Mathematical models are important tools in systems biology, since the regulatory networks in biological cells are too complicated to understand by biological experiments alone. Analytical solutions can be derived only for the simplest models and numerical simulations are necessary in most cases to evaluate the models and their properties and to compare them with measured data. This thesis focuses on the mesoscopic simulation level, which captures both, space dependent behavior by diffusion and the inherent stochasticity of cellular systems. Space is partitioned into compartments by a mesh and the number of molecules of each species in each compartment gives the state of the system. We first examine how to compute the jump coefficients for a discrete stochastic jump process on unstructured meshes from a first exit time approach guaranteeing the correct speed of diffusion. Furthermore, we analyze different methods leading to non-negative coefficients by backward analysis and derive a new method, minimizing both the error in the diffusion coefficient and in the particle distribution. The second part of this thesis investigates macromolecular crowding effects. A high percentage of the cytosol and membranes of cells are occupied by molecules. This impedes the diffusive motion and also affects the reaction rates. Most algorithms for cell simulations are either derived for a dilute medium or become computationally very expensive when applied to a crowded environment. Therefore, we develop a multiscale approach, which takes the microscopic positions of the molecules into account, while still allowing for efficient stochastic simulations on the mesoscopic level. Finally, we compare on- and off-lattice models on the microscopic level when applied to a crowded environment.

Ce mémoire portera sur le problème de la signification, dans la pensée de Heidegger, de la métaphysique moderne, à partir de la conception de l’histoire de l’être qu’il développe dans les années 1930. Plus précisément, nous nous baserons sur l’écrit Die Zeit des Weltbildes, que l’on retrouve dans le recueil nommé Holzwege, mais également, dans une moindre mesure, sur l’écrit Niezsches Wort « Gott ist tot » du même recueil. Nous commencerons par introduire le lecteur à l’idée qu’il se fait de la métaphysique en général dans son rapport à l’homme, et du nihilisme que constitue son histoire, lequel s’accentue à l’époque moderne. Nous rentournerons alors brièvement aux premiers commencements de la métaphysique, chez Parménide et Platon principalement, dans le but de dégager les aspects de la métaphysique moderne qui y ont trouvé leur source. C’est alors que nous entrerons dans le vif du sujet, en expliquant en quoi consiste l’inauguration de la métaphysique moderne chez Descartes qui, face à l’obligation religieuse, pose la confirmation autonome de la vérité qui trouve son lieu propre dans la conscience de soi. Il sera dès lors question de montrer précisément comment se fait cette confirmation par soi-même du vrai, au travers de certaines notions centrales de l’analyse heideggerienne : la pro-position, la présentation et la représentation, l’instauration, la production, l’obtention, la préhension et la compréhension, notamment. Nous analyserons ensuite le mouvement de la volonté du sujet qui sous-tend cette confirmation autonome du savoir jusqu’à son aboutissement chez des penseurs tels que Schopenhauer. Nous mettrons par le fait même en évidence le rapport fondamental, souligné par Heidegger, entre le sujet et son objet, l’homme moderne se soulèvant et se donnant lui-même le statut éminent de centre de référence de toute chose, rapportant à lui-même tout chose. Ce mémoire se terminera par l’analyse que fait Heidegger d’un phénomène propre à la modernité, et donc émanent de la métaphysique qui aura été examinée au préalable, soit la science moderne. Celle-ci constitue la voie privilégiée où l’homme moderne, après avoir sciemment pris position au centre du monde, peut « procéder » dans le monde comme dans son royaume, un monde qui se révèle alors comme étant essentiellement à sa disposition. La science, émanant selon Heidegger de la conception moderne de la vérité et de l’étant, se révèle alors non seulement comme une réalisation de la métaphysique qui aura été analysée dans les chapitres précédents, mais peut-être même comme le phénomène duquel Heidegger semble s’être inspiré pour développer son idée de la métaphysique moderne. / The present thesis explores the nature of the Heideggerian critique of Modern Times and of the metaphysics that constitutes their foundation, a critique that is based on the notion of the history of Being as conceived by Heidegger in the1930s. We will do so through a close reading of Die Zeit des Weltbildes, as well as of Nietzsches Wort « Gott ist tot », two essential writings found in the collection of texts called Holzwege. First, we will have a look at his idea of metaphysics in general, and of nihilism as the principle behind it’s history, of which we will then examine the first phases, leading to the emergence of Modern Times. At that point, we will explain of the nature of the inauguration of this era in Descartes’ philosophy, where he opposes the self-confirmation of truth by the human subject to religious obligation, a confirmation happening in self-consciousness. The modalities of this modern principle of knowledge will be examined, through key notions of Heidegger’s analysis: proposition, presentation, representation, production, objet, prehension, comprenhension, etc. After which a look at the human will as the main motor of this autonomous confirmation of truth, all through modern history up to philosophies such as that of Schopenhauer, is necessary to understand how Heidegger interprets this determination of truth in the light of the relation between man and his world. In his eyes, the Modern Times see man standing up to consciously assert himself as the center of reference of the whole world, bringing everything back to himself, therefore reducing ontology to anthropology. This paper will then, at the end of it’s path, take a close look at the way Heidegger interprets one of Modern Time’s main phenomena, originating according to him in modern metaphysics, that is to say modern science. It will reveal itself to be the privileged way by which man, after his positioning at the center of the world, proceeds through the world as his kingdom, all beings essentially being at his disposal. Modern science, this accomplishment of modern thought, almost seems to be the main inspiration from which he derives his theory concerning the essence of this thought.

This study analyses the administrative and economic career of Francesco De Gratta (1613–1676) as Royal Postmaster, Royal Secretary, and trader within the postal and fiscal systems of the Polish-Lithuanian Commonwealth. This investigation focuses mainly on his network and career strategies and is based on various sources from a number of European archives and libraries, mainly those situated in Italy, Poland and Germany. The study presents the family De Gratta and the familial social actions that Francesco used in order to root his children and family in the Polish-Lithuanian noble culture. Next, the analysis shows that the career of Francesco De Gratta was inextricably correlated with the establishment of the early modern royal postal system in Gdańsk (the city of Gdańsk fulfilled an important bridging role within the Poland-Lithuanian Commonwealth) as well as his close contacts with different Polish kings and queens. The career followed distinct stages, tying him ever closer with the Crown, the nobility as well as the merchants in Gdańsk. It all started with his position as Head Postmaster in Gdańsk, in 1654. In 1661, he became Postmaster General of Royal Prussia, Courland, Semigallia and Livonia. After these initial steps, Francesco immersed in creditor activities and close contacts with the Royal Prussian cities, royal authorities, and not the least different Polish mint masters. He also got involved in the potash trade with his later son-in-law Jan Wawrzyniec Wodzicki, first as his factor and later as a co-owner of Wodzicki’s company. The study finally traces his social and economic advancement by the analysis of Francesco De Gratta’s legacies and their importance for his heirs’ social status. The summary compares the career of Francesco De Gratta with that of other postmasters and mint masters of Italian origin in Poland-Lithuania. / Denna studie analyserar Francesco De Grattas (1613-1676) ekonomiska och administrativa karriär som kunglig postmästare, kunglig sekreterare och köpman i det polsk-litauiska samväldet. Denna undersökning är främst inriktad på nätverks- och karriärsanalys och bygger på olika arkivkällor från en rad europeiska arkiv och bibliotek, främst från Italien, Polen och Tyskland. Studien presenterar familjen De Gratta och de familjära sociala strategier som Francesco använde för att förankra sin familj i det polsk-litauiska samväldets adelskultur. Därefter visar analysen att De Grattas karriär kan förstås mot bakgrund av upprättandet av det tidigmoderna kungliga postsystemet i Gdańsk (Gdańsk hade en viktig överbryggande roll inom Polen-Litauen), liksom hans nära kontakter med olika polska kungar och drottningar. Hans karriär följde olika distinkta steg som möjliggjorde för honom att närma sig kronan, adeln och köpmännen i Gdańsk. År 1654 blev han huvudpostmästare i Gdańsk och 1661 fick han ämbetet som huvudpostmästare för Kungliga Preussen, Kurland, Semgallen och Livland. Senare utvecklade Francesco De Gratta sin kreditverksamhet parallellt med utbyggnaden av sitt kontaktnätverk med kungliga preussiska städer, kungliga myndigheter och inte minst olika polska myntmästare. Han blev också involverad i handel med pottaska (kaliumkarbonat) tillsammans med sin svärson Jan Wawrzyniec Wodzicki, först som hans agent och senare som delägare i Wodzickis företag. Slutligen spårar studien Francesco De Grattas sociala och ekonomiska framåtskridande genom en analys av hans arv och dess betydelse för hans arvingars sociala status. Sammanfattningsvis jämförs Francesco De Grattas karriär med andra postmästare och myntmästare av italienskt ursprung i Polen-Litauen. / Information Infrastructure in the Baltic Area. Nodes, News and News Agents, c. 1650 - 1700

Nuclear magnetic resonance (NMR) provides a convenient probe for the study of molecular reorientation in liquids because nuclear spin-lattice relaxation times are dependent upon the details of molecular motion. The combined application of Raman and Infrared (IR) lineshape analysis can furnish more complete information to characterize the anisotropic rotation of molecules. Presented here are the studies of NMR relaxation times, together with Raman/IR Mneshape analysis of the solvent and temperature dependence of rotational diffusion in 1,3,5-tribromobenzene and 1,3,5-trifluorobenzene. In these experiments, it was found that the rotational diffusion constants calculated from Perrin's stick model were two to three times smaller than the measured values of D, and D,,. Similarly, rotational diffusion constants predicted by the Hu-Zwanzig slip model were too large by a factor of 2. Application of the newer Hynes-Kapral-Weinberg model furnished rotational diffusion constants that were in reasonable agreement with the experimental results. The vibrational peak frequencies and relaxation times of the isotropic Raman spectra of the υ1 modes of CD2Br2 and CHBr3 were studied in solution. The frequency shifts in non-interactive solvents were explained well on the basis of solution variations in the dispersion energy. In Lewis bases, the displacements were in some, but not all, cases greater than predicted. On the other hand, it was found that the vibrational relaxation times of the C-H/C-D modes decreased dramatically in all Lewis base solvents. Therefore, it was concluded that relaxation times of the υ1 modes, rather than frequency shifts, furnish a more reliable measure of hydrogen bonding interactions of halomethanes in solution.

"The development of newspapers in Dallas can be classified into certain definite dates: 1849-1865---the founding of the first newspaper to the Reconstruction period following the Civil War; 1865-1885--the postwar period and the expansion of newspapers; 1885-1906--the development of the present newspapers, the Dallas Morning News and the Dallas Times Herald, and others; 1906-1942--the advent of sensational journalism and the emergence of the newspaper as big business; and 1942 to the present--a decade of unprecedented growth and entrenchment."--leaf iv.

Pour répondre aux exigences du gouvernement fédéral quant aux temps d’attente pour les chirurgies de remplacement du genou et de la hanche, les établissements canadiens ont adopté des stratégies de gestion des listes d’attentes avec des niveaux de succès variables. Notre question de recherche visait à comprendre Quels facteurs ont permis de maintenir dans le temps un temps d’attente répondant aux exigences du gouvernement fédéral pendant au moins 6-12 mois? Nous avons développé un modèle possédant quatre facteurs, inspiré du modèle de Parsons (1977), afin d’analyser les facteurs comprenant la gouvernance, la culture, les ressources, et les outils. Trois études de cas ont été menées. En somme, le 1er cas a été capable d’obtenir les exigences pendant six mois mais incapable de les maintenir, le 2e cas a été capable de maintenir les exigences > 18 mois et le 3e cas a été incapable d’atteindre les objectifs. Des documents furent recueillis et des entrevues furent réalisées auprès des personnes impliquées dans la stratégie. Les résultats indiquent que l’hôpital qui a été en mesure de maintenir le temps d’attente possède certaines caractéristiques: réalisation exclusive de chirurgie de remplacement de la hanche et du genou, présence d’un personnel motivé, non distrait par d’autres préoccupations et un esprit d’équipe fort. Les deux autres cas ont eu à faire face à une culture médicale moins homogène et moins axés sur l’atteinte des cibles; des ressources dispersées et une politique intra-établissement imprécise. Le modèle d’hôpital factory est intéressant dans le cadre d’une chirurgie surspécialisée. Toutefois, les patients sont sélectionnés pour des chirurgies simples et dont le risque de complication est faible. Il ne peut donc pas être retenu comme le modèle durable par excellence. / In response to federal government requirements regarding wait times for elective hip and knee surgery, hospitals have adopted wait list management strategies, with variable success. This research examined organizational and systemic factors that made it possible to keep wait times within federally established limits of 6-12 months. We used a model based on Parsons’ model. Four dimensions were used to analyze the following factors: governance, culture, resources, and tools. Three cases studies were done: Case 1 was able to meet the requirements for six months but unable to sustain this level; Case 2 was able to maintain compliance with requirements for > 18 months; and Case 3 was never able to meet the requirements. Documents were collected and interviews conducted with people involved in the strategies. In all, eight interviews were conducted at each site and all documents related to each strategy were collected. The results indicated that the one hospital that was able to maintain compliance with the wait time requirements had specific characteristics: an exclusive mandate to do only hip and knee replacement surgery; motivated staff who were not distracted by other concerns; and a strong team spirit. The two other cases had to contend with a medical culture that was less homogeneous and they were less focused on meeting targets and had resources that were dispersed as well as unclear inter-organizational policies. In the end, the hospital factory model is appealing in the context of superspecialized surgery. However, because patients are selected for simple surgeries, with little risk of complications, it cannot be promoted as a sustainable model of excellence.

Surgeons of Prague in historical sources of 18th and 19th century Abstract This diploma thesis uses the archival sources on the surgeons' guild and the papers of the central authorities to explore the position of the surgeons within the medical structure in modern times. All the materials are taken from Prague City Archives, The National Archives and Archive of Charles University in Prague (e.g. laws and statutes, registers of all types, statutes of the guild or university charters, personal documents of the guilds' members). The text is focused on surgeons' gaining independence compared with doctors of medicine and moving away from barbers craft organization. The process of their transition under the supervision of the medical faculty and the official start of surgical studies at the university are examined. Furthermore, the study includes an analysis of the role of the guild, the social status of the surgeons in Prague and the character of their education including transformation in this field during the Enlightenment reforms till the revolutionary year 1848. The information extracted from the sources allows to follow the development of surgery from disrespected profession into an inherent part of medical sciences by exploring all the phenomena concerned with the education of surgeons and legal aspects of...

The main aim of the master thesis is an evaluation of archaeological textiles from the site Na Rejdišti 1 - Praha 1, which are coming from the rubbish dump. They are dated from the 16th to the 18th century. Key sources of information are analogical situations coming mainly from Poland and Germany where the textile fragments have been evaluated from rubbish dumps, water wells, cesspits and sewers. Outcome of the paper is also a tabular catalogue of findings. Key words textile, clothing, late Middle Ages, modern times, town, central Europe, dump, Na Rejdiši, Praha

The Development of Relations to Education in the 17th Century in the Context of Burgher Testaments (the Example of New Prague Town) Abstract Early modern testaments represent a unique source of information about many areas of life at a given historical period. They are frequently used in various areas of historical research, including Czech historiography and its new cultural history. Although the cultural history covers many topics, surprisingly, the field of education has been somewhat forgotten. The testaments, which unite the official information and personal testimonies, provide a unique chance to see the attitude of the society towards education in a historical context of a certain era. The testaments might become important especially when researching those periods of the development of scholarly systems and education that have been overlooked by historians, e.g. the development of town schools; respectively, the development of urban education in the period after the Battle of White Mountain (1620). The limited interest of historians has been caused mainly by the lack of information sources that could explain the changes in the organization of the newly formed confessional educational system after the Battle of White Mountain. These changes launched the process of recatholization of the Czech lands...

The dissertation D-Day and VE-Day in Czechoslovakian/Czech, British, American and Russian Newspapers deals with comparison and analysis of methods used by central newspapers published in Czechoslovak Socialist Republic/Czech Republic, Great Britain, USA and Soviet Union/Russian Federation in order to provide readers with information about D-Day in Normandy and Victory Day (VE-Day) in Europe. The articles published in selected periodicals Rudé právo/Právo, The Guardian, The New York Times and Izvestija are analysed from the 1980s to 2015. The first chapter focuses on description of historical background and circumstances which led to the Allied invasion to Normandy in June 1944 and subsequent liberation of Europe in May 1945. The end of the first chapter concentrates description of current situation connected to commemoration of these two anniversaries in 2014 and 2015. The aims and methods of the research as well as the development of the press in Czechoslovak Socialist Republic/Czech Republic, Great Britain, USA and Soviet Union/Russian Federation are characterised in the second chapter. In the third chapter the selected periodicals are examined and then compared. The end of the third chapter is devoted to verification of initial hypothesis. The conclusion is drawn in the Czech language and is...