of Diagnostic Medicine/Pathobiology / Wenjun Ma / With introduction of the 2009 pandemic H1N1 virus (pH1N1) into swine herds, reassortment between the pH1N1 and endemic swine influenza viruses (SIVs) has been reported worldwide. Recently, reassortant H3N2 and H1N2 variant SIVs that contain the M gene from pH1N1 virus and the remaining seven genes from North American triple-reassortant (TR) SIVs have emerged. These variant viruses have caused more than 300 cases of human infections and one death in the USA, creating a major public health concern. To date, the pathogenicity and transmissibility of H1N2 variant viruses in pigs has not been investigated. Through passive surveillance, we have isolated two genotypes of reassortant H1N2 viruses with pH1N1 genes from diseased pigs in Kansas. Full genome sequence and phylogenetic analysis showed that one is a swine H1N2 variant virus (swH1N2v) with the M gene from pH1N1; the other is a reassortant H1N2 virus (2+6 rH1N2) with six internal genes from pH1N1 and the two surface genes from endemic North American TR H1N2 SIVs. Furthermore, we determined the pathogenicity and transmissibility of the swH1N2v, a human H1N2 variant (huH1N2v), and the 2+6 rH1N2 in pigs using an endemic TR H1N2 SIV (eH1N2) isolated in 2011 as a control. All four viruses were able to infect pigs and replicate in the lungs. Both H1N2 variant viruses caused more severe lung lesions in infected pigs when compared to the eH1N2 and 2+6 rH1N2 viruses. Although all four viruses are transmissible in pigs and were detected in the lungs of contact animals, the swH1N2v shed more efficiently than the other three viruses in the respective sentinel animals. The huH1N2v displayed delayed and inefficient nasal shedding in sentinel animals. Taken together, the human and swine H1N2 variant viruses are more pathogenic and the swH1N2v more transmissible in pigs and could pose a threat to public and animal health.

This diploma thesis targets the evaluation of fifteen chosen EU countries using the methods of multicriteria decision-making. The topic is elaborated from the perspective of a student of the University of Economics, Prague, who chooses a suitable country to gain experience abroad. Students' preferences are recorded in a questionnaire and grouped using direct weights estimation method. The ORESTE, WSA, TOPSIS, PROMETHEE II and MAPPAC methods are described in the thesis and applied to the data using an add-on of Microsoft Excel -- Sanna. Since the questionnaire contains a question on the students' subjective ranking of countries, it is possible to compare the two rankings (subjective and calculated) to determine whether they are comparable and the students' decision-making is consistent.

The diploma Thesis is aimed to the application of strategy planning cycle for the small and medium enterprise operating in the waste management industry. The main goals of the Thesis were the internal and external analysis of the company. Considering the results to propose and evaluate some strategic options for the further development of the company and make an appropriate recommendation to the management. According to the results of the analysis the competitive advantage of the company is its specific know-how and the strong work team. The two proposed strategy variants are based on the gained data of the analysis. The first option of the company development is focused on the improvement of its processes and the company as a whole. The second strategy variant is aimed to the development of services provided. After the assessment of the variants from the three points of view: suitability, acceptability and feasibility, only the first variant seemed to be acceptable. Eventually the first option was recommended to the management of the company.

La reconstruction 3D par coupes sériées en microscopie optique est un moyen efficace pour étudier des spécimens biologiques fluorescents. Dans un tel système, la formation d'une image peut être représentée comme une convolution linéaire d'un objet avec une réponse impulsionnelle optique de l'instrument (PSF). Pour une étude quantitative, une estimation de l'objet doit être calculée en utilisant la déconvolution qui est le phénomène inverse de la convolution. Plusieurs algorithmes de déconvolution ont été développés en se basant sur des modèles statistiques ou par inversion directe, mais ces algorithmes se basent sur la supposition de l'invariance spatiale de la PSF pour simplifier et accélérer le processus. Dans certaines configurations optiques la PSF 3D change significativement en profondeur et ignorer ces changements implique des erreurs quantitatives dans l'estimation. Nous proposons un algorithme (EMMA) qui se base sur une hypothèse où l'erreur minimale sur l'estimation par un algorithme ne tenant pas compte de la non-invariance, se situe aux alentours de la position (profondeur) de la PSF utilisée. EMMA utilise des PSF à différentes positions et fusionne les différentes estimations en utilisant des masques d'interpolation linéaires adaptatifs aux positions des PSF utilisées. Pour obtenir des PSF à différentes profondeurs, un algorithme d'interpolation de PSF a également été développé. La méthode consiste à décomposer les PSF mesurées en utilisant les moments de Zernike pseudo-3D, puis les variations de chaque moment sont approximés par une fonction polynomiale. Ces fonctions polynomiales sont utilisées pour interpoler des PSF aux profondeurs voulues. / The 3-D fluorescence microscope has become the method of choice in biological sciences for living cells study. However, the data acquired with conventional3-D fluorescence microscopy are not quantitatively significant because of distortions induced by the optical acquisition process. Reliable measurements need the correction of theses distortions. Knowing the instrument impulse response, also known as the PSF, one can consider the backward process of convolution induced by the microscope, known as "deconvolution". However, when the system response is not invariant in the observation field, the classical algorithms can introduce large errors in the results. In this thesis we propose a new approach, which can be easily adapted to any classical deconvolution algorithm, direct or iterative, for bypassing the non-invariance PSF problem, without any modification to the later. Based on the hypothesis that the minimal error in a restored image using non-invariance assumption is located near the used PSF position, the EMMA (Evolutive Merging Masks Algorithm) blends multiple deconvolutions in the invariance assumption using a specific merging mask set. In order to obtain sufficient number of measured PSF at various depths for a better restoration using EMMA (or any other depth-variant deconvolution algorithm) we propose a 3D PSF interpolation algorithm based on the image moments theory using Zernike polynomials as decomposition base. The known PSF are decomposed into Zernike moments set and each moment's variation is fitted into a polynomial function, the resulting functions are then used to interpolate the needed PSF's Zernike moments set to reconstruct the interpolated PSF.

Lima-Silva TB. Funcionalidade e desempenho cognitivo na demência frontotemporal variante comportamental. [Dissertação]. São Paulo: Faculdade de Medicina, Universidade de São Paulo, 2012. Resumo Introdução: Existem poucos estudos sobre alterações funcionais na Demência Frontotemporal variante comportamental (DFTvc). Subtipos de demência menos estudados, como a DFTvc, vêm ganhando destaque, por também apresentarem importância epidemiológica. Objetivou-se no presente estudo: 1. Caracterizar o desempenho funcional e cognitivo de pacientes com diagnóstico prévio de DFTvc, atendidos em ambulatórios de Neurologia e Psiquiatria e compará-los a pacientes com Doença de Alzheimer (DA) e controles saudáveis; 2. Examinar a correlação entre o desempenho em escalas funcionais (DAFS-BR, DAD e PFAQ) e o desempenho cognitivo; 3. Avaliar a acurácia diagnóstica da DAFS-BR para a detecção da DFTvc e da DA. Métodos: Participaram 96 indivíduos com idade igual ou superior a 45 anos, com escolaridade formal acima de dois anos. Destes, 31 haviam recebido o diagnóstico de DFTvc, 31 de DA e 34 eram adultos saudáveis pareados aos pacientes com DFTvc e DA para idade e escolaridade. Foram aplicados: questionário sociodemográfico e de variáveis clínicas; Escala de Depressão Geriátrica (Geriatric Depression Scale - GDS) de 15 itens, Escala de Ansiedade Geriátrica (Geriatric Anxiety Inventory - GAI), Addenbrooke Cognitive Examination-Revised (ACE-R) que engloba as questões do Mini Exame do Estado Mental (MEEM), Executive Interview (EXIT-25), Direct Assessment of Functional Status (DAFS-BR). O protocolo dos acompanhantes conteve a Escala Cornell de Depressão em Demência, Pfeffer Functional Activities Questionnaire (PFAQ), Disability Assessment for Dementia (DAD), Inventário Neuropsiquiátrico (NPI) e a Escala de Avaliação Clínica da Demência (CDR). Resultados: Pôde-se observar que o grupo com DFTvc apresentou pior desempenho em Alimentação na DAFS-BR e nos domínios de Iniciação e Planejamento/Organização na DAD, comparado aos idosos com DA, sugerindo que a dependência na DFTvc é mais acentuada. A pontuação mais elevada na PFAQ, sugeriu que a dependência na DFTvc é mais acentuada. Foram encontradas correlações significativas entre o desempenho cognitivo e funcional. Os dados de acurácia para a DAFS-BR sugeriram que a escala pode auxiliar na identificação das demências, apresentando limitações no diagnóstico diferencial entre os subtipos. Considerações finais: Os resultados apresentados sugerem que indivíduos com DFTvc apresentam maior prejuízo funcional, quando comparados com participantes com DA e adultos saudáveis. Os resultados apresentados destacaram a importância da avaliação funcional de pacientes com suspeita de DFTvc, devido à relevância destas alterações para o diagnóstico e manejo clínico deste subtipo de demência. / Summary Introduction: There are but a few research studies on functional impairment in behavioral variant Frontotemporal Dementia. Less studied dementia subtypes, such as bvFTD, have been gaining prominence due to their epidemiological significance. The objectives of the present research were to: 1. Characterize the functional and cognitive performance of patients previously diagnosed with bvFTD treated at outpatient clinics of Neurology and Psychiatry, and compare their performance with that of patients with AD and normal controls; 2. Examine the correlation between performance in the functional scales (DAFS-BR, DAD e PFAQ) and cognitive performance; and 3. Evaluate the diagnostic accuracy of the DAFS-BR for detecting bvFTD and AD. Methodology: The sample consisted of 96 individuals aged 45 or older, with at least two years of formal education. Of these, 31 had been diagnosed with bvFTD, 31 with AD, and 34 were healthy adults paired with the patients with bvFTD and AD for age and education. The following instruments were used: sociodemographic and clinical questionnaire; 15-item Geriatric Depression Scale (GDS); Geriatric Anxiety Inventory (GAI); Addenbrooke Cognitive Examination-Revised (ACE-R), which includes the questions of the Mini Mental State Examination (MMSE); Executive Interview (EXIT-25); and the Direct Assessment of Functional Status Revised (DAFS-BR). The protocol for caregivers included the Cornell Scale for Depression in Dementia, Pfeffer Functional Activities Questionnaire (PFAQ), Disability Assessment for Dementia (DAD), Neuropsychiatric Inventory (NPI) and the Clinical Dementia Rating scale (CDR). Results: Individuals in the bvFTD group had lower performance in the ´Eating skills´ item of the DAFS-BR, and in ´Initiation´ and in ´Planning/Organization´ in the DAD, suggesting a higher level of dependence in bvFTD, and Higher scores in the PFAQ suggested that dependence in bvFTD is more pronounced. Significant correlations were found between cognitive and functional performances. The accuracy data for the DAFS-BR indicated that the scale can help identify dementia however, it has limitations in the differential diagnosis among subtypes. Final Considerations: The results suggest that individuals with bvFTD display greater functional impairment when compared to individuals with AD and to healthy adults. These results highlight the importance of assessing functionality status among patients suspected to have bvFTD. These deficits are relevant for the diagnosis and clinical management of this subtype of dementia.

Lianas de Bignoniaceae são reconhecidas por apresentarem uma variação cambial em seus caules, que promove a formação de cunhas de floema que interrompem o xilema. Uma grande diversidade de formas anatômicas foram descritas para esta variação, assim como o floema resultante dela também foi descrito como sendo distinto do floema normal presente concomitantemente nestes caules. Entretanto, nada se sabe sobre a origem, evolução e diversificação das características anatômicas neste grupo. Por essa razão, o presente estudo teve como objetivo uma análise anatômica dos caules de Bignonieae num contexto filogenético, com o intuito de lançar hipóteses para a evolução da diversidade anatômica na tribo. Para tanto, foi realizada uma análise anatômica caulinar de 54 espécies de Bignonieae, representantes dos 21 gêneros atualmente reconhecidos. Nossos resultados apontam que, não obstante a grande diversidade anatômica presente nos caules de Bignonieae, todas compartilham estágios comuns de desenvolvimento, seguidos de adições terminais que promoveram o aumento da complexidade em seus caules. Além disso, vimos que as diferenças entre o floema normal e o variante tem aumentado ao longo da evolução e está presente em todos os tipos celulares do floema. Vimos ainda que o floema secundário em Bignonieae evolui em direções opostas em diferentes linhagens da tribo, evidenciando que a evolução do floema não segue uma única direção, mas várias. Por fim, este estudo demonstra que análises anatômicas dentro de um contexto filogenético são primordiais por permitirem um maior entendimento dos processos que promoveram a evolução e diversificação dos grupos. / Lianas in Bignoniaceae are well known for presenting a cambial variant in their stems, which develops into phloem wedges that deep furrows the xylem. An enormous diversity of anatomical forms were described as resulting from this cambial variant, as well as the phloem produced by the cambial variant was described as being distinct from the regular phloem concurrently present in these stems. However, nothing is known about the origin, evolution, and diversification of the anatomical traits in this group. Therefore, the present study aimed to provide an anatomical analysis of the stems of Bignonieae (Bignoniaceae) within a phylogenetic framework, in order to address questions on the evolution of anatomical diversity in this tribe. For that reason, here we analyzed the stems of 54 species of Bignonieae, representative of the 21 genera currently known for the tribe. Our results show that, despite the great anatomical diversity present in the stems of Bignonieae, all of them share common developmental stages, which are then followed by subsequent terminal additions that are though to have promoted an augment in the complexity of these stems. Furthermore, our results indicate that the differences found between regular and variant phloem is increasing along time and is present in all cell types of the phloem. Moreover, we found that the secondary phloem in Bignonieae is evolving in opposite directions in distinct lineages of the tribe, evidencing that the evolution of the phloem is not constraint to a single line of specialization. In conclusion, this study demonstrates the importance of anatomical analyses within a phylogenetic framework, allowing for the detection of the processes that have been involved in the evolution and diversification of plant groups.

Les systèmes décrits par les équations aux dérivées partielles, appartiennent à la classe des systèmes dynamiques impliquant des fonctions dépendantes de plusieurs variables, comme le temps et l'espace. Déjà fortement répandus pour la modélisation mathématique de phénomènes physiques et environnementaux, ces systèmes ont un rôle croissant dans les domaines de l'automatique. Cette expansion, provoquée par les avancées technologiques au niveau des capteurs facilitant l'acquisition de données et par les nouveaux enjeux environnementaux, incite au développement de nouvelles thématiques de recherche. L'une de ces thématiques, est l'étude des problèmes inverses et plus particulièrement l'identification paramétrique des équations aux dérivées partielles. Tout abord, une description détaillée des différentes classes de systèmes décrits par ces équations est présentée puis les problèmes d'identification qui leur sont associés sont soulevés. L'accent est mis sur l'estimation paramétrique des équations linéaires, homogènes ou non, et sur les équations linéaires à paramètres variant. Un point commun à ces problèmes d'identification réside dans le caractère bruité et échantillonné des mesures de la sortie. Pour ce faire, deux types d'outils principaux ont été élaborés. Certaines techniques de discrétisation spatio-temporelle ont été utilisées pour faire face au caractère échantillonné des données; les méthodes de variable instrumentale, pour traiter le problème lié à la présence de bruit de mesure. Les performances de ces méthodes ont été évaluées selon des protocoles de simulation numérique reproduisant des situations réalistes de phénomènes physique et environnementaux, comme la diffusion de polluant dans une rivière / A large variety of natural, industrial, and environmental systems involves phenomena that are continuous functions not only of time, but also of other independent variables, such as space coordinates. Typical examples are transportation phenomena of mass or energy, such as heat transmission and/or exchange, humidity diffusion or concentration distributions. These systems are intrinsically distributed parameter systems whose description usually requires the introduction of partial differential equations. There is a significant number of phenomena that can be simulated and explained by partial differential equations. Unfortunately all phenomena are not likely to be represented by a single equation. Also, it is necessary to model the largest possible number of behaviors to consider several classes of partial differential equations. The most common are linear equations, but the most representative are non-linear equations. The nonlinear equations can be formulated in many different ways, the interest in nonlinear equations with linear parameters varying is studied. The aim of the thesis is to develop new estimators to identify the systems described by these partial differential equations. These estimators must be adapted with the actual data obtained in experiments. It is therefore necessary to develop estimators that provide convergent estimates when one is in the presence of missing data and are robust to measurement noise. In this thesis, identification methods are proposed for partial differential equation parameter estimation. These methods involve the introduction of estimators based on the instrumental variable technique

O teste de programas concorrentes é uma atividade custosa devido principalmente à quantidade de sequências de sincronização que devem ser testadas para validar tais programas. Uma das técnicas mais utilizadas para testar a comunicação e sincronização de programas concorrentes é a geração automática de diferentes pares de sincronização ou, em outras palavras, a geração de variantes de disputa (race variant). Nesta técnica as variantes de disputa são geradas a partir de arquivos de rastro de uma execução não-determinística e algoritmos de execução determinística são utilizados para forçar que diferentes sincronizações sejam cobertas. Este trabalho aborda de maneira abrangente este problema, cujo objetivo principal é reduzir o tempo de resposta da atividade de teste estrutural de programas concorrentes quando diferentes variantes de disputa são executadas. Há três principais contribuições neste trabalho: (1) geração de arquivos de rastro e execução determinística total/parcial, (2) geração automática de variantes e (3) paralelização da execução das variantes. Diferentemente de outros trabalhos disponíveis na literatura, os algoritmos propostos consideram programas concorrentes que interagem simultaneamente com passagem de mensagens e memória compartilhada. Foram consideradas seis primitivas com semânticas distintas: ponto-a-ponto bloqueante/não bloqueante, coletivas um-para-todos/todos-para-um/todos-para-todos e semáforos. Os algoritmos foram desenvolvidos no nível de aplicação em Java, são ortogonais à linguagem de programação utilizada e não requerem privilégios de sistema para serem executados. Estas três contribuições são descritas, detalhando seus algoritmos. Também são apresentados os resultados obtidos com os experimentos feitos durante as fases de validação e avaliação de cada contribuição. Os resultados demonstram que os objetivos propostos foram atingidos com sucesso para cada contribuição e, do ponto de vista do testador, o tempo de resposta da atividade de teste estrutural de programas concorrentes foi reduzido enquanto a cobertura de programas concorrentes com ambos os paradigmas aumentou com procedimentos automatizados e transparentes. Os experimentos mostram speedups próximos ao linear, quando comparadas as versões sequencial e paralela dos algoritmos. / The testing of concurrent programs is an expensive task, mainly because it needs to test a high number of synchronization sequences, in order to validate such programs. One of the most used techniques to test communication and synchronization of concurrent programs is the automatic generation of different synchronizations pairs (or generation of race variants). Race variants are generated from the trace files of a nondeterministic execution, and the deterministic executions force the coverage of different synchronizations. This work approaches this problem in a more general way. It reduces the response time of the structural testing of concurrent programs when different variants are required. There are three main contributions in this work: the generation of trace files and the total or partial deterministic execution, the automatic generation of race variants and the parallelization of execution of race variants. The proposed algorithms take into account concurrent programs that interact simultaneously with message passing and shared memory, including six primitives with distinct semantics: blocking and non-blocking point-to-point, all-to-all/one-to-all/all-toone collectives and shared memory. The algorithms have been implemented in Java in the application level, they are language independent and do not need system privileges to execute. Results obtained during the validation and evaluation phase are also presented and they show that the proposed objectives are reached with success. From the tester viewpoint, the response time of structural testing of concurrent programs was reduced, while the coverage of the concurrent programs with both paradigms increased with automatic and transparent procedures. The experiments showed speedups close to linear, when comparing the sequential and parallel versions.

La fibrillation atriale (FA) est un problème de santé publique majeur dans le monde entier. Le remodelage électrique, structurel et neuronal est sous-jacent à la myopathie atriale. La pharmacothérapie actuelle est souvent inefficace en raison du manque de connaissance de la pathophysiologie de la FA.Pour comprendre comment se réalise le remodelage atrial, une approche Omique qui explore le transcriptome, l'épigénome (méthylome et microOme) et le génome de patients atteints de FA a été réalisée. Parallèlement, le phénotype de vieux rats spontanément hypertendus (SHRs) a été caractérisé et une étude pharmacologique avec la décitabine (5-Aza-2'-deoxycitidine) a été menée. Les patients atteint de FA présentent un profil transcriptomique et d'expression de miRNA alteré dans l'oreillete gauche (OG), soulignant le rôle important d'un processus de "œmorphogénèse de la structure anatomique". L'expression réduite de Pitx2 était inversement corrélée à la taille de l'OG et ne pouvait pas être expliquée ni par le facteur de transcription ni par la surexpression de Smyd2, une cible de miR-519b. Les SHRs, similairement aux observations chez l'homme, ont développé des arythmies dépendantes de l'âge associées au remodelage atrial et ventriculaire gauche. La FA a été trouvée associée à l'hyperméthylation du promoteur de Pitx2 à la fois chez l'homme et chez les SHRs. L'agent hyperméthylant décitabine a amélioré le profil arhytmique de l'ECG et les activités SOD, et la réduction de la fibrose dans le ventricule gauche des SHRs. En utillisant une approche NGS basée sur un panel personnalisé de 55 gènes candidats à la myopathie atriale dans une cohorte de 94 patients atteints de FA, 11 nouvelles variantes faux-sens potentiellement pathogènes impliqués dans le remodelage structurel ont été identifiés. Des études fonctionnelles de ces variants ont débuté. Trois patients sont également des porteurs de variantes dans les gènes connus de FA. Les résultats actuels suggèrent que 1) la régulation épigénétique peut jouer un rôle dans la pathophysiologie de la FA 2) les agents hypométhylants doivent être considérés comme une nouvelle thérapie de la FA 3) une approche Omique peut aider à découvrir de nouveaux mécanismes sous-jacents à la myopathie atriale / Atrial fibrillation (AF) is a major public health care problem worldwide. Electrical, structural, and neural remodeling underlie atrial myopathy. Current pharmacotherapy is often ineffective due to the lack of knowledge of AF pathophysiology. To understand how atrial remodeling occurs, an Omic approach that explore the transcriptome, epigenome (methylome and microOme) and genome of AF patients was performed. In parallel, ageing spontaneously hypertensive rats (SHRs) were phenotypically characterised and a pharmacological study with decitabine (5-Aza-2’-deoxycitidine) was conducted. AF patients presented an altered transcriptomic and microRNA expression profile in the left atria (LA), emphasizing the important role of an "anatomical structure morphogenesis" process. The Pitx2 reduced expression was inversely correlated with LA size, and could not be explained by transcriptor factor. Smyd2 is a target of miR-519b-3p. SHRs, similar to what is observed in humans, developed age-dependent arrhythmias associated with left atrial and ventricular remodeling. AF was found to be associated with Pitx2 promoter hypermethylation both in humans and in SHRs. The hypomethylating agent decitabine improved ECG arrhythmic profiles and superoxide dismutase activities, and reduced fibrosis in the left ventricle of SHRs. Using a next-generation sequencing approach based on a custom panel of 55 atrial myopathy candidate genes in a cohort of 94 AF patients, 11 novel potentially pathogenic missense variants involved in structural remodeling were identified. Functional studies of these variants have started. Three patients were also carriers of variants in known AF-causing genes. The present results suggest that 1) epigenetic regulation may play a role in the pathophysiology of AF 2) hypomethylating agents have to be considered as a new AF therapy 3) an Omic approach may help to uncover new mechanisms underlying atrial myopathy

During loss-of-coolant accidents (LOCA) and reactivity-initiated accidents (RIA), nuclear fuel rods experience high heating rates that change the microstructure and properties of zirconium cladding materials, which are in forms of stress-relieved, like cold-worked (CW) or recrystallised (RX) microstructure. The present study aimed to determine how different fast heating rates and starting microstructures affect the kinetics of phase transformation, the transformation textures and eventually the mechanical response in the dual-phase region. The LOCA/RIA cycles from heating at 8 to 100C/s to alpha+beta or above beta transus temperature were achieved via resistive heating in an electro-thermal-mechanical tester. Synchrotron X-ray diffraction (SXRD) and electrical resistivity measurements showed that the approach curves of CW Zircaloy-4 shift to higher temperature at faster constant heating rates and change to a new approach curve when changing rates. 2-second holding at two-phase temperature produces identical phase fractions as equilibrium. These observations are consistent with the diffusional character of the phase trans- formation. Heated at 100oCs1, RX samples transform with 2D beta-growth while CW ones show simultaneous beta-nucleation and growth. The difference arises because the fast heating rate helps preserve low-angle grain boundaries (GB) in the CW microstructure up to phase transformation temperature, increasing beta nucleation sites and prevent beta-growth. This gives rise to different textures of RX and CW materials before transformation, producing different textures, which are weak in both cases. However, this difference is enhanced during grain growth and transformation on cooling. Thus, the RX material shows strong final alpha texture with 0002 maxima aligned in TD and tilted 20deg from ND towards TD while the CW reveals an essentially random one. In both RX and CW materials, variant selection does not occur during transformation on heating. During beta-grain growth, although there is variability in beta-textures measured by SXRD and EBSD beta reconstruction, it is clear that variant selection occurs, leading to strengthening of the beta texture. During transformation on cooling, variant selection occurs early in nucleation of the alpha phase from the shared 110 beta GB in the RX condition. The flow stresses of CW Zircaloy-4 in the two-phase regime at a given temperature depend on the heating rates, despite having the same phase fractions. Heated at a slower rate, the material shows an upper yield stress followed by softening behaviour while that heated faster has a smaller yield stress followed by a high work-hardening rate and then stable flowing stresses. The evolution of diffraction elastic strains and intensity suggest the upper yield stress and softening are due to stress-induced transformation of the harder alpha grains into large and isolated softer beta grains. In contrast, the sample heated faster develops an almost continuous film of beta grains along the GB of unrecrystallised alpha-grains which results in early beta-yielding and coherent deformation of the two phases, leading to constant flow stresses. The findings will improve the accuracy of inputs from phase fractions, microstructure and texture of zirconium claddings when modelling LOCA/RIA. A crystal plasticity model should consider the effects of heating rates and cold-work, which are often ignored. The link between deformation, fast heating rates and microstructure evolution might be relevant to other processes like additive layer manufacturing and even forging in the two-phase region.