The main purpose of this study is to develop a predictive model capable to forecast residential real estate prices in the city of Prague using Artificial Intelligence methods. The first part of this study discusses fundamentals of Artificial Neural Networks and Fuzzy Inference Systems in the context of real estate valuation. The second part demonstrates a development and testing of such models using a dataset of real estate market transactions. In the third part, results are compared to Multiple Regression and an explanatory power of each model is evaluated. Conclusions of this research are: (1) Artificial Neural Networks and Fuzzy Inference Systems give more accurate estimates of market values of residential real estates than Multiple Regression; (2) Artificial Neural Networks and Fuzzy Inference Systems represent an efficient way of modeling and analyzing residential real estate prices in Prague.

DC to DC converters stabilize the voltage obtained from voltage sources such as solar power system, wind energy sources, wave energy sources, rectified voltage from alternators, and so forth. Hence, the need for improving its control algorithm is inevitable. Many algorithms are applied to DC to DC converters. This thesis designs fuzzy adaptive dynamic programming (Fuzzy ADP) algorithm. Also, this thesis implements both adaptive dynamic programming (ADP) and Fuzzy ADP on DC to DC converters to observe the performance of the output voltage trajectories.

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Les cellules neuroendocrines possèdent d’une part la voie de sécrétion constitutive, existant dans tous les types cellulaires, qui permet le renouvellement continu de la membrane plasmique et de la matrice extracellulaire, et d’autre part la voie de sécrétion régulée, spécifique aux cellules sécrétrices, qui permet la sécrétion d’hormones suite à la stimulation de la cellule. Les organites impliqués dans cette dernière voie sont des granules de sécrétion à cœur dense (GS), sui stockent les hormones ainsi que les glycoprotéines solubles, les granines. Parmi ces dernières, la chromogranine A (CgA) joue un rôle majeur dans la biogénèse des GS mais les mécanismes moléculaires ne sont pas clairement définis. Dans une lignée de cellules non-endocrines COS7 (dépourvues de granines et donc de voie de sécrétion régulée), mon équipe d’accueil a démontré que l’expression de la CgA induit la formation de vésicules présentant une structure et des fonctions caractéristiques des GS. L’analyse du protéome des GS purifiés à partir d’une lignée de cellules COS7 exprimant de manière stable la CgA (COS7-CgA) a révélé la présence de protéines liant les éléments du cytosquelette et le calcium. Durant ma thèse, nous avons focalisé notre attention sur la myosine 1b (myo1b), l’actine et le complexe de nucléation de l’actine Arp2/3 du fait de leur capacité à induire le bourgeonnement de compartiments post-golgiens dans des cellules non-endocrines. Nous avons montré (i) que la myo1b contrôle la formation des GS ainsi que la sécrétion régulée au sein des cellules COS7-CgA et des cellules neuroendocriniennes PC12, et (ii) que la myo1b et le complexe Arp2/3 permettent le recrutement d’actine fibrillaire dans la région golgienne et la formation des GS. Ces travaux montrent pour la première fois l’implication du complexe actomyosine dans la formation des GS. Afin d’identifier le lien moléculaire entre la CgA luminale et la myo1b cytosolique, nous avons recherché les interactions potentielles de la CgA avec les lipides de la membrane du réseau trans-golgien (TGN). Nous avons montré (i) que la CgA interagit avec l’acide phosphatidique (PA), (ii) que les espèces de PA prédominantes sont communes dans les membranes golgienne et granulaire, (iii) que la CgA est capable d’interagir spécifiquement avec des espèces de PA intégrées avec des membranes artificielles et (iv) que l’inhibition de la production du PA au niveau golgien altère significativement la formation des GS et la sécrétion régulée dans les cellules neuroendocrines. L’ensemble des résultats obtenus dans le cadre de ma thèse suggère que l’interaction entre la CgA et le PA est cruciale pour la biogenèse de GS à partir de la membrane du TGN. Nous émettons l’hypothèse que cette interaction est à l’origine de la formation de microdomaines enrichis en PA qui contrôleraient la courbure de la membrane du TGN et le recrutement du complexe actomyosine. / Neuroendocrine cells exhibit the constitutive secretory pathway which is common all cell types and allows the continuous renewal of the plasma membrane and the extracellular matrix, and the regulated secretory pathway, which is specific to secretory cells and allows hormone secretion following cell stimulation. The organelles supporting the latter pathway are dense-core secretory granules (SG), which store hormones and soluble glycoproteins, called granins. Among these, chromogranin A (CgA) plays a major role in the biogenesis of SG but the molecular mechanisms underlying this process are not clearly understood. Using non-endocrine COS7 cell line (which are devoid of granins and regulated secretory pathway), my host team has demonstrated that the CgA expression induces the formation of vesicles with structural and functional characteristic of SG. The proteome analysis of purified SG from a COS7 cell line stably expressing CgA (COS7-CgA) revealed the presence of cytoskeleton- and calcium-binding proteins. During my thesis, we focused our attention on myosin 1b (myo1b), actin and actin nucleation complex Arp2/3 due to their ability to induce the budding of post-Golgi compartments in non-endocrine cells. We have shown (i) that myo1b controls SG formation as welle as the regulated secretion in COS7-CgA and PC12 neuroendocrine cells, (ii) that myo1b and Arp2/3 complex are required to recruit fibrillar actin (F-actin) to the Golgi region and to SG formation. These results highlight for the first time the involvement of the actomyosin complex in SG formation. In order to identify the molecular link between luminal CgA and Cytosolic myo1b, we investigated the potential interactions of CgA with lipids of the trans-Golgi network (TGN) membrane. We showed (i) that CgA interacts with phosphatidic acid (PA), (ii) that the predominant PA species are common in Golgi and granular membranes, (iii) that Cg Ais able to interact specifically with these PA species included in artificial membranes, and (iv) that inhibition of PA production at the Golgi level significantly alters SG formation and regulated secretion in neuroendocrine cells. All these results obtained during my thesis suggest that the interaction between CgA and PA is crucial for SG biogenesis from the TGN membrane. We suggest that this interaction is at the origin of the formation of PA-enriched microdomains that could control the curvature of the TGN membrane and the recruitment of the actomyosin complex.

Die zuverlässige Einhaltung von Lieferzusagen stellt ein wichtiges Kriterium bei der Auswahl der Teilnehmer eines auftragsbezogenen Produktionsnetzes dar. Für die objektive Bewertung der Lieferzuverlässigkeit der potenziellen Netzwerkteilnehmer bedarf es der Quantifizierung der relevanten Unsicherheiten integriert in einen allgemein gültigen Ansatz der Verfügbarkeitsprüfung. Die Arbeit stellt daraus resultierend Ansätze zur Berechnung der Unsicherheit vor. Durch die Quantifizierung der Unsicherheit innerhalb der Unternehmen ergibt sich zudem die Möglichkeit der flexiblen, situationsabhängigen Nutzung des für langfristige Rahmenverträge reservierten Sicherheitsbestandes zur Befriedigung kurzfristiger Anfragen. Diese Aufgabe unterstützt ein konfigurierbares Modell zur Entscheidungsunterstützung, das auf einem Neuro-Fuzzy-System basiert. Die Kennzahlen der Lieferzuverlässigkeit unterliegen einem dynamischen Verhalten während des Wertschöpfungsprozesses in dem auftragsbasierten Produktionsnetz. Durch die Integration dieser Kennzahlen in das Management dieses Prozesses ergibt sich die Möglichkeit, aus der Zunahme der Unsicherheit mögliche Störungen und deren Auswirkungen bereits vor ihrem Eintreten zu erfassen und im Rahmen eines präventiven Störungsmanagements zu agieren.

Le contrôle postural fait intervenir l’intégration cérébelleuse de différentes entrées sensorielles (le vestibule, la vision, la somesthésie). Nous avons évalué le contrôle postural à l’aide de différents dispositifs : la plateforme Techno Concept®, le Multitest Framiral® et les mouvements oculaires avec l’oculomètre : le Mobile e(ye)BRAIN T2® chez des participants contrôles et des enfants présentant des déficits neuro-développementaux, troubles appartenant au spectre autistique et dyslexie. Au cours de nos travaux, nous avons décrit un aspect développemental physiologique des indices posturaux et oculomoteurs et également un déficit de ces indicateurs auprès d’enfants avec retards d’apprentissage. En effet, chez ces enfants, la stabilité posturale est déficitaire et les stratégies d’exploration sont différentes par rapport aux contrôles. Nous avons basé nos hypothèses sur le fait que ce déficit serait du à un défaut d’utilisation des informations sensorielles ainsi qu’à une mauvaise intégration cérébelleuse. Les résultats de nos études nous permettent de mieux préciser les caractéristiques neuropsychologiques impliquant les fonctions cérébelleuses chez ces enfants afin de pouvoir suggérer des prises en charge thérapeutiques multimodales capables d’entrainer simultanément plusieurs fonctions. Notre objectif final est de pouvoir identifier une médiation thérapeutique spécifique pour ces enfants. / Postural control involves cerebellar integration of several sensory inputs (vestibular, visual and somesthesic). We evaluated postural control with force plateform: Techno Concept®, Multitest Framiral® and the eye movements with the Mobile e(ye)BRAIN T2® in healthy children population as well as in children with developmental disorders (autistic spectrum desorders and dyslexia). The results of our studies showed a developmental aspect of postural and oculomotor factors in healthy children and a deficit of both postural and oculomotor control in children with autistic spectrum desorders and with dyslexia. Indeed, in these children postural stability is poor and visual strategy is different with respect to healthy children. Our hypothesis is that these deficits could be due to a lack in using appropriately sensory inputs and of their integration via cerebellar activity. The importance of these studies is to better understand the involvement of cerebellar function in such developmental disorders. Our final goal is to suggest new training tecniques to use sensory inputs more efficiently in these children with developmental disorders.

L'α-Synuclein (αSyn) fibrillaire, impliqué dans la maladie de Parkinson et d’autres synucleinopathies, peut se propager entre cellules de manière « prion-like » et cette propagation est liée à la progression de la maladie. Durant cette étude, nous nous sommes tournés vers les chaperons moléculaires impliqués dans l’agrégation de l’αSyn ou bien dans sa toxicité afin de trouver des candidats capables d’interférer avec la propagation. Nous avons ensuite testé l’effet des chaperons capables de se lier aux fibres d’αSyn sur l’internalisation des fibres d’αSyn par les cellules Neuro-2a. Nous démontrons que l’interaction avec l’αSyn agrégeant avec αB-crystallin (αBc) ou Carboxyl terminus of Hsc70-interacting protein (CHIP) a mené à la formation de fibres qui sont moins internalisées par les cellules. Enfin, en passant par une stratégie de pontage chimique optimisé couplé à la spectrométrie de masse, nous avons identifié les zones d’interaction entre l’αSyn fibrillaire et soit αBc, soit CHIP. Ces résidus issus des chaperons, se trouvant à proximité des fibres d’αSyn dans les complexes, pourraient être développés dans des mini-chaperons peptidiques, capables d’enrober la surface des fibres et ainsi de bloquer la liaison à la membrane et l’internalisation des fibres. De surcroît, des polypeptides issus des partenaires précédemment identifiés d’αSyn ont été testé pour leur liaison aux fibres et leur effet sur la propagation des fibres. / Fibrillar α-Synuclein (αSyn) is the molecular hallmark of Parkinson’s Disease and other synucleinopathies. Its prion-like propagation between cells is linked to disease progression. In this study, we looked to molecular chaperones previously implicated in αSyn fibrillation and/or toxicity to identify proteins capable of binding αSyn fibrillar aggregates in order to target their propagation. We further assessed the effect of the fibril-binding chaperones on internalization of αSyn fibrils by Neuro-2a cells. We demonstrate that the interaction of aggregating αSyn with αB-crystallin (αBc) or Carboxyl terminus of Hsc70-interacting protein (CHIP) led to the formation of fibrils that are less internalized by cells. Finally, using an optimized chemical cross-linking and mass spectrometry strategy, we identified the interaction areas between fibrillar αSyn and either αBc or CHIP. These chaperone residues, located proximally to αSyn fibrils, could be subsequently developed into peptidic mini chaperones, capable of coating the fibril surface and thereby blocking fibrillar cell binding and internalization. Furthermore, polypeptides derived from previously identified αSyn binding partners were tested for their binding to αSyn fibrils and subsequent effect on fibril propagation.

Die multimediale Aufbereitung von Lerninhalten zu E-Learning Einheiten ist heute in der Aus- und Weiterbildung allgegenwärtig. Häufig wird dabei jedoch die Perspektive der Nutzer der virtuellen Lehr-/Lernsysteme vernachlässigt [1]. In der Regel erfolgt eine standardisierte Aufbereitung der Lerninhalte, welche während der Konzeptionsphase die späteren Konsumenten der E-Learning Einheiten weitestgehend außer Acht lässt. Entsprechend werden meistens weder die Potenziale zur Kostenersparnis durch Teilstandardisierung von Weiterbildungsmodulen noch zur Qualitätssteigerung durch verstärkte Individualisierung annähernd ausgeschöpft. [2] Dabei bleiben individuellen Lernpräferenzen der Teilnehmer unberücksichtigt und Potenziale zur Verbesserung der Lernergebnisse werden nicht genutzt. Um diese Lücke zu schließen, wird basierend auf der Theorie der neurolinguistischen Programmierung ein Online-Werkzeug entwickelt, welches die zur Informationsaufnahme präferierten Sinneskanäle der einzelnen Teilnehmer analysiert und auswertet. Mit diesem Wissen kann die zukünftige Entwicklung und Aufbereitung von E-Learning Inhalten individueller auf die jeweiligen Konsumenten zugeschnitten werden. Zusätzlich soll das Online-Werkzeug den Nutzern Empfehlungen geben, wie sie ihren Lernerfolg verbessern können.

Rationale: The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely cisatracurium, rocuronium, and vecuronium, for skin prick/intradermal testing. Methods: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed and compared to a freshly prepared set of reference dilutions. Results: The results are measured as beyond use date (BUD) defined as recovery of drug versus the reference (90-110%). Based on the LC-MS/MS data, the BUD for cisatracurium diluted to 10x and 100x is 96 hours. Higher dilutions (1,000x to100,000x) should be used immediately following preparation (within less than 24 hours). Vecuronium at 10x and 100x, also has a BUD of 96 hours, and the 1,000x dilution is stable for 24 hours. The 10,000x dilution should be used immediately. Rocuronium at 10x to 1,000x has a BUD of 48 hours, yet higher dilutions (10,000x and 100,000x) should be used immediately. Conclusions: With increasing dilution factors, the stability of these drugs in saline decreases, increasing deviation between samples and references. The most stable dilutions for each of the drugs tested were 10x and 100x. Stability of these drugs is likely compromised by hydrolysis of the ester bonds in the drug molecules.

The military recently recognized the importance of taking sociocultural factors into consideration. Therefore, Human Social Culture Behavior (HSCB) modeling has been getting much attention in current and future operational requirements to successfully understand the effects of social and cultural factors on human behavior. There are different kinds of modeling approaches to the data that are being used in this field and so far none of them has been widely accepted. HSCB modeling needs the capability to represent complex, ill-defined, and imprecise concepts, and soft computing modeling can deal with these concepts. There is currently no study on the use of any computational methodology for representing the relationship between adverse events and infrastructure development investments in an active war theater. This study investigates the relationship between adverse events and infrastructure development projects in an active war theater using soft computing techniques including fuzzy inference systems (FIS), artificial neural networks (ANNs), and adaptive neuro-fuzzy inference systems (ANFIS) that directly benefits from their accuracy in prediction applications. Fourteen developmental and economic improvement project types were selected based on allocated budget values and a number of projects at different time periods, urban and rural population density, and total adverse event numbers at previous month selected as independent variables. A total of four outputs reflecting the adverse events in terms of the number of people killed, wounded, hijacked, and total number of adverse events has been estimated. For each model, the data was grouped for training and testing as follows: years between 2004 and 2009 (for training purpose) and year 2010 (for testing). Ninety-six different models were developed and investigated for Afghanistan iv and the country was divided into seven regions for analysis purposes. Performance of each model was investigated and compared to all other models with the calculated mean absolute error (MAE) values and the prediction accuracy within ±1 error range (difference between actual and predicted value). Furthermore, sensitivity analysis was performed to determine the effects of input values on dependent variables and to rank the top ten input parameters in order of importance. According to the the results obtained, it was concluded that the ANNs, FIS, and ANFIS are useful modeling techniques for predicting the number of adverse events based on historical development or economic projects’ data. When the model accuracy was calculated based on the MAE for each of the models, the ANN had better predictive accuracy than FIS and ANFIS models in general as demonstrated by experimental results. The percentages of prediction accuracy with values found within ±1 error range around 90%. The sensitivity analysis results show that the importance of economic development projects varies based on the regions, population density, and occurrence of adverse events in Afghanistan. For the purpose of allocating resources and development of regions, the results can be summarized by examining the relationship between adverse events and infrastructure development in an active war theater; emphasis was on predicting the occurrence of events and assessing the potential impact of regional infrastructure development efforts on reducing number of such events.