Au cours de la méiose, les points chauds de recombinaison sont le siège de la formation de cassures double-brin de l’ADN. Ces dernières sont ensuite réparées par un processus qui, chez de nombreuses espèces, favorise la transmission des allèles G et C : la conversion génique biaisée vers GC (gBGC). L’intensité de cet important distorteur de la ségrégation méiotique varie fortement entre espèces mais les facteurs déterminant son évolution sont toujours inconnus. Nous avons donc voulu quantifier directement le biais de transmission chez la souris et comparer les paramètres dont il dépend avec d’autres mammifères. Dans cette étude, en couplant des développements bioinformatiques à une technique de capture ciblée d’ADN suivie de séquençage haut-débit (capture-seq), nous avons réussi à mettre au point une approche qui s’est révélée 100 fois plus performante pour détecter les événements de recombinaison que les méthodes existant actuellement. Ainsi, nous avons pu identifier 18 821 crossing-overs (COs) et non-crossovers (NCOs) à très grande résolution chez des individus uniques, ce qui nous a permis de caractériser minutieusement la recombinaison chez la souris. Chez cette espèce, les points chauds de recombinaison sont ciblés par la protéine PRDM9 et sont donc soumis à une deuxième forme de conversion génique biaisée (BGC) : le biais d’initiation (dBGC). La quantification du dBGC et du gBGC à partir de nos données nous a permis de mettre en lumière le fait que, au moment où des populations structurées s’hybrident, le gBGC des lignées parentales est propagé par un phénomène d’auto-stop génétique (genetic hitchhiking) provenant du dBGC. Nous avons ensuite pu observer que, chez les souris mâles, seuls les NCOs — et plus particulièrement les NCOs contenant un seul marqueur génétique— contribuent à l’intensité du gBGC. En comparaison, chez l’Homme, à la fois les NCOs et au moins une part des COs (ceux qui présentent des tracts de conversion complexes) distordent les fréquences alléliques. Ceci suggère que la machinerie de réparation des cassures double-brin qui induit le biais de conversion génique (BGC) présente des variations au sein des mammifères. Nos résultats sont aussi en accord avec l’hypothèse selon laquelle une pression de sélection limiterait l’intensité de ce processus délétère à l’échelle de la population. Cela se traduirait par une compensation de la taille efficace de population à de multiples niveaux : par le taux de recombinaison, par la longueur des tracts de conversion et par le biais de transmission. Somme toute, notre travail a permis de mieux comprendre la façon dont la recombinaison et la conversion génique biaisée opèrent chez les mammifères. / During meiosis, recombination hotspots host the formation of DNA double-strand breaks (DSBs). DSBs are subsequently repaired through a process which, in a wide range of species, is biased towards the favoured transmission of G and C alleles: GC-biased gene conversion (gBGC). The intensity of this fundamental distorter of meiotic segregation strongly varies between species but the factors dictating its evolution are not known. We thus aimed at directly quantifying the transmission bias in mice and comparing the parameters on which it depends with other mammals. Here, we coupled capture-seq and bioinformatic techniques to implement an approach that proved 100 times more powerful than current methods to detect recombination. With it, we identified 18,821 crossing-over (CO) and non-crossover (NCO) events at very high resolution in single individuals and could thus precisely characterise patterns of recombination in mice. In this species, recombination hotspots are targeted by PRDM9 and are therefore subject to a second type of biased gene conversion (BGC): DSB-induced BGC (dBGC). Quantifying both dBGC and gBGC with our data brought to light the fact that, in cases of structured populations, past gBGC from the parental lineages is hitchhiked by dBGC when the populations cross. We next observed that, in male mice, only NCOs — and more particularly single-marker NCOs — contribute to the intensity of gBGC. In contrast, in humans, both NCOs and at least a portion of COs (those with complex conversion tracts) distort allelic frequencies. This suggests that the DSB repair machinery leading to gBGC varies across mammals. Our findings are also consistent with the hypothesis of a selective pressure restraining the intensity of the deleterious gBGC process at the population-scale: this would materialise through a multi-level compensation of the effective population size by the recombination rate, the length of conversion tracts and the transmission bias. Altogether, our work has allowed to better comprehend how recombination and biased gene conversion proceed in the mammalian clade

No description available.

High defect rates are associated with novel nanodevice-based systems owing to unconventional and self-assembly based manufacturing processes. Furthermore, in emerging nanosystems, fault mechanisms and distributions may be very different from CMOS due to unique physical layer aspects, and emerging circuit and logic styles. Thus, theoretical fault models for nanosystems are necessary to extract detailed characteristics of fault generation and propagation. Using the intuition garnered from the theoretical analysis, modular and structural redundancy schemes can be specifically tailored to the intricacies of the fabric in order to achieve higher reliability of output signals. In this thesis, we develop a detailed analytical fault model for the Nanoscale Application Specific Integrated Circuits (NASIC) fabric that can determine probabilities of output faults taking into account the defect scenarios, the logic and circuit style of the fabric as well as structural redundancy schemes that may be incorporated in the circuits. Evaluation of fault rates using the analytical model for single NASIC tiles show an inequality of the probability of output faulty ‘1’s and ‘0’s. To mitigate the effects of the unequal fault rates, biased voting schemes are introduced and are shown to achieve up to 27% improvement in the reliability of output signals compared to conventional majority voting schemes. NASIC circuits have to be cascaded in order to build larger systems. Furthermore, modular redundancy alone will be insufficient to tolerate high defect rates since multiple input modules may be faulty. Hence incorporation of structural redundancy is crucial. Thus in this thesis, we study the propagation of faults through a cascade of NASIC circuits employing the conventional structural redundancy scheme which is referred to here as the Regular Structural Redundancy. In our analysis we find that although circuits with Regular Structural Redundancy achieve greater signal reliability compared to non-redundant circuits, the signal reliability rapidly drops along the cascade due to an escalation of faulty ‘0’s. This effect is attributed to the poor tolerance of input faulty ‘0’s exhibited by circuits with the Regular Structural Redundancy. Having identified this, we design a new scheme called the Staggered Structural Redundancy prioritizing the tolerance of input faulty ‘0’s. A cascade of circuits employing the Staggered Structural Redundancy is shown to maintain signal reliability greater than 0.98 for over 100 levels of cascade at 5% defect rate whereas the signal reliability for a cascade of circuits with the Regular Structural Redundancy dropped to 0.5 after 7 levels of cascade.

Research on hate crime has tended to utilize sociological frameworks to best explain the incidence of such offending, but little research has been conducted to determine whether political factors may play a role. Although Olzak (1990) touched upon the relationship between racial violence and third-party politics during the American Progressive era (1882-1914), the research did not fully articulate how political competition may influence the commission of hate crime. The current study seeks to fill this gap, while also extending concepts associated with social disorganization theory and the defended communities perspective. It does so by utilizing a longitudinal research design to assess the impact of theoretical predictors and political competition measures on hate crime prevalence in counties across three states (Tennessee, Virginia & West Virginia) over a seven-year span (2010-2016).

[pt] A ascenção dos computadores e da banda-larga móvel e fixa são fatores importantes nas mudanças observadas no mercado de trabalho dos países ricos. Conforme o mundo tecnológico rapidamente evolui e cada vez mais rápida conectividade surge, há pouca evidência dos impactos das atuais tecnologias nos países em desenvolvimento. O Brasil, em particular, durante a última década, observou uma notória expansão do acesso à internet móvel. Nesta dissertação, explora-se o rápido avanço da cobertura de 4G para estimar os efeitos causais de internet móvel rápida para mercados locais de trabalho formal no Brasil. Como as tecnologias de 4G não são instaladas randomicamente, compromissos de abrangência, presentes nos contratos entre operadores nacionais da banda de 4G e a agência nacional de telecomunicações (ANATEL), servem como variável instrumental para presença de internet. O crescimento médio observado na amostra de número de operadores presente em cada mercado local é responsável por uma redução de 8 porcento nos contratos formais de trabalho (40 porcento da variação no período). Esta redução é causada por (i) redução de rotatividade e por (ii) efeitos de desemprego. Consistentes com a hipótese de rotineirização, o 4G reduz a demanda de trabalho para tarefas rotineiras e manuais. Com isso, há um aumento da proporção de trabalhadores com ensino superior e em ocupações que exigem maior qualificação. Os efeitos são concentrados no extremo da distribuição dos setores em termos de uso de tecnologias, mas não houve efeitos na composição das indústrias. Identifica-se evidência sugestiva de que banda-larga móvel está associada à polarização nos empregos. / [en] The rise of computerization and fixed and mobile broadband has been an important factor for changes in the labor market of rich countries. However, as the world of tech rapidly evolves and even faster mobile internet emerges, there is still little evidence about the impact of current mobile technologies in developing countries. Brazil, in particular, during the last decade, has seen a remarkable increase in mobile internet access. In this dissertation, I explore this rapid expansion of 4G coverage to estimate the causal effects of fast mobile internet in formal local labor markets in Brazil. Since 4G technologies are not rolled out randomly, provision commitments in contracts between 4G national operators and Brazilian regulatory agency of telecommunications (ANATEL) work as an instrumental variable to internet presence. The average increase of mobile operators observed in sample is responsible for a reduction of 8 percent in formal employment contracts (about 40 percent of the variation in period). This reduction is explained by (i) reduced turnover and by (ii) displacement effects. Consistent with the routinization hypothesis, 4G expansion shifts labor demand away from manual and routine tasks. This, in turn, has benefited more high-skilled workers, increasing the share of college-graduates in the labor force and the average skill level index of local labor markets. Effects are driven by the extremes of the distribution of technological intensity but there are no changes in the industry-composition of labor markets. I also show suggestive evidence that mobile broadband is associated with job polarization.

[pt] Desde sua introdução, a comunicação móvel sem fio cresceu e se modificou severamente. Seu crescimento acentuado significa que a alocação de diferentes parâmetros para rádios ou estações-base ganhou diversos graus de complexidade. Um parâmetro é o Root Sequence Index (RSI), relacionado com os preâmbulos do Random Access Channel (PRACH), usado para alocar canais de upload entre o equipamento do usuário e a estação rádio-base. A alocação de RSIs próximos a radios ou antenas vizinhas pode causar colisões, que são responsáveis por falhas no estabelecimento do serviço de comunicação e, portanto, degradação no desempenho da rede. Em geral, tais problemas de alocação são modelados como um Problema de Coloração de Grafos, incluindo diversas restrições. Contudo, não há estudos que foquem na alocação de RSI e colisões. O objetivo deste estudo é explorar e comparar modelos exatos e heurísticos para esse problema. Para isso, diversos modelos matemáticos foram elaborados, além de um algoritmo genético de chaves aleatórias viciadas. Os resultados apontam que a utilização de uma estratégia baseada nas relações de vizinhança é eficaz para a obtenção de boas soluções. / [en] Since its introduction, mobile wireless communication has grown and changed substantially. This massive growth leads to different levels of complexity, mainly concerned with the assignment of different parameters to radio or base stations. One parameter is the Root Sequence Index (RSI), related to the Physical Random Access Channel (PRACH) preambles, used to allocate uplink channels between the user equipment and the base station. The assignment of RSIs close-in-range to neighbor antennas may cause collisions, which are responsible for failures on service establishment, and therefore, performance degradation. Such allocation problems can be modeled as Graph Coloring Problems, including several additional constraints. However, few studies focus on RSI allocation and collisions from the optimization perspective. The objective of this study is to develop methods for allocating the RSI, trying to lessen the risk of collision, and obeying other constraints. In this study, both exact and heuristics methods are explored and compared. For this, several mathematical models were made, alongside a biased random key genetic algorithm. The results show that the utilization of an allocation strategy based on neighbor relations is efficient for finding good solutions.

Polycrystalline NiTi shape memory alloys have the ability to recover their original, pre-deformed shape in the presence of external loads when heated through a solid-solid phase transformation from a lower-symmetry B19' martensite phase to a higher-symmetry B2 austenite phase. The strain associated with a shape memory alloy in an actuator application typically has thermal, elastic and inelastic contributions. The objective of this work was to investigate the aforementioned strains by recourse to in situ neutron diffraction experiments during selected combinations of heating, cooling and/or mechanical loading. The primary studies were conducted on polycrystalline Ni49.9Ti50.1 specimens on the Spectrometer for MAterials Research at Temperature and Stress (SMARTS) at Los Alamos National Laboratory. Quantitative information on the phase-specific strain, texture and phase fraction evolution was obtained from the neutron data using Rietveld refinement and single-peak analyses, and compared with macroscopic data from extensometry. First, the lattice strain evolution during heating and cooling in an unloaded sample (i.e., free-recovery experiment) was studied. The lattice strain evolution remained linear with temperature and was not influenced by intergranular stresses, enabling the determination of a thermal expansion tensor that quantified the associated anisotropy due to the symmetry of B19' NiTi. The tensor thus determined was subsequently used to obtain an average coefficient of thermal expansion that was consistent with macroscopic dilatometric measurements and a 30,000 grain polycrystalline self-consistent model. The accommodative nature of B19' NiTi was found to account for macroscopic shape changes lagging (with temperature) the start and finish of the transformation. Second, the elastic response of B19' martensitic NiTi variants during monotonic loading was studied. Emphasis was placed on capturing and quantifying the strain anisotropy which arises from the symmetry of monoclinic martensite and internal stresses resulting from intergranular constraints between individual variants and load re-distribution among variants as the texture evolved during variant reorientation and detwinning. The methodology adopted took into account both tensile and compressive loading given the asymmetric response in the texture evolution. Plane specific elastic moduli were determined from neutron measurements and compared with those determined using a self-consistent polycrystalline deformation model and from recently reported elastic stiffness constants determined via ab initio calculations. The comparison among the three approaches further helped understand the influence of elastic anisotropy, intergranular constraint, and texture evolution on the deformation behavior of polycrystalline B19' NiTi. Connections were additionally made between the assessed elastic properties of martensitic NiTi single crystals (i.e., the single crystal stiffness tensor) and the overall macroscopic response in bulk polycrystalline form. Lastly, the role of upper-cycle temperature, i.e., the maximum temperature reached during thermal cycling, was investigated during load-biased thermal cycling of NiTi shape memory alloys at selected combinations of stress and temperature. Results showed that the upper-cycle temperature, under isobaric conditions, significantly affected the amount of transformation strain and thus the work output available for actuation. With the objective of investigating the underlying microstructural and micromechanical changes due to the influence of the upper-cycle temperature, the texture evolution was systematically analyzed. While the changes in transformation strain were closely related to the evolution in texture of the room temperature martensite, retained martensite in the austenite state could additionally affect the transformation strain. Additionally, multiple thermal cycles were performed under load-biased conditions in both NiTi and NiTiPd alloys, to further assess and understand the role of retained martensite. Dimensional and thermal stabilities of these alloys were correlated with the volume fraction and texture of retained martensite, and the internal strain evolution in these alloys. The role of symmetry, i.e., B19' monoclinic martensite vs. B19 orthorhombic martensite in these alloys was also assessed. This work not only established a methodology to study the thermal and elastic properties of the low symmetry B19' monoclinic martensite, but also provided valuable insight into quantitative micromechanical and microstructural changes responsible for the thermomechanical response of NiTi shape memory alloys. It has immediate implications for optimizing shape memory behavior in the alloys investigated, with extension to high temperature shape memory alloys with ternary and quaternary elemental additions, such as Pd, Pt and Hf. This work was supported by funding from NASAÂ s Fundamental Aeronautics Program, Supersonics Project (NNX08AB51A) and NSF (CAREER DMR-0239512). It benefited additionally from the use of the Lujan Neutron Scattering Center at Los Alamos National Laboratory, which is funded by the Office of Basic Energy Sciences (Department of Energy) and is operated by Los Alamos National Security LLC under DOE Contract DE-AC52-06NA25396.

[pt] O Algoritmo Genético de Chaves Aleatórias Enviesadas (BRKGA) é uma metaheurística populacional utilizada na obtenção de soluções ótimas ou quase ótimas para problemas de otimização combinatória. A parametrização do algoritmo é crucial para garantir seu bom desempenho. Os valores dos parâmetros têm uma grande influência em determinar se uma boa solução será encontrada pelo algoritmo e se o processo de busca será eficiente. Uma maneira de resolver esse problema de configuração de parâmetros é por meio da abordagem de parametrização online (ou controle de parâmetros). A parametrização online permite que o algoritmo adapte os valores dos parâmetros de acordo com os diferentes estágios do processo de busca e acumule informações sobre o espaço de soluções nesse processo para usar as informações obtidas em estágios posteriores. Ele também libera o usuário da tarefa de definir as configurações dos parâmetros, resolvendo implicitamente o problema de configuração. Neste trabalho, avaliamos duas estratégias para implementar o controle de parâmetros no BRKGA. Nossa primeira abordagem foi adotar valores de parâmetros aleatórios para cada geração do BRKGA. A segunda abordagem foi incorporar os princípios adotados pelo irace, um método de parametrização do estado da arte, ao BRKGA. Ambas as estratégias foram avaliadas em três problemas clássicos de otimização (Problema de Permutação Flowshop, Problema de Cobertura de Conjuntos e Problema do Caixeiro Viajante) e levaram a resultados competitivos quando comparados ao algoritmo tunado. / [en] The Biased Random-Key Genetic Algorithm (BRKGA) is a populationbased metaheuristic applied to obtain optimal or near-optimal solutions to combinatorial problems. To ensure the good performance of this algorithm (and other metaheuristics in general), defining parameter settings is a crucial step. Parameter values have a great influence on determining whether a good solution will be found by the algorithm and whether the search process will be efficient. One way of tackling the parameter setting problem is through the parameter control (or online tuning) approach. Parameter control allows the algorithm to adapt parameter values according to different stages of the search process and to accumulate information on the fitness landscape during the search to use this information in later stages. It also releases the user from the task of defining parameter settings, implicitly solving the tuning problem. In this work, we evaluate two strategies to implement parameter control in BRKGA. Our first approach was adopting random parameter values for each of BRKGA s generations. The second approach was to introduce the principles adopted by Iterated Race, a state-of-the-art tuning method, to BRKGA. Both strategies were evaluated in three classical optimization problems (Flowshop Permutation Problem, Set Covering Problem, and the Traveling Salesman Problem) and led to competitive results when compared to the tuned algorithm.

No description available.

In dieser interdisziplinär geprägten Arbeit wird zunächst eine Übersicht über kugelbasierte Modelle und die algorithmischen Ansätze zur Generierung zufälliger Kugelpackungen gegeben. Ein Algorithmus aus der Gruppe der Kollektiven-Umordnungs-Algorithmen -- der Force-Biased-Algorithmus -- wird ausführlich erläutert und untersucht. Dabei werden die für den Force-Biased-Algorithmus als essenziell geltenden Verschiebungsfunktionen bezüglich ihres Einflusses auf den erreichbaren Volumenanteil der Packungen untersucht. Nicht nur aus der Literatur bekannte, sondern auch neu entwickelte Verschiebungsfunktionen werden hierbei betrachtet. Daran anschließend werden Empfehlungen zur Auswahl geeigneter Verschiebungsfunktionen gegeben. Einige mit dem Force-Biased-Algorithmus generierte Kugelpackungen, zum Beispiel hochdichte monodisperse Packungen, lassen den Schluss zu, dass insbesondere strukturelle Umbildungsvorgänge an solchen Packungen sehr gut zu untersuchen sind. Aus diesem Grund besitzt das Modell der mit dem Force-Biased-Algorithmus dicht gepackten harten Kugeln große Bedeutung in der Materialwissenschaft, insbesondere in der Strukturforschung. In einem weiteren Kapitel werden wichtige Kenngrößen kugelbasierter Modelle erläutert, wie z. B. spezifische Oberfläche, Volumenanteil und die Kontaktverteilungsfunktionen. Für einige besonders anwendungsrelevante Kenngrößen (z. B. die spezifische Oberfläche) werden Näherungsformeln entwickelt, an Modellsystemen untersucht und mit bekannten Näherungen aus der Literatur verglichen. Zur Generierung und Analyse der Kugelpackungen wurde im Rahmen dieser Arbeit die Simulationssoftware „SpherePack“ entwickelt, deren Aufbau unter dem Aspekt des Softwareengineerings betrachtet wird. Die Anforderungen an dieses Simulationssystem sowie dessen Architektur werden hier beschrieben, einschließlich der Erläuterung einzelner Berechnungsmodule. An ausgewählten praxisnahen Beispielen aus der Materialwissenschaft kann die Vielfalt der Einsatzmöglichkeiten eines Simulationssystems zur Generierung und Analyse von zufälligen dicht gepackten Kugelsystemen gezeigt werden. Vor allem die hohe Aussagekraft der Untersuchungen in Bezug auf Materialeigenschaften unterstreicht die Bedeutung des Modells zufällig dicht gepackter harter Kugeln in der Materialforschung und verwandten Forschungsgebieten.