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BURBA, ILARIA. "Analysis of differentiation, plasticity and biological activity of human endothelian progenitor cells (HEPC): insights from epigenetic assessment and clinical applications." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2010. http://hdl.handle.net/10281/20193.
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Despite advances in the management of CVDs, they continue to be a major medical problem in western countries. Current pharmacologic and interventional strategies fail to regenerate dead myocardium and are often insufficient to avoid ventricular remodelling. In this context cell therapy is emerging, and in particular stem cell therapy, due to the great potential of these cells. In this framework we attempted to provide a contribution in three main issues relative to EPC therapy:
1) We established standard operating procedures (SOPs) to purify human CB CD133+ cells using CliniMACS and applied these procedures to obtain BM-derived CD133 cells for an ongoing clinical trial in patients with chronic cardiac ischemia.
2) We assessed the effect of VPA, a chromatin remodelling agent, to improve human CD34+ cells repair potential in a context of acute myocardial ischemia. Our data showed that VPA-treated cells have an improved myocardial protection ability through epigenetic regulated enhancement of stem cell self renewal capacity.
3) We studied the biological properties of mobilized EPCs in a clinical trial that was designed to evaluate the effect of G-CSF as a non-invasive cell delivery strategy in AMI patients. Our trial suggests that in a specific subgroup of patients, early administration (<12 hours) of high-dose G-CSF may attenuate 6-months unfavourable remodelling. This occurred despite the biological function of the mobilized progenitors was depressed likely due to G-CSF effects on EPC clonogenic activity.
2
Kelur, Ashok. "Model checking of multicore software using CBMC." Thesis, Uppsala universitet, Institutionen för informationsteknologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-182169.
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Computers have been key subsystems in various complex systems. As computers are adapted into various fields, hardware and software are increasing in size and complexity. It is evident that parallel computing is the way to solve large scale complex information technology problems. Engineers designing hardware and software are required to verify the system for correctness. As system's size and complexity increases, it is difficult to perform manual system verification. Model checking converts a hardware or software solution into temporal logic and uses solvers to assert on properties of solution. A Bounded Model Checker can verify properties of program/logic within bounded limits. CBMC is a Bounded Model Checker for ANSI-C and C++ programs. Thesis work is done considering an Ericsson's multicore platform as case study, which uses DSP-C as programming language. DSP-C is a set of language extensions on ISO C programming language. These extensions allow programmers to describe features of Digital Signal Processor (DSP). The work includes extending CBMC to support DSP-C, identifying Bounded Model Checking (BMC) techniques to cope-up with concurrency of Ericsson's multicore Digital Signal Processor (DSP) platform and implementing new features in CBMC to detect issues with Ericsson's parallel software.
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Joshi, Kaushal V. "Novel Neuroprotectants for Sarin plus CBDP induced convulsions." Wright State University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=wright1253321185.
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Mora, Carlos A. "Comparison of computation methods for CBM production performance." [College Station, Tex. : Texas A&M University, 2007. http://hdl.handle.net/1969.1/ETD-TAMU-1958.
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Corral, Rego Lía. "Validación del Cuestionario de Sesgos Cognitivos para la Psicosis (CBQp): Relación con sintomatología, insight y neurocognición." Doctoral thesis, Universitat Rovira i Virgili, 2019. http://hdl.handle.net/10803/670511.
Texte intégralRésumé :
Introducció: Els biaixos cognitius són clau en la formació i manteniment dels deliris en la psicosi. El Cognitive Biases Questionnaire for Psychosis (CBQp) avalua cinc tipus de biaixos cognitius en la psicosi. L'objectiu d'aquest treball es validar la versió espanyola del CBQp, i estudiar la relació d'aquests biaixos cognitius amb la simptomatologia psicòtica, l’insight i la neurocognició. Material i mètode: La versió espanyola autoritzada del CBQp va ser obtinguda segons el procés de traducir-retrotraducció. La mostra va estar composta per 171 subjectes amb diagnòstics de psicosis. Una anàlisi factorial confirmatòria (AFC) va testar tres models alternatius del constructe. Es van dur a terme comparacions entre pacients amb psicosis i un grup control (N = 30) en relació a les subescales del CBQp. L'associació entre els biaixos del CBQp, les escales d’insight clínic (SUMD) i cognitiu (BCIS), les avaluacions de la simptomatologia psicòtica (PANSS i PDI) i la bateria neurocognitiva MATRICS va ser estudiada mitjançant correlació, diferència de mitjanes i regressions lineals. Resultats: En l’AFC, el CFI va mostrar valors entre 0.94 i 0.95 per als models de 1, 2 i 5 factors, amb valors de RMSEA de 0.031 i 0.029. La fiabilitat del CBQp va ser de 0.87. Els subjectes amb psicosis van puntuar significativament més alt en tots els biaixos cognitius, a excepció de Catastrofisme i Salt a conclusions, en comparació amb el grup control. Es van obtenir associacions entre els biaixos cognitius i les escales d'auto-certesa i insight cognitiu de la BCIS, les escales de malestar, preocupació, convicció i total del PDI, així com amb la simptomatologia positiva avaluada mitjançant la PANSS. El CBQp es va relacionar amb el rendiment cognitiu general avaluat mitjançant la MATRICS, més concretament, amb Velocitat de processament, Solució de problemes i Cognició social. Conclusions: La versió espanyola del CBQp ha mostrat una adequada fiabilitat i validesa. Un model d'1 factor podria ser més adequat per a explicar el constructe de l'escala, suggerint que el CBQp avalua un biaix de pensament general. Els biaixos avaluats pel CBQp implicarian major presència de deliris, malestar, convicció i preocupació respecte a aquests, major simptomatologia positiva, així com un pitjor insight cognitiu i un pitjor rendiment neurocognitiu general.<br>Introducción: Los sesgos cognitivos son clave en la formación y mantenimiento de los delirios en la psicosis. El Cognitive Biases Questionnaire for Psychosis (CBQp) es un cuestionario que evalúa cinco tipos de sesgos cognitivos en la psicosis. El objetivo de este trabajo es validar la versión española del CBQp, y estudiar la relación de dichos sesgos con la sintomatología psicótica, el insight y la neurocognición. Material y método: La versión española autorizada del CBQp fue obtenida mediante traducción-retrotraducción. La muestra estuvo compuesta por 171 sujetos con diagnósticos de psicosis. Un análisis factorial confirmatorio (AFC) testó tres modelos alternativos del constructo. Se llevaron a cabo comparaciones entre pacientes con psicosis y un grupo control (N = 30) en relación a las subescalas del CBQp. La asociación entre los sesgos del CBQp, el insight clínico (SUMD) y cognitivo (BCIS), la sintomatología psicótica (PANSS y PDI) y la batería neurocognitiva MATRICS fue estudiada mediante correlación, diferencia de medias y regresiones lineales. Resultados: En el AFC, el CFI mostró valores entre 0.94 y 0.95 para los modelos de 1, 2 y 5 factores, con valores de RMSEA de 0.031 y 0.029. La fiabilidad del CBQp fue de 0.87. Los sujetos con psicosis puntuaron significativamente más alto en todos los sesgos cognitivos, a excepción de Catastrofismo y Salto a conclusiones, en comparación con el grupo control. Se obtuvieron asociaciones entre los sesgos cognitivos y las escalas de auto-certeza e insight cognitivo de la BCIS, las escalas de malestar, preocupación, convicción y total del PDI, así como con la sintomatología positiva evaluada mediante la PANSS. El CBQp se relacionó con el rendimiento cognitivo general evaluado mediante la MATRICS, y más concretamente con Velocidad de procesamiento, Solución de problemas y Cognición social. Conclusiones: La versión española del CBQp ha mostrado una adecuada fiabilidad y validez. Un modelo de 1 factor podría ser más adecuado para explicar el constructo de la escala, sugiriendo que el CBQp evalúa un sesgo de pensamiento general. Los sesgos evaluados por el CBQp implicarían mayor presencia de delirios, malestar, convicción y preocupación respecto a éstos, mayor sintomatología positiva, así como un peor insight cognitivo y peor rendimiento neurocognitivo general.<br>Introduction: Cognitive biases are key factors in the development and maintenance of delusions in psychosis. The Cognitive Biases Questionnaire for Psychosis (CBQp) evaluates five types of cognitive biases that are relevant in psychosis. The aim of this study is to validate the Spanish version of the CBQp, and to study the relationship between these biases and psychotic symptoms, insight and neurocognition. Materials and methods: The Spanish authorized version of the CBQp was obtained by a translation and back-translation procedure. A sample of 171 patients with different diagnoses of psychosis was included. A confirmatory factorial analysis (CFA) tested three different models of the construct. Comparisons of CBQp scales were analysed between patients with psychosis and a control group (N = 30). Associations between the CBQp biases, clinical and cognitive insight (SUMD and BCIS), symptoms (PANSS and PDI) and neurocognition (MATRICS), were studied by correlation and means differences and linear regressions. Results: CFA showed CFI values of 0.94 and 0.95 for the models with 1, 2 and 5 factors, with RMSEA values of 0.031 and 0.029. The reliability of the CBQp was 0.87. When compared with the group of healthy subjects, patients with psychosis scored significantly higher in all cognitive biases, except in Catastrophising (Cat) and Jumping to conclusions (JTC). Associations between cognitive biases and the self-certainty and the total cognitive insight scale of the BCIS were found. In the same way, associations between conviction, distress, preoccupation and total scales of the PDI and cognitive biases were found. The CBQp was also related with positive symptoms evaluated with the PANSS, and with general cognitive performance, specifically with Processing speed, Problem solving and Social cognition. Conclusions: The Spanish version of the CBQp shows high reliability and adequate internal consistency. A one-factor model might be more appropriate for explaining the construct of the scale, suggesting that the CBQp evaluates a general thinking bias rather than different cognitive errors. Cognitive biases involved a greater frequency of delusions, distress, conviction, and preoccupation, and more positive symptoms, as well as worse cognitive insight and worse global neurocognitive performance.
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Claeson, Holmgren Mathilda, and Tilda Göransson. "Cirkulär ekonomi på mikronivå : En fallstudie om hur ett mikroföretag imodebranchen kan agera för att sluta kretsloppet." Thesis, Högskolan i Borås, Akademin för textil, teknik och ekonomi, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:hb:diva-14768.
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I Sverige är 93% av alla existerande företag i mikrostorlek. Trots det finns det väldigt lite forskning på hur de ska gå tillväga för att implementera en cirkulär affärsmodell. Syftet med studien är att undersöka vilka förutsättningarna ett modeföretag i mikrostorlek kan ha för att implementera cirkulära affärsmodeller. Dagens ekonomiska system bygger på linjära affärsmodeller. Det betyder att människor köper, använder och sedan slänger produkter som fortfarande har ett potentiellt ekonomiskt värde. Cirkulära affärsmodeller utgör ett alternativ till dagens ekonomiska system. Det bygger på att produkter efter brukningsperiod återanvänds eller återvinns för att bibehålla det ekonomiska värdet och sparar på resurser som är skadliga för miljö och människor. I teorin presenteras tidigare forskning som gjorts kring cirkulär ekonomi, innovativa affärsmodeller och ramverk samt mikroföretagets roll i en cirkulär ekonomi. Ostrukturerade intervjuer med verksamma inom återvinning, återanvändning och ekodesign samt semistrukturerade intervjuer med produktionschef och produktutvecklare på fallföretaget har utförts. Detta har givit en bred och djup kunskap kring vilka förutsättningar som finns och vilka tillvägagångssätt mikroföretag kan tillämpa för att fortsätta resan mot en mer cirkulär affärsmodell. Resultatet av studien visar att fallföretaget idag på många sätt agerar cirkulärt, men att kompletterande aktiviteter och tekniker gällande återtagningssystem och externa införningfaktorer saknas.<br>In Sweden 93% of the existing companies are microbusinesses. Despite this, there is a lack of research on how they can implement circular business models. The purpose of this study is to investigate what prerequisites a micro business within the fashion industry can have to implement a circular business model. Today’s economic system is supported by linear business models. This means that people buy, use and dispose of goods that may have a potential continuous economic value. Circular business models offer an alternative to the current economic system. They are based on reuse and recycling to upkeep economic value and cut down on byproducts that are harmful to the environment and people. Earlier research regarding circular economy, innovative business models and framework are presented in this study. Unstructured interviews with people working actively within fields such as reuse, recycle and eco-design have been held, as well as semi-structured interviews with the production manager and product developer at the case business of this study. The interviews have provided a wide knowledge around what prerequisites and course of action a micro business within the fashion industry can apply, to continue working against a more circular business model. The result of the study show that the micro business can operate in a circular manner, but require complementing activities and technologies regarding take back systems and external adoption factors.
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Rosén, Joel, and Magnus Olsson. "Tillståndsbaserat underhåll till sjöss : Vad föranleder den begränsade användningen av tillståndsbaserat underhåll (CBM) till sjöss?" Thesis, Linnéuniversitetet, Sjöfartshögskolan (SJÖ), 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-25461.
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Today, maintenance is a big part of the daily life on board ships. It is also one of the bigger expenses a shipping company has and without any loss of quality tries to run as economically advantageous as possible. In the hunt for economical savings the shore-based industry has subsequently applied the use of condition based maintenance, CBM, were a component is maintained according to its actual state. This leads to a reduction of maintenance costs since no parts are unnecessarily replaced. However, within the maritime sector a periodical maintenance is still the most commonly used maintenance system.The purpose of this paper is to chart the factors that are the reason for the low implementation of CBM on board the Swedish merchant fleet's ships. The investigation was carried out according to the qualitative method. Three shipping companies were interviewed, all carrying slow speed, two-stroke crosshead engines.The result from the interviews were evaluated and analyzed and the contributing factors of the low implementation of CBM on board has been identified.The result of this paper shows that the unique conditions on board ships reduces the advantages, normally received in the shore-based industry by using CBM.<br>Underhåll är en stor del av vardagen till sjöss. Det är även en av de stora utgiftsposterna för ett rederi och utan att tumma på kvaliteten vill man bedriva detta så ekonomiskt fördelaktigt som möjligt. I jakten på besparingar har den landbaserade industrin mer och mer övergått till ett tillståndsbaserat underhåll, s.k. condition based maintenance - CBM. Då bedrivs underhållet utifrån en komponents faktiska tillstånd. Detta leder till minskade underhållskostnader eftersom komponenter inte utbytes i onödan. Inom sjöfarten är dock det periodiskt baserade underhållet fortfarande dominerande.Syftet med denna undersökning är att kartlägga de faktorer som ligger till grund för den ringa utsträckningen av tillståndsbaserat underhåll, CBM på den Svenska handelsflottans fartyg. Undersökningen utfördes enligt den kvalitativa metoden. Tre rederier intervjuades, samtliga med fartyg i oceantrafik där framdrivningsmaskineriet består av långsamtgående, 2-takts tvärstycksmaskiner. Intervjuerna utvärderades och analyserades varpå de bidragande faktorerna till den begränsade användningen identifierades.Resultatet av undersökningen visar på att de unika förutsättningar som råder på ett fartyg minskar fördelarna, som man normalt erhåller med CBM inom den landbaserade industrin.
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Delvecchio, Manuela. "Mécanisme de régulation de l'acétyltransférase p300/CBP." Phd thesis, Université de Grenoble, 2011. http://tel.archives-ouvertes.fr/tel-00631344.
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Le p300/CBP acétyltransférase est un co-activateur transcriptionnel très important qui est impliqué dans la régulation d'un grand nombre de processus biologiques, comme la transcription d'ADN, le développement et l'immunité innée. Jusqu'à présent, le rôle de p300/CBP dans la régulation de l'expression des gènes a été largement étudiée, mais les mécanismes qui régulent son activité enzymatique sont encore peu connus. Des études ont montré que le dysfonctionnement de p300/CBP est associé à plusieurs formes de cancer et de maladies neurodégénératives. Dés lors, chaque progrès concernant les mécanismes de régulation de p300/CBP est devenu primordial pour le développement de nouvelles thérapies. Le 'noyau' de p300/CBP contient deux domaines pour la reconnaissance des modifications post-traductionnelles (MPTs), un bromodomaine et un PHD finger (le module BP), adjacent à un domaine HAT (ou domaine histone acétyltransférase). Plusieurs enzymes, modifiant la chromatine, contiennent des domaines de reconnaissance des MPTs. Fréquemment des groupements particuliers de ces domaines sont très conservés et liés, au sein de la même protéine ou du même complexe protéique, suggérant qu'ils réalisent des fonctions coordonnées. Ces domaines adjacents peuvent agir en concertation dans la reconnaissance simultanée de différents MPTs ou peuvent exercer des fonctions différentes de celles qui sont effectuées par ces deux domaines particuliers, tels que les fonctions de régulation enzymatique. Plusieurs études suggèrent que les cycles acétylation/désacétylation dans la boucle d'auto-inhibition, à l'intérieur du domaine HAT, jouent un rôle important dans la régulation de l'activité enzymatique de p300/CBP. La proximité du module BP et du domaine HAT suggère que la spécificité de liaison, appartenant au module BP, peut être intrinsèquement liée à la régulation de l'activité du domaine HAT. L'objectif de ma thèse est de déterminer le rôle du module BP dans la régulation de l'activité du domaine HAT. Je propose que le module BP soit impliqué dans la régulation de p300/CBP de deux façons. La première consiste à établir un lien avec le domaine HAT qui stabilise la conformation auto-inhibée de l'enzyme. La deuxième exige que le module BP joue un rôle dans le choix des substrats de p300/CBP. J'ai été en mesure de montrer que BP peut se lier au domaine HAT et à la chromatine modifiée et qu'il peut reconnaître les modifications effectuées par p300/CBP lui-même. Les données obtenues indiquent que le module BP peut être impliqué dans la régulation de l'activité de p300/CBP et dans son ciblage à la chromatine.
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Klein, Fabrice. "Etudes structurales des interactions CBP-récepteurs nucléaires." Université Louis Pasteur (Strasbourg) (1971-2008), 2003. http://www.theses.fr/2003STR13241.
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Les récepteurs nucléaires (NRs) forment une famille de facteurs de transcription dont l'activité est contrôlée par la fixation de ligands. La liaison à un ligand agoniste permet le recrutement de coactivateurs transcriptionnels, comme les p300/CREB‑BindingProtein (p300/CBP) et les p160/Steroid‑Receptor‑Coactivator (p160/SRC). Ces protéines possèdent plusieurs motifs LxxLL (L = Leucine ; X = n'importe quel acide aminé), responsables de l'interaction aux NRs. Nous avons caractérisé le domaine de CBP interagissant aux LBDs et co‑cristallisé un complexe de l'extrémité Nterminale de CBP (Nter‑CBP) et du LBD du Peroxisome Proliferator‑Activated Receptor gamma (lbd‑PPARg). La mauvaise qualité des cristaux de Nter‑CBP/lbd‑PPARg n'a pas permis de déterminer la structure du complexe. L'étude de Nter‑CBP par résonance magnétique nucléaire (RMN) montre que ce fragment isolé est peu structuré. Son interaction aux LBDs de trois NRs - PPARg, Retinoid X Receptor alpha (RXRa) et Estrogen Related Receptor gamma (ERRg) - a été étudiée par RMN. En raison d'une forte atténuation du signal des résidus impliqués dans l'interaction aux LBDs, la structure du fragment de mCBP en complexe à un LBD n'a pu être résolue, mais la zone d'interaction a été cartographiée : les résidus de CBP impliqués dans l'interaction représentent deux fragments discontinus, délimités par les acides aminés (31 à 38) et (61 à 80), la zone (61 à 80) contenant un LxxLL. L'interaction de fragments de CBP ou de SRCs aux LBDs de PPARg et RXRa a été étudiée de façon comparative par résonance plasmonique de surface (SPR) et par électrophorèse en conditions natives (N‑PAGE). Les résultats montrent l'existence d'interactions préférentielles entre RXRa et les SRCs, et entre PPARg et CBP. Les conclusions de nos travaux suggèrent que CBP puisse être recruté directement par l'hétérodimère PPARg/RXRa, ce qui pourrait jouer un rôle dans la permissivité de cet hétérodimère<br>Nuclear receptors form a large family of transcription factors, whose activities are often controled by the fixation of small ligands. Binding to an agonist ligand allows the recruitment of transcriptional coactivators, like the p300/CREB‑BindingProtein (p300/CBP) or the p160/Steroid‑Receptor‑Coactivator (p160/SRC). Those coactivators possess several LxxLL motifs (L = Leucine ; X = any aminoacid), mainly responsible for the interaction with NRs. We characterized the aminoterminal (Nter) domain of CBP responsible for the interaction with NR Ligand Binding Domains (LBDs) and cocrystallized it together with the Peroxisome Proliferator‑Activated Receptor gamma LBD (lbd‑PPARg). The poor diffraction properties of the crystals did not allow us to solve the structure of this (Nter-CBP/lbd-PPARg) complex. Nuclear Magnetic Resonance (NMR) experiments demonstrate that Nter-CBP is poorly structured on its own. Its interaction with the LBDs of 3 different NRs - PPARg, Retinoid X Receptor alpha (RXRa) and Estrogen Related Receptor gamma (ERRg) – was studied by NMR. The structure of CBP in complex with any of these LBDs could not be solved, because of a strong signal attenuation of the residues implied in the interaction. Nevertheless, the aminoacids of CBP that interact with those 3 NRs could be mapped by this technique : they correspond to 2 discontinuous zones, delimited by the aminoacids (31 to 38) and (61 to 80), the latter containing the LxxLL motif. We also studied the interaction between CBP or SRCs fragments with lbd-PPARg and lbd-RXRa, in a comparative manner, by surface plasmon resonance and native electrophoresis. Our results show that CBP interacts preferentially with PPARg, whereas SRCs show a better affinity towards RXRa. We suggest that CBP might be directly recruited by PPARg/RXRa, which could play a role in the permissivity of this heterodimer
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Xue, Lili. "Numerical well testing of coalbed methane (CBM) reservoir." Thesis, Heriot-Watt University, 2012. http://hdl.handle.net/10399/2655.
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Numerical experiments and field applications proved that there exist percolation non-linearity and fluid multi-variability in low permeability CBM reservoirs. The percolation of fluid needs to overcome threshold pressure gradient, and klinkenberg effects will restrict the gas permeability. In addition, production enhancement and ultimate recovery improvement have given multi-branch horizontal wells the advantage over the vertical wells in many CBM marginal reservoirs. Moreover, Enhance Coalbed Methane (ECBM) recovery through injection of gases has been publicly proven, and can increase gas resources, however, its application in some actual field failed to address the good history matching. In this thesis, the numerical simulation and well testing problems encountered in the reservoir exploration and production are investigated. Firstly, a new dual porosity, single permeability model was developed, which reflects the high velocity non-Darcy flow that considers the threshold pressure, gas slippage and matrix shrinkage effects. It is solved using the fully implicit numerical method, a computer programme called COAFOR has been developed for this purpose. Secondly, an advanced non-analytical coupled CBM model is developed for predicting the flux in the CBM reservoir and single or multi-branch wellbore simultaneously. Thirdly, a coupled compositional triple porosity horizontal wellbore model for CBM reservoir considering the gas slippage and threshold pressure gradient effects is proposed with a newly developed permeability model. The simulator, called TRIPLE-COAL, was developed for this model. Finally, the new models developed in this thesis are validated by applying them into Heshun block, Yanchun South block and Zhijin block respectively. The history matching results checked the reasonability and accuracy of the models built in this thesis. The coupled multi-branch horizontal triple porosity model shows better matching result in Zhijin block than the coupled multi-branch horizontal dual porosity model in Yanchuan South block.
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Xu, Lan. "Integration of signal-induced transcriptional activation by CBP /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1998. http://wwwlib.umi.com/cr/ucsd/fullcit?p9911841.
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Kang, Hyun-Seo. "Structural foundation for transcriptional regulation by Ets1 and CBP." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/28866.
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Using cell-based assays and biophysical measurements, we have defined the mechanism by which Ras/MAP kinase signaling enhances Ets1 regulated gene expression via phosphorylation-enhanced recruitment of the transcriptional co-activator CBP. As confirmed by ³¹P/¹³C-NMR experiments, the MAP kinase ERK2 phosphorylates Thr38 and Ser41 within the unstructured region of Ets1, immediately N- terminal to the PNT domain. The NMR-derived structure of residues 29-138 of Ets1 revealed that the PNT domain is composed of a core four-helix bundle (H2-H5), also known as the SAM fold, appended with two additional helices (H0-H1). Most importantly, helix H0 is only marginally stable as shown by various NMR methods, including chemical shift, amide hydrogen exchange, and ¹⁵N relaxation analyses.
Dual phosphorylation of Ets1 perturbs a "closed-open" conformational equilibrium of the PNT domain, displacing the dynamic helix H0 from the core bundle. These modifications increase the affinity of Ets1 for the TAZ1 (or CH1) domain of CBP by ~30 fold as measured with isothermal titration calorimetry (Kd ~ 60 to 2 μM). NMR-monitored titration experiments mapped the interaction surfaces of the TAZ1 domain and Ets1, the latter encompassing both the phosphoacceptors and PNT domain, also showing sensitivity to ionic strength. Charge complementarity of these surfaces indicates that electrostatic forces act in concert with the conformational equilibrium to mediate phosphorylation effects.
We conclude that the dynamic helical elements of Ets1, appended to a conserved structural core, constitute a "phospho-switch" to direct Ras/MAPK signaling to downstream changes in gene expression. This detailed structural and mechanistic information illustrates an evolutionary development within a gene family to increase the capacity for biological regulation.
We also discovered that the CBP TAZ1 domain associates intramolecularly with residues 28-82 in its N-terminal nuclear receptor interacting domain (NRID). NMR studies indicated that the NRID undergoes a coil-helix conformational transition upon binding the same interface on TAZ1 as recognized by many transcription factor partners. This led us to hypothesize that CBP is regulated by an auto-inhibitory mechanism. In support of this model, affinity of the hypoxia inducible factor HIF-1α for TAZ1 is reduced competitively by the presence of the NRID.
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Francis, Yitshak Itsik. "The role of CBP and p300 in Alzheimer's Disease." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1443955/.
Texte intégralRésumé :
Studies of the mechanisms underlying memory formation have defined central roles for CRE-dependent gene expression, which is mediated by the transcription factor CREB and the coactivator CBP. CBP creates a bridge between CREB and the basal transcriptional machinery and acetylates histones, which induces chromosomal changes and results in loss of chromosomal repression. This allows successful transcription of the underlying genes needed for synthesis of proteins underlying memory formation. CBP has been linked to neurodegenerative diseases and cerebral CBP levels were shown to reduce in mice lacking functional presenilins (PSs), a class of enzymes that has been associated with Alzheimer's Disease (AD). In this thesis it is shown that WT PS1 stimulates the transcriptional activating ability of CBP and its close homolog p300, whereas an Alzheimer's disease- associated N terminal mutant of PS1 did not produce this effect. Interestingly, PS1 C terminal mutants produced a reduction in CBP transcriptional activating ability, compared to control levels. Additionally, we showed that wild type PS1 increases the endogenous CBP level. Moreover, an increase in CBP endogenous levels was noted when the cells were transfected with the -M146L N-terminal mutant of PSI. However, these levels were still significantly lower when compared to cells transfected with wild type PSI. We were also able to show that knockdown of endogenous PSI leads to a decrease in endogenous CBP levels and a decrease in CBP activity. Hence, PSI can affect both the level and the activity of CBP. In addition, the activation of CBP by WT PSI involves the PI 3-kinase, p38 MAP kinase and p42/p44 MAP kinase pathways and targets primarily the C terminus of CBP. It is also shown that the effect of wild-type PSI is dependent on the histone acetyltransferase activity (HAT) of CBP. Moreover, it was demonstrated that WT PSI, but not its M146L mutant, could increase the promoter activity of c-fos, a CBP HAT dependent target gene. Additionally, we showed that application of the histone deacetylase inhibitor, TSA, rescued the long-term potentiation and long-term memory defects shown by APP/PS1 mutant mice. Moreover, it was shown that the acetylation level of histone H4 in APP/PS1 mice is lower than that of WT littermates and that TSA injection restores the acetylation of these histones. This is the first study to identify AD as a disease of epigenetic etiology and suggests that enhancing histone acetylation may have potential for the treatment of AD.
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Gusterson, Rosalind Jane. "The role of CBP and p300 in cardiac hypertrophy." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399576.
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Sajtar, Eric T. "Toolbox to evaluate treatment technologies for PRB CBM water." Laramie, Wyo. : University of Wyoming, 2008. http://proquest.umi.com/pqdweb?did=1594485851&sid=1&Fmt=2&clientId=18949&RQT=309&VName=PQD.
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Ramaswamy, Sunil. "Selection of best drilling, completion and stimulation method for coalbed methane reservoirs." Texas A&M University, 2007. http://hdl.handle.net/1969.1/85835.
Texte intégralRésumé :
Over the past three decades, coalbed methane (CBM) has moved from a mining
hazard and novel unconventional resource to an important fossil fuel that
accounts for approximately 10% of the U.S. natural gas production and reserves.
The expansion of this industry required development of different drilling,
completion and stimulation practices for CBM in specific North American basins,
owing to the complex combinations of geologic settings and reservoir parameters
encountered. These challenges led to many technology advances and to
development of CBM drilling, completion and stimulation technology for specific
geologic settings.
The objectives of this study were to (1) determine which geologic parameters
affect CBM drilling, completion and stimulation decisions, (2) identify to the
engineering best practices for specific geologic settings, and (3) present these findings in decision charts or advisory systems that could be applied by industry
professionals.
To determine best drilling, completion and stimulation practices for CBM
reservoirs, I reviewed literature and solicited opinions of industry experts through
responses to a questionnaire. I identified thirteen geologic parameters (and their
ranges of values) that are assessed when selecting CBM drilling, completion and
stimulating applications. These are coal thickness, number of seams, areal
extent, dip, depth, rank, gas content, formation pressure, permeability, water
saturation, and compressive strength, as well as the vertical distribution of coal
beds and distance from coal reservoirs to fracture barriers or aquifers. Next, I
identified the optimum CBM drilling, completion and stimulating practices for
specific combinations of these geologic parameters. The engineering best
practices identified in this project may be applied to new or existing fields, to
optimize gas reserves and project economics.
I identified the best engineering practices for the different CBM basins in N.A and
combined these results in the form of two decision charts that engineers may use
to select best drilling and completion practices, as well as the optimal stimulation
methods and fluids for specific geologic settings. The decision charts are
presented in a Visual Basic Application software program to facilitate their use by
engineers.
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Sudwell, Mark Ian. "Chronic back pain : a narrative analysis." Thesis, University of Exeter, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367457.
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Alvarez, David 1971. "The involvement of CBP/14-3-3 in DNA replication /." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82819.
Texte intégralRésumé :
Initiation of DNA replication is a cellular process whose regulation is not well understood yet. It certainly depends on cis-acting elements, or origins of DNA replication sequences, and trans-acting factors, or initiator proteins. Here, we have characterized the Cruciform Binding Protein (CBP) as an origin binding protein and its role in initiation of DNA replication.<br>CBP was previously shown to contain the β, ɣ, ε, and ζ isoforms of the 14-3-3 family, which is composed of seven mammalian isoforms (β, ɣ, ε, η, σ, τ, and ζ) that can form homo- and heterodimers, and plays a variety of roles in different cellular processes. In this thesis, I showed by Western blot analysis with anti-14-3-3σ antibody, which partially interfered with the CBP-cruciform DNA complex formation, that the isolated CBP-cruciform DNA complex contained also the σ isoform. The same antibody reduced the in vitro DNA replication efficiency of HeLa cell total extracts, in an assay that used p186, a plasmid bearing the 186-bp minimal origin of ors8, as template DNA. Similarly, I found that antibodies against 14-3-3 isoforms β, ɣ, ε, and ζ also interfered with the CBP-cruciform DNA complex formation, and reduced the in vitro p186 replication efficiency of HeLa cell total extracts. The five isoforms of 14-3-3 (β, ɣ, ε, σ, and ζ) were found to associate with the monkey cell (CV-1) origins of DNA replication ors8 and ors12 in a cell cycle-dependent manner, the association being higher at the G1/S phase. Furthermore, we found that 14-3-3 yeast homologues, Bmh1p and Bmh2p, were able to bind cruciform DNA in vitro, and to associate in vivo with the autonomous replication sequence 307 (ARS307) in a cell cycle-dependent manner, again the association being higher at G1/S. Finally, I showed that recombinant 14-3-3ζ, tagged with maltose-binding protein (r14-3-3ζ-MBP), could only bind cruciform DNA after pre-incubation with a CBP-enriched HeLa cell extract (FTH), in which it heterodimerized with endogenous 14-3-3 isoforms β and ε. Addition of r14-3-3ζ-MBP to HeLa cell total extracts increased the in vitro replication of p186, suggesting that increased CBP activity could lead to multiple rounds of initiation of DNA replication.
19
Songkumarn, Pattavipha. "Identification and Characterization of In-planta Expressed Secreted Effector Proteins from Magnaporthe oryzae." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1357158502.
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Feldmann, Gregory Michael. "Early numeracy: technical adequacy of select kindergarten and first grade screening measures." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/2869.
Texte intégralRésumé :
Because of a greater need to focus on early achievement in mathematics and increased global competition in this area, emphasis is increasingly being placed upon screening and monitoring of math development in early elementary to ensure progress for all students. Although protocols for early literacy assessment exist, research of psychometrically sound and instructionally useful early numeracy assessment methods is still developing. Thus, the current study was undertaken to further develop and examine early numeracy measures. In a two-year investigation, 72 kindergarten and 57 first-grade students completed a set of existing and newly developed early numeracy curriculum-based measurement (EN-CBM) tools. Reliability and validity of these measures were examined both within and across years. The nature of score change across the academic year was also analyzed. Findings were generally similar to those published in previous EN-CBM research. Alternate-form reliability estimates were largely adequate for screening purposes. Although concurrent and predictive validity estimates varied as a function of screening period and the outcome criterion, these estimates were generally moderate to strong. EN-CBM discriminant validity evidence was mixed for the kindergarten measures but more evident for first-grade tools. All measures demonstrated score change that was statistically significant over time with at least moderate to large effect sizes for most measures. Implications for EN-CBM use as screening tools are discussed. Study limitations are presented as are suggestions for future EN-CBM research.
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Sebastianelli, Massimo. "World Class Manufacturing : approccio ad un sistema di manutenzione predittiva (CBM)." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2016.
Trouver le texte intégralRésumé :
L’oggetto di analisi del presente lavoro di tesi è il modello di Operational Excellence noto come World Class Manufacturing in particolare l’approccio allo step 6 del pilastro Professional Maintenance, dove si richiede l’implementazione di un sistema di manutenzione PREDITTIVA, la cosiddetta CBM (Conditional Based Maintenance) .
Il modello a cui si fa riferimento fu teorizzato dal professore giapponese H. Yamashina verso la metà degli anni 2000 e giunse in Italia attorno al 2005, quando Fiat Group (oggi FCA) lo adottò come approccio standard alla gestione della produzione.
Questo tipo di analisi, orientata verso una prospettiva pratica più che teorica, deriva direttamente da un’esperienza sul campo che ho svolto all’interno di un’azienda che ha aderito al World Class Manufacturing (WCM).
Nel capitolo 1 verrà proposto un excursus delle metodologie alla base del WCM e del percorso storico che ha portato alla formulazione del modello.
Nel secondo capitolo verrà proposto un caso di applicazione del WCM all'interno di un Gruppo, nella fattispecie Ariston Thermo Group (ATG).
Dopo un’overview sul Gruppo e sulla storia della sua adesione al programma di miglioramento, la trattazione si focalizza sull'approccio di ATG al WCM.
Nel terzo capitolo verrà introdotta la Manutenzione Professionale secondo le principali politiche manutentive schematizzate dal WCM. Verranno presentate singolarmente per sottolineare i loro obiettivi seguiti dai vantaggi e svantaggi che si possono ottenere nell’implementare ogni singola politica.
Nel quarto capitolo verranno specificate sotto un aspetto prettamente pratico le varie attività svolte dalla PM così da evidenziare lo sviluppo e il miglioramento continuo che essa sta ottenendo dall’introduzione del WCM; principalmente la presentazione delle varie attività si riferiscono al passaggio allo step 6 della PM, dove verrà presentata approfonditamente elencando e analizzando tutte le attività svolte per approcciarsi alla CBM.
22
Gensterblum, Yves [Verfasser]. "CBM and CO2-ECBM related sorption processes in coal / Yves Gensterblum." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2013. http://d-nb.info/1047230712/34.
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Gao, Wenxue [Verfasser], and Reinhard [Akademischer Betreuer] Männer. "Active Buffer Development in CBM Experiment / Wenxue Gao ; Betreuer: Reinhard Männer." Heidelberg : Universitätsbibliothek Heidelberg, 2012. http://d-nb.info/1179784413/34.
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Soremekun, Mishael. "Readmission in psychosis and in CBTp : associations with patient education level and belief flexibility status." Thesis, Royal Holloway, University of London, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604562.
Texte intégralRésumé :
Background and objectives Previous studies have shown that Cognitive Behavioural Therapy for psychosis (CBTp) does not reduce readmission rates. This could be due to particular patient characteristics. This study sought to assess whether patients' education level and belief flexibility status were associated with readmission following CBTp treatment. The association between other psycho-social factors and readmission was also explored. Method Using the South London and Maudsely NHS Trust case register, 3025 adult patients with an F20-F29 ICD-1O diagnosis, discharged from inpatient care to the community during 2008-2009 were identified. They were categorised on the basis of their level of education, belief flexibility status and other psycho-social variables and followed-up until December 2011 , to ascertain their time to readmission. Results Cox proportional regression analyses showed that those with a G.C.S.E. level education were significantly less likely to readmit when compared with those with no qualifications. A trend for lower readmission was also observed in the A' level and above group. There was no evidence of an association between belief flexibility and readmission in patients who had CBTp treatment (N=469). A trend for a lower rate of readmission was observed for those with a G.C.S.E. level education in the CBTp sample. Other psycho-social factors were strongly associated with readmission for all patients. Conclusion These findings suggest that some psycho-social factors are important for readmission in psychosis, but not belief flexibility. Structural changes to mental health service provision in the UK are indicated to tackle this client group who experience high levels of social adversity. Modifications to CaTp provision to increase access to a full course ofCBTp are also needed. Future studies with larger CaTp samples that explore the relationship between belief flexibility and readmission and the impact of structural-level interventions could help further our understanding in this area.
25
Ramírez, Sandra. "Role du coactivateur cbp dans l activite du sre de c-fos." Paris 12, 1999. http://www.theses.fr/1999PA120092.
Texte intégralRésumé :
La proteine cbp, connue pour etre un coactivateur de plusieurs facteurs de transcription dependants du signal est un integrateur des differents voies de signalisation et elle est aussi impliquee dans la regulation de la transcription du proto-oncogene c-fos. Nous avons partie de la hypothese que cbp cooperer avec srf pour la l'activation transcriptionnelle en reponse au serum l'element sre. Dans une premiere etude faite dans la lignee cellulaire f9 nous avons montre que cbp stimule de facon dose dependante l'activite du gene rapporteur luciferase sous le controle de l'element sre du promoteur de c-fos. La partie amino-terminale de la proteine cbp est suffisante pour activer cette transcription. De plus nos resultats montrent que l'activation est independant du motif reconnu par les proteines ets, la boite ets dans sre. Par ailleurs, nous avons montre que la proteine cbp forme un complexe in vivo avec la proteine srf dans des cellules u20s. Tous ces resultats montrent que cbp joue un role de coactivateur de la transcription du facteur de transcription srf dans l'activation du proto-oncogene c-fos via le sre. Un de mecanismes par lesquels cbp peut cooperer dans l'activation de la transcription est en faisant le pont entre les facteurs de transcription et la machinerie basale de transcription. Il est connu que cbp interagit avec certaines facteurs generaux de la transcription, tels que tbp et tfiib. Un deuxieme mecanisme pourrait etre la modulation de la structure chromatinienne grace a l'activite hat intrinseque de cbp ou a une activite hat recrute par elle meme ou de facon independant de cbp. Nous avons montre que cbp est phosphorylee pendant la transition g1/s du cycle cellulaire et que pendant cette meme periode l'activite hat de cbp est maximale. Nous avons egalement demontre que cbp peut etre phosphorylee, dans sa region carboxyterminale, en dehors de son domaine a activite hat, par les mapks et particulierement par erk2. Avec l'aide du test hat mis au point par mr. Ait-si-ali dans notre laboratoire, nous avons trouve que cette phosphorylation stimule de facon significative l'activite hat de la proteine cbp. Ces donnees permettent de mieux comprendre le role important de la proteine cbp dans le controle de la transcription et son implication dans le bon deroulement de la proliferation et de la differentiation cellulaires.
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Menezes, Sean Christopher. "Examining the effect of CBP on the E2A-PBX1 and HOXB4 interaction." Thesis, Kingston, Ont. : [s.n.], 2008. http://hdl.handle.net/1974/1534.
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Kavoosi, Mojgan. "The CBM9 fusion tag : a new technology for inexpensive production and affinity purification of recombinant proteins." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31363.
Texte intégralRésumé :
Downstream processing of proteins and other biological products has long been dominated by packed-bed chromatography (Rankin 2003). Despite the generally high cost of the technique, chromatography remains widely used because it offers extraordinarily high resolution under conditions that do not denature or alter the chemistry of the product, an imperative for therapeutic proteins since purity and activity are strict requirements. However, the inability of patients and governments to meet the rising costs of healthcare, particularly the cost of recombinant protein therapeutics, and the sharp increase in competition over the past decade for market share of recombinant-protein based treatments of major illnesses have led to intense downward pressure on the cost of goods, especially for high volume products such as monoclonal antibodies and other recombinant proteins (Morrow 2002). Industry is therefore seeking to develop more cost effective downstream processes, including cheaper and more selective forms of chromatography. Generic affinity chromatography based on affinity-tag technology has the potential to simplify downstream processing by achieving higher yields and purities than conventional modes of chromatography. However, the high cost of current affinity tag technologies, due mainly to the expense of their associated affinity chromatography media, limits their application at production scales. This thesis addresses this problem by reporting on a novel affinity chromatography platform utilizing the family 9 carbohydrate-binding module (CBM9) of xylanase 10A from T. maritima , a new affinity tag that binds to both soluble sugars and insoluble cellulose to permit the highly efficient capture and purification of CBM9-tagged fusion proteins on a very inexpensive cellulose-based affinity media. Development of this technology has required (i) design of a generic CBM9 expression vector for production of chimeric fusions containing an N-terminal CBM9, a linker region containing a suitable processing site at its C-terminus for efficient removal of the affinity tag following affinity purification, and a C-terminal target protein, (ii) development of an effective strategy to design a linker sequence to stably connect the CBM9 tag to the target protein and to permit efficient tag removal through enzyme-catalyzed cleavage, (iii) derivation and validation of a mathematical model to predict binding and elution behavior of CBM9 fusion proteins on a high-capacity cellulose column, (iv) solutions to certain technology scale-up issues, including the synthesis of a mechanically stable stationary phase, and finally, (v) validation of the performance of the technology in terms of product yield, purity and concentration factor. Two bioinformatics-based strategies were developed to successfully identify a linker with improved resistance to endogeneous proteases of the host when compared against the popular poly-glycine based linker. A simple and effective assay was developed to identify the optimal conditions for efficient tag removal post-purification. The technique, based on Luminescence Resonance Energy Transfer (LRET) prescreens a library of linkers and processing enzymes to identify a CBM9-target protein fusion with enhanced processing efficiency. A novel two-zone model (TZM) of pore diffusion is presented to describe the rate of uptake of CBM9 fusion proteins within the stationary phase of the associated affinity chromatography column and thereby provide improved predictions of product breakthrough, including elution behavior from a bacterial lysate feed. Finally, a mechanically stable cellulose-based chromatography media was synthesized to allow preparative-scale purification of recombinant proteins using CBM9. A fixed-effect two-way response surface methodology was used to optimize the concentrations of the two primary reactants, epichlorohydrin and dimethyl sulfoxide (DMSO), required to cross-link the starting material, Perloza(TM) MT100, a compressible cellulose-based chromatography resin. This resulted in a cross-linked affinity chromatography media capable of operating at an order-of-magnitude higher linear velocity than permitted by unmodified MT100. In sharp contrast to MT100, the mechanical stability and purification performance of the cross-linked media are not diminished by scale-up or repeated column use. The results of this thesis thereby provide industry with a ready-made expression vector that can be used to express any target protein as a CBM9 fusion protein and to then inexpensively purify the target recombinant protein at an overall level of performance that is either superior or comparable to current commercially available fusion-tag technologies.<br>Applied Science, Faculty of<br>Chemical and Biological Engineering, Department of<br>Graduate
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Smyth, Amy Marie. "An investigation into the initial validity of the Canterbury behaviour screening protocol (CBSP): a pilot study." Thesis, University of Canterbury. Health Sciences, 2006. http://hdl.handle.net/10092/1406.
Texte intégralRésumé :
This study was a pilot investigation of the initial validity of a newly developed behaviour-screening instrument for early intervention service providers. Group Special Education, Early Intervention (GSE/EI) (2005) adapted the Canterbury Behaviour Screening Protocol (CBSP) from a widely used behaviour-screening instrument the Early Screening Project. The CBSP consisted of 49 items in 2 checklists. GSE/EI identified 10 early childhood centres with a total roll of 712 to participate in the study. Staff were asked to categorise children's problem behaviours as either withdrawn/isolated or aggressive/oppositional, using profiles provided. Next, they were asked to nominate 2 children in each category, and an additional 2 children in either category, and to rank them from most concerning to least concerning. Centres identified 25 children in the withdrawn/isolated category, and 28 children in the aggressive/oppositional category. Staff completed checklists for children with parent/carer consent, which were scored according to preset protocols. Scores on the CBSP were assigned risk values ranging from "extreme" to "no risk". The estimated prevalence of "high" to "extreme" behaviour problems was 7.2% based on CBSP protocols and teacher nominations. The level of agreement between teacher rank and CBSP score was 79%, and this determined the initial specificity. Next, independent observations of the behaviour of the nominated children were conducted during free play periods at the centres by an observer blind to the children's nominated category, teacher ranking or checklist score. Risk levels were assigned based on the observation scores, using a cut-off value of 37% time spent in problem behaviour for girls and 40% for boys. There was agreement in terms of teacher rank and observation scores, (categorised into either "no risk" and "at/high/extreme risk) for 65% for children in the withdrawn/isolated category, and 75% for children in the aggressive/oppositional category. The level of agreement between the CBSP score and the observations (categorised into either "no risk" or "at/high/extreme" risk) was 40% for children in the withdrawn/isolated category, and 46% for children in the aggressive/oppositional category. Using the cut-off values, a prevalence estimate for high risk or extreme risk for behaviour disorders, based on independent observation of children, was 3.2%. Centre staff completing a feedback form determined the social validity of the CBSP. Although responses were generally favourable, a number of suggestions were also made to improve the procedure. Despite limitations in the design of the draft, the CBSP shows promise for a first step in a screening procedure designed to screen New Zealand early childhood centres for children who may be at risk for developing behaviour and/or social emotional problems. The independent observation may also be useful as a second step, prior to extensive eligibility assessment. A number of suggestions were made for future drafts such as addressing the limitations specified, conducting the CBSP with a greater number of children, and determining the concurrent validity, and test-retest reliability.
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De, Santis Paola. "Contagious bovine pleuropneumonia (CBPP) : studies on the disease and causative agent (Mycoplasma mycoides subsp. mycoides SC)." Thesis, King's College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425092.
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GRIGORIADIS, ILIAS. "Evaluation of a Contactless Excitation and Response System for Condition Based Maintenance." Thesis, KTH, Industriell produktion, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-192809.
Texte intégralRésumé :
New environmental regulations as well as the increasing industrial competitiveness have set new more demanding rules on the manufacturing industry. In order to abide by those rules not only from the legal point of view but also to be able survive, manufacturing has to be more sustainable from many aspects, especially the economical one. One way to achieve the previous target is an unfortunately often oversighted aspect of the industry sector, the maintenance strategy. Condition based maintenance, CBM, can be used successfully in the industry and accurate estimation of spindle life time can lead to large savings in downtime and cost. CBM requires accurate sensors and equipment in order to get the right indicators whether equipment performance is deteriorating or not. One performance factor when planning a machining process is chatter vibration and one way to avoid this deteriorating phenomenon is to choose cutting parameters that allow stable machining. Various types of sensors are available for vibration and other CBM related measurements. Depending on the situation, the most applicable sensor is selected. The core of this thesis is to investigate the usefulness of measurements with the contactless excitations and response unit in terms of condition based maintenance. In the first part of the thesis, some of the theoretical aspects of maintenance are extensively elaborated upon and later on, the experimental part is presented along with the results’ discussion. The hardware required by the experiments has been provided by KTH and the experiments took place in two of an automotive industry’s production sites. There have been two visits at site A and one at site B, apart from the initial meetings. The measurements have been analyzed with the use of MATLAB.<br>Nya miljöregler samt ökande industriell konkurrens har satt nya mer krävande regler för tillverkningsindustrin. För att följa dessa regler, inte bara ur rättslig synpunkt utan också för att kunna överleva, behöver tillverkningen ske mer hållbar ur många aspekter, särskilt den ekonomiska. Ett sätt att uppnå målen är via, en tyvärr ofta underskattad metod, underhållsstrategin. Tillståndsbaserat underhåll, CBM, kan användas med framgång inom branschen och korrekt uppskattning av spindellivstid kan leda till stora besparingar genom minskade driftstopp och kostnader. CBM kräver noggranna sensorer och utrustning för att få rätt indikatorer för att avgöra om utrustningens prestanda försämras eller ej. En prestationsavgörande faktor vid planering av bearbetningsprocesser är vibrationer. Ett sätt att undvika dessa försämrade fenomen är att välja skärparametrar som tillåter stabil bearbetning. Olika typer av sensorer finns tillgängliga för vibrations- och andra CBM-relaterade mätningar. Beroende på situation, väljs den mest lämpliga sensorn. Kärnan i denna rapport är att undersöka nyttan av mätningar med en beröringsfri excitations- och mätenhet för tillståndsbaserat underhåll. I de första avsnitten av rapporten redogörs några av de teoretiska aspekterna av underhåll och i de senare är den experimentella delen presenterad, tillsammans med diskussion kring resultat. Hårdvaran som krävs för experimenten har tillhandahållits av KTH och experimenten ägde rum på två produktionsanläggningar hos en fordonstillverkare. Det har varit två besök på plats A och ett besök på plats B, bortsett från inledande möten. Mätningarna har analyserats med hjälp av MATLAB.
31
Gouveia, Ayden. "The Atypical Protein Kinase C - Creb Binding Protein Pathway Regulates Post-Stroke Neurovascular Remodeling and Functional Recovery." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/35674.
Texte intégralRésumé :
Ischemic stroke related brain damage causes loss of multiple cell types, including neural and vascular cells. The extent of post-stroke neurogenesis and angiogenesis predicts the level of functional regeneration/recovery after stroke. In this regard, my thesis was focused on defining the molecular process that modulates post-stroke functional recovery by co-ordinating post-stroke neurovascular remodeling. Since stroke-related brain damage releases enriched local microenvironmental cues, I examined the role of a signaling-induced epigenetic pathway, an atypical protein kinase C (aPKC)-mediated phosphorylation of CREB Binding Protein (CBP), in regulating post-stroke neurovascular remodeling and functional recovery. This pathway has previously been shown to be activated by metformin, an adenosine monophosphate kinase (AMPK) activator, to promote the differentiation of neural precursors in the developing and adult brain. Here, I first developed a murine focal cortical ischemic stroke model with persistent motor function deficits by combined intra-cortical injections of endothelin-1 (ET-1) and L-NAME into the sensorimotor cortex. Second, I applied the ET-1/L-Name-induced focal cortical stroke model in a knock-in mouse CBPS436A where the aPKC-CBP pathway is deficient, and showed that the aPKC-CBP pathway is involved in post-stroke functional recovery by coordinating neurovascular remodeling. Specifically, CBPS436A-KI mice displayed reduced motor recovery, correlated with reduced vascular remodeling and impaired post-stroke angiogenesis. Intriguingly, I also observed that CBPS436A-KI mice showed a reduction in the population of stroke-induced newborn pericytes but an increase in the population of perivascularly-derived neural precursors, implying that the aPKC-CBP pathway may be involved in the process that reprograms pericytes into neural precursors. Together, this study elucidates the novel role of the aPKC-CBP pathway in modulating neurovascular remodeling and functional recovery following focal ischemic cortical stroke.
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Sköld, Michael, and Almbladh Jacob. "Kartläggning och analys av scanias tillsynsprogram : Ett verktyg för förbättring." Thesis, Uppsala universitet, Industriell teknik, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-202001.
Texte intégralRésumé :
Scania intends to introduce a new maintenance program for their rolling fleet. Withthis new program Scania hopes to increase their competiveness and add furthercustomer value. This thesis report is a mapping of the current maintenance program,along with its problematic features. Furthermore the report intends to describe thenew program, Condition Based Maintenance (CBM) and the problems that Scaniamust deal with before they can implement it.The report compiles basic information on how a mapping should be performed.Further on it will describe some of the theories of LEAN and leadership. Which aretwo of the most important features in this thesis work.The work has been performed through visits in different workshops, whereinterviews have taken place. The interviews have a big impact in this report, as theycompile different people’s thoughts about the consisting work and the problems withit. All the information that has been collected has then been analyzed and discussed,to give a better understanding of the actual situation in the workshops.The field studies have been collected in a mapping report, in which the problems withimplementing CBM have been summarized. These problems have then been analyzedto generate solutions. The biggest problems in the workshops today, concernleadership and proactivity.<br>Scania vill införa ett nytt tillsynsprogram för sin rullande flotta. På detta sätthoppas Scania kunna stärka sin konkurrenskraft och öka kundnyttan. Dennarapport är en kartläggning av det tillsynsprogram Scania tillämpar idag, samtdess faktiska arbetssätt och problem. Vidare syftar rapporten till att beskrivadet tilltänkta programmet, Condition Based Maintenance (CBM), samt deproblemställningar som Scania måste tampas med innan implementationen.Rapporten sammanställer grundläggande information om hur ett arbete avkartläggande karaktär bör utföras. Vidare beskrivs teorier om LEAN ochledarskap. Vilket är två av de viktigaste faktorerna i detta arbete.Arbetet har utförts genom besök i verkstäder, där intervjuer har gjorts.Intervjuerna tar upp en stor del i rapporten då de sammanställer synpunkteroch brister i dagens arbetsätt. Den insamlade informationen har sedananalyserats och diskuterats, för att ge en bättre förståelse för den faktiskasituationen ute i verkstäderna.Arbetet har resulterat i en kartläggning, som samlat de problem Scania måsteåtgärda innan implementeringen av CBM. Dessa problem har sammanställtsoch analyserats för att sedan kunna generera lösningsförlag. De störstaproblemen ute i verkstäderna är ledarskap och rutiner gällande ett proaktivtarbetsätt gentemot kund.
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Fan, Chung-Hau. "An examination of the equivalence of the first grade DIBELS oral reading fluency probes." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/2698.
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Given the change in federal legislation allowing the consideration of a Response-To-Intervention (RTI) approach to making eligibility decisions for specific learning disabilities (IDEIA, 2004), it is crucial to establish sufficient evidence for using curriculum-based measurements (CBM) or CBM-like measures (e.g., Dynamic Indicators of Basic Early Literacy Skills; DIBELS) for monitoring students' responses to interventions as part of the identification process for Specific Learning Disabilities. One critical component in an effective RTI model is the availability of parallel measures suited for frequent progress monitoring to index student performance over time. The current study investigated the equivalence of the twenty first grade DIBELS Oral Reading Fluency (DORF) progress monitoring probes' using a one-way ANOVA for repeated-measures. Participants were 68 first grade students (36 females and 32 males) from two Midwestern elementary schools. No selection criteria other than parental consent were used. The DORF probes were given in a pseudo-counterbalanced order across four days at the end of the school year to avoid instruction and practice effects. The standard error of measurement (SEM) of the twenty first grade DORF progress monitoring probes was calculated using alternate form reliability coefficients. Results suggested that the equivalence assumption of the first grade DORF was not held. Most of the probes were significantly different in their difficulty level from each other and did not yield consistent mean levels of performance. The findings also suggested a significant magnitude of score fluctuation at the individual student level. The average SEM value was about 9 (ranging from 8 to 10), similar to previous research findings using test-retest reliability for calculation. Limitations, educational implications for CBM ORF users and researchers, and directions for future research are presented.
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Hancock, Kyle Max. "The Utility of Mathematics Curriculum-Based Measurement to Predict Student Risk Status on Standardized Academic Achievement Measures." DigitalCommons@USU, 2009. https://digitalcommons.usu.edu/etd/435.
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The predictive utility of mathematics curriculum-based measurement (MCBM) to identify students who are at risk for failure on important educational measures is an emerging area of study in need of further investigation. The present study sought to identify which of four MCBM probes could be accurately used to determine students' risk status on selected subtests of three important educational measures commonly used to make educational placement decisions (WIAT-II, WJ-ACH-III, and KM 3) in grades 2 (n = 49), 4 (n = 48), and 6 (n = 47). The study also sought to determine which type of student performance measurement strategy (i.e., level, slope, or dual discrepancy) on each of the four types of MCBM probes proved to be the best method to determine student risk status. The results of the study indicated that the ability of the MCBM probes to identify students' risk status was generally poor. However, evidence indicated that MCBM probes could be used more reliably and accurately to determine students in the low risk category than those in the high risk category across all probe types and administration times. Finally, the level method generated the greatest support and the slope method generated the least support for identification of high and low risk student status on each probe or combination of probes.
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Hassan, Ali Mohamed. "Couplage diagnostic pronostic pour la maintenance prévisionnelle des systèmes photovoltaïques." Thesis, Amiens, 2018. http://www.theses.fr/2018AMIE0016.
Texte intégralRésumé :
Dans ce travail, nous avons développé une méthode de couplage d'un processus de diagnostic à base de modèle avec un processus de prognostic issu de l'expérience au moyen d'une architecture OSA-CBM (Open System Architecture for Condition Based Maintenance). Pour cela, le modèle 2M7P de la cellule photovoltaïque est optimisé par la mise en œuvre d'une méthode métaheuristique d'extraction des sept paramètres, FodPSO. Cette optimisation permet de mieux reproduire la performance de la cellule surtout en conditions réelles de fonctionnement. L'approche du diagnostic est traitée par la quantification du résidu différentiel au moyen de la distance euclidienne en vue de caractériser la signature électrique des cinq défauts ciblés. La connaissance de la signature des défauts permet la détection puis la discrimination. La partie pronostic évolue depuis une première approche issue des modèles de dégradation de Pan et Monroe d'une part et de Vazquez et al. d'autre part vers une approche par analyse de fiabilité basée sur l'expérience. Le couplage proposé dans ce travail, consiste en un échange d'information entre les deux processus de diagnostic et de pronostic pour l'aide à la décision selon une architecture où les décisions sont faites grâce à un test de seuil sur l'indicateur choisi, le Corrected Performance Ration. Les informations sont restituées à l'utilisateur sur la dernière couche de l'architecture. L'ensemble des approches ont été validées avec les données expérimentales issues de différentes centrales solaires (UPJV, Catania Univ…)<br>In this work, we have developed a method of coupling a model-based diagnostic process with a prognostic process derived from the experience using an OSA-CBM (Open System Architecture for Condition Based Maintenance) architecture. For that, the 2M7P model of the photovoltaic cell is optimized by the implementation of a metaheuristic method of extraction of seven parameters, FodPSO. This optimization makes it possible to better reproduce cell's performance, especially under actual operating conditions. The diagnostic approach is treated by quantifying the differential residual using Euclidean distance in order to characterize electrical signatures of five targeted faults. The knowledge of faults signatures allows detection and discrimination. The prognostic part evolves since a first approach resulting from models of degradation of Pan and Monroe on the one hand and Vazquez et al. on the other hand towards a reliability analysis approach based on experience. The coupling proposed in this work consists of an exchange of information between the two diagnostic and prognostic processes for decision support according to an architecture where decisions are made by means of a threshold test on the selected indicator, the Corrected performance Ratio. Information is returned to the user on last layer of the OSA-CBM architecture. All approaches have been validated with experimental data from different plants (UPJV Platform, Catania University…)
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Xanidis, Nikos. "Exploring the implementation of Cognitive Behavioural Therapy for psychosis (CBTp) using the Normalisation Process Theory (NPT) framework." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/30812/.
Texte intégralRésumé :
Objective: Evidence suggests that only a minority of service users experiencing psychosis have access to Cognitive Behavioural Therapy for psychosis (CBTp). Normalisation Process Theory (NPT) is a theoretical framework which focuses on processes by which interventions are implemented and normalised in clinical practice. This study explored the views and experiences of mental health professionals regarding the implementation of CBTp. Barriers and facilitators to implementation were explored using the NPT framework. Design: A qualitative methodology was adopted involving semi-structured focus groups and individual interviews. Methods: A total of 14 members of staff working in the community and crisis mental health teams were recruited. Thematic analysis was used to generate initial themes. The Framework approach was utilised to map initial themes to the NPT framework. Results: Inductive coding generated five overarching themes consisting of 15 individual subthemes which captured the perceived barriers to engagement; contextual barriers to implementation; optimisation of implementation; positive attitudes towards implementation; and expectations of implementing CBTp. All but two subthemes mapped on to the NPT framework. The deductive analysis suggested that difficulties in making sense of CBTp among professionals were reflected as service level barriers which impeded wider implementation. Conclusion: The results of this study suggested a mixture of barriers and facilitators to CBTp implementation. Interpreting our findings within an NPT framework indicates the importance of strong clinical leadership to address difficulties in sense-making and service investment in CBTp.
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Hauser, Fabien. "Expression augmentée de la protéine de signalisation Cbp/PAG dans les lymphomes malins /." Genève : [s.n.], 2004. http://www.unige.ch/cyberdocuments/theses2004/HauserF/these.pdf.
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Zhang, Zuwen. "Functional analysis of the mouse CBP gene in the adult central nervous system." Thesis, Open University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390810.
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Wenk, Sandra. "Epigenetic regulation of nuclear receptor mediated transcription : Arginine methylation of the coactivator CBP." Université Louis Pasteur (Strasbourg) (1971-2008), 2007. http://www.theses.fr/2007STR13135.
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Akande, Oluwatoyin E. "INVESTIGATING THE MECHANISM OF THE COMPARTMENTALIZED CBP (CREB-BINDING PROTEIN) UBIQUITIN LIGASE ACTIVITIES." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4438.
Texte intégralRésumé :
CBP (CREB Binding Protein) is global transcriptional co-activator and histone acetyltransferase. CBP is involved in the modulation of the transcription of many genes via histone acetylation at the promoter regions of the target genes. Also, non-histone proteins and transcription factors can be acetylated by CBP to promote their transcriptional activation. In addition to its transcription co-activator role, CBP is involved in many other pathological and physiological cellular processes such as cell growth and differentiation, cell transformation and development, response to stress, cell cycle regulation and apoptosis.
CBP and its paralogue p300, play double-edged roles in the regulation of p53, a well characterized tumor suppressor protein, via ubiquitination and acetylation activities. Prior work has shown that CBP and p300 contribute to the maintenance of physiologic p53 levels in unstressed cells via a cytoplasmic but not nuclear, p53-directed E4 polyubiquitin ligase activity, subsequently leading to p53 proteasomal degradation. Our previous work also revealed that CBP and p300 possess intrinsic cytoplasmic but not nuclear E3 autoubiquitination activity in the absence of cellular stress. The mechanism of the compartmentalized CBP/p300 ubiquitin ligase activities was not studied. In this thesis, I present insights gained from efforts to determine the regulation of CBP ubiquitin ligase activities in the cytoplasm versus nucleus, in the absence and presence of DNA damage stress. Chapter two discusses the effect of DNA damage on CBP E3 autoubiquitination activity and also addresses the differential post translational modifications between cytoplasmic and nuclear CBP, in the absence and presence of DNA damage. Aspects of the regulation of the compartmentalized CBP ubiquitin ligase activities in the absence of cellular stress were covered in chapter three. We employed Multidimensional Protein Identification Technology (MudPIT) and mass spectrometry analysis of purified cytoplasmic and nuclear CBP to identify nuclear and cytoplasmic CBP interacting proteins. MudPIT analysis revealed that Cell Cycle and Apoptosis Regulator protein (CCAR2), also known as Deleted in Breast Cancer 1 protein (DBC1), is a novel CBP-interacting protein, in the cytoplasmic and nuclear compartments. Functional analysis suggested that DBC1 directly regulates cellular compartmentalization of CBP E3 and p53-directed E4 ubiquitination activities. This work identifies the different regulatory mechanisms of differential CBP ubiquitin ligase activities in the absence and presence of DNA damage. Remarkably, DBC1 was identified as a novel binding partner of CBP and a critical regulator of CBP ubiquitination activities towards p53.This work may provide novel strategies for the development of cancer therapeutics against tumors maintaining wild type p53, which have deleted DBC1.
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Wong, King Hei. "Solving combinatorial based chemical engineering problems via parallel evolutionary approaches /." View abstract or full-text, 2009. http://library.ust.hk/cgi/db/thesis.pl?CBME%202010%20WONGK.
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Xu, Jingjing. "Magnetic particle based sensing platform for oligonucleotide and PCR amplicon detection /." View abstract or full-text, 2010. http://library.ust.hk/cgi/db/thesis.pl?CBME%202010%20XU.
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Zhang, Haifeng. "Reduction of methanol crossover in direct methanol fuel cells by an integrated anode structure and composite electrolyte membrane /." View abstract or full-text, 2010. http://library.ust.hk/cgi/db/thesis.pl?CBME%202010%20ZHANG.
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Xu, Ruoyu. "Downstream processing of microalgal biodiesel production /." View abstract or full-text, 2010. http://library.ust.hk/cgi/db/thesis.pl?CBME%202010%20XUR.
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Zhou, Ping. "Preparation, characterization and in vivo evaluation of polyether polyol-platinate conjugate /." View abstract or full-text, 2010. http://library.ust.hk/cgi/db/thesis.pl?CBME%202010%20ZHOU.
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Lau, Richard Yiu-Ting. "Study of surfaces of semi-crystalline polymers by static time-of-flight secondary ion mass spectrometry /." View abstract or full-text, 2010. http://library.ust.hk/cgi/db/thesis.pl?CBME%202010%20LAU.
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Chan, Sen Ki. "Development and characterization of functionalized magnetic nanoparticle-based method for species-specific genomic DNA extraction /." View abstract or full-text, 2008. http://library.ust.hk/cgi/db/thesis.pl?CBME%202008%20CHAN.
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Chan, Yik Chung. "Solubility measurement apparatus for rapid determination of solid-liquid equilibrium behavior /." View abstract or full-text, 2008. http://library.ust.hk/cgi/db/thesis.pl?CBME%202008%20CHANY.
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Wang, Huan. "Synthesis, purification and applications of carbon nanomaterials and their polymer nanocomposites /." View abstract or full-text, 2008. http://library.ust.hk/cgi/db/thesis.pl?CBME%202008%20WANG.
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Lu, Junde. "Model migration based on process similarity /." View abstract or full-text, 2008. http://library.ust.hk/cgi/db/thesis.pl?CBME%202008%20LU.
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