Cells process information from their environment, such as the stimuli to grow, divide, or die, via cell signaling. Deregulated processing of extracellular stimuli can lead to aberrant cell responses and cause cancer. Given that the in vivo cell environment constantly changes, it is important to understand how cells incorporate the context of their environment into their decision making processes. The idea of responding to relative, not absolute, changes in stimuli was first proposed in studies of human perception and became known as Weber's Law. Although, evidence of Weber's Law at the molecular level has been previously presented in studies of several organisms, to the best of our knowledge, it has never been explored in the case of relative sensing of extracellular stimuli in mammalian signaling cascades. The Mitogen-Activated Protein Kinase (MAPK) signaling pathway has been implicated in multiple human diseases, including cancers, and therefore cell signaling through this pathway is an important subject of research. Here we present a theoretical framework and an experimental validation of the mechanism of Weber's Law in the ability of cells to sense relative changes in the levels of extracellular stimuli in the MAPK signaling pathway. In particular, in this work we consider relative sensing in levels of Epidermal Growth Factor (EGF) in the MAPK pathway. We derive an analytical model of steady state behavior of the MAPK signaling pathway stimulated with constant doses of EGF. We demonstrate a mechanism that produces phosphorylation responses proportional to relative changes in ligand concentrations. The mechanism of Weber's Law presented here entails the retention of memory of the dose of the past chronic stimulation with EGF. The molecular mechanisms responsible for Weber's Law in MAPK signaling are likely to contribute to many other receptors signaling systems. Therefore, the mechanism of relative sensing of extracellular ligand concentrations derived here can be generalized beyond the EGF-activated MAPK signaling pathway to many other cell signaling systems. This thesis also presents a probabilistic framework to explore the parameter space of a detailed mechanistic ODE model of EGFR signaling cascades. The application of the model simulation allows us to generate probabilistic predictions of EGFR system behavior and to explore structure-to-function relationships between the model's parameter space and EGFR system responses. Overall, this work suggests an alternative view on the role of cellular endocytosis in the MAPK signaling in vivo. Specifically, traditionally viewed as a mechanism to downregulate and terminate cell signaling, endocytosis may enable cells to dynamically adjust their sensitivity to extracellular stimuli, and hence allow cells to integrate information about the past stimulations into the cell responses to the consequent stimulations and thus, cell fate decisions.

Hourya Sinaceur présente dans son ouvrage Corps et Modèles la théorie des caractéristiques de Kronecker comme la fin d’« un cycle d’idées sturmiennes », la situant ainsi dans une histoire de l’algébrisation du théorème de Sturm. Pourtant, cette théorie est souvent aussi présentée comme le point de départ de certains des premiers travaux de topologie de la toute fin du dix-neuvième siècle. Nous souhaitons dans cette thèse rendre compte de la façon dont ces deux histoires se rencontrent au sein de la théorie de Kronecker. Pour cela, nous disposons d’un matériel particulièrement éclairant et jusqu’alors très peu exploité : les manuscrits des cours que Kronecker a donnés à l’Université de Berlin entre 1872 et 1891 sur la Théorie des équations algébriques. Nous commencerons par présenter ces manuscrits, leur contenu et leur contexte de rédaction. Nous nous intéresserons ensuite plus précisément à la reprise du théorème de Sturm par Kronecker, et nous montrerons que la théorie des caractéristiques n’est pas seulement un prolongement algébrique de ce théorème, mais qu’elle se transforme pour fournir certains des outils analytiques que Poincaré utilisera lors de la construction de son Analysis Situs. L’exposition de la théorie des caractéristiques dans ses cours est l’occasion pour Kronecker de reprendre trois des quatre démonstrations que Gauss a données du théorème fondamental de l’algèbre, et nous montrerons comment, dans la pratique de Kronecker, la notion même de racine est interrogée / In her book Corps et Modèles, Hourya Sinaceur presented Kronecker’s theory of characteristics as the end of a “cycle of Sturmian ideas”, making it a step in history of the algebraization of Sturm’s theorem. However, this theory is often also introduced as the starting point of some of the early works of topology of the very end of the nineteenth century. In this PhD thesis, I will describe how these two stories are connected in Kronecker’s theory. To achieve this, I used material which has seldom been discussed before : the manuscripts of the courses that Kronecker gave at the University of Berlin between 1872 and 1891 on the Theory of algebraic equations. I begin with the presentation of these manuscripts, their contents and their writing contexts. I then look more closely at Kronecker’s rework of the theorem of Sturm and show that the theory of characteristics is not only an algebraic extension of this theorem but also that it is transformed in order to provide some of the analytic tools that Poincaré will use for the construction of his Analysis Situs. The exposition of the theory of characteristics in his courses is an opportunity for Kronecker to take up three of the four demonstrations from Gauss of the fundamental theorem of algebra, and I will show how, in Kronecker’s practice, the very notion of root is questioned

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The problem. The problem in the study of the history of Plain City was to show that community backgrounds do affect the lives of individuals. Greater social achievement can be attained within the framework of a good foundation in education a solidarity of home life, a respect for mankind and attention to religious beliefs.

Peach production in Utah is an important enterprise. In 1946 the crop of 700,000 bushels was valued at $1,085,000, which was approximately one percent of the value of all agricultural commodities grown in the state. The estimate average annual production over the ten-year period, 1936 to 1945, was 636,000 bushels. About 95 percent of the peach trees are located in Washington county and along the Wasatch Front in Utah, Salt lake, Davis, Weber, and Box Elder counties. Small-scale family type units characterize the production of peaches in Utah. The 5,071 farmers who reported growing peach trees in 1944 had an average of 146 trees per farm. In the state, peach production is concentrated on well-drained open soils which require frequent irrigation. The usual practice is to disk several times during the growing season. Some operators leave the ground between the trees bare during the winter months, while others prefer to leave an undergrowth of clover, grass, or weeds. The enterprise is most successful if located where air currents protect the orchards from early spring frosts. In Utah the freestone varieties predominate. The Early and Late Elbertas are most common, followed by J. H. Hale, Late Crawford, Heath Cling, Rochester, Greensboro and other less popular varieties. Golden Jubilee and Halbertas were also found. Canning factories provide a market for a small portion of the peach crop, but most of them must be marketed fresh by peddling and at roadside stands or shipped out of the state through marketing associations and brokers. The competitive nature of agriculture makes it necessary for successful farmers to attempt to keep costs at a minimum. Present high production costs and the likelihood of lower prices for farm products in the future make this problem vitally important to Utah peach growers and to farmers in general. The purposes of this study are (1) to determine the unit cost of producing peaches in Utah and the items comprising the costs, and (2) to discover what methods of production are associated with success in the peach industry.

River barriers, such as dams, culverts and diversions are important for water conveyance, but disrupt river ecosystems and hydrologic processes. River barrier removal is increasingly used to restore and improve river habitat and connectivity. Most past barrier removal projects prioritized individual barriers using score-and-rank techniques, neglecting the spatial structure and cumulative change from multiple barrier removals. Similarly, most water demand models satisfy human water uses or, only prioritize aquatic habitat, failing to include both human and environmental water use benefits. In this study, a dual objective optimization model identified in-stream barriers that impede quality-weighted aquatic habitat connectivity for Bonneville cutthroat trout. Monthly streamflow, stream temperature, channel gradient and geomorphic condition were indicators of aquatic habitat suitability. Solutions to the dual objective problem quantify and graphically present tradeoffs between quality-weighted habitat connectivity and economic water demands. The optimization model is generalizable to other watersheds, but it was applied as a case study in Utah’s Weber Basin to prioritize removal of environmentally-harmful barriers, while maintaining human water uses. Modeled results suggest tradeoffs between economic costs of removing barriers and quality-weighted habitat gains. Removing 54 in-stream barriers increases quality-weighted habitat by about 160 km and costs approximately $10M, after which point the cost effectiveness of removing barriers to connect river habitat slows. In other words, there is decreasing benefit of removing barriers, so that after removing the first 54 barriers, it costs more to connect more high-quality habitat. Removing reservoirs or diversions that result in large economic losses did not substantially increase habitat. This suggests that removing numerous small barriers results in greater increases in habitat for the same removal costs, without significant water scarcity losses. The set of barriers prioritized for removal varied monthly depending on limiting habitat conditions for Bonneville cutthroat trout. The common barriers removed in the model were identified to communicate the most environmentally harmful barriers to local stakeholders and inform decision-making. Additionally, limiting the budget or number of barrier removal projects resulted in a different set of barriers removed. This research helps prioritize barrier removals and future restoration decisions in the Weber Basin although the model formulation is generalizable to other watersheds. Available data and a simplified approach limit the scope of this model. The modeling approach expands current barrier removal optimization methods by explicitly including economic and environmental water uses.

Memoria (licenciado en ciencias jurídicas y sociales / El presente ensayo realizará en un análisis de los aspectos relevantes de la obra de Immanuel Kant para aproximarse al positivismo durante el siglo XX, entendiendo que el intento kantiano de depurar el trabajo científico al intentar establecer los límites del conocimiento humano y modelos formales para una ética universal significó una metodología rigurosa en forma temprana en términos históricos, comprendiendo así la extensión de la obra del filósofo en el trabajo de autores fundamentales para el desarrollo intelectual de la etapa señalada en el marco de las ciencias sociales y en particular del derecho, para posteriormente aproximarse, desde la perspectiva kantiana comentada, tanto a la propuesta de Max Weber, quien elaboró una metodología para la investigación de los fenómenos propios de las ciencias sociales, para el desarrollo efectivamente científico de estas y comprendiendo estos avances como fundamentales para tal disciplina en el contexto al cual pertenece, como también a la Teoría Pura del Derecho de Hans Kelsen, la cual comparte la finalidad pretendida por Weber pero respecto de la comprensión de aquello que es propiamente jurídico en forma depurada de otras disciplinas y teniendo un éxito bastante amplio en el debate jurídico. Finalmente, desde la teoría del reconocimiento extraída a partir de los escritos de Jena realizados por G. W. F. Hegel, se criticará la posición adoptada por Kant, extendiendo dicho ejercicio al trabajo de los autores influidos por el filósofo antes señalados, analizando la posibilidad de existencia de un método diverso al sostenido por Weber y Kelsen, tanto en las ciencias sociales como en el derecho, desde una comprensión integral de la realidad empírica y además desde la eticidad como totalidad respecto de la relación entre los fenómenos estudiados por estas ciencias y los seres humanos, particularmente como alternativa a los esfuerzos más influidos por la filosofía pura.

本篇論文主要是採取「紀律與個人身體」和「紀律與社會身體」這兩個面向來進行。在論文的第二章首先處理的是紀律與個人身體。我們經由空間的角度切入，說明紀律權力如何透過不同的封閉空間、及空間的分類，對人的身體所進行的控制；而接下來對於時間的討論，紀律對於時間的運用也如同空間一般，強調精細的劃分，宗教的時間表與軍隊的時間運用皆扮演著關鍵性的角色；第三節則是討論，人的身體是作為紀律權力施行的最終目標。紀律權力經由宗教、政治與經濟領域的控制，造就了（make）個人的出現。而紀律對於個人身體所造成的可怕監視措施，普遍地存在軍隊、醫院、工廠、學校之中，進而導致了紀律權力對於社會的全面性滲透。因此，我們在第三章處理紀律與社會身體。我們先處理的是紀律如何經由現代資本主義的各種機制來控制大量的人口，主要分別是從生產與消費這兩個面向來加以討論；而後，官僚制與全景敞視的出現更是說明了紀律權力的最高展現，以及官僚制與全景敞視對於國家的控制。第四章則是本篇論文的一個總整理，除了再次說明韋伯與傅柯對話的可能性之外，更重要的是，本篇論文只是在於揭露紀律對於人的身體所進行的種種控制，進而引發出人類身處在這個時代人們對於自身的關懷，而非在於提供紀律的解決之道。 目 錄 第一章 導論 第一節 研究命題 第二節 方法論的考慮與策略 2-1比較性研究的問題 2-2研究的策略 第二章 紀律與個人身體 第一節 紀律對於空間的分配 1-1空間的歷史 1-2空間--圍場 1-3空間--分類與單元性原則 第二節：紀律對於時間的控制 2-1宗教上的時間表 2-2操練 2-3時間對身體的徹底榨取 第三節：身體作為紀律的擔綱者 3-1禁慾的身體 3-2政治身體 3-3機械的身體 第三章 紀律與社會身體 第一節 紀律在現代資本主義的位置 1-1理性社會 1-2消費社會 第二節 官僚制與全景敞視（Ⅰ） 2-1凝視 2-2知識 2-3檔案 第三節 官僚制與全景敞視的國家控制（Ⅱ） 3-1統治術 3-2警察 第四章 結論 參考書目 / This theis is depended on the perspectives of M.Weber and M.Foucault to explore the disciple imposed on the individual body.I try to explain this in two diemensions.We will discuss the relationship of the disciple and individual body.The disciple proceeds from the distribution in space and then elabrate the individual act by time.The disciple is intended to make the individuals finally. Second,I want to expatiate the relationship between the disciple and social body by Panopticism and modern Bureaucracy. In a work,my purpose is to wake up people to concern their own fate.

Aristóteles desarrolló un concepto de prudencia, como instancia ordenadora de la vida política, cuyo olvido por parte de la modernidad daña irreparablemente al pensamiento político,tal como queda reflejado en la reflexión weberiana. Para demostrar tal tesis recorremos el siguiente camino: en primer lugar, analizamos a fondo el papel que desempeña la prudencia política en el conjunto de la filosofía política aristotélica, especialmente en relación con los conceptos de vida política, amistad, bien común, naturaleza, ley, orden político y acción política. En segundo lugar, rastreamos el concepto de prudencia política a lo largo de la historia del pensamiento poniendo de realce el contraste entre Aristóteles y la modernidad con especial énfasis en el estudio de autores como Maquiavelo, Hobbes, Spinoza y Kant. En tercer lugar, y como término principal de comparación con la prudencia política aristotélica, la confluencia sui generis en la obra de Max Weber de los principales elementos de la filosofía política moderna, teñidos de nietzscheanismo, justifica el análisis de aquellos aspectos de su obra relacionados con cuestiones como la vida política, el líder político y la misión y alcance del conocimiento político práctico. Su perspicacia al juzgar tales asuntos, le lleva en ocasiones, a pesar de sus propios presupuestos ideológicos y metodológicos, a coincidir parcialmente con la caracterización aristotélica de la prudencia política. Pero, sobre todo, la idea weberiana de política, con sus tensiones internas, da testimonio del olvido y ausencia en la modernidad de aquella noción aristotélica. Precisamente la presunta rehabilitación de la phronesis en el siglo XX, retorno que se revela insuficiente, sirve para concluir un recorrido en el que quedan manifiestas las implicaciones del moderno olvido de la prudencia política: la racionalidad de la phronesis queda sustituida por una dialéctica insalvable entre racionalismo e irracionalismo; la atención a la realidad de las cosas queda mermada por el nihilismo en que desemboca la modernidad; la noción misma de orden político queda imposibilitada por la negación de un bien común objetivo, convirtiendo la acción política en voluntad de poder y desvirtuando irremediablemente el sentido originario de la vida política.

La vocation est un concept omniprésent dans la pensée de Max Weber. De son ouvrage phare sur l'Éthique protestante à ses deux célèbres conférences sur le savant et le politique, Weber analyse cette conduite de vie méthodique comme un modèle de personnalité éthique en s'inspirant de l'exemple archétypal du protestant ascétique. Comme diagnostic de la modernité et comme idéal normatif, l'étude de la vocation permet d'interpréter le travail comparatif wébérien tout en dégageant les fondements d'une éthique individuelle et politique. Ethos typique de la doctrine protestante, la vocation recouvre une transformation de la considération éthique du monde dont les effets se sont rationalisés dans l'exercice de la profession quotidienne. À la suite des transformations apportées par l'histoire, le désenchantement du monde et son intellectualisation, la conduite de vie méthodique propre à la vocation doit être recomposée selon ses nouvelles conditions historiques de possibilité. Éthique d'un métier spécialisé et ascétique, porteur d'un engagement normatif et responsable dans le monde, Weber édifie un modèle de personnalité à même de répondre aux défis politiques et intellectuels de son temps. Face à la lutte et à la sélection inéluctable des qualités et des types d'hommes, la défense pugnace de la vocation contient en elle la volonté de préserver le potentiel de transformation immanent d'une telle conduite menacé par les processus endémiques de différenciation et de dépersonnalisation des ordres de vie tels que la bureaucratisation. Modeler les conditions historiques nécessaires à l'engagement vocationnel pour le constituer comme un modèle dominant d'ethos, voilà ce qui guide la préoccupation anthropologique de Weber. À cette fin, le charisme et la virtuosité sont indispensables pour apprécier les ressorts et la portée de la définition de ce type d'homme d'élite adéquat pour prendre en main son histoire. Constamment préoccupé par la qualité des hommes du futur, Weber offre à travers la vocation une incitation aux hommes d'aujourd'hui à ne pas renoncer à agir décisivement pour déployer leur conception du monde différenciée. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Max Weber, vocation, éthique, conduite de vie, type d'homme.