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Konge, Julie. "Le TGF-β1 module la transition épithéliale-mésenchymateuse et le pool de cellules souches cancéreuses dans les cellules tumorales mammaires humaines : impact sur la radiosensibilité". Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS044.
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Ce travail s’inscrit dans la caractérisation des cellules radiorésistantes dans les cancers du sein, à l’origine des rechutes après traitement. Si de nombreuses données de la littérature indiquent un lien étroit entre la présence des « Cellules Souches Cancéreuses » (CSC) et la résistance aux traitements anticancéreux, la radiorésistance « intrinsèque » des CSC ainsi que les mécanismes impliqués restent encore mal définis.L’équipe du Dr. Weinberg a développé un modèle cellulaire in vitro permettant la génération de CSC mammaires humaines, « CD24-CD44+ », à la suite d’une transition épithélio-mésenchymateuse (TEM) induite par une exposition au TGF-β1. Basée sur l’utilisation de cellules mammaires humaines saines qui ont été ensuite immortalisées puis transformées, ce modèle a permis d’approfondir la compréhension de nombreux processus tumoraux tels que la TEM.Ainsi, dans ce contexte, mon projet de thèse a consisté à utiliser ce modèle afin de comparer la radiosensibilité des cellules « CD24-CD44+ » à celle des cellules « CD24+CD44- ». Le choix du modèle repose sur le fait qu’il permet la comparaison de cellules à deux stades différents de la progression tumorale.Après un rappel des connaissances nécessaires à la compréhension de ce travail, le manuscrit présente dans un premier temps la caractérisation du modèle cellulaire utilisée puis la réponse à l’irradiation des cellules du modèle. L’étude de la réponse à l’irradiation a permis de décrire le phénotype de radiorésistance des cellules « CD24-CD44+ » à travers un faible blocage en G2/M, une faible proportion de cellules polyploïdes ainsi qu’une capacité accrue à donner une descendance après irradiation (10 Gy).Ensuite, l’implication des mécanismes de mort apoptotique des cellules « CD24-CD44+ » dans le phénotype de radiorésistance a été montré. Ainsi, la mort cellulaire réduite retrouvée dans les « CD24-CD44+ » est liée à une plus faible activation des voies apoptotiques.Dans un dernier temps, l’identification d’une signature transcriptionnelle de gènes de détoxification lors de la caractérisation des cellules de notre modèle a permis de mettre en évidence la modulation radioinduite de deux de ces gènes, SOD2 et HMOX1, après stress radioinduit dans les cellules « CD24-CD44+ »<br>This works aims at characterizing radioresistant cells within human breast cancer development that is responsible for treatment failure and cancer recurrences. Although the literature is flourishing with papers tightly linking the presence of "Cancer Stem Cells" to cancer treatment resistance, the intrinsic radioresistance of those "CSC" and the mechanism involved have yet to be established.Dr. Weinberg and his team have developed an in vitro cell model that produces mammary tumor cells noted « CD24-CD44+ » after an epithelial-to-mesenchymal transition (EMT) induced by TGF-β1. This model is based on healthy human mammary cells that have been immortalized and transformed.Within this context, my Ph.D. project has focused on using this new model in order to compare the radiosensibility of two cell lines: the « CD24-CD44+ » cells and the « CD24+CD44- » one. Underlying this choice is the fact this model allows for a comparison of two cellular populations at distinct stage of the tumor’s development.This work has shed light on apoptotic and detoxification mechanism involved in the radio resistant behavior of the « CD24-CD44+ » cells. After a brief introduction of key concepts required to the understanding of this work, this manuscript will begin by presenting the characterization of the chosen model, then a study of the radiation response that enabled a first description of the « CD24-CD44+ » cell radioresistant phenotype through a mild stop at the G2/M stage of the cell cycle, the presence of polypoid cells and a high progeny generation ability after exposure to radiation.Furthermore, this works shows implications of apoptotic mechanism of « CD24-CD44+ » cells with a radioresistance phenotype. Hence, we were able to show that reduced cell death observed for the « CD24-CD44+ » cells is linked to a lower activation of apoptotic pathways.Finally, the last part will present detoxification mechanism involved in « CD24-CD44+ » radioresistance phenotype, showing an altered transcriptional signature of two detoxication genes SOD2 and HMOX1 after exposure to radiation
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Satanassi, Sara. "Quantum computers for high school: design of activities for an I SEE teaching module." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amslaurea.unibo.it/18157/.
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The thesis is situated within the I SEE project (Inclusive STEM Education to Enhance the capacity to aspire and imagine future careers), a triennial ERASMUS+ project involving six partners, started in 2016 and coordinated by the University's Department of Physics and Astronomy of the University of Bologna (https://iseeproject.eu/). The main goal of I SEE is the design of teaching approaches and modules on advanced interdisciplinary topics such as climate change, artificial intelligence and quantum computers for secondary school. The modules aim to: i) improve students' ability to imagine the future and to aspire to STEM careers; ii) develop transversal skills that allow students to play an active and conscious role in a global, fragile and constantly changing world. The work of this thesis started from the analysis of an I SEE module on quantum computers realized by the Finnish partners of the project and consists in a revision and integration of their activities in order to solve some problems they encountered during the implementation. This revision aimed to build a better connection between quantum computers and future and to search for a global approach to lead students to understand the physics behind these new technologies without getting trapped in the technical details. In particular, the work I have developed for the present thesis concerns the choice of teleportation as an emblematic case of the quantum protocol and sets as objectives: i) the comparison between the teleportation experiment and the circuit that realizes it, highlighting how the experiment can be reread in terms of logic gates and quantum circuits; ii) the educational transposition and the design of the teaching activity within the module.
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Dikina, Anna D. "ENGINEERED CARTILAGE COMPOSED OF MESENCHYMAL STEM CELL CONDENSATES AS MODULES WITH CONTROLLED SHAPE AND SIZE FOR MULTI-TISSUE TYPE CONSTRUCTS, AS MATERIALS FOR CHONDROCONDUCTIVE SCAFFOLDS AND AS MECHANORESPONSIVE TISSUES." Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1459254069.
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Gallego, Diego. "On the Two-Step Moduli Stabilization." Doctoral thesis, SISSA, 2009. http://hdl.handle.net/20.500.11767/3980.
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We analyze the circumstances under which part of the information in the full Lagrangian of certain supersymmetric theories can be neglected. More precisely, we study when heavy moduli can be frozen out rather than being properly integrated out, and still get a reliable low energy effective action around nearly supersymmetric solutions.....
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Kaláb, Ctibor. "Modul parního generátoru." Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2010. http://www.nusl.cz/ntk/nusl-229195.
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The thesis deals with a project of a steam generator heated with liquid sodium. The first section describes some types of steam generators at nuclear power plants which have been projected or put into use. The next part presents a draft concept of the steam generator, solved by this work. The implementation of the steam generator module has been selected from several options, based on the thermal, hydraulic and stress calculations and on the chosen criteria. The conclusion of this thesis deals with the evaluation of the final solution in terms of nuclear safety and technical solutions, and compares this solution to similar projects following various criteria.
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Glauche, Ingmar. "Theoretical studies on the lineage specification of hematopoietic stem cells." Doctoral thesis, Universitätsbibliothek Leipzig, 2010. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-62448.
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Hämatopoetische Stammzellen besitzen die Fähigkeit, die dauerhafte Erhaltung ihrer eigenen Population im Knochenmark zu gewährleisten und gleichzeitig zur Neubildung der verschiedenen Zelltypen des peripheren Blutes beizutragen. Die Sequenz von Entscheidungsprozessen, die den Übergang einer undifferenzierten Stammzelle in eine funktionale ausgereifte Zelle beschreibt, wird als Linienspezifikation bezeichnet. Obwohl viele Details zu den molekularen Mechanismen dieser Entscheidungsprozesse mittlerweile erforscht sind, bestehen noch immer große Unklarheiten, wie die komplexen phänotypischen Veränderungen hervorgerufen und reguliert werden.
Im Rahmen dieser Dissertation wird ein geeignetes mathematisches Modell der Linienspezifikation hämatopoetischer Stammzellen entwickelt, welches dann in ein bestehendes Modell der hämatopoetischen Stammzellorganisation auf Gewebsebene integriert wird. Zur Verifizierung des theoretischen Modells werden Simulationsergebnisse mit verschiedenen experimentellen Daten verglichen. Der zweite Teil dieser Arbeit konzentriert sich auf die Beschreibung und Analyse der Entwick- lungsprozesse von Einzelzellen, die aus diesem integrierten Modell hervorgehen. Aufbauend auf den entsprechenden Modellsimulationen wird dazu eine topologische Charakterisierung der resultierenden zellulären Genealogien etabliert, welche durch verschiedener Maße für deren Quantifizierung ergänzt wird.
Das vorgestellte mathematische Modell stellt eine neuartige Verknüpfung der intrazellulären Linienspezifikation mit der Beschreibung der hämatopoetischen Stammzellorganisation auf Populationsebene her. Dadurch wird das Stammzellm- odell von Röder und Löffler um die wichtige Dimension der Linienspezifikation ergänzt und damit in seinem Anwendungsbereich deutlich ausgedehnt. Durch die Analyse von Einzelzellverläufen trägt das Modell zu einem grundlegenden Verständnis der inhärenten Heterogenität hämatopoetischer Stammzellen bei.
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Wu, Yingxiang. "Describing Integrated Power Electronics Modules using STEP AP210." Thesis, Virginia Tech, 2004. http://hdl.handle.net/10919/9928.
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The software environment for power electronics design is comprised of tools that address many interrelated disciplines including circuits design, physical layout, thermal management, structural mechanics, and electromagnetics. This usually results in a number of separate models that provide various views of a design, each of which is usually stored separately in proprietary formats. The problem is that the relationships between views (e.g., the circuit design that defines the functional connectivity between components, and the physical layout that provides physical paths to implement connections), are not explicitly captured. This makes it difficult to synchronize and maintain data consistency across all models as changes are made to the respective views.
This thesis addresses this problem by describing power electronics modules using STEP AP210, the STandard for the Exchange of Product data, Application Protocol 210; which has been designated as ISO 10303-210. A multidisciplinary model was implemented for an integrated power electronics module (IPEM). It consists of two views of the IPEM: a functional network definition of the IPEM, and a physical implementation that satisfies the functional connectivity requirements. The relationships between these two views are explicitly recorded in the model. These relationships allow for the development of a method which verifies whether the connectivity data in both views are consistent. Finally, this thesis provides guidance for deploying STEP AP210 to unify multidisciplinary data resources during the design of integrated power electronics.<br>Master of Science
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Holland, Peter. "A CAD module for the extraction of geometric features from STEP files." Thesis, University of Nottingham, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430626.
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Ciani, Yari. "Regulatory modules discovery and mesenchymal stem cells characterization from high-throughput cancer genomics data." Doctoral thesis, Università degli studi di Trieste, 2015. http://hdl.handle.net/10077/11111.
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2013/2014<br>Il tumore è una malattia caratterizzata da un’estrema complessità molecolare. Gli approcci di tipo “omic”, collezionando dati sull’intero genoma, sui trascritti e proteine in dataset pubblici, permettono di superare questa complessità e di trovare moduli funzionali che eseguono le funzioni coinvolte nei processi tumorali. Ad esempio, i profili di espressione genica da tessuti vengono usati per definire firme di geni e testarne la rilevanza clinica. Ho usato questo tipo di informazione per caratterizzare specifici geni di interesse in modelli di tumore al seno. Uno dei più recenti progetti di tipo “omic” è il FANTOM5. Questo progetto ha generato una risorsa unica: il primo atlante di espressione in mammifero basato su sequenziamento a singola molecola. Il sistema CAGE (Cap Analysis of Gene Expression) è stato usato per misurare i siti di inizio trascrizione (TSS) e l’utilizzo dei promotori in una collezione di campioni umani: in questo modo sono stati misurati i livelli di espressione di gran parte dei trascritti codificanti e non-codificanti nel genoma umano.
Ho usato questo tipo di informazione per caratterizzare una linea staminale mesenchimale/stromale (MSC) derivante da tumori sierosi ovarici di alto grado (HG-SOC-MSCs) o da tessuti normali (N-MSCs) inclusi nel dataset FANTOM5. Ho messo in luce programmi funzionali condivisi tra le due linee cellulari e osservato che le differenze principali tra le funzioni attivate nelle due linee sono di tipo quantitativo più che qualitativo. I risultati suggeriscono inoltre che le HG-SOC-MSCs sono simili alle cellule mesoteliali e alle cellule del tessuto muscolare liscio.
Inoltre, ho analizzato l’intero dataset usando ScanAll, un nuovo software utile a predire ab initio la presenza di elementi arricchiti nelle regioni geniche che circondano i promotori trovati del progetto FANTOM5. Ho individuato moduli di regolazione, ossia gruppi di motif che si trovano a distanze predefinite sul genoma uno rispetto all’altro. Questi moduli sono arricchiti in regioni del genoma co-espresse rispetto a sequenze generate casualmente. Infine ho creato un compendio di fattori di trascrizione espressi e che partecipano ad interazione proteina-proteina.<br>Cancer is a disease characterized by an extreme molecular complexity. Omics approaches, collecting data in public databases for all the genome, transcripts and proteins, attempt to overcome this complexity and find the functional modules that perform the functions involved in tumour related processes. For instance, cancer tissues gene expression profiles are widely used to define genes signatures and test their clinical relevance. I used this kind information in order to characterise interesting genes in breast cancer models. On the other hand, cellular models datasets could provide data that permits to focus on specific molecular mechanisms and probe the effects of molecules in a specific cancer model. One of the most recent omics project is the FANTOM5 project, that has generated a unique resource, the first single molecule sequencing-based expression atlas in mammalian systems. Cap analysis of gene expression (CAGE) was used to measure transcription start sites (TSS) and promoter usage across a wide collection of human samples thereby identifying and measuring levels of the majority of coding and non-coding transcripts in the human genome.
I used this information to characterize a mesenchymal/stromal stem cell line (MSC) derived from high-grade serous ovarian cancer (HG-SOC-MSCs) or derived from normal tissue (N-MSCs) included in the entire FANTOM5 human dataset. I highlighted shared functional programs between HG-SOC-MSCs and N-MSCs suggesting that the global differences between the two cell lines are based on quantitative levels of transcriptional output rather than on qualitative differences. The results suggested that HG-SOC-MSCs are close relatives of mesothelial cells and smooth muscle cells.
Furthermore, we analysed the entire dataset using ScanAll, a newly developed software, to ab initio predict the presence of enriched elements in the genomic regions surrounding FANTOM5 promoters. I pinpointed regulatory modules, i.e. groups of enriched motifs co-occurring in co-expressed regions within a fixed distance. These modules are enriched in the co-expressed sequences in each sample respect to random generated sequences. Finally, I created a Compendium of putative expressed and directly interacting transcription factors.<br>XXVII Ciclo<br>1986
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Omer, Amir Isam. "The effect of thermal-cycling on the bond strength of a two step and single-step dentin bonding agent." Thesis, University of the Western Cape, 2010. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_1007_1318491744.
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The aim and objective of this study was to determine the bond strength of a twostep and a single-step dentin bonding agent and to determine the effect of repeated thermal-cycling from 50C and 550C on the bond strength values of these dentin bonding agents.
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Tee, Jing Yang. "Olfactory Stem Cells as Disease Models for Schizophrenia." Thesis, Griffith University, 2019. http://hdl.handle.net/10072/388987.
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Schizophrenia is a strongly heritable multifactorial mental disorder that affects 1% of any population, but disease etiology is not yet fully understood. The limitations of using animal models, post-mortem brain studies and difficulty to obtain human brain biopsies have impeded the understanding of this disease from the biological perspective. There is a consensus, based on epidemiology and post-mortem human brains that schizophrenia is a neurodevelopmental disorder, but cellular and molecular mechanisms for this hypothesis are lacking. We have developed a model to address this using human olfactory neurosphere-derived (hONS) ‘stem’ cells, which were obtained non-invasively from human participants, expressed neural stem cell markers and allows comparative analyses of age- and sex-matched cell lines from patients diagnosed with schizophrenia with cell lines from healthy participants. Patient cells from various sources have a common dysregulation to gene pathway networks involved in axonal guidance, cell adhesion, cytoskeletal remodeling, focal adhesion signaling and reelin signaling - all important pathways that regulate cell migration.
A high throughput live cell tracking technique was developed to unbiasly quantify cell motility in vitro. At baseline on uncoated tissue culture plastic (TCP), patient cells moved longer distances than control cells. Patient cells were unable to respond to their microenvironment when increasing concentrations of well-defined ECM proteins were coated on TCP cell culture surfaces. This was despite patient cells expressing the necessary cell surface integrin receptors measured by flow cytometry, which meant they have the capacity to bind and recognize all tested ECM proteins. Patient cells have consistently lower levels of cytoskeletal proteins in filamentous actin (F-actin) and stable microtubules, which became more evident when cultured on ECM proteins. Despite being able to adjust their cell sizes and shapes, patient cells were consistently smaller than control cells. Focal adhesion kinase (FAK) levels were consistently lower in patient cells and they were unable to manufacture enough focal adhesions of the correct sizes upon contact with ECM proteins. These findings highlighted a global deficit to cell migration in schizophrenia that was not limited to just Fibronectin but also on all ECM proteins, which were caused by disease-dependent intracellular deficits in patient cell cytoskeleton and focal adhesions. Reelin is an important brain ECM protein that orchestrates neuronal migration during neurodevelopment and its expression is reduced in post-mortem brain tissues from patients with schizophrenia. In this study, reelin protein levels were also reduced in patient hONS cells compared to control cells. Despite having the capabilities to bind to reelin through expression of key reelin signaling pathway accessory protein Dab1 and reelin-binding receptors ApoER2 and VLDLR, patient cells were unable to respond to extracellular reelin. Patient cells were unable to adjust their movement track lengths when tracked on surfaces coated with full length reelin. Similar to our previous findings on other ECM proteins, patient cells had lower levels of F-actin and stable microtubules, and were consistently smaller in size compared to control cells. Our findings suggested that non-responsive cell migration deficits were caused by defective focal adhesion responses to extracellular reelin. Instead of producing more focal adhesions that were larger in response to reelin, patient cells reduced both the densities and sizes of their focal adhesions at the peripheral region of the cell where lamellipodia forms. This was the first study to demonstrate a biological link between reelin signaling and schizophrenia, with a focus on the effects of reelin on cell migration.
Published computer programs were used in silico to investigate the mechanistic components of cell migration and to further investigate reasons why patient cells were unable to respond to their ECM microenvironment. X-Y displacement coordinates for each individually tracked cell were analyzed by the DiPer and migration phase/cell turning analysis programs to compute cell movement variables in directionality, diffusivity, persistence and idling and turning. At baseline on TCP, patient cells did not move at the correct trajectories, failed to make directional changes, paused less and turned less when tracked for 24 h. When tracked on ECM proteins, it was difficult to pinpoint one explanation to explain our non-responsive cell migration findings as various mechanistic variables played a collective part to potentially give rise to the observed non-responsive cell migration phenotype. One explanation was that patient cells spent more time in persistent movement and were unable to make necessary changes to their directions. Another explanation was the unchanged cell pausing tendencies on Type I Collagen as a plausible explanation for observed non-responsive changes to motility on that ECM protein. The same in silico computational analyses showed that patient cells did not respond to extracellular reelin because they could not reduce the rate at which they changed the straightness of their movement trajectories. Patient cells were also unable to make well-timed changes to the direction of their movement trajectories by being more persistent in one direction for longer. Decreased densities and sizes of focal adhesions in patient cells upon contact with extracellular reelin resulted in patient cells not decreasing their turn angles, but instead made larger uncoordinated turns. The way that control cells responded negatively to extracellular reelin supported the hypothesis in the field that reelin acts as a “stop signal” for actively moving neuronal cells, which was disrupted in patient cells.
In conclusion, this thesis has uncovered a novel non-responsive cell migration phenotype in schizophrenia, which was broadly relevant on different ECM proteins, to suggest consistent defects in how patient cells respond to their surrounding microenvironment. Findings from this thesis also showed that observed cell migration deficits were caused by differences to intracellular components such as cell cytoskeleton and focal adhesions, coupled to previously published findings that FAK, integrin and actin signaling pathways were all dysregulated in schizophrenia. Using an analogy of patient cells as a moving vehicle, our findings showed a global defect to many parts of this faulty “vehicle”, such as defective “ignition” in FAK signaling, uncoordinated “wheels” in the lamellipodia and consistent faults to the “clutch” mechanism in the focal adhesions. All working in concert to cause patient cells to move in a less coordinated fashion and unable to make controlled mechanistic changes to their movement, causing them to ultimately lose their way.<br>School of Environment and Sc<br>Science, Environment, Engineering and Technology<br>Full Text
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Damian, Camilla, Zehra Eksi-Altay, and Rüdiger Frey. "EM algorithm for Markov chains observed via Gaussian noise and point process information: Theory and case studies." De Gruyter, 2018. http://dx.doi.org/10.1515/strm-2017-0021.
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In this paper we study parameter estimation via the Expectation Maximization (EM) algorithm for a continuous-time hidden Markov model with diffusion and point process observation. Inference problems of this type arise for instance in credit risk modelling. A key step in the application of the EM algorithm is the derivation of finite-dimensional filters for the quantities that are needed in the E-Step of the algorithm. In this context we obtain exact, unnormalized and robust filters, and we discuss their numerical implementation. Moreover, we propose several goodness-of-fit tests for hidden Markov models with Gaussian noise and point process observation. We run an extensive simulation study to test speed and accuracy of our methodology. The paper closes with an application to credit risk: we estimate the parameters of a hidden Markov model for credit quality where the observations consist of rating transitions and credit spreads for US corporations.
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Jamwal, Goldee. "Effective use of Interactive Learning Modules in Classroom Study for Computer Science Education." DigitalCommons@USU, 2012. http://digitalcommons.usu.edu/etd/1358.
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The National Science Foundation (NSF) is spending substantial resources to improve science, technology, engineering, and mathematics (STEM) education in the United States. The ultimate goal of these programs is to produce students with a better knowledge of math and science and who are more likely to pursue careers in STEM fields. Interactive learning modules can be used in the classroom environment for effective learning.
This study examines the learning preferences of Logan High School (located in Logan, Utah) students and evaluates the impacts of using interactive learning modules with classroom lectures compared to other traditional methods of teaching.
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Schiffmann, Patrick. "Three step modelling approach for the simulation of industrial scale pervaporation modules." Doctoral thesis, Technische Universitaet Bergakademie Freiberg Universitaetsbibliothek "Georgius Agricola", 2014. http://nbn-resolving.de/urn:nbn:de:bsz:105-qucosa-150446.
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The separation of aqueous and organic mixtures with thermal separation processes is an important and challenging task in the chemical industry. Rising prices for energy, stricter environmental regulations and the increasing demand for high purity chemicals are the main driving forces to find alternative solutions to common separation technologies such as distillation and absorption. These are mostly too energy consumptive and can show limited separation performance, especially when applied to close boiling or azeotropic mixtures. Pervaporation can overcome these thermodynamic limitations and requires less energy because only the separated components need to be evaporated. This separation technology is already well established for the production of anhydrous solvents, but not yet widely distributed in the chemical and petrochemical industry due to some crucial challenges, which are still to overcome.
Besides the need of high selective membranes, the development of membrane modules adapted to the specific requirements of organoselective pervaporation needs more research effort. Furthermore, only few modelling and simulation tools are available, which hinders the distribution of this process in industrial scale.
In this work, these issues are addressed in a combined approach. In close collaboration with our cooperation partners, a novel membrane module for organophilic pervaporation is developed. A novel technology to manufacture high selective polymeric pervaporation membranes is applied to produce a membrane for an industrially relevant organic-organic separation task. A three step modelling approach ranging from a shortcut and a discrete to a rigorous model is developed and implemented in a user interface. A hydrophilic and an organophilic membrane are characterised for the separation of a 2-butanol/water mixture in a wide range of feed temperature and feed concentration in order to establish a generally valid description of the membrane performances. This approach is implemented in the three developed models to simulate the novel membrane module in industrial scale. The simulations are compared to the results of pilot scale experiments conducted with the novel membrane module. Good agreement between simulated and experimental values is reached.
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Lei, Lin. "Identification of portal mesenchymal stem cells and derived myofibroblasts in liver fibrosis." Thesis, Sorbonne université, 2020. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2020SORUS099.pdf.
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Les travaux antérieurs ont montré que les myofibroblastes portaux (PMFs) contribuaient de manière significative à la fibrogenèse et à l'angiogénèse dans la fibrose hépatique. L'objectif principal de cette thèse était de cartographier les cellules mésenchymateuses portales, et plus particulièrement la niche des cellules souches mésenchymateuses portales. Nous avons caractérisé la variété des cellules mésenchymateuses portales du foie de souris. Résultat important, nous avons identifié une population de cellules mésenchymateuses portales ayant les caractéristiques de cellules souches mésenchymateuses, désignées cellules souches mésenchymateuses portales (PMSCs), qui ont la capacité de se transformer en PMFs in vitro. Nous avons identifié Slit2 comme un marqueur des PMSCs par scRNA-seq et bulk RNA-seq. In vivo, nous avons mis en évidence l'expansion de PMSCs dans le foie de modèles murins de fibrose hépatique et de patients ayant une maladie chronique du foie. Nous avons identifié des signatures transcriptomiques spécifiques des PMSCs d’une part et des cellules étoilées du foie (CEF), de l’autre. Les résultats obtenus par l’utilisation de ces marqueurs, renforcent nos conclusions selon lesquelles les PMSCs s’accumulent de façon corrélée avec la fibrogenèse et l'angiogenèse, tandis que la signature des CEFs ne varie pas. En conclusion, nos travaux apportent des éléments à la connaissance des populations de cellules mésenchymateuses portales du foie. Ils ont permis d’identifier et caractériser les PMSCs ainsi que les myofibroblastes qui en dérivent, ouvrant de nouvelles perspectives dans le domaine des thérapies ciblées et des biomarqueurs pour la pratique clinique<br>Previous work has demonstrated that portal myofibroblasts (PMFs) significantly contributed to liver fibrogenesis and modulated angiogenesis in liver fibrosis. The main aim of this thesis was to elucidate the landscape of portal mesenchymal cells, with a particular focus on a portal mesenchymal stem cell niche. We characterized the murine normal liver portal mesenchymal cell landscape. Importantly, we revealed a portal mesenchymal cell population with the features of mesenchymal stem cells (MSCs), designated portal mesenchymal stem cells (PMSCs) that possessed the ability to give rise to PMFs in vitro. Furthermore, we identified Slit2 as a new marker of PMSCs based on scRNA-seq and bulk RNA-seq analysis. In vivo, we observed PMSC expansion (measured by the expression of Slit2) in liver from both animal fibrosis models (DDC and CDAA) and patients with chronic liver disease (NASH, PSC and other liver disease). Notably, we defined the specific gene signatures for PMSCs and hepatic stellate cells (HSCs), respectively. By using these markers, we provide further evidence indicating that PMSCs expand in correlation with fibrogenesis and angiogenesis in different murine and human liver diseases, whereas the HSCs gene signatures did not vary. In conclusion, our work collectively offers insights into the components and functions of the mammalian liver portal mesenchymal cell populations, and in particular, identify and characterize PMSCs and their derived myofibroblasts, opening up the possibility for the development of novel targeted drugs or biomarkers of clinical significance with increased precision
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Jacquet, Laureen Esther-Mae. "Human pluripotent stem cell models of Huntington's disease." Thesis, King's College London (University of London), 2014. https://kclpure.kcl.ac.uk/portal/en/theses/human-pluripotent-stem-cell-models-of-huntingtons-disease(7a0094c3-3266-4191-bbdb-8542f2ec1a81).html.
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Huntington’s disease (HD) is a late-onset, autosomal, dominant and progressive neurodegenerative disorder for which there is no disease-modifying therapy. An abnormal trinucleotide CAG repeats expansion (>36 CAG repeats) in exon 1 of the gene coding for the Huntingtin (HTT) protein is the causative mutation for the disease. Animal models of HD, such as the R6/2 mouse model, already exist. Yet, in order to understand the disease at a molecular level, cellular models of HD are also needed. At the beginning of this project, existing models had been developed from tumour cell lines using genome-integrating lentiviral delivery system carrying a mutated HTT exon 1. This model was not optimal, as the cells will always have noninnate extra copies of HTT, which expression is driven by exogenous promoter. In order to circumvent this, we were aiming to develop two human stem cell models of HD and use them as tools in drug discovery and further understanding of molecular mechanisms of the disease. The first model is human embryonic stem cells (hESCs) isolated from clinically unsuitable embryos, donated by consenting couples. The embryos carrying a mutation in HTT gene, as determined by Preimplantation Genetic Diagnosis (PGD), were used to derive HD-specific mutation-carrying hESC lines (HD-hESC). Seven HD- hESCs lines were derived at the Assisted Conception Unit (ACU) at Guy’s Hospital, King’s College London (KCL). The second model is induced pluripotent stem cells (iPSCs) that I would derive from keratinocytes obtained from plucked hairs of consenting HD patients. Their greater availability means that we would be able to derive lines representing a larger spectrum of HD phenotype due to variations in CAG repeats expansion. Reprogramming will be done using a combination of modified mRNAs and/or a lentiviral vector encoding the transcription factors needed for reprogramming. The overall goal of the project was to optimize culture conditions for the HD-hESC and HD-iPS cell lines, fully characterise them, and differentiate them in vitro. Epidemiology studies suggest that cardiac failure is the second cause of death in HD patients. For this reasons, HD-ESCs were differentiated into cardiac cells (cardiomyocytes) in order to define and characterize the cardiac HD phenotype. Here, I am describing thorough characterization of normal and HD-hESC lines and their differentiation into cardiomyocytes. I am also presenting my data on reprogramming of human fibroblasts into iPSC using synthetic modified mRNA. Due to time limit and several technical issues outlined in the text, I was unable to successfully reprogram cells from keratinocytes obtained from plucked hairs of consenting HD patients.
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Lundberg, Anders, and Tobias Jansson. "Preliminary study of a frame for a two module turbine system." Thesis, Linköpings universitet, Maskinkonstruktion, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-72082.
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The development of steam turbines is continuously moving forward and the aim is oftento develop configurations with higher power output. Siemens Industrial Turbomachinery AB is currently in the beginning of a development project which replaces a single turbine with two interconnected turbines with higher pressure and temperature of the steam than before. To ensure reliable quality and hold down costs is it an advantage to do most of the assembly before delivery to site.This thesis work at Linköping University has been written in collaboration with Siemens Industrial Turbomachinery AB, Finspång. The objective of this work is to investigate the possibility to mount two turbines and a gearbox on a turbine frame. Theframe will be used both for transportation and during operation.The thesis considerate analyses of the turbine layout and critical parameters that may affect a turbine frame. In addition was a frame concept developed and evaluated with respect to solid mechanics and alignment of the shaft arrangement.Our conclusion is that there are good possibilities to install the equipment on a frame and achieve demands due to solid mechanics and alignment of the shaft arrangement.We recommend Siemens Industrial Turbomachinery AB to carry on with the project and do further investigations of the natural frequency of the frame concept, compare financial advantages and disadvantages together with possibilities for transportation.
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Zachos, Terri A. "Gene-augmented mesenchymal stem cells in bone repair." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1146076285.
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Wills, Lauren Raquel. "Investigating Induced Pluripotent Stem Cells for Tissue Engineering and Hepatotoxicity Applications." Thesis, Virginia Tech, 2019. http://hdl.handle.net/10919/101006.
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Induced pluripotent stem cells (iPSCs) can be differentiated into multiple cell types in the body while maintaining proliferative capabilities. The generation of human iPSC-derived hepatocytes (iPSC-Heps) has resulted in a new source for hepatic cells. The current available options for human hepatocytes are primary human hepatocytes (PHHs) and cell lines. PHHs isolated from healthy human donors are difficult to obtain, while cell lines exhibit reduced hepatotoxic sensitivity. iPSC-Heps are being investigated as an alternative option as they are derived from a continuous, stable source and are able to maintain their original donor genotype, which opens the door for patient-specific studies. iPSC-Heps show promise for utilization in tissue engineering, hepatotoxicity studies as well as screening for patient-specific therapeutics. Various reports have concluded that iPSC-Heps exhibit reduced hepatocyte function in comparison to PHHs. Prior reports on iPSC-Heps have focused on improving their adult phenotype functions through variations in differentiation protocols or by altering their in vitro culturing environment. This thesis focuses on incorporating hepatic non-parenchymal cells to more closely mimic the tissue and cell architecture found in the liver tissue. We designed and assembled a 3D iPSC-Hep model that integrates liver sinusoidal endothelial cells, with the goal of achieving functional maturity. Hepatotoxicants were administered to our models and various hepatic markers were measured to analyze the toxic response. This work demonstrates the need for the inclusion of hepatic non-parenchymal cells in iPSC-derived liver tissues, specifically for hepatotoxicity applications.<br>Master of Science
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Wallerman, Jörgen. "Remote sensing aided spatial prediction of forest stem volume /." Umeå : Dept. of Forest Resource Management and Geomatics, 2003. http://epsilon.slu.se/s271.pdf.
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Kessal, Ahcène. "Intégration d'un module d'analyse de structures par une approche à base d'entités topologiques." Compiègne, 1997. http://www.theses.fr/1997COMP991S.
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Les entreprises doivent réduire, sans cesse, les délais de mise sur le marché ainsi que les coûts de production, tout en améliorant la qualité et les procédés de fabrication. Elles doivent pouvoir réutiliser les résultats de précédents développements, superviser toutes les étapes du cycle de vie d'un produit et avoir des équipes, à différents niveaux, qui travaillent de concert. De plus en plus fréquemment, les entreprises travaillent en étroite collaboration avec d'autres, en vue de la conception et de l'élaboration de produits de complexes. Les différents systèmes d'information doivent pouvoir cohabiter et inter changer des données. Le terme clé, pour répondre à ces exigences, est données ; les données doivent être disponibles au moment approprié là où nous en avons besoin et sous la forme qui convient. L'ingénierie concourante dans un environnement intégré constitue un cadre adéquat pour répondre à ces besoins. Le projet FIRES s'inscrit dans cette optique. La diversité des activités concernées et les besoins de chacune d'elles en terme de données font qu'une représentation unifiée pour la conception, l'analyse et la fabrication est un préalable à toute perspective d'intégration. L'approche à base de feature paraît très prometteuse. FIRES (Featured-based Integrated Rapid Engineering System) est un projet ESPRIT (ESPRIT III 6090), il est le fruit de la collaboration de six partenaires issus de quatre pays européens. FIRES vise l'élaboration d'un prototype d'une nouvelle génération de logiciels d'aide à l'ingénierie, basés sur la notion de features. Dans notre travail de thèse, nous nous sommes intéressés à l'interface d'analyse. Les développements ont couvert trois axes principaux : implémentation d'un nombre limité de features, réalisation d'une interface avec le modèle neutre de données et la dérivation du modèle d'analyse puis la génération du maillage associé<br>Companies today need to reduce time to market and costs, while continuously improving quality and processes. These companies need to build on previous efforts, address total product life cycle, and have effective cross-functional product teams. Increasingly these companies work closely with other companies in the design and manufacture of ever more complex products. All information systems need to work together and share data. The key to meeting these needs is data, that data has to be available when needed and where needed and in the suitable form. Concurrent engineering technology, based on an integrated environment, could be a solution to meet such requirements. FIRES project lies in this perspective. In seeking this integration, it is recognized that the diversity of activities and consequent needs for data can be best served by a single representation for design, analysis and manufacturing, and that a strong candidate for this descriptive role is a feature representation. FIRES (Featured-based Integrated Rapid Engineering System) is an ESPRIT project (ESPRIT III 6090), it involves six partners from four countries. FIRES project aims to prototype a new generation of computer-aided engineering software based on feature approach and neutral data models. In our thesis work we have focused on the analysis interface, development have been separated in three main stages : implementation of some basic features, developpment of an interface to the neutral part model and finally model derivation and mesh generation
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Chambolle, Frédéric. "Un modèle produit piloté par les processus d'élaboration : application au secteur automobile dans l'environnement STEP." Châtenay-Malabry, Ecole centrale de Paris, 1999. http://www.theses.fr/1999ECAP0623.
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Dans un contexte de forte concurrence, l'industrie automobile doit réduire ses couts et délais de conception et réalisation de produits. Pour ce faire, des coopérations avec des partenaires extérieurs et une intégration des métiers et des applications doivent être réalisées. Cela nécessite l'introduction du travail en ingénierie concourante, en entreprise entendue, le développement de la maquette numérique et des systèmes de gestion de données techniques, pour lesquels l'étude d'un modèle de produit fédérateur et intégrateur des données de l'entreprise adéquat est ici menée, la communication entre les systèmes internes, ceux des partenaires et les progiciels devant être assurée. Ce travail de thèse propose un modèle de produit automobile basé sur le protocole d'application 214 (AP214) de la norme internationale STEP. Une méthodologie d'analyse a été développée pour permettre la prise en compte des informations pré-existant dans l'entreprise telles que les processus et données manipulées. Sur la base de ce modèle produit, différentes fonctionnalités d'exploitation des données qui y ont été instanciées ont été développées. Ce sont des fonctionnalités de navigation exploitant les liens établis entre les éléments majeurs du modèle, de renseignement consistant en une extraction des données fournissant des informations complémentaires sur le produit (personnes, services, poids, matériau, documents, ), et avancées qui exploitent le modèle en profondeur pour, par exemple, extraire la nomenclature d'un véhicule. Une première mise en application est présentée au travers de la plateforme MicroSTEP 214 qui est l'implémentation au sein d'un SGBD du modèle produit proposé et des fonctionnalités associées. Un jeu de données industrielles a été utilise pour la validation du modèle et de ses fonctionnalités. Une seconde mise en application concerne l'application de la méthodologie proposée dans un scenario d'échange en co-conception. Celui-ci a pour objectif de valider les aptitudes du protocole d'application 203 (AP203) de la norme STEP à répondre aux besoins de l'industrie automobile. Une plateforme d'échange opérationnelle a été réalisée sur la base du sous-modèle AP203 retenu pour ces échanges.
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Wang, Yanli. "Mathematical models of budding yeast colony formation and damage segregation in stem cells." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1500544727569612.
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Ferrand, Jonathan. "Helicobacter pylori dans un modèle de carcinogenèse gastrique impliquant les cellules souches mésenchymateuses." Thesis, Bordeaux 2, 2009. http://www.theses.fr/2009BOR21627/document.
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L’infection par Helicobacter pylori touche environ la moitié de la population mondiale et est responsable de plusieurs pathologies gastrointestinales incluant l’adénocarcinome gastrique. Le développement récent d’un modèle d’étude chez l’animal a permis d’identifier la nature des cellules à l’origine de la transformation cancéreuse en réponse à l’infection chronique par Hélicobacter. Les cellules souches mésenchymateuses de la moelle osseuse (MSC) seraient recrutées au niveau de la muqueuse gastrique afin de reconstituer, par un mécanisme de différenciation épithéliale, les glandes lésées par l’infection. L’adénocarcinome gastrique se développerait à partir des glandes reconstituées par les MSC. Les objectifs de ces travaux ont été d’analyser, in vitro par une approche séquentielle, les différentes étapes responsables de l’initiation tumorale incluant le recrutement des MSC au niveau gastrique, leur différenciation en cellules épithéliales et leur transformation tumorale lors de l’infection par H. pylori. Ces travaux ont tout d’abord démontré que les cellules épithéliales infectées par H. pylori peuvent recruter les MSC après sécrétion de certaines chimiokines. Nous avons ensuite montré que les MSC sont capables de fusionner avec les cellules épithéliales gastriques aboutissant à l’obtention de cellules épithéliales dérivées des MSC. Finalement, les interactions entre H. pylori et les MSC ont été étudiées et ont fourni des premiers éléments de compréhension des mécanismes de l’initiation tumorale. Nos résultats permettent de mieux comprendre le mécanisme physiopathologique de l’adénocarcinome gastrique et seront utiles à la compréhension d’autres cancers dans lesquels le rôle des MSC comme cellules initiatrices de tumeur est suggéré<br>Helicobacter pylori infection is found in about half of the world population and can induce several gastrointestinal pathologies including gastric adenocarcinoma. An animal model recently led to the hypothesis of a cellular origin for the cancer initiating cells after Helicobacter infection. Bone marrow-derived mesenchymal stem cells (MSC) are believed to be recruited in the gastric mucosa in order to repair the damages due to infection, by an epithelial differentiation. Gastric carcinoma may rise from MSC reconstituted gastric glands. This study aimed to analyze, by sequential in vitro approaches, the different steps allowing tumor initiation including MSC recruitment by infected epithelial cells, epithelial differentiation of MSC, and cancer marker appearance after H. pylori infection. We first demonstrated that H. pylori infected epithelial cells may recruit MSC by a secretion of cytokines. We then showed that MSC fuse with gastric epithelial cells leading to MSC-derived epithelial cells. Finally, we studied the interaction between H. pylori and epithelial cells providing a preliminary explanation for cancer initiation. Our results allow a better understanding of gastric adenocarcinoma pathophysiology and will be helpful for the understanding of other cancers in which the role of MSC as cancer initiating cells is suspected
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Edwards, Jane Ann. "Expression of antisense RNA to investigate the interaction between unique and shared receptor subunits in the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor." Thesis, St George's, University of London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322069.
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Tuhý, Luboš. "Výukový modul pro měření v předmětu Výkonová elektronika 1." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2014. http://www.nusl.cz/ntk/nusl-220550.
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This thesis describes the design and implementation of the transistor inverter to the subject of power electronics first outcome of this thesis will transistorized inverter that will serve as a demonstration tool in laboratory practice course electrical power. The laboratory preparation, students will be able to virtually test your theory acquired knowledge of the issue. Part of the theoretical analysis will be proposed circuit simulation program through classes Spice.
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Söderdahl, Therese. "Characterization of biotransformation systems in human cells : focus on stem cells and their progeny /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-206-4/.
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Plattard, Odile. "Repenser l'évacuation d'une population littorale en milieu urbain dans un contexte multi-risques : le modèle STEP." Thesis, Paris 1, 2019. http://www.theses.fr/2019PA01H087.
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Cette thèse questionne l’évacuation piétonne d’une population littorale en milieu urbain en cas de tsunami et séisme, à travers la mise en place du modèle STEP. Deux sites d’études ont été considérés : Saint-Laurent-du-Var (France) et Syracuse (Italie), qui présentent des configurations d’exposition aux risques et des stratégies d’évacuation de la population différentes. L’espace urbain est au cœur du questionnement de cette thèse. Premièrement, à travers l’influence que la lisibilité du milieu urbain peut avoir sur une évacuation piétonne. Deuxièmement, par la prise en compte du contexte multi-risques et des dommages d’un séisme précurseur sur les constructions, en questionnant la praticabilité des itinéraires d’évacuation en milieu urbain. STEP est un modèle hybride alliant le multi-agents et les automates cellulaires et implémenté sur la commune de Saint-Laurent-du-Var. Son environnement est construit à partir des données géographiques de terrain (topographie, bâtiments). Le tsunami est implémenté à partir des données issues de simulation événements de référence. La lisibilité de l’espace urbain est construite à travers la mise en place de zones de non-visibilité des zones refuge générées en fonction de leur hauteur et de celle des bâtiments. La praticabilité de l’espace urbain se traduit par la mise en place d’une probabilité d’effondrement des constructions en fonction de l’intensité sismique, pouvant obliger les individus à trouver un autre itinéraire jusqu’aux zones refuge. Trois scénarios principaux ont été mis en place, se basant sur des événements de références et explorés par variation des paramètres liés aux agents et zones refuge ; ces trois scénarios principaux font varier la lisibilité et la praticabilité de manière indépendante afin de mieux en percevoir les effets sur les résultats. Au final, la variation de la localisation des zones refuges ainsi que la prise en compte du contexte multi-risques en milieu urbain ont une influence importante sur les résultats issus des simulations de STEP. Cette thèse met donc en avant l’importance de la considération de la spécificité d’une évacuation en milieu urbain ainsi que du contexte multi-risques pour la mise en place de stratégies d’évacuation de population sur un territoire<br>This thesis explore the issue of a pedestrian evacuation of coastal population in an urban environment in case of tsunami and seism, through the implementation of the model STEP. Studies examine two fields: Saint-Laurent-du-Var (France) and Siracusa (Italy). They provide varied configurations of disaster risk exposure and different evacuation strategies for a coastal urban population. Urban environment is the central point of this thesis. First, visibility in an urban context is evaluated through its effect on pedestrian evacuation. Second, by taking into account multi-hazard context through the impacts on buildings from a precursor earthquake and questioning the walkability of evacuation routes to safe areas. The STEP model is a hybrid modelisation combining agent-based and cellular automatons. It is implemented on Saint-Laurent-du-Var based on geographical data (topography, buildings). The tsunami is based on worst-case simulation data. Visibility in an urban context is determined by the height of safe areas and surrounding buildings; it creates “shadow-zones” where people have no line-of-sight to safe areas around them. Walkability of the urban environment is based on the probability of a building collapse according to seismic intensity. Debris may obstruct streets and force people to seek alternative routes to safe areas. According to the worst-case simulation data, three main evacuation scenarios were implemented and explored through parameters related to agents and safe areas. These three scenarios vary the visibility and walkability independently in order to better evaluate the effects of the results. The greatest impact seen within STEP simulations is determined by the location of safe areas and paying attention to seismic activity in an urban environment. This thesis shows the importance of considering specific evacuation requirements for coastal urban environments. It also demonstrates that multi-hazards should be a central concern when defining evacuation strategies for populations
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Luce, Eléanor. "Hépatocytes différenciés à partir de cellules souches pluripotentes induites : modèle pour la thérapie cellulaire et génique autologue de l'hémophilie B et modèle préclinique chez le primate." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS520/document.
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Ce projet de thèse vise à modéliser puis à apporter la preuve de concept d’une thérapie cellulaire et génique autologue de maladies héréditaires du foie par la transplantation d’hépatocytes différenciés à partir des cellules souches pluripotentes induites (iPSC) spécifiques du patient, une fois celles-ci corrigées du défaut génétique. L’hémophilie B (HB) est une maladie héréditaire causée par une mutation du gène F9, codant le facteur IX (FIX) de la coagulation synthétisé dans le foie par les hépatocytes. Des fibroblastes d’un patient porteur de la « mutation royale » ont été reprogrammés en iPSC puis différenciés en hépatocytes. L’étude de l’ARNm du F9 par séquençage haut débit a confirmé la présence d’un site d’épissage anormal codant une protéine tronquée. D’autres iPSC ont été obtenues à partir des cellules d’un second patient HB exprimant un FIX inactif. Après insertion ciblée d’une cassette thérapeutique codant le FIX dans un site génomique sûr à l’aide d’endonucléases artificielles (CRISPR/Cas9), nous avons différencié les iPSC corrigées et non corrigées en hépatocytes (respectivement corr-HB-Heps et HB-Heps) et confirmé une expression plus importante de l’ARNm du F9 et de la protéine FIX dans les corr-HB-Heps. En revanche, nous n’avons pas détecté d’activité du FIX transgénique sans doute à cause d’une différenciation incomplète des hépatocytes. Nous avons alors développé un protocole de différenciation en sphéroïdes permettant une différenciation plus efficace confirmée aux niveaux ARN et protéine FIX. L’analyse de l’activité du FIX produit nous permettra de valider la correction in vitro avant de la valider in vivo en transplantant les corr-HB-Heps dans un modèle de souris F9KO. Finalement, la dernière partie de ce travail a consisté à développer un protocole de différenciation d’iPSC de singe en hépatocytes en vue d’une transplantation autologue dans le foie de l’animal donneur pour valider la faisabilité et la sécurité de cette approche chez le gros animal<br>This PhD project aims to model and to bring a proof of concept for autologous cell/gene therapy of inherited liver diseases by transplanting hepatocytes differentiated from patient-specific induced pluripotent stem cells (iPSCs), after correction of the genetic defect. Hemophilia B (HB) is an inherited disease caused by a mutation in the F9 gene encoding clotting factor IX (FIX), synthesized in the liver by hepatocytes. Fibroblasts of a patient with the "royal mutation" were reprogrammed in iPSCs then differentiated into hepatocytes. The study of the F9 mRNA by high-throughput sequencing confirmed the presence of an abnormal splice site leading to a truncated protein explaining hemophilia. Other iPSCs were obtained and characterized from the cells of a second HB patient expressing an inactive FIX. By targeting in these iPSCs the insertion of a therapeutic cassette encoding FIX into a safe harbor site using artificial endonucleases (CRISPR/Cas9), we differentiated the corrected and non-corrected iPSC into hepatocytes. Quantitative analyzes confirmed a higher expression of F9 mRNA and FIX protein in the corrected clones. In contrast, we did not detect transgenic FIX activity due to a lack of post-translational modifications necessary for FIX activity. We then developed a protocol of differentiation in spheroids quantitatively more efficient to produce FIX. Detection of FIX activity will validate our in vitro approach before validation in vivo by transplanting the corrected hepatocytes in a F9KO mouse model. Finally, the last part of this work consisted in the development of a differentiation protocol of nonhuman primate iPSCs into hepatocytes for autologous transplantation into the liver of the donor animal in order to validate the feasibility and the safety of such an approach in the large animal
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Gatinois, Vincent. "Pathologies des hélicases et vieillissement précoce : modèle d'étude par dérivation de cellules souches pluripotentes induites (iPS)." Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTT042/document.
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Les hélicases sont des enzymes ubiquitaires catalysant la séparation de l’ADN double-brin et impliquées dans la réplication, la réparation de l’ADN et dans le maintien des télomères. Chez l’Homme, 3 hélicases présentent des mutations responsables de syndromes cliniques : WRN pour le syndrome de Werner, BLM pour le syndrome de Bloom et RECQL4 pour le syndrome de Rothmund-Thomson. Tous ces syndromes associent un vieillissement pathologique accéléré à un risque accru de développement de cancer notamment par une augmentation de l’instabilité génomique. Les connaissances sur les mécanismes moléculaires et cellulaires impliqués dans ces maladies du vieillissement sont encore très partielles, notamment en ce qui concerne le lien entre l’instabilité génomique et le vieillissement. Au cours de ce projet, l'utilisation de prélèvements sanguins et cutanés de patients atteints de ces pathologies rares a permis de générer des modèles de cellules souches pluripotentes induites (iPS). Ces cellules présentent l’avantage de s’auto-renouveler et de pouvoir théoriquement se différencier dans tous les types cellulaires d’un organisme. Parallèlement, un témoin de sénescence a été généré de la même manière avec des cellules d’un patient souffrant du syndrome de la progéria de Hutchinson-Gilford. Après caractérisation de ces cellules, nous avons identifié des ensembles de phénotypes cellulaires et moléculaires dans le but de récapituler in vitro les pathologies. Nous avons également engagé les cellules iPS dans des voies de différenciation proches des tissus atteints dans les pathologies in vivo. Enfin, nous avons étudié la stabilité génomique de ces lignées dans les différents types cellulaires cultivés. Ainsi nous avons observé que la lignée Bloom est le siège de recombinaisons particulièrement fréquentes et est caractérisée par une instabilité du génome dans tous les types cellulaires étudiés. Egalement, la lignée Werner semblerait se distinguer par une instabilité de ses télomères. Enfin, l’ensemble des lignées des pathologies du vieillissement prématuré présenterait un défaut mitochondrial<br>Helicases process the double-stranded DNA dissociation. They are involved in replication, DNA repair and maintenance of telomeres. In human, 3 helicases display mutations responsible for clinical syndromes: WRN for the Werner syndrome, BLM for the Bloom syndrome and RECQL4 for the Rothmund-Thomson syndrome. All these diseases cause premature ageing and high risk of cancer. Molecular and cellular mechanisms involved in these diseases are not well defined. Particularly, little is known concerning the link between genomic instability and ageing. During this project, we used blood samples and skin biopsies of affected patients to generate models by reprogramming cells to induced pluripotent stem cells (iPSCs). These cells have the advantage of self-renewing and theoretically could be differentiated in all cell types. At the same time, an iPSC senescence control was performed from cells of a Hutchinson-Gilford Progeria syndrome patient. iPSCs were characterized for pluripotency. In the aim of recapitulate these pathologies in vitro, we identified sets of cellular and molecular phenotypes. We also engaged differentiation of iPSCs in cell pathways closed to the affected tissues in vivo. Finally, we studied the genomic stability of iPSCs and derived cells. We observed that Bloom cells are susceptible to frequent recombinations and are characterized by a genome instability through all studied cell types. Werner cells showed an instability of telomeres length. Finally, all premature ageing diseases displayed mitochondrial defects
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Lavorata, PhD Dr Reagan Lorraine. "Science Technology Engineering Math (STEM) Classes and Females' Career Choices." ScholarWorks, 2017. https://scholarworks.waldenu.edu/dissertations/3353.
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Females have been discouraged from taking science, technology, engineering, and math (STEM) classes during high school and college, resulting in limited access to high-paying STEM careers. Therefore, these females could miss opportunities for these high-paying careers. The rationale of this research was to quantify the relationship between the number of STEM classes the sampled females took, the number of female role models they had during high school and college, their career choices, and salaries. The theoretical construct was based on Erikson's social developmental theory, which postulates a relationship between earlier life events and later life events, and Acker's masculinity theory, which postulates that females in traditionally male fields may be uneasy performing functions opposite to what they naturally perform. Key questions examined the relationships between STEM classes, role models, career choices, and salaries. The sample was a stratified random sample (n = 48) of female alumnae of 4 universities, born after 1980. Data were collected from a designed online instrument, validated by a pilot. The data were analyzed with a multiple regression and an analysis of variance. The findings revealed a significant relationship between the number of STEM classes, career choices and salary. However, there was no significance found between the numbers of role models, career choices and salary The implication for social change is that by making scholars in the fields of education and management aware about the relationship between the number of STEM classes taken, career choices, and salaries, females can be more encouraged to become interested in STEM courses earlier in life, making it more likely they will choose STEM careers This can be accomplished through scholarly journals, which hopefully will improve perceptions of the STEM abilities of females.
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Parker, Reginald. "Towards a comprehensive kinetic model for step-growth polymerization." Diss., Georgia Institute of Technology, 2000. http://hdl.handle.net/1853/10995.
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Ottosson, Fredrik, and My Håkansson. "Spring Step : Utvecklandet av fotsteg för yrkesfordon." Thesis, Högskolan i Halmstad, Akademin för ekonomi, teknik och naturvetenskap, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-34758.
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Yrkeschaufförer som hämtar och levererar paket, använder sig ofta av LVC-fordon (Light Commercial Vehicle). Dessa fordon är vanligtvis försedda med skjutdörr på ena sidan, samt dörrar baktill. För att underlätta in-och urstigning bak på fordonet så är fotsteg monterat under dörrarna. När föraren ska hämta eller lämna paket backar de mot lastkajen för att kunna lasta in eller ur via bakdörren på fordonet. Man önskar att komma så nära intill lastkajen som möjligt och backar tills det att fotsteget där bak tar emot, detta ger föraren en smidig och effektiv indikator på att önskad position är uppnådd. Problemet som uppstår när denna manöver upprepas är att fotsteget tillslut backas sönder. Att åka till verkstad för att laga det trasiga fotsteget prioriteras bort eftersom det tar tid och kostar pengar. Två utvecklingsingenjörer har i samarbete med företaget Modul-System HH AB tagit fram en lösning på detta problem. Med hjälp av vetenskapliga metoder, analyser och andra verktyg har produkten Spring Step utvecklats och är fotsteget med lång livslängd som hjälper företag att både spara tid och pengar. Spring Step är det fjädrande fotsteget som med hjälp av bladfjädrar skjuts in under bilen när det utsätts för horisontella krafter. Produkten är anpassningsbar på alla typer av LVC-fordon eftersom det finns en skena på fotstegets undersida där ett justerbart skruvförband.<br>Package delivery drivers often use Light Commercial Vehicles. This kind of vehicles are equipped with a sliding door on the side and two doors at the back. To make it easier to enter and exit the back of the vehicle, there is a step mounted to the chassis. When the driver picks up or delivers a package, he reverses towards the loading dock to able to load or unload through the back doors. You want to be as close as possible to the dock which is why you reverse until the step and the dock collides, this maneuver serves as an effective indicator to when the desired position is reached. The problem occur by repeating the maneuver is that step eventually breaks. Repairing the step is often not high priority due to high costs and long lead times. Two Innovation engineers has in collaboration with Modul-System HH AB developed a solution to this problem. Using product- and project development models, Spring Step has been developed which has a longer life span and saves transportation companies a lot of time and money. Spring Step is the resilient step that uses plate springs to shove the step under the vehicle during horizontal force. The product is customizable to any light commercial vehicle on the market due to the rail and bolts under the step.
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Li, Yang. "The time-series approaches in forecasting one-step-ahead cash-flow data of mining companies listed on the Johannesburg Stock Exchange." Thesis, University of the Western Cape, 2007. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_1552_1254470577.
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<p>Previous research pertaining to the financial aspect of the mining industry has focused predominantly on mining products' values and the companies' sensitivity to exchange rates. There has been very little empirical research carries out in the field of the statistical behaviour of mning companies' cash flow data. This paper aimed to study the time-series behaviour of the cash flow data series of JSE listed mining companies.</p>
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Gamal, Wesam. "Real-time bioimpedance measurements of stem cellbased disease models-on-a-chip." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/20444.
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In vitro disease models are powerful platforms for the development of drugs and novel therapies. Stem-cell based approaches have emerged as cutting-edge tools in disease modelling, allowing for deeper insights into previously unknown disease mechanisms. Hence the significant role of these disease-in-a-dish methods in therapeutics and translational medicine. Impedance sensing is a non-invasive, quantitative technique that can monitor changes in cellular behaviour and morphology in real-time. Bioimpedance measurements can be used to characterize and evaluate the establishment of a valid disease model, without the need for invasive end-point biochemical assays. In this work, two stem cell-based disease models-on-a-chip are proposed for acute liver failure (ALF) and age-related macular degeneration (AMD). The ALF disease model-on-a-chip integrates impedance sensing with the highly-differentiated HepaRG cell line to monitor in real-time quantitative and dynamic response to various hepatotoxins. Bioimpedance analysis and modelling has revealed an unknown mechanism of paracetamol hepatotoxicity; a temporal, dose-dependent disruption of tight junctions (TJs) and cell-substrate adhesion. This disruption has been validated using ultrastructural imaging and immunostaining of the TJ-associated protein ZO-1. Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world with a need for disease models for its currently incurable forms. Human induced pluripotent stem cells (hiPSCs) technology offers a novel approach for disease modelling, with the potential to impact translational retinal research and therapy. Recent developments enable the generation of Retinal Pigment Epithelial cells from patients (hiPSC-RPE), thus allowing for human retinal disease in vitro studies with great clinical and physiological relevance. In the current study, the development of a tissue-on- a-chip AMD disease model has been established using RPE generated from a patient with an inherited macular degeneration (case cell line) and from a healthy sibling (control cell line). A reproducible Electric Cell-substrate Impedance Sensing (ECIS) electrical wounding assay was conducted to mimic RPE damage in AMD. First, a robust and reproducible real-time quantitative monitoring over a 25-day period demonstrated the establishment and maturation of RPE layers on microelectrodes. A spatially-controlled RPE layer damage that mimicked cell loss in AMD was then initiated. Post recovery, significant differences in migration rates were found between case and control cell lines. Data analysis and modelling suggested this was due to the lower cell-substrate adhesion of the control cell line. These findings were confirmed using cell adhesion biochemical assays. Moreover, different-sized, individually-addressed square microelectrode arrays with high spatial resolution were designed and fabricated in-house. ECIS wounding assays were performed on these chips to study immortalized RPE migration. Migration rates comparable to those obtained with ECIS circular microelectrodes were determined. The two proposed disease-models-on-a-chip were then used to explore the therapeutic potential of the antioxidant N-Acetyl-Cysteine (NAC) on hiPSC-RPE and HepaRG cell recovery. Addition of 10 mM NAC at the end of a 24h paracetamol challenge caused a slight increase in the measured impedance, suggesting partial cell recovery. On the other hand, no effect on case hiPSC-RPE migration has been observed. More experiments are needed to examine the effect of different NAC concentrations and incubation periods. The therapeutic potential of electrical stimulation has also been explored. A preliminary study to evaluate the effect of electrical stimulation on RPE migration has been conducted. An externally applied direct current electric field (DC EF) of 300 mV/mm was found to direct the migration of the immortalized RPE cell line (hTERT-RPE1) perpendicular to the EF. The cells were also observed to elongate and to realign their long axes perpendicular to the applied EF. The proposed tissue-on-a-chip disease models are powerful platforms for translational studies. The potential of such platforms has been demonstrated through revealing unknown effects of acetaminophen on the liver as well as providing deeper insights into the underlying mechanisms of macular degeneration. Combining stem cell technology with impedance sensing provides a high throughput platform for studying patient-specific diseases and evaluating potential therapies.
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Luk, Sze-ue, and 陸施妤. "The potential effect of bioactive food supplements in targeting prostate cancer stem cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43223795.
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Larbi, Aniya. "Les cellules souches embryonnaires humaines, un modèle d’étude des étapes précoces de la lymphopoïèse." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA114808.
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Les cellules souches embryonnaires humaines (CSEh) sont des outils puissants pour explorer la genèse des différents tissus de l’organisme, notamment le tissu hématopoïétique. Dans le but d’obtenir des types cellulaires cliniquement utiles, la majorité des travaux se sont concentrés sur l’obtention des cellules hématopoïétiques terminales, notamment des cellules lymphoïdes (lymphocytes B, lymphocyte T et cellules NK), à partir des cellules souches pluripotentes humaines. En revanche, le rendement des cellules hématopoïétiques obtenues dans ce modèle reste faible. D’autre part, les étapes précoces de l’hématopoïèse, notamment l’identification de la cellule souche hématopoïétique (CSH), des progéniteurs myéloïdes et lymphoïdes à partir des cellules souches pluripotentes, sont encore très peu définies. Nous nous sommes intéressés aux étapes précoces de la lymphopoïèse dans le modèle des CSEh. Dans un premier temps, nous avons étudié le rôle de l’homéoprotéine HOXB4 dans l’expansion des progéniteurs NK dérivés des CSEh. Nous avons montré que l’exposition des cellules des corps embryonnaires (EB pour Embryoid Body), dérivées de la différenciation des CSEh, à la lignée MS-5/SP-HOXB4, une lignée modifiée qui exprime constitutivement HOXB4, induit une expansion des progéniteurs NK dérivées des CSEh. De plus, les cellules NK qui en dérivent sont matures et fonctionnelles, de part leur activité cytolytique vis-à-vis d’une lignée érythro-leucémique (K562). Outre l’effet de HOXB4 sur l’expansion des progéniteurs NK, cette étude a permis de démontrer en particulier le rôle de la lignée stromale MS-5 dans l’induction de la spécification lymphoïde à partir des CSEh. Dans un deuxième temps, nous avons analysé plus précisément les étapes précoces de la lymphopoïèse humaine à partir des CSEh. En effet, nous avons montré, au cours de la première partie, que la coculture des cellules dérivées des EB avec MS-5 induit l’expression en surface du CD45RA, un marqueur de spécification lymphoïde, au sein des progéniteurs hématopoïétiques CD34+. Ainsi, sur la base de ces données et des données antérieurs concernant les étapes précoces de la lymphopoïèse humaine fœtale et adulte, nous avons identifié et caractérisé in vitro à partir des CSEh deux populations originales de progéniteurs lymphoïdes précoces multipotents (MELP pour Myeloid Early Lymphoid Progenitor): La progéniteur CD34+CD45RA+CD7+ dont le potentiel de différenciation est biaisé vers le lignage T et NK ; et le progéniteur CD34+CD45RA+CD7- a un potentiel de différenciation biaisé vers les lymphocytes B. Cette étude a un intérêt dans la compréhension du processus de la lymphopoïèse humaine dans le modèle des cellules souches pluripotentes. En perspective, ces données pourraient avoir également un intérêt dans la modélisation de maladie de défauts génétiques de développement du système lymphoïde<br>Human embryonic stem cells (hESC) are powerful tools to explore tissue genesis of the organism, especially hematopoietic tissue. In order to obtain cellular types clinically useful, the majority of works have been focalised on final output of hematopoietic cells, especially lymphoid cells (lymphocyte B, lymphocyte T and NK cells), from human pluripotent stem cells. However, the obtained hematopoietic cells yield is very poor. In the other hand, initial steps of hematopoiesis, especially the identification of the hematopoietic stem cell, myeloid and lymphoid progenitors, from pluripotent stem cells, are poorly defined. We were interested to early steps of lymphopoisis in the hESC model. Initially, we studied the role of HOXB4 homeprotein on CSEh-derived NK progenitor. We showed that exposure of embryoid body (EB), derived from hESC, to the modified line that express constitutively HOXB4 “MS-5/SP-HOXB4”, induce hESC-derived NK progenitor expansion. Furthermore, the derived NK cells are mature and fonctionnal, by cytolytic activity on erythro-leucemic line K562. Furthermore the effect of HOXB4 on NK progenitor expansion, this study demonstrated, particularly the role of MS-5 line on the lymphoid specification from hESC.Secondly, we analysed more precisely the early steps of human lymphopoiesis from hESC. We showed, in the first part, that MS-5 coculture of the EB-derived cells induce surface expression of CD45RA (marker of lymphoid specification) on hematopoietic progenitor CD34+. Thus, on the basis of these data and previous data concerning the initial steps of fetal and adult lymphopoiesis, we identified and characterized in vitro from hESC, two populations of multipotent early lymphoid progenitor (MELP): the CD34+CD45RA+CD7+ progenitor whose the differentiation potential is biased to T and NK lineage, and the CD34+CD45RA+CD7- progenitor has differentiation potential biased to B lineage. This study is essential in understanding of normal and pathological lymphopoisis process in pluripotent stem cells model. Additionally, this study paves the way for the modeling of genetic disorders of lymphoid system
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Xiong, Anqi. "Novel Regulators of Brain Tumor Development : – From neural stem cell differentiation to in vivo models." Doctoral thesis, Uppsala universitet, Institutionen för immunologi, genetik och patologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-264470.
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Malignant brain tumors are diseases with poor prognosis and/or severe long-term side effects of treatment. This thesis aimed to discover novel regulators in brain tumor development, based on studying neural stem cell and progenitor cell (NSPC) differentiation and using animal models to introduce new insights to mechanisms of human brain tumors. The enzyme heparanase (HPSE) that degrades heparan sulfate (HS) is active in cell signaling and ECM remodeling. In paper I, we found an enhanced differentiation to oligodendrocytes in ES cell-derived NSPCs overexpressing HPSE. Further analysis suggested that this enhanced formation of oligodendrocytes was associated with alterations in receptor tyrosine kinase signaling, and that HPSE might also exert anti-apoptotic functions. Subsequently, in paper II we studied the involvement of HPSE in glioma development. We observed that high HPSE levels associated with poor survival in glioma patients. In experimental models, we found that HPSE promoted glioma growth, and that an inhibitor of HPSE reduced glioma progression both in vitro and in vivo. We hypothesize that regulators in NSPC differentiation could have a potential role in brain tumor development. In paper III, we explored the function of NRBP2, a pseudokinase that is up-regulated during NSPC differentiation. We found low expression of NRBP2 in brain tumors, in comparison to normal brain. In medulloblastoma, in particular, low NRBP2 expression is linked to poor prognosis. Overexpression of NRBP2 in medulloblastoma cells led to impaired cell growth and migration, concomitant with an increased cell death. In paper IV, we searched for novel glioma susceptibility genes by sequencing dog breeds from the same ancestor but with different glioma incidence. In this way we identified three new glioma-associated genes. Two of these are significantly regulated in human glioma and one of those might have a role in glioblastoma stem cell differentiation.
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Johnejack, Kent Robert 1958. "SEDIMENT TRANSPORT IN STEP-POOL MOUNTAIN STREAMS (IDAHO)." Thesis, The University of Arizona, 1987. http://hdl.handle.net/10150/291992.
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Lin, Kaili. "Neural stem cells as therapeutic agents for treatments of Parkinson's disease in rat model." HKBU Institutional Repository, 2019. https://repository.hkbu.edu.hk/etd_oa/692.
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Parkinson's disease (PD) is the second most common neurodegenerative disease. With the rapid global increase in population aging, neurodegenerative diseases are considered a primary threat to human health. As dopaminergic neuronal cell death and dysfunction are the main pathogenic mechanisms of PD, neural stem cell (NSC) replacement therapy has been identified as a potentially effective and indeed ideal therapeutic strategy. However, current in vitro stem cell culture methods, which require various chemical growth factors (GFs), are unsafe and relatively inefficient. To solve this problem, we developed two strategies for enhancing the proliferation and differentiation of NSCs in vitro based on extracellular nanomatrices and natural active ingredients. First, we developed novel nanomatrices comprising biomaterials used for promoting NSCs proliferation and differentiation without requiring additional GFs. We developed two types of inorganic sculptured extracellular nanomatrices comprising SiO2 (iSECnMs) which deposited by glancing angle deposition (GLAD). The physiological properties of nanomatrices mediate the activation of multiple bio-signaling pathways. Accordingly, iSECnMs, especially those sculptured in zigzag forms, can significantly promote the proliferation and specific neuronal phenotypic differentiation of NSCs without requiring additional GFs. The differentiated neurons survived well in vivo and achieved outstanding therapeutic effects in a rat model of 6-OHDA-induced parkinsonism. Second, 20(S)-protopanaxadiol (PPD) and oleanolic acid (OA), two crucial active ingredients derived from ginseng, significantly enhanced the proliferation and neuronal differentiation of NSCs through activating Wnt/GSK-3β/β-catenin pathway. This research is expected to promote significant developments in the induction of NSCs and provide insights into stem cell therapies for PD without undesirable prognoses
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Zhao, Ming. "Neurorestorative strategies involving neurogenesis, neuronal precursors and stem cells in animal models of Parkinson's disease." Stockholm : Unit Injury and Repair in the Nervous System, Karolinska Institutet, 2009. http://diss.kib.ki.se/2009/978-91-7409-649-1/.
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CABRAL, EDUARDO L. L. "Modelo matematico para o estudo do comportamento dinamico de geradores de vapor de tubos em U com circulacao natural." reponame:Repositório Institucional do IPEN, 1985. http://repositorio.ipen.br:8080/xmlui/handle/123456789/9256.
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Patel, Nirmal Praful School of Medicine UNSW. "Olfactory progenitor cell transplantation into the mammalian inner ear." Awarded by:University of New South Wales. School of Medicine, 2006. http://handle.unsw.edu.au/1959.4/26180.
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A practical consideration in the development of cellular therapy technology for the inner ear is the development of an in vitro model for assessing the optimal conditions for successful application of cells. The first part of this thesis describes the adaptation of the cochleovestibular structure harvested from P1 mouse pups for analysis of factors critical for the optimal implantation of stem cells in the inner ear. Results of these studies establish that the c17.2 neural stem cell line can be introduced into the cochleovestibular structure in vitro. Using this model, c17.2 cells demonstrated survival predominantly within the vestibule and basal spiral ganglion regions. Furthermore, the addition of the ototoxin, cisplatin and the neurotrophin, Brain Derived Neurotrophic Growth Factor (BDNF) enhanced the survival and migration/dispersion of c17.2 cells within the cochleovestibular explant. The second part of this thesis examines the hypothesis that olfactory neurosphere (ONS) and progenitor cells harvested from the olfactory epithelium represent a viable source of graft material for potential therapeutic applications in the inner ear. Olfactory epithelium represents a unique source of pluripotent cells that may serve as either homografts or autografts. The feasibility of ONSs to survive and integrate into a mammalian cochlea in vivo was assessed. The ONSs were isolated as a crude fraction from the olfactory epithelium of P1 to P3 day old swiss webster mouse pups, ubiquitously expressing the Green Fluorescent Protein (GFP) marker. The ONSs were microinjected into the cochleae of adult CD1 male mice. Four weeks following their implantation, ONS cells expressing the GFP marker and stained by Nestin were identified in all areas of the cochlea and vestibule, including the spiral ganglion. Robust survival and growth of the implanted ONS and ONS derived cells in the cochlea also included the development of ???tumor-like??? clusters, a phenomenon not observed in control animals implanted with c17.2 neural stem cells. Collectively, the results of this thesis illustrate the potential of olfactory neurosphere and progenitor cells to survive in the inner ear and expose a potential harmful effect of their transplantation.
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Krolák, David. "Modul pro verifikaci rotačních pozičních senzorů." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2016. http://www.nusl.cz/ntk/nusl-242153.
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This master‘s thesis deals with design and realisation of a control module for automated measurements of the modern contactless inductive position sensors by a mechanical rotational system consisting of a DC motor and an incremental quadrature encoder. The thesis presents methods of driving DC motor and recording of measured data by a microcontroller. The thesis presents a communication protocol between the control module and personal computer via USB interface. A part of this thesis is also to develop a control software and firmware, including the measurement and evaluation of properties of the control module.
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Ni, Meng, and 倪萌. "Mathematical modeling of solid oxide steam electrolyzer for hydrogen production." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39011409.
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Perez, Guillaume. "Stratégies de médecine "régénérative" pour la réparation de la peau dans un modèle murin de brûlure profonde." Thesis, Toulouse 3, 2015. http://www.theses.fr/2015TOU30096/document.
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La cicatrisation et la régénération sont les deux processus de réparation observés dans le règne animal. Toutefois, les mammifères ne sont susceptibles de réparer une blessure que par la constitution d'une cicatrice qui ne restitue point la structure et les propriétés du tissu initial. Dans un contexte de brûlure profonde, la cicatrisation, le plus souvent excessive, peut retentir négativement sur la vie de l'individu. A cette aune, nous nous somme proposé de mettre au point des thérapies innovantes, dans un modèle murin de brûlure, dans le but de réduire ou de réorienter une réaction cicatricielle anormale. La première stratégie était une thérapie cellulaire basée sur l'utilisation des cellules stromales mésenchymateuses du tissu adipeux. Bien que les études effectuées aient révélé des aptitudes immunomodulatrices encourageantes, l'utilisation de ces cellules n'a pas apporté de résultats probants pour prétendre combattre la cicatrisation excessive de notre modèle. La seconde stratégie s'appuyait sur les enseignements tirés de la première approche et de la régénération animale. Les brûlures ont été traitées par des jets de plasma froid à pression atmosphérique. La prise en charge des lésions par ce nouvel outil entraina singulièrement une diminution de la zone cicatricielle. Les expériences montrèrent que le plasma circonscrivit la cicatrisation par l'atténuation de l'inflammation et du dépôt matriciel subséquent ; il en résulta une fibrose dermique quasi-inexistante, l'émergence de follicules pileux en régénération et une récupération de l'hypoderme. En conclusion, le plasma froid améliore significativement la cicatrisation des brûlures profondes<br>Scarring and regeneration are both repair processes observed in the animal kingdom, even though mammals always heal by a scar tissue formation that never restitute the initial tissue structure and properties. Burns healing can become abnormal and may subsequently affect the person's daily life. Considering pathological healings, we developed innovative regenerative medicine strategies to reduce or redirect the wound healing process towards a better issue in a mouse model of skin burn. First, we performed a cell therapy based on the administration of adipose mesenchymal stromal cells. Although the experiments showed promising immunomodulatory abilities, such cells failed to provide convincing results in our model of excessive burn healing. The second intent was designed after findings from the first approach and knowledge from regenerative models. Deep skin burns were treated by cold atmospheric plasma. We found that plasma-treated lesions were repaired by a considerably diminished scar. Experiments showed that the plasma treatment resulted in almost inexistent fibrosis through a reduction of inflammation and matrix deposition, emergence of regeneration follicles regeneration and a better restitution of hypodermis. In conclusion, cold atmospheric plasma significantly improves healing when applied on skin burns
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Ait-Hamou, Nafissa. "Développement d’un modèle d’étude du vieillissement tissulaire basé sur l’utilisation de cellules souches à pluripotence induite par reprogrammation cellulaire." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT032/document.
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En dehors du cadre pathologique, la notion de temps est la base essentielle dans le processus de vieillissement de l’organisme et des systèmes associés. Ces derniers vont progressivement présenter un déclin de leur(s) fonction(s) où de nombreux mécanismes complexes vont intervenir à différents niveaux. Parmi les premiers constats proposés, le vieillissement est la conséquence d’un processus inéluctable, d’une succession d’agressions au niveau cellulaires qui pourraient être réparées voire évitées, ouvrant ainsi la voie à de futures études qui permettront à terme de proposer une explication détaillée, complète et claire de ce processus. Pour exemple, les travaux que nous avons menés tentent d’apporter un élément de réponse afin d’établir un lien entre sénescence et vieillissement, avec pour base de générer par reprogrammation cellulaire des cellules hiPSCs à partir de cellules issues de biopsies de patients jeunes et âgées, sénescentes ou prolifératives. Outre la caractérisation de leur état pluripotent comparable à celui des cellules souches embryonnaires, nous avons également mis en évidence après une différenciation spécifique en fibroblastes, que les caractéristiques cellulaires de ces fibroblastes présentaient un effacement des marques du vieillissement, signe d’une plasticité cellulaire possible au cours du vieillissement. A présent, étendre une telle étude au modèle tissulaire cutané par la mise en place de protocoles de différenciation dans le lignage épidermique permettra à l’avenir de mieux comprendre pour mieux appréhender les pathologiques associées au vieillissement, et ainsi pouvoir offrir aux patients une médecine appropriée et concrète<br>Beside the pathological context, time is the essential basis in the aging process of the body and associated systems. These will gradually introduce a decline in function(s) where many complex mechanisms will take part at different levels. Among proposed findings, aging is the result of an inevitable process, a succession of cellular stress that could be prevented or repaired, opening the way for future studies that will eventually offer an explanation detailed, clear and complete which occur. For example, our work provide a response element to establish a link between senescence and aging, based on the generation of hiPSCs by cellular reprogramming of cells from biopsies of young, older, senescent and proliferating cells patients. Further characterization of their pluripotent state comparable to that of human embryonic stem cells, we have also showed by a specific differentiation into fibroblasts, that cellular characteristics of those fibroblasts had erased aging features. Next step, is to extend such study in cutaneous tissue model by the introduction of differentiation protocols in the epidermal lineage which will able us to better understand aging-associated diseases, and thus bring the ability to propose an appropriate and cocnrete medicine to aged patients
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Tian, Lu. "Isolement et caractérisation de cellules souches cancéreuses dans un modèle murin de tumorigénèse mammaire." Thesis, Lille 2, 2018. http://www.theses.fr/2018LIL2S001/document.
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Le cancer du sein est le cancer est le plus fréquent chez la femme. Les patientes traitées par chirurgie, radiothérapie et/ou chimiothérapie peuvent souffrir de rechute et de métastases à plus ou moins long terme. Il est à présent admis qu’une sous-population de cellules particulières dénommées cellules souches cancéreuses (CSC) jouent un rôle important dans ces événements. Il est donc crucial d’isoler et de caractériser ces cellules pour comprendre leurs propriétés particulières d’autorenouvellement et de résistance aux traitements, ce qui permettra de les cibler pour obtenir des traitements plus efficaces. C’est dans ce contexte que s’inscrit ma thèse. Au laboratoire, j’ai mis en place un modèle de souris bi-transgéniques (bi-Tg) en croisant les souris C3(1)-Tag qui est un modèle de tumorigenèse mammaire (et prostatique) bien établi, avec les souris Tg s-SHIP-GFP qui ont déjà permis l’isolement de CS normales mammaires (et prostatiques). Dans ces souris, le promoteur de s-SHIP contrôle l’expression de la protéine fluorescente GFP ce qui permet de marquer et d’isoler les cellules. Dans les tumeurs mammaires développées par ces souris biTg, j’ai isolé une population rare de cellules s-SHIP/GFP+ possédant des propriétés de CSC, surtout une capacité à former des sphères en culture non adhérente et à générer des tumeurs par transplantation en série très supérieure à celle des autres cellules de la tumeur. Une analyse transcriptomique globale qui compare les gènes dérégulés dans les cellules GFP+ et GFP- a mise en évidence le rôle d’un composant de la voie Notch dans le maintien de la pluripotence.Nous avons également dérivé plusieurs lignées cellulaires dénommées MAM (pour mammary) à partir des tumeurs mammaires. L’une d’entre, MAM326 est une lignée de cellules épithéliales cancéreuses avec environ 10 % de cellules GFP+ et j’ai démontré que les cellules GFP+ sont plus résistantes à différentes drogues anti-cancéreuses ainsi qu’à l’irradiation. Une analyse transcriptomique a été réalisée pour déterminer la signature moléculaire de cette résistance. Cette analyse a mis en évidence une vingtaine de gènes significativement surexprimés dans les cellules GFP+, et dont la nature et/ou la fonction est pertinente dans le contexte d’une résistance aux traitements antitumoraux. L'un de ces gènes est la synucléine-gamma dont le rôle dans la radiorésistance du cancer du sein a été suggéré mais non démontré expérimentalement. Par la surexpression ectopique et l’inhibition par siRNA, nous avons démontré que la synucléine gamma peut induire la radiorésistance dans plusieurs lignées cellulaires de cancer du sein. En conclusion, ces résultats démontrent que l’expression de s-SHIP est un marqueur de CSC mammaires chez la souris et son intérêt dans l’étude du cancer du sein<br>Breast cancer is the most common cancer in women worldwide. The isolation and characterization of breast cancer stem cells (CSC) are crucial for understanding cancer biology and revealing potential therapeutic targets. One of the major issues in the study of CSC is the lack of reliable markers. A transgenic mouse model (Tg 11.5kb–GFP) was generated using the 11.5kb s-SHIP (stem-SH2-containing 5’-Inositol Phosphatase) promoter that specifically expressed enhanced green fluorescent protein (GFP) in embryonic and various tissue stem cells. In the mammary gland, previous experiments showed that GFP labels puberty cap cells and pregnancy basal alveolar bud cells, and it has been demonstrated that these mammary GFP+ cells are activated tissue stem cells. In order to determine if s-SHIP promoter expression could also mark mammary cancer stem cells, we generated a bi-transgenic mouse model by crossing Tg 11.5kb-GFP mice with Tg C3(1)/Tag mice. Tg C3(1)/Tag mice express SV40 T antigen under the regulatory control of the rat prostatic steroid binding protein C3(1) gene. In female mice, the transgene is expressed primarily in the mammary gland. Mice develop mammary hyperplasia by 3 months of age with subsequent development of mammary adenocarcinoma by 6 months of age.Here we show the presence of a rare population of GFP+ cells, which are also CD24+/CD49f+/CD29+ in mammary tumors of female bi-transgenic mice. As compared to GFP- cells, GFP+ cells exhibit both a higher tumor sphere-forming potential, and a higher tumorigenicity when transplanted into SCID and FVB recipient mice. Moreover, upon subsequent transplantation, the GFP+ cells generated heterogeneous tumors that displayed properties similar to the primary tumor. Transcriptomic analysis of these GFP+ vs GFP- cells revealed several differentially expressed genes including one protein implicated in the Notch pathway. In addition, from the murine mammary tumor, I have derived a cell line containing a s-SHIP/GFP+ subpopulation that shows resistance to chemotherapy and radiation. I have further studied this subpopulation and found that synuclein gamma could confer radiation resistance to breast cancer cells. Altogether, these results demonstrate that s-SHIP promoter expression is a marker of mammary CSC that enables their identification and isolation via a single consistent parameter
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Moreno, Oswaldo. "Design of the step-feed activated sludge process." Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=64054.
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Nicaise, Charles. "Etude du modèle de rat pour la sclérose latérale amyotrophique: caractérisation de la barrière hémato-encéphalique et applications thérapeutiques." Doctoral thesis, Universite Libre de Bruxelles, 2010. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210014.
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The selective degeneration of motoneurons in the spinal cord, the brainstem and the brain cortex is the core pathology of amyotrophic lateral sclerosis (ALS), but evidences suggest that the neighbouring non-neuronal cells are also involved in the disease progression. Beside Riluzole, only drug approved to treat this fatal neurodegenerative disease, new pharmaceutical agents or novel strategies including stem cell therapy are currently under development and evaluated preclinically in front line on mutant SOD1 rodents mimicking all hallmarks of the human disease. <p>Current intravenously delivered drugs tested in ALS therapy assume an intact blood-brain barrier and suppose the passage across the endothelium to hit their targets in the CNS parenchyma. If BBB impairment occurs in ALS, it may lead to revision of planned pharmaceutical treatment. In the first part of the work, we have validated the mutant SOD1 rat model of ALS and we characterized properties and integrity of its BBB. We observed a significant BBB disruption at symptomatic phase of ALS, evidenced by blood protein leakage, IgG accumulation and microhemorrhage. To look for the mechanism of BBB opening, we demonstrated that the expression of key genes involved in the BBB integrity was decreased. At the ultrastructure, the morphology of endothelial cells and vascular astrocyte end-feet was altered. Our results suggest that BBB disruption is a late event in ALS disease course and appears like a consequence of the local degenerative process or neuroinflammation rather than a cause. Since a lot of extracellular oedema and swollen astrocyte end-feet were found in mutant SOD1 rats, we also looked at the expression and localization of aquaporin-4, a key protein involved in CNS water movement. We found that its expression was highly increased in the symptomatic phase of ALS course and we hypothesize that this overexpression might be related to the resolution of oedema after BBB opening. <p>In the second part of the work, we considered an original, easy, non-invasive and safe therapeutical approach of stem cell delivery in ALS rats. Since ALS affects the motoneurons throughout the CNS, we decided to use the bloodstream to deliver neural stem cells. We studied cell homing, survival, proliferation, integration and differentiation. Interestingly, the highest efficiency of cell delivery to the CNS was found in symptomatic ALS and the lowest in healthy animals. Neural stem cells injected into ALS animals preferentially colonized the motor cortex, hippocampus and spinal cord. We detected their successful differentiation into neural lineages by the appearance of MAP2-, GFAP-positive cells and the decrease of nestin expression.<p>One of the realistic near-term clinical goals for ALS is the transplantation of stem cells that counteract the loss of motoneurons by secreting neuroprotective factors. Accordingly, we evaluated in vitro the expression of neurotrophic factors released by stem cells after stimulation with tissue extracts from ALS rats. The aim of this paradigm was to determine whether the ALS environment triggers neuroprotective factors release from stem cells. Mesenchymal stem cells and neural stem cells were able to express a wider range of growth factors than fibroblasts. According to the stem cell population stimulated, we obtained differential expression pattern, raising the choice of cell population for appropriate clinical applications in ALS.<p><br>Doctorat en Sciences biomédicales et pharmaceutiques<br>info:eu-repo/semantics/nonPublished