Chemotherapy induces canalization of cell state in childhood B-cell precursor acute lymphoblastic leukemia

Comparison of intratumor genetic heterogeneity in cancer at diagnosis and relapse suggests that chemotherapy induces bottleneck selection of subclonal genotypes. However, evolutionary events subsequent to chemotherapy could also explain changes in clonal dominance seen at relapse. We therefore investigated the mechanisms of selection in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) during induction chemotherapy where maximal cytoreduction occurs. To distinguish stochastic versus deterministic events, individual leukemias were transplanted into multiple xenografts and chemotherapy administered. Analyses of the immediate post-treatment leukemic residuum at single-cell resolution revealed that chemotherapy has little impact on genetic heterogeneity. Rather, it acts on extensive, previously unappreciated, transcriptional and epigenetic heterogeneity in BCP-ALL, dramatically reducing the spectrum of cell states represented, leaving a genetically polyclonal but phenotypically uniform population, with hallmark signatures relating to developmental stage, cell cycle and metabolism. Hence, canalization of the cell state accounts for a significant component of bottleneck selection during induction chemotherapy

A contribution to support decision making in energy/water sypply chain optimisation

The seeking of process sustainability forces enterprises to change their operations. Additionally, the industrial globalization implies a very dynamic market that, among other issues, promotes the enterprises competition. Therefore, the efficient control and use of their Key Performance Indicators, including profitability, cost reduction, demand satisfaction and environmental impact associated to the development of new products, is a significant challenge. All the above indicators can be efficiently controlled through the Supply Chain Management. Thus, companies work towards the optimization of their individual operations under competitive environments taking advantage of the flexibility provided by the virtually inexistent world market restrictions. This is achieved by the coordination of the resource flows, across all the entities and echelons belonging to the system network. Nevertheless, such coordination is significantly complicated if considering the presence of uncertainty and even more if seeking for a win-win outcome. The purpose of this thesis is extending the current decision making strategies to expedite these tasks in industrial processes. Such a contribution is based on the development of efficient mathematical models that allows coordinating large amount of information synchronizing the production and distribution tasks in terms of economic, environmental and social criteria. This thesis starts presents an overview of the requirements of sustainable production processes, describing and analyzing the current methods and tools used and identifying the most relevant open issues. All the above is always within the framework of Process System Engineering literature. The second part of this thesis is focused in stressing the current Multi-Objective solution strategies. During this part, first explores how the profitability of the Supply Chain can be enhanced by considering simultaneously multiple objectives under demand uncertainties. Particularly, solution frameworks have been proposed in which different multi-criteria decision making strategies have been combined with stochastic approaches. Furthermore, additional performance indicators (including financial and operational ones) have been included in the same solution framework to evaluate its capabilities. This framework was also applied to decentralized supply chains problems in order to explore its capabilities to produce solution that improves the performances of each one of the SC entities simultaneously. Consequently, a new generalized mathematical formulation which integrates many performance indicators in the production process within a supply chain is efficiently solved. Afterwards, the third part of the thesis extends the proposed solution framework to address the uncertainty management. Particularly, the consideration of different types and sources of uncertainty (e.g. external and internal ones) where considered, through the implementation of preventive approaches. This part also explores the use of solution strategies that efficiently selects the number of scenarios that represent the uncertainty conditions. Finally, the importance and effect of each uncertainty source over the process performance is detailed analyzed through the use of surrogate models that promote the sensitivity analysis of those uncertainties. The third part of this thesis is focused on the integration of the above multi-objective and uncertainty approaches for the optimization of a sustainable Supply Chain. Besides the integration of different solution approaches, this part also considers the integration of hierarchical decision levels, by the exploitation of mathematical models that assess the consequences of considering simultaneously design and planning decisions under centralized and decentralized Supply Chains. Finally, the last part of this thesis provides the final conclusions and further work to be developed.La globalización industrial genera un ambiente dinámico en los mercados que, entre otras cosas, promueve la competencia entre corporaciones. Por lo tanto, el uso eficiente de las los indicadores de rendimiento, incluyendo rentabilidad, satisfacción de la demanda y en general el impacto ambiental, representa un area de oportunidad importante. El control de estos indicadores tiene un efecto positivo si se combinan con la gestión de cadena de suministro. Por lo tanto, las compañías buscan definir sus operaciones para permanecer activas dentro de un ambiente competitivo, tomando en cuenta las restricciones en el mercado mundial. Lo anterior puede ser logrado mediante la coordinación de los flujos de recursos a través de todas las entidades y escalones pertenecientes a la red del sistema. Sin embargo, dicha coordinación se complica significativamente si se quiere considerar la presencia de incertidumbre, y aún más, si se busca exclusivamente un ganar-ganar. El propósito de esta tesis es extender el alcance de las estrategias de toma de decisiones con el fin de facilitar estas tareas dentro de procesos industriales. Estas contribuciones se basan en el desarrollo de modelos matemáticos eficientes que permitan coordinar grandes cantidades de información sincronizando las tareas de producción y distribución en términos económicos, ambientales y sociales. Esta tesis inicia presentando una visión global de los requerimientos de un proceso de producción sostenible, describiendo y analizando los métodos y herramientas actuales así como identificando las áreas de oportunidad más relevantes dentro del marco de ingeniería de procesos La segunda parte se enfoca en enfatizar las capacidades de las estrategias de solución multi-objetivo, durante la cual, se explora el mejoramiento de la rentabilidad de la cadena de suministro considerando múltiples objetivos bajo incertidumbres en la demanda. Particularmente, diferentes marcos de solución han sido propuestos en los que varias estrategias de toma de decisión multi-criterio han sido combinadas con aproximaciones estocásticas. Por otra parte, indicadores de rendimiento (incluyendo financiero y operacional) han sido incluidos en el mismo marco de solución para evaluar sus capacidades. Este marco fue aplicado también a problemas de cadenas de suministro descentralizados con el fin de explorar sus capacidades de producir soluciones que mejoran simultáneamente el rendimiento para cada uno de las entidades dentro de la cadena de suministro. Consecuentemente, una nueva formulación que integra varios indicadores de rendimiento en los procesos de producción fue propuesta y validada. La tercera parte de la tesis extiende el marco de solución propuesto para abordar el manejo de incertidumbres. Particularmente, la consideración de diferentes tipos y fuentes de incertidumbre (p.ej. externos e internos) fueron considerados, mediante la implementación de aproximaciones preventivas. Esta parte también explora el uso de estrategias de solución que elige eficientemente el número de escenarios necesario que representan las condiciones inciertas. Finalmente, la importancia y efecto de cada una de las fuentes de incertidumbre sobre el rendimiento del proceso es analizado en detalle mediante el uso de meta modelos que promueven el análisis de sensibilidad de dichas incertidumbres. La tercera parte de esta tesis se enfoca en la integración de las metodologías de multi-objetivo e incertidumbre anteriormente expuestas para la optimización de cadenas de suministro sostenibles. Además de la integración de diferentes métodos. Esta parte también considera la integración de diferentes niveles jerárquicos de decisión, mediante el aprovechamiento de modelos matemáticos que evalúan lasconsecuencias de considerar simultáneamente las decisiones de diseño y planeación de una cadena de suministro centralizada y descentralizada. La parte final de la tesis detalla las conclusiones y el trabajo a futuro necesario sobre esta línea de investigaciónPostprint (published version

A survey of distributed data aggregation algorithms

Distributed data aggregation is an important task, allowing the decentralized determination of meaningful global properties, which can then be used to direct the execution of other applications. The resulting values are derived by the distributed computation of functions like COUNT, SUM, and AVERAGE. Some application examples deal with the determination of the network size, total storage capacity, average load, majorities and many others. In the last decade, many different approaches have been proposed, with different trade-offs in terms of accuracy, reliability, message and time complexity. Due to the considerable amount and variety of aggregation algorithms, it can be difficult and time consuming to determine which techniques will be more appropriate to use in specific settings, justifying the existence of a survey to aid in this task. This work reviews the state of the art on distributed data aggregation algorithms, providing three main contributions. First, it formally defines the concept of aggregation, characterizing the different types of aggregation functions. Second, it succinctly describes the main aggregation techniques, organizing them in a taxonomy. Finally, it provides some guidelines toward the selection and use of the most relevant techniques, summarizing their principal characteristics.info:eu-repo/semantics/publishedVersio

Antecipação na tomada de decisão com múltiplos critérios sob incerteza

Orientador: Fernando José Von ZubenTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de ComputaçãoResumo: A presença de incerteza em resultados futuros pode levar a indecisões em processos de escolha, especialmente ao elicitar as importâncias relativas de múltiplos critérios de decisão e de desempenhos de curto vs. longo prazo. Algumas decisões, no entanto, devem ser tomadas sob informação incompleta, o que pode resultar em ações precipitadas com consequências imprevisíveis. Quando uma solução deve ser selecionada sob vários pontos de vista conflitantes para operar em ambientes ruidosos e variantes no tempo, implementar alternativas provisórias flexíveis pode ser fundamental para contornar a falta de informação completa, mantendo opções futuras em aberto. A engenharia antecipatória pode então ser considerada como a estratégia de conceber soluções flexíveis as quais permitem aos tomadores de decisão responder de forma robusta a cenários imprevisíveis. Essa estratégia pode, assim, mitigar os riscos de, sem intenção, se comprometer fortemente a alternativas incertas, ao mesmo tempo em que aumenta a adaptabilidade às mudanças futuras. Nesta tese, os papéis da antecipação e da flexibilidade na automação de processos de tomada de decisão sequencial com múltiplos critérios sob incerteza é investigado. O dilema de atribuir importâncias relativas aos critérios de decisão e a recompensas imediatas sob informação incompleta é então tratado pela antecipação autônoma de decisões flexíveis capazes de preservar ao máximo a diversidade de escolhas futuras. Uma metodologia de aprendizagem antecipatória on-line é então proposta para melhorar a variedade e qualidade dos conjuntos futuros de soluções de trade-off. Esse objetivo é alcançado por meio da previsão de conjuntos de máximo hipervolume esperado, para a qual as capacidades de antecipação de metaheurísticas multi-objetivo são incrementadas com rastreamento bayesiano em ambos os espaços de busca e dos objetivos. A metodologia foi aplicada para a obtenção de decisões de investimento, as quais levaram a melhoras significativas do hipervolume futuro de conjuntos de carteiras financeiras de trade-off avaliadas com dados de ações fora da amostra de treino, quando comparada a uma estratégia míope. Além disso, a tomada de decisões flexíveis para o rebalanceamento de carteiras foi confirmada como uma estratégia significativamente melhor do que a de escolher aleatoriamente uma decisão de investimento a partir da fronteira estocástica eficiente evoluída, em todos os mercados artificiais e reais testados. Finalmente, os resultados sugerem que a antecipação de opções flexíveis levou a composições de carteiras que se mostraram significativamente correlacionadas com as melhorias observadas no hipervolume futuro esperado, avaliado com dados fora das amostras de treinoAbstract: The presence of uncertainty in future outcomes can lead to indecision in choice processes, especially when eliciting the relative importances of multiple decision criteria and of long-term vs. near-term performance. Some decisions, however, must be taken under incomplete information, what may result in precipitated actions with unforeseen consequences. When a solution must be selected under multiple conflicting views for operating in time-varying and noisy environments, implementing flexible provisional alternatives can be critical to circumvent the lack of complete information by keeping future options open. Anticipatory engineering can be then regarded as the strategy of designing flexible solutions that enable decision makers to respond robustly to unpredictable scenarios. This strategy can thus mitigate the risks of strong unintended commitments to uncertain alternatives, while increasing adaptability to future changes. In this thesis, the roles of anticipation and of flexibility on automating sequential multiple criteria decision-making processes under uncertainty are investigated. The dilemma of assigning relative importances to decision criteria and to immediate rewards under incomplete information is then handled by autonomously anticipating flexible decisions predicted to maximally preserve diversity of future choices. An online anticipatory learning methodology is then proposed for improving the range and quality of future trade-off solution sets. This goal is achieved by predicting maximal expected hypervolume sets, for which the anticipation capabilities of multi-objective metaheuristics are augmented with Bayesian tracking in both the objective and search spaces. The methodology has been applied for obtaining investment decisions that are shown to significantly improve the future hypervolume of trade-off financial portfolios for out-of-sample stock data, when compared to a myopic strategy. Moreover, implementing flexible portfolio rebalancing decisions was confirmed as a significantly better strategy than to randomly choosing an investment decision from the evolved stochastic efficient frontier in all tested artificial and real-world markets. Finally, the results suggest that anticipating flexible choices has lead to portfolio compositions that are significantly correlated with the observed improvements in out-of-sample future expected hypervolumeDoutoradoEngenharia de ComputaçãoDoutor em Engenharia Elétric

Constructing Geometries for Group Control: Methods for Reasoning about Social Behaviors

Social behaviors in groups has been the subjects of hundreds of studies in a variety of research disciplines, including biology, physics, and robotics. In particular, flocking behaviors (commonly exhibited by birds and fish) are widely considered archetypical social behavioris and are due, in part, to the local interactions among the individuals and the environment. Despite a large number of investigations and a significant fraction of these providing algorithmic descriptions of flocking models, incompleteness and imprecision are readily identifiable in these algorithms, algorithmic input, and validation of the models. This has led to a limited understanding of the group level behaviors. Through two case-studies and a detailed meta-study of the literature, this dissertation shows that study of the individual behaviors are not adequate for understanding the behaviors displayed by the group. To highlight the limitations in only studying the individuals, this dissertation introduces a set of tools, that together, unify many of the existing microscopic approaches. A meta-study of the literature using these tools reveal that there are many small differences and ambiguities in the flocking scenarios being studied by different researchers and domains; unfortunately, these differences are of considerable significance. To address this issue, this dissertation exploits the predictable nature of the group’s behaviors in order to control the given group and thus hope to gain a fuller understanding of the collective. From the current literature, it is clear the environment is an important determinant in the resulting collective behaviors. This dissertation presents a method for reasoning about the effects the geometry of an environment has on individuals that exhibit collective behaviors in order to control them. This work formalizes the problem of controlling such groups by means of changing the environment in which the group operates and shows this problem to be PSPACE-Hard. A general methodology and basic framework is presented to address this problem. The proposed approach is general in that it is agnostic to the individual’s behaviors and geometric representations of the environment; allowing for a large variety in groups, desired behaviors, and environmental constraints to be considered. The results from both the simulations and over 80 robot trials show (1) the solution can automatically generate environments for reliably controlling various groups and (2) the solution can apply to other application domains; such as multi-agent formation planning for shepherding and piloting applications

A bi-objective turning restriction design problem in urban road networks

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Self-Evaluation Applied Mathematics 2003-2008 University of Twente

This report contains the self-study for the research assessment of the Department of Applied Mathematics (AM) of the Faculty of Electrical Engineering, Mathematics and Computer Science (EEMCS) at the University of Twente (UT). The report provides the information for the Research Assessment Committee for Applied Mathematics, dealing with mathematical sciences at the three universities of technology in the Netherlands. It describes the state of affairs pertaining to the period 1 January 2003 to 31 December 2008

2018 IMSAloquium, Student Investigation Showcase

This is IMSA\u27s 31st year of leading in educational innovation and the 30th year of the Student Inquiry and Research Program (SIR)! ... These studies have all happened during the past year in a variety of laboratories, real or virtual, on and off campus. Students were asked to not only learn a great deal about complex topics, but to contribute to them in meaningful ways. The presentations you hear today reflect the various stages of their work on a myriad of projects.https://digitalcommons.imsa.edu/archives_sir/1028/thumbnail.jp