Development of a perturbation generator for vortex stability studies

Theory predicts vortex instability when subjected to certain types of disturbances. It was desired to build a device which could introduce controlled velocity perturbations into a trailing line vortex in order to study the effects on stability. A perturbation generator was designed and manufactured which can be attached to the centerbody of an airfoil type vortex generator. Details of design tests and manufacturing of the perturbation generator are presented. The device produced controlled perturbation with frequencies in excess of 250 Hz. Preliminary testing and evaluation of the perturbation generator performance was conducted in a 4 inch cylindrical pipe. Observations of vortex shedding frequencies from a centerbody were measured. Further evaluation with the perturbation generator attached to the vortex generator in a 2 x 3 foot wind tunnel were also conducted. Hot-wire anemometry was used to confirm the perturbation generator's ability to introduce controlled frequency fluctuations. Comparison of the energy levels of the disturbances in the vortex core was made between locations 42 chord lengths and 15 chord lengths downstream

Genealogy Reconstruction: Methods and applications in cancer and wild populations

Genealogy reconstruction is widely used in biology when relationships among entities are studied. Phylogenies, or evolutionary trees, show the differences between species. They are of profound importance because they help to obtain better understandings of evolutionary processes. Pedigrees, or family trees, on the other hand visualize the relatedness between individuals in a population. The reconstruction of pedigrees and the inference of parentage in general is now a cornerstone in molecular ecology. Applications include the direct infer- ence of gene flow, estimation of the effective population size and parameters describing the population’s mating behaviour such as rates of inbreeding. In the first part of this thesis, we construct genealogies of various types of cancer. Histopatho- logical classification of human tumors relies in part on the degree of differentiation of the tumor sample. To date, there is no objective systematic method to categorize tumor subtypes by maturation. We introduce a novel algorithm to rank tumor subtypes according to the dis- similarity of their gene expression from that of stem cells and fully differentiated tissue, and thereby construct a phylogenetic tree of cancer. We validate our methodology with expression data of leukemia and liposarcoma subtypes and then apply it to a broader group of sarcomas and of breast cancer subtypes. This ranking of tumor subtypes resulting from the application of our methodology allows the identification of genes correlated with differentiation and may help to identify novel therapeutic targets. Our algorithm represents the first phylogeny-based tool to analyze the differentiation status of human tumors. In contrast to asexually reproducing cancer cell populations, pedigrees of sexually reproduc- ing populations cannot be represented by phylogenetic trees. Pedigrees are directed acyclic graphs (DAGs) and therefore resemble more phylogenetic networks where reticulate events are indicated by vertices with two incoming arcs. We present a software package for pedigree reconstruction in natural populations using co-dominant genomic markers such as microsatel- lites and single nucleotide polymorphism (SNPs) in the second part of the thesis. If available, the algorithm makes use of prior information such as known relationships (sub-pedigrees) or the age and sex of individuals. Statistical confidence is estimated by Markov chain Monte Carlo (MCMC) sampling. The accuracy of the algorithm is demonstrated for simulated data as well as an empirical data set with known pedigree. The parentage inference is robust even in the presence of genotyping errors. We further demonstrate the accuracy of the algorithm on simulated clonal populations. We show that the joint estimation of parameters of inter- est such as the rate of self-fertilization or clonality is possible with high accuracy even with marker panels of moderate power. Classical methods can only assign a very limited number of statistically significant parentages in this case and would therefore fail. The method is implemented in a fast and easy to use open source software that scales to large datasets with many thousand individuals.:Abstract v Acknowledgments vii 1 Introduction 1 2 Cancer Phylogenies 7 2.1 Introduction..................................... 7 2.2 Background..................................... 9 2.2.1 PhylogeneticTrees............................. 9 2.2.2 Microarrays................................. 10 2.3 Methods....................................... 11 2.3.1 Datasetcompilation ............................ 11 2.3.2 Statistical Methods and Analysis..................... 13 2.3.3 Comparison of our methodology to other methods . . . . . . . . . . . 15 2.4 Results........................................ 16 2.4.1 Phylogenetic tree reconstruction method. . . . . . . . . . . . . . . . . 16 2.4.2 Comparison of tree reconstruction methods to other algorithms . . . . 28 2.4.3 Systematic analysis of methods and parameters . . . . . . . . . . . . . 30 2.5 Discussion...................................... 32 3 Wild Pedigrees 35 3.1 Introduction..................................... 35 3.2 The molecular ecologist’s tools of the trade ................... 36 3.2.1 3.2.2 3.2.3 3.2.1 Sibship inference and parental reconstruction . . . . . . . . . . . . . . 37 3.2.2 Parentage and paternity inference .................... 39 3.2.3 Multigenerational pedigree reconstruction . . . . . . . . . . . . . . . . 40 3.3 Background..................................... 40 3.3.1 Pedigrees .................................. 40 3.3.2 Genotypes.................................. 41 3.3.3 Mendelian segregation probability .................... 41 3.3.4 LOD Scores................................. 43 3.3.5 Genotyping Errors ............................. 43 3.3.6 IBD coefficients............................... 45 3.3.7 Bayesian MCMC.............................. 46 3.4 Methods....................................... 47 3.4.1 Likelihood Model.............................. 47 3.4.2 Efficient Likelihood Calculation...................... 49 3.4.3 Maximum Likelihood Pedigree ...................... 51 3.4.4 Full siblings................................. 52 3.4.5 Algorithm.................................. 53 3.4.6 Missing Values ............................... 56 3.4.7 Allelefrequencies.............................. 58 3.4.8 Rates of Self-fertilization.......................... 60 3.4.9 Rates of Clonality ............................. 60 3.5 Results........................................ 61 3.5.1 Real Microsatellite Data.......................... 61 3.5.2 Simulated Human Population....................... 62 3.5.3 SimulatedClonalPlantPopulation.................... 64 3.6 Discussion...................................... 71 4 Conclusions 77 A FRANz 79 A.1 Availability ..................................... 79 A.2 Input files...................................... 79 A.2.1 Maininputfile ............................... 79 A.2.2 Knownrelationships ............................ 80 A.2.3 Allele frequencies.............................. 81 A.2.4 Sampling locations............................. 82 A.3 Output files..................................... 83 A.4 Web 2.0 Interface.................................. 86 List of Figures 87 List of Tables 88 List Abbreviations 90 Bibliography 92 Curriculum Vitae

The effect of peripheral inflammation on in vivo functional properties of cortical networks

To fight pathogens is a major challenge of the immune system and it involves a cascade of mechanisms coupled together to defend the body against harmful stimuli. Injection of the endotoxin Lipopolysaccharide (LPS), a part of the cell wall of gram-negative bacteria activates peripheral immune cells and provokes an inflammatory cytokine response propagating to the brain. Aim of this work is to investigate the in vivo functional properties of cortical networks during peripheral inflammation. Our results demonstrate that under inflammatory conditions, the properties of the cortical network in the intact brain are shifted towards a hyperactive state. Microglia and neurons react to peripheral inflammation, induced by LPS injections, with a clear increase of their spontaneous calcium signaling. By using in vivo two-photon-calcium-imaging, we characterized the behavior of these two cell types over time and provided insights into the mechanisms involved. We found evidence that the activation of specific cytokines is underlying the altered brain signaling and showed that neurons react to this inflammatory condition in a microglia-independent manner.Die Bekämpfung von Krankheitserregern ist eine große Herausforderung für das Immunsystem und beinhaltet eine Kaskade verschiedener miteinander gekoppelter Mechanismen, um den Körper gegen schädliche Einflüsse zu schützen. Die Injektion des Endotoxins Lipopolysaccharid (LPS), eines Zellwandbestandteils gram-negativer Bakterien, führt zur Aktivierung peripherer Immunzellen und provoziert eine entzündliche Zytokinreaktion, die sich bis zum Gehirn ausbreitet. Ziel dieser Arbeit ist es, die funktionellen Eigenschaften des kortikalen Netzwerks während einer peripheren Entzündung unter in vivo Bedingungen zu untersuchen. Unsere Ergebnisse zeigen, dass das kortikale Netzwerk im intakten Gehirn bei einer Entzündung in einen hyperaktiven Zustand versetzt wird. Sowohl Mikroglia als auch Neurone reagieren auf eine durch LPS-Injektion hervorgerufene periphere Entzündung mit einer deutlichen Zunahme ihrer spontanen Kalzium-Signalgebung. Mit Hilfe von in vivo Zwei-Photonen-Kalzium-Mikroskopie haben wir das Verhalten dieser beiden Zelltypen über die Zeit charakterisiert und Einblicke in die beteiligten Mechanismen gegeben. Wir fanden Hinweise darauf, dass die Aktivierung bestimmter Zytokine der veränderten Signalgebung zugrunde liegt und zeigten, dass Neurone unabhängig von Mikrogliazellen auf diesen Entzündungszustand reagieren

Self-other agreement and leader effectiveness: An examination of differences across rater sources and leader behaviors

The study sought to identify the specific leadership behaviors and rater sources for which self-other agreement is most predictive of leader effectiveness. Hypotheses were based on the premise that certain sources may be better suited to provide feedback on specific leadership behaviors because they observe the individual in different setting and have a unique understanding of what it takes to effectively demonstrate certain behaviors. Participants included 847 leaders who, along with their observers, completed the Leadership Effectiveness Analysis (LEA; Management Research Group, 1992) as part of a leadership development program. Results revealed that self-other agreement may not be an important predictor of leader effectiveness. Instead, observer ratings of leadership behaviors were the most powerful predictors of leader effectiveness. Furthermore, results indicated that unique relationships exist between leadership behaviors and perceived effectiveness. For certain behaviors, higher ratings were related to greater effectiveness, while for others, lower or moderate levels of the behavior were viewed as more effective. Although not the focus of this study, results may point to the importance of considering the situational factors embedded in the organizational culture to provide a better understanding of the relationship between multi-source ratings of leadership behaviors and perceived leader effectiveness

Focus Triggers and Focus Types from a Corpus Perspective

The article discusses several issues relevant for the annotation of written and spoken corpus data with information structure. We discuss ways to identify focus top-down (via questions under discussion) or bottom-up (starting from pitch accents). We introduce a two-dimensional labelling scheme for information status and propose a way to distinguish between contrastive and non-contrastive information. Moreover, we take side in a current debate, claiming that focus is triggered by two sources: newness and elicited alternatives (contrast). This may lead to a high number of semantic-pragmatic foci in a single sentence. In each prosodic phrase there can be one primary focus (marked by a nuclear pitch accent) and several secondary foci (marked by weaker prosodic prominence). Second occurrence focus is one instance of secondary focus

FRANz: reconstruction of wild multi-generation pedigrees

Summary: We present a software package for pedigree reconstruction in natural populations using co-dominant genomic markers such as microsatellites and single nucleotide polymorphisms (SNPs). If available, the algorithm makes use of prior information such as known relationships (sub-pedigrees) or the age and sex of individuals. Statistical confidence is estimated by Markov Chain Monte Carlo (MCMC) sampling. The accuracy of the algorithm is demonstrated for simulated data as well as an empirical dataset with known pedigree. The parentage inference is robust even in the presence of genotyping errors