Mutational Analysis

This monograph extends the classical concept of ordinary differential equations in the Euclidean space to nonempty sets which are just supplied with a family of "continuous" distance functions. In particular, these sets are not supposed to have any linear structure or to be metric spaces. The main goal is a joint framework for continuous dynamical systems beyond the traditional border of vector spaces so that examples of completely different origins can be coupled in systems. It is motivated by the mutational equations introduced by Jean-Pierre Aubin in the 1990s. Some of the examples discussed here are: nonlocal set evolutions, semilinear evolution equations, nonlinear transport equations for finite Radon measures, functional stochastic differential equations, parabolic differential equations in noncylindrical domains. This monograph is my revised Habilitationsschrift (i.e. thesis for a postdoctoral lecture qualification in Germany) submitted to the Faculty of Mathematics and Computer Science at Heidelberg University in January 2009

Detection of Power Disturbances for Power Quality Monitoring Using Mathematical Morphology

In power quality monitoring, determining the type of power quality disturbance occurring in the power system is important. Some disturbances such as, voltage dip, momentary interruption, voltage swell, or oscillatory transients in power systems may result internal-function or failure in the operation of some devices. Knowing the location where the disturbances occur in the system can yield an effective and efficient result when an appropriate method is applied in the attempt to solve the power quality issues. Some traditional strategies such as, wavelet or Fast Fourier transforms have been applied to detect and locate power quality disturbances, suffer from the complexity of the algorithm and the calculation load. In this thesis, mathematical morphology has been investigated for this purpose due to the merits of robustness and the simple calculations needed. In this thesis, some novel strategies using mathematical morphology are presented to find the time location of the disturbances, that is defined as the start and end points when the disturbance occur in the time domain. The first method was using morphology gradient, top-hat transform, and Skeletonization to identify the time location of the disturbances and noise in the system, and then plotting the results in 3D for pattern recognition. This Skeletonization is also combined with Morphology Edge Detection to find the accurate time location of disturbances in the system for both noise free signals and signals with noise. The overall result shows the reduction of the error was significant compared to the result of morphology edge detection strategy. Another novel strategy is presented by converting a signal to an image then applying image processing techniques, which are then evaluated using a control chart to find the time location of any disturbances. This conversion strategy is also applied for detecting the times of power quality disturbances uses short data samples of the signal (4 samples), so that it can be implemented as a real time detection strategy. The results show an accurate strategy in detecting disturbances. Half Multi-resolution Morphology Gradients (HMMG) based on multi-resolution morphology gradients (MMG) is also presented as a novel strategy and it operates in level 1 only, reducing the processing and increase the speed of detection of disturbance. The results show accurate detection when disturbances occur in the system. Other applications of MM are also presented such as a new alternative method in estimating the frequency in a signal based on top-hat and bottom-hat transforms with the results showing the ability of this method to handle low frequencies when the signal is a noise free signal. Neural networks are also implemented with MM for the identification and classification of disturbances. All the novel strategies using Skeletonization, signal/image conversion and HMMG for disturbances detection were then evaluated using a real dataset and an experimental dataset. Overall results show that this three methods can detect disturbances accurately

Phylogeographic and morphometric studies on the Eurasian pygmy shrew Sorex minutus: insights into its evolutionary history and postglacial colonisation in Europe

Here, I investigate the phylogeography and morphology of the Eurasian pygmy shrew Sorex minutus, searching for significantly differentiated lineages, colonisation routes and demographic parameters that would explain the effects of the Quaternary glaciations on the current distribution of the species. I also explore the genetic and morphological diversity and origin of pygmy shrew populations in the British Isles, particularly focusing on Ireland and the Orkney islands. Mitochondrial and nuclear DNA markers were used for the phylogeographic analyses, and a geometric morphometrics approach was implemented on mandible and skull samples. There was an evident phylogeographic structure across Eurasia consistent with occurrence of southern glacial refugia, and there were two distinct lineages in Northern-Central Europe and near the Pyrenees supporting the existence of northern glacial refugia through the characteristics of their distribution and population expansion. Haplotypes from Britain belonged to these two northern lineages, with the Pyrenean lineage forming a peripheral ‘Celtic fringe’. I show that it is most likely that pygmy shrews on both Ireland and Orkney were introduced by humans from mainland British Celtic fringe rather than further afield, even though there is a haplotype found in Northern Spain identical to one in Ireland. Mandible size increased noticeably with decreasing latitude, but skulls showed no evident trend in size variation. Shape variation was significant but modest when analysing the sample divided into phylogeographical groups. However, the samples from different islands within the British Isles show that island evolution played an important role in morphological diversity, with mandible and skull shape divergence on small islands and low genetic diversity. These results notably expanded previous findings and indicate that S. minutus is an excellent model for understanding the effects of climate change on biological diversity, colonisation and differentiation in refugia, and island evolution, useful for the conservation of genetic and morphological diversity

Investigation of intra-tumour heterogeneity to identify texture features to characterise and quantify neoplastic lesions on imaging

The aim of this work was to further our knowledge of using imaging data to discover image derived biomarkers and other information about the imaged tumour. Using scans obtained from multiple centres to discover and validate the models has advanced earlier research and provided a platform for further larger centre prospective studies. This work consists of two major studies which are describe separately: STUDY 1: NSCLC Purpose The aim of this multi-center study was to discover and validate radiomics classifiers as image-derived biomarkers for risk stratification of non-small-cell lung cancer (NSCLC). Patients and methods Pre-therapy PET scans from 358 Stage I–III NSCLC patients scheduled for radical radiotherapy/chemoradiotherapy acquired between October 2008 and December 2013 were included in this seven-institution study. Using a semiautomatic threshold method to segment the primary tumors, radiomics predictive classifiers were derived from a training set of 133 scans using TexLAB v2. Least absolute shrinkage and selection operator (LASSO) regression analysis allowed data dimension reduction and radiomics feature vector (FV) discovery. Multivariable analysis was performed to establish the relationship between FV, stage and overall survival (OS). Performance of the optimal FV was tested in an independent validation set of 204 patients, and a further independent set of 21 (TESTI) patients. Results Of 358 patients, 249 died within the follow-up period [median 22 (range 0–85) months]. From each primary tumor, 665 three-dimensional radiomics features from each of seven gray levels were extracted. The most predictive feature vector discovered (FVX) was independent of known prognostic factors, such as stage and tumor volume, and of interest to multi-center studies, invariant to the type of PET/CT manufacturer. Using the median cut-off, FVX predicted a 14-month survival difference in the validation cohort (N = 204, p = 0.00465; HR = 1.61, 95% CI 1.16–2.24). In the TESTI cohort, a smaller cohort that presented with unusually poor survival of stage I cancers, FVX correctly indicated a lack of survival difference (N = 21, p = 0.501). In contrast to the radiomics classifier, clinically routine PET variables including SUVmax, SUVmean and SUVpeak lacked any prognostic information. Conclusion PET-based radiomics classifiers derived from routine pre-treatment imaging possess intrinsic prognostic information for risk stratification of NSCLC patients to radiotherapy/chemo-radiotherapy. STUDY 2: Ovarian Cancer Purpose The 5-year survival of epithelial ovarian cancer is approximately 35-40%, prompting the need to develop additional methods such as biomarkers for personalised treatment. Patient and Methods 657 texture features were extracted from the CT scans of 364 untreated EOC patients. A 4-texture feature ‘Radiomic Prognostic Vector (RPV)’ was developed using machine learning methods on the training set. Results The RPV was able to identify the 5% of patients with the worst prognosis, significantly improving established prognostic methods and was further validated in two independent, multi-centre cohorts. In addition, the genetic, transcriptomic and proteomic analysis from two independent datasets demonstrated that stromal and DNA damage response pathways are activated in RPV-stratified tumours. Conclusion RPV could be used to guide personalised therapy of EOC. Overall, the two large datasets of different imaging modalities have increased our knowledge of texture analysis, improving the models currently available and provided us with more areas with which to implement these tools in the clinical setting.Open Acces

Aerospace medicine and biology: A cumulative index to the continuing bibliography of the 1973 issues

A cumulative index to the abstracts contained in Supplements 112 through 123 of Aerospace Medicine and Biology A Continuing Bibliography is presented. It includes three indexes: subject, personal author, and corporate source

Safety and efficacy of NovaSil clay as a dietary supplement to prevent aflatoxicosis

It is well documented that aflatoxin contamination in foods presents significant economic and public health burdens worldwide. Aflatoxins, particularly aflatoxin B1 (AFB1), have been implicated in the etiology of disease and death in many parts of the world, necessitating research initiatives for intervention strategies designed to diminish biological exposure. Calcium montmorillonite clays (e.g. NovaSil Plus, NSP) have been found to tightly bind and inactivate aflatoxins in the gastrointestinal tract of multiple animal species. In the future, the hypothesis is that this strategy may also be appropriate for humans. Thus, the overall research goal was to investigate NSP suitability for human use through in vitro characterization followed by in vivo evaluation of NSP-AFB1 sorption and most importantly, safety of the clay. The first objective was to characterize the in vitro and in vivo sorption efficiency of NSP-AFB1 sorption and determine potential interactions with vitamin A (VA). Isothermal analysis suggested that NSP binds AFB1 with high capacity, affinity, and specificity in aqueous solution and further indicated that NSP does not appear to interact with VA. Subsequent short-term studies in Sprague-Dawley (S-D) rats and broiler chicks indicated that dietary inclusion of NSP (0.25%) significantly reduced AFB1 bioavailability without exerting overt toxicity. The second objective was to evaluate potential adverse effects of chronic ingestion of dietary NSP using male and female S-D rats in the absence of aflatoxins. Although statistically significant changes to a few parameters were noted, the differences did not appear to be NSP- or dose-dependent, suggesting that NSP at dietary inclusion levels as great as 2.0% (w/w) does not produce overt toxicity. Thus, this information increases the feasibility for using NSP in human trials in populations at high risk for aflatoxicosis. The third objective was to establish representative baseline data on human exposure to aflatoxins by collecting and quantifying urinary AFM1 in volunteers living in four separate communities in Ejura district of Ghana. Results revealed that urinary AFM1 in the study population was substantially high (mean = 1,850.86 ± 274.59 pg/mg creatinine), indicating that this particular population was highly exposed to aflatoxins and could be used for future intervention trials

Phylogeographic and morphometric studies on the Eurasian pygmy shrew Sorex minutus : insights into its evolutionary history and postglacial colonisation in Europe

Here, I investigate the phylogeography and morphology of the Eurasian pygmy shrew Sorex minutus, searching for significantly differentiated lineages, colonisation routes and demographic parameters that would explain the effects of the Quaternary glaciations on the current distribution of the species. I also explore the genetic and morphological diversity and origin of pygmy shrew populations in the British Isles, particularly focusing on Ireland and the Orkney islands. Mitochondrial and nuclear DNA markers were used for the phylogeographic analyses, and a geometric morphometrics approach was implemented on mandible and skull samples. There was an evident phylogeographic structure across Eurasia consistent with occurrence of southern glacial refugia, and there were two distinct lineages in Northern-Central Europe and near the Pyrenees supporting the existence of northern glacial refugia through the characteristics of their distribution and population expansion. Haplotypes from Britain belonged to these two northern lineages, with the Pyrenean lineage forming a peripheral ‘Celtic fringe’. I show that it is most likely that pygmy shrews on both Ireland and Orkney were introduced by humans from mainland British Celtic fringe rather than further afield, even though there is a haplotype found in Northern Spain identical to one in Ireland. Mandible size increased noticeably with decreasing latitude, but skulls showed no evident trend in size variation. Shape variation was significant but modest when analysing the sample divided into phylogeographical groups. However, the samples from different islands within the British Isles show that island evolution played an important role in morphological diversity, with mandible and skull shape divergence on small islands and low genetic diversity. These results notably expanded previous findings and indicate that S. minutus is an excellent model for understanding the effects of climate change on biological diversity, colonisation and differentiation in refugia, and island evolution, useful for the conservation of genetic and morphological diversity.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Atherogenesis

This monograph will bring out the state-of-the-art advances in the dynamics of cholesterol transport and will address several important issues that pertain to oxidative stress and inflammation. The book is divided into three major sections. The book will offer insights into the roles of specific cytokines, inflammation, and oxidative stress in atherosclerosis and is intended for new researchers who are curious about atherosclerosis as well as for established senior researchers and clinicians who would be interested in novel findings that may link various aspects of the disease