Modelling and analysis of nonlinear multibody dynamic systems

Modular self-reconfigurable robots are characterised by a high versatility. While most robots are designed for a special purpose these robots are designed to be multi-talented and adaptive. This thesis uses a modern framework for the automatic model generation of these modular self-reconfigurable robots. Based on a two-step Newton-Euler approach in combination with elements of screw-theory, this framework provides an elegant way to automatically calculate the equations of motion in a closed form. To simulate the kinematics and dynamics the framework has been implemented in MATLAB. To verify both the implementation and modelling, the equations of motion of two robot structures have been calculated using the framework and compared to the equations obtained by a Lagrangian approach. Finally it is shown that the linearisation and decoupling of the systems concerned in this thesis can be done easily using feedback linearisation. For completion two ways to control these linearised systems are demonstrated

Genome-wide SNP analysis reveals population structure and demographic history of the ryukyu islanders in the southern part of the Japanese archipelago.

The Ryukyu Islands are located to the southwest of the Japanese archipelago. Archaeological evidence has revealed the existence of prehistoric cultural differentiation between the northern Ryukyu islands of Amami and Okinawa, and the southern Ryukyu islands of Miyako and Yaeyama. To examine a genetic subdivision in the Ryukyu Islands, we conducted genome-wide single nucleotide polymorphism typing of inhabitants from the Okinawa Islands, the Miyako Islands, and the Yaeyama Islands. Principal component and cluster analyses revealed genetic differentiation among the island groups, especially between Okinawa and Miyako. No genetic affinity was observed between aboriginal Taiwanese and any of the Ryukyu populations. The genetic differentiation observed between the inhabitants of the Okinawa Islands and the Miyako Islands is likely to have arisen due to genetic drift rather than admixture with people from neighboring regions. Based on the observed genetic differences, the divergence time between the inhabitants of Okinawa and Miyako islands was dated to the Holocene. These findings suggest that the Pleistocene inhabitants, whose bones have been found on the southern Ryukyu Islands, did not make a major genetic contribution, if any, to the present-day inhabitants of the southern Ryukyu Islands

Rapid niche expansion by selection on functional genomic variation after ecosystem recovery

It is well recognized that environmental degradation caused by human activities can result in dramatic losses of species and diversity. However, comparatively little is known about the ability of biodiversity to re-emerge following ecosystem recovery. Here, we show that a European whitefish subspecies, the gangfisch Coregonus lavaretus macrophthalmus, rapidly increased its ecologically functional diversity following the restoration of Lake Constance after anthropogenic eutrophication. In fewer than ten generations, gangfisch evolved a greater range of gill raker numbers (GRNs) to utilize a broader ecological niche. A sparse genetic architecture underlies this variation in GRN. Several co-expressed gene modules and genes showing signals of positive selection were associated with GRN and body shape. These were enriched for biological pathways related to trophic niche expansion in fishes. Our findings demonstrate the potential of functional diversity to expand following habitat restoration, given a fortuitous combination of genetic architecture, genetic diversity and selection

A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans

As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major populations detected with two detection methods. This catalog enables us to systematically study mutation rates, population segregation, genomic distribution, and functional properties of MEI polymorphisms and to compare MEI to SNP variation from the same individuals. Population allele frequencies of MEI and SNPs are described, broadly, by the same neutral ancestral processes despite vastly different mutation mechanisms and rates, except in coding regions where MEI are virtually absent, presumably due to strong negative selection. A direct comparison of MEI and SNP diversity levels suggests a differential mobile element insertion rate among populations

Population genomics of speciation and admixture

The application of population genomics to the understanding of speciation has led to the emerging field of speciation genomics. This has brought new insight into how divergence builds up within the genome during speciation and is also revealing the extent to which species can continue to exchange genetic material despite reproductive barriers. It is also providing powerful new approaches for linking genotype to phenotype in admixed populations. In this chapter, we give an overview of some of the methods that have been used and some of the novel insights gained. We also outline some of the pitfalls of the most commonly used methods and possible problems with interpretation of the results

Vanishing refuge? Testing the forest refuge hypothesis in coastal East Africa using genome-wide sequence data for seven amphibians

High‐throughput sequencing data have greatly improved our ability to understand the processes that contribute to current biodiversity patterns. The “vanishing refuge” diversification model is speculated for the coastal forests of eastern Africa, whereby some taxa have persisted and diversified between forest refugia, while others have switched to becoming generalists also present in non‐forest habitats. Complex arrangements of geographical barriers (hydrology and topography) and ecological gradients between forest and non‐forest habitats may have further influenced the region's biodiversity, but elucidation of general diversification processes has been limited by lack of suitable data. Here, we explicitly test alternative diversification modes in the coastal forests using genome‐wide single nucleotide polymorphisms, mtDNA, spatial and environmental data for three forest (Arthroleptis xenodactyloides, Leptopelis flavomaculatus and Afrixalus sylvaticus) and four generalist (Afrixalus fornasini, A. delicatus, Leptopelis concolor, L. argenteus) amphibians. Multiple analyses provide insight about divergence times, spatial population structure, dispersal barriers, environmental stability and demographic history. We reveal highly congruent intra‐specific diversity and population structure across taxa, with most divergences occurring during the late Pliocene and Pleistocene. Although stability models support the existence of some forest refugia, dispersal barriers and demographic models point toward idiosyncratic diversification modes across taxa. We identify a consistent role for riverine barriers in the diversification of generalist taxa, but mechanisms of diversification are more complex for forest taxa and potentially include topographical barriers, forest refugia and ecological gradients. Our work demonstrates the complexity of diversification processes in this region, which vary between forest and generalist taxa, but also for ecologically similar species with shared population boundaries

Population genomics reveals that an anthropophilic population of Aedes aegypti\textit{Aedes aegypti} mosquitoes in West Africa recently gave rise to American and Asian populations of this major disease vector

$\textbf{BACKGROUND}$: The mosquito $\textit{Aedes aegypti}$ is the main vector of dengue, Zika, chikungunya and yellow fever viruses. This major disease vector is thought to have arisen when the African subspecies $\textit{Ae. aegypti}$ formosus evolved from being zoophilic and living in forest habitats into a form that specialises on humans and resides near human population centres. The resulting domestic subspecies, $\textit{Ae. aegypti aegypti}$, is found throughout the tropics and largely blood-feeds on humans. $\textbf{RESULTS}$: To understand this transition, we have sequenced the exomes of mosquitoes collected from five populations from around the world. We found that $\textit{Ae. aegypti}$ specimens from an urban population in Senegal in West Africa were more closely related to populations in Mexico and Sri Lanka than they were to a nearby forest population. We estimate that the populations in Senegal and Mexico split just a few hundred years ago, and we found no evidence of $\textit{Ae. aegypti aegypti}$ mosquitoes migrating back to Africa from elsewhere in the tropics. The out-of-Africa migration was accompanied by a dramatic reduction in effective population size, resulting in a loss of genetic diversity and rare genetic variants. $\textbf{CONCLUSIONS}$: We conclude that a domestic population of $\textit{Ae. aegypti}$ in Senegal and domestic populations on other continents are more closely related to each other than to other African populations. This suggests that an ancestral population of $\textit{Ae. aegypti }$evolved to become a human specialist in Africa, giving rise to the subspecies $\textit{Ae. aegypti aegypti}$. The descendants of this population are still found in West Africa today, and the rest of the world was colonised when mosquitoes from this population migrated out of Africa. This is the first report of an African population of Ae. aegypti aegypti mosquitoes that is closely related to Asian and American populations. As the two subspecies differ in their ability to vector disease, their existence side by side in West Africa may have important implications for disease transmission.This work was funded by European Research Council grant Drosophila Infection 281668 to FMJ, a KAUST AEA award to FMJ and AP, a Medical Research Council Centenary Award to WJP and a National Institutes of Health Ruth L. Kirschstein National Research Service Award to JC

A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis

Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8), a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3–6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40–80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5–24 hours, which may reduce survival to 13%. In severe sepsis, an extracorporeal treatment which modulates CXCR-1/2 levels has therapeutic potential, but also potential for harm. Further development of the computational model will help guide optimal device development and determine which patient populations should be targeted by treatment