62 research outputs found

    Controling the number of focal elements

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    A basic belief assignment can have up to 2^n focal elements, and combining them with a simple conjunctive operator will need O(2^2n) operations. This article proposes some techniques to limit the size of the focal sets of the bbas to be combined while preserving a large part of the information they carry. The first section revisits some well-known definitions with an algorithmic point of vue. The second section proposes a matrix way of building the least committed isopignistic, and extends it to some other bodies of evidence. The third section adapts the k-means algorithm for an unsupervized clustering of the focal elements of a given bba.Comment: Belief 2012, Compi\`egne : France (2012

    An integrative study of bird migration: From the migratory phenotype to its gene regulation mechanisms and back.

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    Life goes out of equilibrium; it is in constant movement. Animals, especially, move as part of their life cycle. An outstanding example is bird migration. Some birds adopt migration as a strategy to survive the harsh conditions of weather seasonality in temperate regions. Different sources of evidence indicate that seasonal migration is innate, and it can be inherited. Mutations in such heritable behaviour create an array of diversity in migratory traits: timing, orientation and distance. The diversity of migratory traits can affect ecological speciation. Migratory divides, for instance, are geographical areas where birds with different migratory orientations hybridise. If the differences in migratory behaviour are strong enough to create reproductive barriers, this could evolve into population divergence and eventually, speciation. However, to understand the potential processes of divergence caused by migratory behaviours, a crucial element is missing: the identity of the molecular mechanisms involved in migration. Genome-wide studies in bird species with migratory divides find several different genomic regions with species-specific signature. Similarly, gene expression approaches in different organs and species find groups of individual differentially expressed genes. These results suggest an intricate mechanism for the genetics of migration with potential species-specific characteristics. This thesis analyses the migratory behaviour from different angles spanning the phenotype to gene regulation, to contribute to the identification of mechanisms and evolution of migration. Most of the chapters of this thesis use the Eurasian blackcap ( Sylvia atricapilla) a species that comprise an extensive repertoire of orientation and distance traits, including entirely resident populations. With blackcaps, we studied the phenotypic variability of migration tracking individuals ithroughout the year (Chapter 2). We used light-level geolocators to obtain migratory routes of individuals from populations in Central Europe and the United Kingdom. We describe for the first time the orientation and timing patterns of individuals from a migratory divide and a recently adapted population in the UK. In chapter 4, we analyse the genomics and evolution patterns of blackcaps. Using whole-genome resequencing of populations covering all the differences in migratory traits, we describe population structure and demography in this species. We found that blackcaps show very little genomic differentiation. The most divergent populations are residents, while migratory populations comprise a single population at the genetic level. Chapter 5 is the first study of gene regulatory mechanisms in the context of bird migration. We characterised the chromatin accessibility landscape in three brain areas contrasting individuals during migration with individuals out of the migratory season. One of the findings is a general pattern of gene repression in relevant brain regions like the Cluster N. Moreover; we found cis-regulatory modules with particular evolutionary trajectories that may play a role in migration. Lastly, we did two comparative approaches to study macroevolutionary patterns related to migration. First, we analysed phylogenetic patterns and structural characteristics of previously proposed candidate genes (chapter 3). We found that the candidate genes do not have structural characteristics correlated with the presence of migration across the avian clade as it does within some species. The second comparative approach (Chapter 6), evaluates the repeatability patterns of genomic divergence in pairs of populations from migratory divides. Our results suggests that the degree of repeatability is mainly driven by how apart in the speciation continuum is the population pair located: if the pair is recently diverging, iifew repeatability is detected, while if the populations are further apart, repeatability is more plausible. Overall, this thesis highlights an essential feature for the study of complex traits like migration: integration of different sources of evidence. Ideally, in these cases, the analysis of phenotype, evolutionary patterns and regulatory mechanisms in the same individuals, should be the standard procedure. We are aware that this is an implausible scenario. However, the integration of different studies, help to guide the search of molecular elements involved in bird migration. This thesis is the first - at least that we are aware of - study compilating research on a variety of topics to understand bird migration. We are still far from getting a definitive understanding of bird migration. Nevertheless, confirming the heritability of the phenotype, describing macro and microevolutionary patterns of migration and specific regulatory elements, will improve the search for new candidate genes for this behaviou

    Managing diversity : the strategic planning of long term technology infrastructure

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    Current methods of addressing uncertainty in the field of technology planning and management rely heavily on the use of forecasting and scenario generation. However, current developments in the planning and systems literature suggest that concepts of diversity and resilience provide an alternative framework for addressing uncertainty. Consequently, this thesis adopts an interdisciplinary approach to investigate three specific aspects of the technology assessment process; the limits to information from quantitative modelling, technological and managerial strategies for combating uncertainty, and the roles of models and modellers in these strategies. As a preface to the study, the nature of resilience in the context of technology planning is reviewed and some propositions are made concerning the matching of planning tools with levels of management sovereignty. A series of simulation models developed as part of the research programme provide some useful insights into the role of diversity in promoting both reduced costs and greater cost stability over the long term. However, they also expose a number of methodological limitations to modelling diversity in technological systems. These limitations are associated with both the representation of diversity and the exposure of multiple solutions. The second strand of investigation shows that the flexibility promoted by managers active in a turbulent operating environment, is focused on organisational and human centred attributes of the firm's activities. The final research activity shows that professional modellers in the U. K. appear to be aware of the limitations of the tools and techniques they utilise and perceive their role as being one of providing a rational / scientific approach to problem solving. Both policy and methodology related conclusions are drawn from the three research activities. Integration of the various strands of the research results emphasises the importance of matching the strategic and decision issue contexts of a policy issue to the analysis and policy tools used. Several recommendations for further research are also provided

    Investigating physical factors that regulate morphogenesis and fate of mouse embryonic midline sutures

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    Stem cells are crucial players during development, homeostasis and tissue regeneration and their interactions with the surrounding microenvironment are key to regulate stem cell fate. The skull's stem cell niches reside in the fibrous joints that connect flat bones of the skull. In the embryo, bone and sutures develop in concert to form a complex, multi-facted structure that requires interaction with multiple differentiating cell types to maintain balance between growth and differentiation. Disruption of this balance drives changes in size and shape of skull bones and can severely impact quality of life. Cranial sutures, often seen as simple extracellular matrix-rich structures bridging the rigid plates of the skull, are major actors in craniofacial morphogenesis of as they harmonize bone growth with expansion of the developing brain and participate in providing osteoblasts during repair. The complexity of the extracellular environment and the important role for sutures in skeletal development makes these niches a compelling structure to investigate how interactions with the surrounding microenvironment can modulate stem cells fate. The key role of sutures in development is highlighted by the numerous severe dysmorphisms arising from failure to maintain suture patency. The ability of the suture to respond to brain growth or trauma and the dysmophisms presented by patients with defective sutures is mediated by both biochemical and mechanical cues but the cell biology of these niches remains elusive, especially during their development. In particular, few studies have shed light on the underlying cellular behaviors behind microenvironmental regulation of cranial suture stem cell fate and what role mechanical inputs play in the establishment of this niche. In my thesis, I addressed gaps in our understanding of suture biology by characterizing the suture stem cell niche microenvironment and exploring how cell-ECM interactions serve as regulators of suture stem cell fate. Making use of various microscopy and analytical techniques I first characterized the composition of the microenvironment in a developing suture niche, such as organization of ECM, cytoskeleton and nuclear morphologies. My work builds on an incomplete transcriptional understanding of suture cell development, such that specific genetic markers are rarely useful for identifying distinct suture cell populations during its morphogenesis. By applying shape description tools to parse suture cells and test whether shape correlates to cell identity, we concluded that suture nuclei are distinct and less spherical than those of other cranial tissues. Using 'global' markers such as nuclear stains, I have also identified physical distinctions between suture nuclei and neighboring tissues, indicating that cell shape is an integral part of midline suture identity and can be used to explore coordination of fate choice and morphogenesis in this enigmatic structure. In addition, I present evidence that supports that maturation of extracellular matrix begins during early stages of suture development. In particular, embryonic midline sutures express high levels of fibrillary collagen, which contributes to the formation of a complex extracellular environment that provides the suture with physical properties distinct from those of developing bones. My work shows the presence of cell-ECM and cell-cell adhesions in the developing midline sutures, as well as a complex actin cytoskeleton that is, in part, mediated by physical stresses resultant from underlying brain expansion. Secondly, I aimed to address how perturbations in ECM composition can affect cell specification. To investigate the importance of ECM maturation in regulating suture cell fate I inhibited the function of lysyl oxidase, a collagen crosslinker, during embryonic development. Disruption of collagen crosslinking altered expression of collagen and ECM receptor encoding genes. In addition, this inhibition induced changes in the shape and size of collagen fibers in the embryonic midline suture and decreased tissue bulk stiffness relative to WT. These abnormal properties of the ECM impact tissue delineation in the cranial mesenchyme through nuclear shape analyses. This might be explained by observed changes in the composition of the nuclear envelop of suture cells as we find altered lamin concentration and localization upon lysyl oxidase inhibition. The work developed during myPhD steps away from the traditional genetic approaches used to study the embryonic suture and provides the first in-depth analysis of the physical properties of the developing midline suture at stages preceding known establishment of the niche. The various methods and analyses applied reveal a complex organization of embryonic suture ECM and its tight relationship with shape and fate in this tissue. This work serves as a foundation for future studies that can explore the mechanisms through which ECM regulates fate and development of the suture niche, and potentially skeletal development more generally

    Functional Magnetic Resonance Imaging

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    "Functional Magnetic Resonance Imaging - Advanced Neuroimaging Applications" is a concise book on applied methods of fMRI used in assessment of cognitive functions in brain and neuropsychological evaluation using motor-sensory activities, language, orthographic disabilities in children. The book will serve the purpose of applied neuropsychological evaluation methods in neuropsychological research projects, as well as relatively experienced psychologists and neuroscientists. Chapters are arranged in the order of basic concepts of fMRI and physiological basis of fMRI after event-related stimulus in first two chapters followed by new concepts of fMRI applied in constraint-induced movement therapy; reliability analysis; refractory SMA epilepsy; consciousness states; rule-guided behavioral analysis; orthographic frequency neighbor analysis for phonological activation; and quantitative multimodal spectroscopic fMRI to evaluate different neuropsychological states

    Approach to identify product and process state drivers in manufacturing systems using supervised machine learning

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    The developed concept allows identifying relevant state drivers of complex, multi-stage manufacturing systems holistically. It is able to utilize complex, diverse and high-dimensional data sets which often occur in manufacturing applications and integrate the important process intra- and inter-relations. The evaluation was conducted by using three different scenarios from distinctive manufacturing domains (aviation, chemical and semiconductor). The evaluation confirmed that it is possible to incorporate implicit process intra- and inter-relations on process as well as programme level through applying SVM based feature ranking. The analysis outcome presents a direct benefit for practitioners in form of the most important process parameters and state characteristics, so-called state drivers, of a manufacturing system. Given the increasing availability of data and information, this selection support can be directly utilized in, e.g., quality monitoring and advanced process control

    Engineering Surfaces to Control Neurogenesis

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    Producing therapeutic neural cell populations in vitro to treat neurodegenerative diseases is a key aim of regenerative medicine. Various protocols have been developed to produce a wide range of neural cell types in vitro, but the protocols are labour and resource intensive. Lower costs will take the cell therapy closer to clinical adoption. Cell-material interactions can be used to control cellular processes and behaviours in the place of expensive reagents. The thesis went about developing superior materials to culture neurons in vitro by using simple surface parameters. By using simple surfaces findings could be leveraged by incorporation in to other materials, and protocols to culture neurons. We have investigated the responses of primary neural tissue derived from rat ventral mesencephalon (VM), interacting with a range of surface chemical functionalities and net molecular properties by using silanes. Specific substrate functionality leads to higher ratios of neurons, longer neurites and neurosphere spreading capacity. All of these characteristics indicate a high neuro-regenerative capacity. Next it became important to optimize the amine functionalised surface with the addition of secondary amines in to the surface. The rational of adding secondary amines to the surface would produce functionalities which have a closer resemblance to biological molecules. The biomimicry in the surfaces provides extra scope for selective surface interactions to provide more control over neural cell culture which could steer protocols away from the use of expensive surfaces which are coated in extra cellular matrix molecules such as laminin. Controlling differentiation with surfaces has long been an aim in regenerative medicine to deliver productive production protocols. It has been shown that surfaces can induce differentiation of stem cells; however there is little control where stem cells and adult cells are simultaneously cultured. To achieve controlled differentiation of neural stem cells a surface gradient of amine polymer lengths, and polymer densities. That is in contrast to the surfaces used in previous chapters which had homogeneous presentations of surface chemistries
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