Markov and Semi-markov Chains, Processes, Systems and Emerging Related Fields

This book covers a broad range of research results in the field of Markov and Semi-Markov chains, processes, systems and related emerging fields. The authors of the included research papers are well-known researchers in their field. The book presents the state-of-the-art and ideas for further research for theorists in the fields. Nonetheless, it also provides straightforwardly applicable results for diverse areas of practitioners

Role Of Sonic Hedgehog Signalling in Human Embryonic Stem Cells And Its Neural Derivatives

Ph.DDOCTOR OF PHILOSOPH

Apathy and Impulsivity in Frontotemporal Lobar Degeneration

Apathy and Impulsivity in Frontotemporal Lobar Degeneration Ian Coyle-Gilchrist Frontotemporal Lobar Degeneration (FTLD) is pathologically heterogeneous group of degenerative diseases of the brain. While there are distinct and highly recognisable clinical syndromes associated with FTLD there is also a wider and more diverse spectrum of progressive changes in movement, coordination, language and behaviour. Correlation between clinical syndrome and pathology is variable. Furthermore, over the course of an individual’s illness their syndrome may change, or they may present with features of more than one syndrome at a given time. Apathy and Impulsivity are common, distressing and disabling across the entire spectrum of FTLD and may be particularly prominent compared to other neurodegenerative diseases. In this thesis I outline the current classification of syndromes associated with FTLD and how this has undergone expansion, refinement and fragmentation over time. Despite changes in nosology and advances in understanding of pathological heterogeneity, I argue that the clinical syndrome of FTLD is highly recognisable and has been described for centuries. I suggest that a more unifying transdiagnostic approach to FTLD may provide useful insights into an increasingly fragmented spectrum of disease. Using this approach I conducted a large epidemiological study of FTLD and report prevalence, incidence and lifetime risk estimates. From this cohort of recruits I then surveyed patients and their carers and used a range of assessments of cognition and behaviour. I showed that while reports of apathy and impulsivity are common in FTLD, patient and carer based reports do not correlate well with each other or predict performance on a range of behavioural measures of decision making or goal directed cognition. I conclude that in FTLD, apathy and impulsivity are overlapping and multidimensional constructs and that no single testing modality used in isolation represents them completely, hence a multimodal approach to their assessment is required

Doctor of Philosophy

dissertationHumans have lived at high altitude for hundreds of generations despite unavoidable challenges imposed by hypobaric hypoxia. The lower barometric pressure at high altitude reduces the number of oxygen molecules available in each breath of air, yet oxygen-dependent physiological processes must be maintained for survival. Cellular and system responses to hypoxic stress can result in altitude illness and may prove fatal in a small proportion of maladapted individuals. Native high-altitude populations, however, exhibit a unique suite of heritable traits that afford tolerance to hypoxia. Compared to lowland visitors and Andean highlanders, Tibetans exhibit lower hemoglobin (Hb) levels at high altitude, which tend to be similar to those expected under sea-level conditions. Such differences suggest this population has unique adaptations to their native environment. It has been hypothesized that genes specifically involved in the hypoxia inducible factor (HIF) pathway could underlie adaptive changes in high-altitude populations. Genome-wide analyses provide the first lines of evidence in support of genetic adaptation to high altitude. Three regions of the genome that contain genes associated with the human response to hypoxia show evidence of selection and are associated with decreased Hb levels, and two of these are also associated with metabolite levels. These phenotypic associations provide corroborative evidence for adaptive roles of genomic regions targeted by strong positive selection in Tibetans. iv While many of the same selection candidate genes are reported by studies of different Tibetan populations, some signals of selection and association are unique to particular groups. The genetic makeup of Tibetan groups located throughout the plateau is therefore important to consider in studies of high-altitude adaptation. Taken together, the data presented in this dissertation demonstrate that multiple genes are involved in Tibetan adaptation to high altitude. Some of these genes have been linked to hematological and metabolic phenotypes characterized thus far, providing further support for roles in physiological adaptation to this extreme environment. Studies aimed to identify associations between specific genetic variants, mechanisms, and phenotypes will help bridge the gap between genetic variation and organismal responses to hypoxia, and will have important implications for understanding human health and disease

Mathematische morfologie in de beeldverwerking Mathematical Morphology in Image Processing

Het verwerken van een afbeelding met de computer laat ons toe de kwaliteit van dit beeld te verbeteren, specifieke objecten uit het beeld te segmenteren, of extra informatie tevoorschijn te halen. Mathematische morfologie is een set van wiskundige technieken uit de beeldverwerking die ons toelaat (de vormen in) beelden te analyseren. Dit proefschrift levert oplossingen voor een aantal problemen uit de beeldverwerking, met behulp van mathematische morfologie. Morfologie toepassen op zwart-wit- of grijswaardenbeelden is relatief eenvoudig, maar de theorie uitbreiden voor kleurbeelden stelt een aantal problemen. Aangezien een kleurbeeld veel meer nuttige informatie kan bevatten dan een grijswaardenbeeld, is zo'n uitbreiding wenselijk. We stellen het meerderheidsordeningsschema (MSS) voor, wat ons toelaat kleuren onderling te ordenen op een logische manier. Morfologische beeldverwerking met kleuren wordt dan mogelijk. Een ander onderzoek betreft polymeren en composieten. Deze materialen worden als glijlagers gebruikt in allerhande voorwerpen, zoals huishoudtoestellen, sluizen, poorten, etc. Vandaar dat de studie van de slijtage hiervan belangrijk is. We gaan na of het morfologische patroonspectrum, alsook vergelijkbare technieken, een bijdrage kan leveren aan het wrijvingsonderzoek van dergelijke materialen. Dit zou de snelheid en efficiëntie van de analyses kunnen verbeteren. We merken op dat de spectrale parameters interessante verbanden vertonen met de parameters van de proefopstelling. Het derde luik van de thesis betreft het ontwikkelen van een interpolatietechniek voor zwart-wit-beelden, gebaseerd op mathematische morfologie, genaamd mmINT. Interpolatie is nodig wanneer we wensen in te zoomen op een beeld of de resolutie van het beeld willen vergroten. Dit kan van pas komen wanneer we ingescande of gedownloade tekeningen van slechte kwaliteit (te lage resolutie) willen verbeteren. mmINT werkt aanzienlijk beter dan bestaande methodes. We ontwikkelden ook een snelle variant, mmINTone, en een uitbreiding voor grijswaardenbeelden, mmINTg

Time Series Modelling

The analysis and modeling of time series is of the utmost importance in various fields of application. This Special Issue is a collection of articles on a wide range of topics, covering stochastic models for time series as well as methods for their analysis, univariate and multivariate time series, real-valued and discrete-valued time series, applications of time series methods to forecasting and statistical process control, and software implementations of methods and models for time series. The proposed approaches and concepts are thoroughly discussed and illustrated with several real-world data examples

Improving the Spectral Coverage and Resolution of the ISOLDE RILIS

This thesis concerns applications and developments of the Resonance Ionization Laser Ion Source (RILIS) at CERN-ISOLDE for ion beam production and laser spectroscopy. Laser developments, including the first operation of a grating-tuned Ti:sapphire combined with a thick etalon for linewidth reduction, the construction and characterization of a seeded Ti:sapphire ring cavity laser and the first demonstration of a Raman laser in the blue spectral range are presented. In-source laser spectroscopy on Dy isotopes has been performed, providing a valuable insight into the nuclear charge radii systematics near proton number Z=64. This work also illustrates the resolution limit imposed by Doppler-broadening of the atomic spectral lines inside the ion source. Addressing this limitation, the Doppler-free 2-photon ionization technique has been developed, leading to its first successful "in-source" application. The future of this approach to significantly increase the spectral resolution of RILIS is discussed

Understanding the Molecular and Cellular Functions of Odd-Skipped Related 1 in Outflow Tract Development

The cardiac outflow tract (OFT) is a transient conduit that connects the embryonic heart chambers to the vascular network. Transcription factor Osr1 promotes the proliferation and cell cycle progression of second heart field (SHF), an essential cell population that contribute to the developing OFT. In this study, we investigated the role of Osr1 in OFT development on cellular and molecular levels using a systems biology approach. We observed OFT rotation and elongation defects, as well as double-outlet right ventricle and overriding aorta as a result of SHF-specific deletion of Osr1. Using genetic inducible fate mapping, we showed that Osr1-expressing SHF cells migrate to the pulmonary trunk, however the cell lineage is ectopically distributed in the aorta, in addition to the pulmonary trunk, in Osr1 knockout embryos. To understand the molecular mechanism that leads to the aberrant localization of the Osr1 cell lineage, we performed transcriptional profiling of the isolated Osr1+ SHF population which showed Osr1-dependent expression of genes involved in tight junctions, cell adhesions, tissue connectivity and movement. Using in vivo and in vitro transcription factor binding assays, qRT-PCR as well as immunohistochemistry, we demonstrated that cell surface receptor Pdgfrb is a novel transcription target of Osr1. Furthermore, we showed that the Drosophila Pdgfrb homolog Pvr is required for the alignment and organization of Odd-expressing pericardial cells in the Drosophila larvae, demonstrating that the Osr1-Pdgfrb function is evolutionarily conserved. The heart is derived from two progenitor pools: first heart field (FHF) and second heart field (SHF). The SHF is a heterogeneous population and consists of subregions anterior SHF (aSHF) and posterior SHF (pSHF). Although being adjacent to each other and of similar cell types, their cell fates significantly differ. In this study, we investigated how epigenetic mechanisms shape the transcriptional profiles of the cardiac progenitor populations. Using Assay for Transposase Accessible Chromatin with high-throughput sequencing, we found that tissue-specific accessible regions are enriched with corresponding cardiac transcription factor binding motifs. Using whole-genome bisulfite sequencing, we showed that hypermethylation correlates with inhibited gene expression for tissue-specific markers. Thus this study addressed a multi-tier regulatory mechanism for cardiac progenitor cells