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1
Honkomp, Tina [Verfasser]. « Intraokulare Druckerhöhung und post-DMEK Glaukom / Tina Honkomp, geb. Wolf ». Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2018. http://d-nb.info/1172206031/34.
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Schwinde, Jan-Hendrik [Verfasser], Gerd [Gutachter] Geerling et Lars [Gutachter] Wojtecki. « Langzeitergebnisse nach Descemet-Membran Endothel Kerato-plastik (DMEK) und Triple-Descemet-Membran Endothel Keratoplastik (Triple-DMEK) im Vergleich / Jan-Hendrik Schwinde ; Gutachter : Gerd Geerling, Lars Wojtecki ». Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2019. http://d-nb.info/1188017888/34.
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3
Pedemonte, Sarrias Eduard. « Tècnica de Muraine per a DMEK : anàlisi comparativa amb la tècnica estàndard ». Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/405259.
Texte intégralRésumé :
La queratoplàstia endotelial de la membrana de Descemet (DMEK) és la tècnica d'elecció actual per al tractament de l’edema corneal irreversible. Després que Melles la desenvolupés el 2006, Muraine va proposar el 2013 una tècnica alternativa per a la dissecció i implantació de l’empelt. Aquesta tècnica aportava dues novetats: la hidrodissecció amb trepanació parcial i curvatura corneal invertida del teixit donant i el plegament de l’empelt amb l'endoteli a la seva cara interna, que afavoria la protecció de l’endoteli i la tendència natural de l’empelt a desplegar-se a la cambra anterior del receptor.
L’objectiu d’aquesta tesi doctoral és comparar la tècnica de Muraine amb la tècnica estàndard analitzant-ne la densitat de cèl·lules endotelials (DCE) i agudesa visual (AV) postoperatòries, els temps quirúrgics i les complicacions intraoperatòries i postoperatòries. Es va dur a terme un estudi de cohorts prospectiu observacional multicèntric en la pràctica clínica habitual a l’Hospital Universitari MútuaTerrassa i l’Institut de Microcirurgia Ocular. El seguiment postoperatori va ser de sis mesos, amb controls com a mínim l’endemà, al cap d’una setmana i al cap d’un, tres i sis mesos de la cirurgia.
Es van incloure 27 ulls de 20 pacients al grup de la tècnica Estàndard i 42 ulls de 40 pacients al grup intervingut amb la tècnica Muraine. La DCE als sis mesos va ser de 1488 (1337-1679) cèl·lules/mm2 al grup Estàndard i de 1170 (734-1614) cèl·lules/mm2 al grup Muraine (P=0.10). L’AV mitja als sis mesos va ser de 0.89 al grup Estàndard i 0.79 al grup Muraine, en l’escala decimal (P=0.19). Al voltant del 80% van assolir una AV de 0.5 o més i el 50-70%, 0.8 o més.
Es va observar que la DCE i el percentatge de pèrdua de DCE al mes de la cirurgia eren equivalents als de la tècnica estàndard. El percentatge de pèrdua de DCE als sis mesos va ser superior amb la tècnica de Muraine, si bé la DCE va ser clínicament comparable. L’AV assolida als sis mesos va ser equivalent. La tècnica de Muraine va ser tan segura com la tècnica estàndard per a l’obtenció de l’empelt. La incidència de complicacions intraoperatòries amb l’empelt preparat amb la tècnica de Muraine en ulls amb facoemulsificació no complicada no va ser estadísticament superior. La dissecció de l’empelt amb la tècnica de Muraine va ser més lenta. El desplegament, per contra, va ser lleugerament més ràpid. Totes dues tècniques van tenir una taxa elevada de supervivència de l’empelt. La complicació postoperatòria més freqüent en ambdós grups va ser l’edema macular quístic. Els empelts dissecats amb la tècnica de Muraine van tenir una major incidència de necessitat de reinsuflació.Descemet’s membrane endothelial keratoplasty (DMEK) is the current gold standard treatment for irreversible corneal oedema. After Melles developed this technique in 2006, Muraine proposed in 2013 an alternative technique for the dissection and implantation of the graft. Its main contributions were: hidrodissecting the graft from a partially trephined, inverted donor tissue, and folding the graft over the endothelial side, which favoured the protection of endothelial cells and the graft’s natural tendency to unfold in the receptor’s anterior chamber. The purpose of this doctoral thesis is to compare Muraine’s technique to the Standard through analysis of the postoperative endothelial cell density (ECD) and visual acuity (VA), surgical time, and intraoperative and postoperative complications. An observational, multicentric, prospective, cohorts trial was carried out in Hospital Universitari MútuaTerrassa and Institut de Microcirurgia Ocular in a daily praxis basis. There were follow-up controls over the six months following the surgery, at least at day one, first week and first, third and sixth months. Twenty-seven eyes from 20 patients were included in the Standard technique group. Forty-two eyes from 40 patients were included in the Muraine’s technique group. The ECD at six months was 1488 (1337-1679) cells/mm2 for the Standard group and 1170 (734-1614) cells/mm2 for Muraine’s group. The mean VA at six months was 0.89 for the Standard group and 0.79 for Muraine’s group, in the decimal scale (P=0.19). Around 80% of the eyes reached a VA of 0.5 or higher and 50-70%, 0.8 or higher. The ECD and the percentage of ECD loss with Muraine’s technique at the first month after surgery were equivalent to the Standard technique’s. The percentage of ECD loss at six months was higher with Muraine’s technique, although the ECD was clinically comparable. The VA achieved at six months was equivalent. Muraine’s technique was as safe as the Standard technique for the graft dissection. The incidence of intraoperative complications among the eyes with uncomplicated phacoemulsification was not statistically higher with Muraine’s technique. The graft dissection with Muraine’s technique was slower. Conversely, the unfolding was slightly faster. Both techniques had a high graft survival rate. The most frequent postoperative complication in both groups was cystoid macular oedema. The grafts dissected with Muraine’s technique had a higher incidence of need for rebubbling.
4
Wardeh, Rima [Verfasser], et Walter [Akademischer Betreuer] Sekundo. « Long-Term Results after DMEK (Descemet’s Membrane Endothelial Keratoplasty) / Rima Wardeh ; Betreuer : Walter Sekundo ». Marburg : Philipps-Universität Marburg, 2020. http://d-nb.info/1205879730/34.
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Schmeckenbächer, Nikola [Verfasser], Theofilos [Akademischer Betreuer] Tourtas et Theofilos [Gutachter] Tourtas. « Zusammenhang von intraoperativ bei DMEK gemessenem Augeninnendruck und postoperativer Transplantatadhäsion / Nikola Schmeckenbächer ; Gutachter : Theofilos Tourtas ; Betreuer : Theofilos Tourtas ». Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2021. http://d-nb.info/1234714213/34.
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6
Abdin, Alaa Din [Verfasser]. « Impact of dextran in organ culture media for preservation of DMEK (Descemet Membrane Endothelial Keratoplasty) precut tissue / Alaa Din Abdin ». Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2020. http://d-nb.info/1216104832/34.
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Borgardts, Klara [Verfasser], Gerd [Gutachter] Geerling et Colin [Gutachter] MacKenzie. « Untersuchung des Glycerinbades als prädiktiver Parameter für den Erfolg nach einer Descemetmembran Endothelkeratoplastik (DMEK) / Klara Borgardts ; Gutachter : Gerd Geerling, Colin MacKenzie ». Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2019. http://d-nb.info/1190350726/34.
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Gerber, Fanny Luise [Verfasser], Björn [Gutachter] Bachmann et Stefan [Gutachter] Haneder. « Korneale Densitometrie als diagnostischer Prädiktor für den postoperativen Visus nach Descemet membrane endothelial keratoplasty (DMEK) / Fanny Luise Gerber ; Gutachter : Björn Bachmann, Stefan Haneder ». Köln : Deutsche Zentralbibliothek für Medizin, 2021. http://d-nb.info/1229352899/34.
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9
Ampazas, Paraskevas [Verfasser], et Walter [Akademischer Betreuer] Sekundo. « Transplantatanlagerate bei Verwendung von 5% SF6- Gas versus Luft bei der Endotamponade im Rahmen der Descemet-Membran Endothelialen Keratoplastik (DMEK) : Eine retrospektive Erhebung. / Paraskevas Ampazas ; Betreuer : Walter Sekundo ». Marburg : Philipps-Universität Marburg, 2018. http://d-nb.info/1161847049/34.
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10
Ostroumov, Ivan Victorovich. « Analysis of DME/DME positioning capabilities for borispil airspace region ». Thesis, ІІ National Scientific Conference of young scientists and students «Problems and prospects of Aeronautics and Astronautics» 23 – 24 October 2013 y – Kyiv, 2013. – P. 21, 2013. http://er.nau.edu.ua/handle/NAU/26591.
Texte intégralRésumé :
Case of on board equipment failure or in case of unavailability of GNSS support (for example: result of some errors), flight management system (FMS) has to use other alternative methods for positioning. FMS has got diferent positioning alghoritms with is grounted on current navigation aids infrastructure [1]. One of them uses distance measurement equipment (DME) for this purpose. DME positioning technics are the most accurate in this situation and avalible on the bigger part of Ukrainian airspace. In this case, it is possible to regard DME like an alternate source of positioning, navigation and timing during the absence of GNSS service. That’s why, DME actively supported by airlines regional carriers and high-end business operators who are equipped with advanced DME avionics.
The main task of distance measuring equipment is to provide pilots with distance information between the aircraft and the ground station and is used in all phases of flight. It`s effective tool for strengthening pilot navigation and increasing situation understanding. This technology gives the able pilots to determine exact locations while en route as well as identify descent points on an instrument approach.
11
Ostroumov, Ivan Victorovich. « Расчёт точности дальномерного оборудования DME для определённой высоты полёта и геометриии взаимного расположения ». Thesis, Национальный авиационный университет, 2017. http://er.nau.edu.ua/handle/NAU/28123.
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Рассмотрен процесс оценивания точности выдерживания заданной лини положения по дальномерному оборудованию DME. Оценивание выполнено для пар навигационных средств с учётом оптимального их расположения в пространстве. Разработана структурная схема программного обеспечения для расчёта точности, выполнено моделирование для конкретной зоны воздушного пространства.
12
Davis, Brigid Michele 1967. « DMPK and myotonic dystrophy : effects of CTG trinucleotide expansion upon DMPK and their contribution to DM pathogenesis ». Thesis, Massachusetts Institute of Technology, 1998. http://hdl.handle.net/1721.1/49633.
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Ito, H., D. Suzuki, Y. Yokochi, S. Kuroda, M. Umemiya, H. Miyasaka, K.-I. Sugiura, M. Yamashita et H. Tajima. « Quasi-one-dimensional electronic structure of (DMET)_2CuCl_2 ». The American Physical Society, 2005. http://hdl.handle.net/2237/7127.
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Moncrieff, Colin Lindsay. « Cloning and characterisation of a novel DMPK-related gene : CDC42BPB ». Thesis, University of Glasgow, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323439.
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Zhu, Xianmin Elefant Felice. « The histone acetyltransferase Dmel\TIP60 Is essential for multicellular development in Drosophila / ». Philadelphia, Pa. : Drexel University, 2007. http://hdl.handle.net/1860/2582.
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Luciano, Brenda Sierra 1965. « Proteomic analysis of the function of DMPK, the myotonic dystrophy protein kinase ». Thesis, Massachusetts Institute of Technology, 2001. http://hdl.handle.net/1721.1/8207.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2001.Includes bibliographical references.
Myotonic Dystrophy type 1 (DM1), the most common form of adult-onset skeletal muscle dystrophy, is caused by expansion of a CTG repeat sequence embedded in the 3'UTR of a gene which encodes a serine threonine kinase, DMPK. The precise mechanism by which CTG repeat expansion causes the complex pathology of DM1 is under active investigation. Repeat expansion leads to a failure of transport of DMPK mRNA from nucleus to cytoplasm indicating that reduction in DMPK expression levels is at least one major consequence of repeat expansion. Mouse models suggest that haploinsufficiency of DMPK accounts for at least a portion of the symptoms of DM1. DMPK -/- mice exhibit a progressive muscle myopathy similar to that seen in DM1, and both DMPK -/- and DMPK +/- mice reiterate cardiac conduction abnormalities characteristic of DM1 patients. However, the in vivo role of DMPK, the identity and nature of its substrate(s) and the biological pathway(s) within which it functions remain to be elucidated. To determine the in vivo function of DMPK I have taken a proteomics-based approach that utilizes 2-dimensional SDS-PAGE and mass spectrometry to compare directly heart proteins of wild-type and DMPK -/- mice in order to identify proteins that are altered in the absence of DMPK.
(cont.) I have identified several proteins with altered mobility on 2D SDS-PAGE gels in mutant versus wild-type cells in heart and peripheral muscle of DMPK-/- animals. Two of these were analyzed by mass spectrometry and identified as fatty acid binding proteins (FABPs). The altered mobility of these proteins suggests that they have different properties in the absence of DMPK. Further investigation of these FABPs could potentially shed light into the in vivo role of DMPK and into the biological pathway(s) in which DMPK functions.
by Brenda Sierra Luciano.
Ph.D.
17
Pantic, Boris. « DMPK prevents ROS-induced cell death by assembling a HK II-Src complex on mitochondrial surface ». Doctoral thesis, Università degli studi di Padova, 2012. http://hdl.handle.net/11577/3422198.
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DMPK is a serine/threonine protein kinase that was initially proposed to be the cause of the most frequent adult muscular dystrophy, myotonic dystrophy 1 (DM1). Recently, it has been shown that DMPK is not the primary determinant of the DM1, but its deletion causes late onset myopathy and cardiac abnormalities in knock-out mice. Evidence present in the literature suggests a mitochondrial localization of high MW DMPK isoforms in muscle and cardiac tissue. However, to date, there is not a single association of mitochondria-anchored isoforms with the respective function of the organelle in the affected tissues. Therefore, we have examined the role of mitochondria-anchored isoform A, either by stably expressing it in cells lacking endogenous protein, or by stably silencing the endogenous one. DMPK significantly decreased levels of mitochondrial superoxide and consequently increased cell survival in prolonged serum and glucose depletion, both in SAOS-2 and rhabdomyosarcoma cells. At the molecular level we have found DMPK to interact with HK II and Src, increasing the HK II association to mitochondria. Detachment of HK II from mitochondria abolished differences in superoxide levels, while a HK II inhibitor 5-TG protected cells from death by stabilizing HK II on the OMM and by decreasing mitochondrial ROS in the absence of DMPK. Src activity was also important for HK II maintenance on OMM since its inhibition sensitized only DMPK-expressing cells to detachment of HK II. These data attribute an antiapoptotic role to DMPK due to an unprecedented link to HK II and its protective effect against mitochondrial ROS.DMPK è la serina/treonina protein kinasi, la quale è stata inizialmente proposta come la causa della più frequente distrofia muscolare negli adulti, la distrofia miotonica del tipo 1 (DM1). Recentemente si è visto che la DMPK non è la causa principale della DM1, ma la sua delezione causa miopatia ad insorgenza tardiva e anomalie cardiache nei topi knock-out. I dati presenti in letteratura attribuiscono la localizzazione mitocondriale alle isoforme ad alto peso molecolare nel muscolo e nel tessuto cardiaco. Comunque, finora non vi sono stati studi volti ad associare il ruolo delle isoforme mitocondriali della DMPK alla funzione dell’organulo nei tessuti in questione. Perciò, abbiamo deciso di esaminare il ruolo dall’isoforma A associata ai mitocondri, sia esprimendola stabilmente nelle cellule prive della DMPK endogena, sia silenziando stabilmente quella endogena. DMPK ha significativamente diminuito i livelli del superossido mitocondriale e, di conseguenza, ha aumentato la sopravvivenza delle cellule SAOS-2 e rabdomiosarcoma in deplezione di siero e glucosio. A livello molecolare, abbiamo trovato che la DMPK interagisce con HK II e Src aumentando l’associazione dell’HK II ai mitocondri. Il distacco dell’HK II dai mitocondri ha cancellato le differenze nei livelli di superossido, mentre l’inibitore dell’HK II 5-TG ha protetto le cellule dalla morte stabilizzando l’HK II sulla membrana mitocondriale esterna e diminuendo i livelli di ROS mitocondriali in assenza della DMPK. Src aveva la funzione di mantenere HK II sulla membrana mitocondriale esterna, in quanto la sua inibizione ha sensibilizzato le cellule al distacco dell’HK II solo se esprimevano la DMPK. Questo studio attribuisce un ruolo anti-apoptotico alla DMPK grazie all’interazione con HK II e la sua funzione protettiva contro i ROS di origine mitocondriale.
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Delgoda, Rupika. « A study of arylamine N-acetyltransferase from Salmonella typhimurium ». Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302221.
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Da, Silva Franck. « Amélioration de la prédiction de la clairance métabolique via l’utilisation de modèles hépatiques innovants ». Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT083.
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La sélection des meilleurs candidats médicament se base sur des choix multiparamétriques réunissant l’efficacité potentielle, les caractéristiques ADME et le profil de sécurité des nouvelles entités chimiques. En ce sens, la prédiction précoce de la pharmacocinétique est élémentaire pour orienter les prises de décision et donner un cap pertinent aux projets. En raison de son rôle central dans le devenir des médicaments, la clairance métabolique médiée principalement par le foie est l’un des paramètres les plus importants. L’objectif de ce projet était d’améliorer la prédiction de la clairance en se concentrant notamment sur les molécules présentant une bonne stabilité métabolique et qui sont de ce fait encore difficiles à étudier. Les travaux menés dans cette thèse nous ont permis d’étoffer nos connaissances sur les modèles hépatiques in vitro et les méthodes d’extrapolation usuelles mais aussi de découvrir et de développer de nouvelles stratégies de prédiction. Nous nous sommes concentrés en profondeur sur la clairance métabolique et à tout ce qui impacte les prédictions. Le modèle de co-culture microorganisée (MPCC) HepatopacTM qui permet de stabiliser les hépatocytes humains sur plusieurs semaines a ainsi été identifié comme une alternative judicieuse aux modèles de routine lorsque les molécules ne peuvent pas être étudiées en culture 2D classique. L’étude de la fraction libre plasmatique et l’intégration de nouvelles hypothèses physiologiques telles que la théorie de « l’uptake facilité par l’albumine » ont également participé à améliorer les prédictions. Compte tenu des performances du modèle HepatopacTM, nous avons développé une approche innovante basée sur le spotting de précision afin de produire tous types de co-cultures microorganisées. Les co-cultures fabriquées grâce à cette technique démontrent que la méthode est robuste, accessible et simple à mettre en œuvre. Notre méthode de spotting a ensuite été utilisée pour faire évoluer le modèle MPCC et l’ouvrir à de nouvelles applicationsThe selection of the best drug candidates is based on multiparametric choices combining the potential efficacy, ADME characteristics and the safety profile of the new chemical entities. In this sense, the early prediction of pharmacokinetic is essential to guide decision-making and provide a relevant course for projects. Because of its central role in drug disposition, metabolic clearance mediated primarily by the liver is one of the most important parameters. The objective of this project was to improve clearance prediction by focusing on low clearance compounds that are still difficult to study. This work allowed us to expand our knowledge on in vitro liver models and usual extrapolation methods but also to discover and develop new prediction strategies. We focused on metabolic clearance and all parameters that impact the predictions. Micropatterned co-cultures (MPCCs) of primary human hepatocytes (HepatopacTM), which stabilizes hepatocytes over several weeks, has been identified as a judicious alternative to routine models when the molecules cannot be studied in conventional monolayer culture. The study of plasma protein binding and the integration of new physiological hypothesis such as the "Albumin-Facilitated Uptake" also contributed to improve the predictions. Given the performance of the HepatopacTM model, we have developed an innovative approach using a digital dispensing system to spot collagen and produce all types of micropatterned co-cultures. Co-cultures manufactured by this technique demonstrate that the method is robust, accessible and easy to use. Our spotting method was used to evolve the MPCC model and explore new applications
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Mbarawa, M., W. Lee, YW Nam et SH Chung. « Ethylene propane and ethylene ester synergistic effects on soot formation ». R&D Journal of the South African Institution of Mechanical Engineering, 2007. http://encore.tut.ac.za/iii/cpro/DigitalItemViewPage.external?sp=1000860.
Texte intégralRésumé :
In this study, the synergistic elfects of ethylene-propane
and ethylene-dimethyl ester (DME) mirtures on soot
formation were investigated experimentully using u coflow
dilfusion flame burnen The soot volume fraction,
soot particle diameter and number density were measured
and compured to the homogenous mixture. Addition
of DME and propane to the ethylene fuel increased
soot volume fraction in the ethylene flames. The ethylene-
propnne has more pronounced synergistic ffict in
compsrison to the ethylene-DME flame* This is due
to the fact that during the decomposition of propane
some methyl radicals are generated, The reuctions
related to these methyl radicals promote the formation
of propargyl rodiculs and conseqaently the formation
of benzene through propargyl self-reaction and finally
to the soot formation. Althoagh DME decomposition
produces methyl, the C-O bond in the DME removes
some carbon from the reaction puth that produces soot,
Hence the soot formation in ethylene-DME mixture is
much slower than that in ethylene-propane mixtuFe,
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Demir, Hakan. « Dimethyl Ether (dme) Synthesis Using Mesoporous Sapo-34 Like Catalytic Materials ». Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613471/index.pdf.
Texte intégralRésumé :
In 21st century, researchers make great effort of finding a clean transportation fuel to
diminish the severe effects of conventional transportation fuel combustion such as global
warming and air pollution. Dimethyl ether is considered as a strong fuel alternative due to its
good burning characteristics and environmentally friendly properties. In order to produce
dimethyl ether, different synthesis routes and solid acid catalysts are being utilized. SAPO-34 is
an aluminophosphate based catalyst having moderate acidity. This property makes it a good
candidate for the synthesis of dimethyl ether. However, SAPO-34 has microporous structure
causing diffusion limitations.
The objective of this study is to synthesize, characterize mesoporous SAPO-34 like
catalytic materials and test the activity of them in methanol dehydration reaction. The benefit of
obtaining mesoporous structure is that the diffusion limitations can be eliminated.
Mesoporous SAPO-34 like catalysts were synthesized through hydrothermal synthesis
route. BET surface areas of these catalysts were 117-133 m2/g. All methanol dehydration
reactions were carried out at a space time of 0.14 s.g/cm3. By using mesoporous SAPO-34 like
catalysts, the highest methanol conversion was 48% obtained at 550°C with DME selectivity and yield values of 1 and 0.49, respectively. Since utilizing microporous SAPO-34 catalyst gave higher methanol conversion, 67%, at lower temperature, 250°
C, with dimethyl ether selectivity of around 1, mesoporous SAPO-34 like catalysts are not suitable for this reaction.
22
Labuschagne, Jeanine. « Molecular methods for genotyping selected detoxification and DNA repair enzymes / J. Labuschagne ». Thesis, North-West University, 2010. http://hdl.handle.net/10394/4599.
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The emerging field of personalized medicine and the prediction of side effects experienced due to pharmaceutical drugs is being studied intensively in the post genomic era. The molecular basis of inheritance and disease susceptibility is being unravelled, especially through the use of rapidly evolving new technologies. This in turn facilitates analyses of individual variations in the whole genome of both single subjects and large groups of subjects.
Genetic variation is a common occurrence and although most genetic variations do not have any apparent effect on the gene product some do exhibit effects, such as an altered ability to detoxify xenobiotics.
The human body has a highly effective detoxification system that detoxifies and excretes endogenous as well as exogenous toxins. Numerous studies have proved that specific genetic variations have an influence on the efficacy of the metabolism of pharmaceutical drugs and consequently the dosage administered.
The primary aim of this project was the local implementation and assessment of two different genotyping approaches namely: the Applied Biosystems SNaPshot technique and Affymetrix DMET microarray. A secondary aim was to investigate if links could be found between the genetic data and the biochemical detoxification profile of participants. I investigated the approaches and gained insight into which method would be better for specific local applications, taking into consideration the robustness and ease of implementation as well as cost effectiveness in terms of data generated.
The final study cohort comprised of 18 participants whose detoxification profiles were known. Genotyping was performed using the DMET microarray and SNaPshot techniques. The SNaPshot technique was used to genotype 11 SNPs relating to DNA repair and detoxification and was performed locally. Each DMET microarray delivers significantly more data in that it genotypes 1931 genetic markers relating to drug metabolism and transport. Due to the absence of a local service supplier, the DMET - microarrays were outsourced to DNALink in South Korea. DNALink generated raw data which was analysed locally.
I experienced many problems with the implementation of the SNaPshot technique. Numerous avenues of troubleshooting were explored with varying degrees of success. I concluded that SNaPshot technology is not the best suited approach for genotyping. Data obtained from the DMET microarray was fed into the DMET console software to obtain genotypes and subsequently analysed with the help of the NWU statistical consultation services. Two approaches were followed: firstly, clustering the data and, secondly, a targeted gene approach. Neither of the two methods was able to establish a relationship between the DMET genotyping data and the detoxification profiling.
For future studies to successfully correlate SNPs or SNP groups and a specific detoxification profile, two key issues should be addressed: i) The procedure for determining the detoxification profile following substrate loading should be further refined by more frequent sampling after substrate loading. ii) The number of participants should be increased to provide statistical power that will enable a true representation of the particular genetic markers in the specific population. The statistical analyses, such as latent class analyses to cluster the participants will also be of much more use for data analyses and interpretation if the study is not underpowered.Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2011.
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Bachir-Cherif, Dalila. « Influence of bile-duct cannulation on the expression of DMPK-relevant enzymes in the rat ». Strasbourg, 2011. https://publication-theses.unistra.fr/restreint/theses_doctorat/2011/BACHIR-CHERIF_Dalila_2011.pdf.
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Lhoumaud, Priscillia. « Rôle de l'histone méthyl-transférase dMes-4 dans l'expression des gènes, la pause et l'épissage ». Toulouse 3, 2014. http://www.theses.fr/2014TOU30096.
Texte intégralRésumé :
Les protéines qui se fixent aux séquences dites 'insulatrices' sont appelées les 'IBPs' (pour 'Insulator Binding Proteins'). Ces facteurs réguleraient de nombreux gènes via leur rôle dans l'organisation de la chromatine. Une hypothèse de travail est que cette fonction des IBPs reposerait sur leur capacité à ouvrir la chromatine localement, favorisant ainsi le recrutement de facteurs impliqués dans la régulation des gènes. Lors de mon travail de thèse, j'ai tout d'abord identifié l'enzyme de méthylation d'histones (HMT), dMes4, comme un partenaire structural et fonctionnel important des protéines insulatrices BEAF-32/dCTCF. Ainsi, mes résultats ont montré que déplétion de dMes4 récapitulait les défauts d'expression obtenus après déplétions des IBPs, démontrant son rôle prépondérant en tant que co-facteur des IBPs. DMes-4 est la seule enzyme capable de di-méthyler l'histone H3 sur la lysine 36 (H3K36me2) chez la Drosophile, une modification d'histone qui jouerait un rôle déterminant dans le recrutement des complexes d'acétylation des histones (HATs) qui permettent l'ouverture de la chromatine. Mes recherches ont par ailleurs souligné le rôle prépondérant des IBPs dans le recrutement de cette HMT, permettant ainsi l'ouverture de la chromatine aux promoteurs de gènes. De plus, j'ai montré que ce mécanisme dMes-4 dépendant était requis pour le recrutement de l'activateur transcriptionnel DREF, un facteur clé dans la régulation des oncogènes. DREF active l'élongation de la transcription par l'ARN polymérase II qui est couplée à la tri-méthylation H3K36me3 par l'enzyme dHypB. De façon intéressante, la tri-méthylation est requise dans le recrutement des facteurs d'épissage et mes résultats ont montré que la marque H3K36me2 servirait dans ce contexte à prédéfinir un état chromatinien 'compétent' pour que l'activation transcriptionnelle soit couplée à la bonne maturation des ARNs. Un deuxième volet de mes travaux a permis de caractériser la fonction de dMes-4 et de dHypB dans la transition entre les étapes de " pause " et d'élongation de l'ARN polymérase II, via le recrutement du complexe P-TEFb, qui est nécessaire à la bonne maturation de l'ARN polymérase II et à la dissociation concomitante du facteur de pause appelé NELF. Mes résultats montrent que NELF servirait de point de contrôle permettant de coupler l'élongation à l'épissage et la maturation des transcrits. Aussi, ce couplage dépendrait notamment de la fonction dMes-4-dépendante dans le recrutement de P-TEFb et de celle de NELF dans le contrôle de la 'maturation' de l'ARN polymérase II. Mes résultats suggèrent que ces défauts de maturation seraient dus à l'incapacité de la forme immature à recruter dHypB, entraînant ainsi des défauts d'épissage dépendants de H3K36me3. Mes travaux permettent ainsi de mieux comprendre le rôle de la pause dans la maturation des ARNs, via les HMTs dMes-4/dHypBThe Drosophila insulator-binding proteins (IBPs) Beaf32/dCTCF regulate gene expression, through mechanisms that may involve their role in chromatin organization. One hypothesis is that chromatin insulators may lead to open chromatin locally, thereby recruiting factors involved in transcriptional activation. During my PhD, I have identified a key histone modifier, dMes-4, as a novel co-factor of IBPs involved in chromatin accessibility, which specifically co-regulates hundreds of genes flanked by Beaf32/dCTCF. DMes-4, the only H3K36me2 histone methyltransferase in Drosophila, may play a key role in the recruitment of Histone acetyltransferases (HATs) leading to a chromatin opening. Our results show that dMes-4 is recruited at gene promoters through IBPs, thereby opening chromatin locally for the recruitment of the transcriptional activator DREF. Such transcriptional activation is involved in oncogene activation. Our results show that DREF triggers RNAPII elongation concomitantly with the trimethylation of H3K36 (H3K36me3) by dHypB, thereby allowing H3K36me3-dependent RNA splicing. Our work highlights a key role of IBPs/dMes-4 in presetting chromatin for transcriptional activation and proper RNA splicing. A second part of my Ph. D. Work was to characterize the respective roles of dMes-4 and dHypB in the "switch" from RNAPII pausing to transcription elongation, through the recruitment of the complex P-TEFb. We show that P-TEFb is required for the maturation of RNAPII, which is under the control of the paused factor NELF. My data show that NELF may serve as a "checkpoint" coupling RNAPII maturation with RNA splicing. This checkpoint may involve both dMes-4 in recruiting P-TEFb, and of NELF in preventing the release of RNAPII before its "maturation". Our data further show that NELF depletion leads to splicing defects due to the impaired recruitment of dHypB on such immature RNAPII, leading to defects in H3K36me3 deposition. As such, my work highlights a key function of the HMTs dMes-4/dHypB and of NELF-mediated RNAPII pausing in RNA maturation
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Arinan, Ayca. « Direct Synthesis Of Dimethyl Ether (dme) From Synthesis Gas Using Novel Catalysts ». Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/3/12611490/index.pdf.
Texte intégralRésumé :
Increasing prices of crude oil derived transportation fuels ascended the
researches on seeking alternative fuels, in last decades. Moreover, the increasing rate
of global warming, because of high greenhouse gas emissions initiated new research
for environment-friendly clean alternative fuels. Due to its low NOx emission, good
burning characteristics and high cetane number, dimethyl ether (DME) attracted
major attention as a transportation fuel alternative. Two possible pathways have been
proposed for DME production. One of these pathways is DME synthesis through
conventional methanol dehydration. More recently, direct DME synthesis in a single
step has attracted significant attention of researchers and fuel producers. Catalysts
having two active sites are required for direct DME synthesis from synthesis gas.
The aim of this work was to synthesize novel bifunctional direct DME
synthesis catalysts and test their activity in a high pressure fixed bed flow reactor.
Bifunctional mesoporous catalysts were synthesized by using one-pot hydrothermal
synthesis, impregnation and physical mixing methods. These materials were characterized by XRD, EDS, SEM, N2 physisorption and diffuse reflectance FT-IR
(DRIFTS) techniques.
Characterization results of the catalysts synthesized by one-pot hydrothermal
synthesis procedures in basic and acidic routes showed that pH value of the synthesis
solution was highly effective on the final physical structure and chemical nature of
the catalysts. Increase in the pH value promoted the incorporation of Cu, Zn and Al
into the mesoporous MCM-41 structure. Also, effects of Na2CO3 addition on the
catalyst structure during the hydrothermal synthesis procedure were investigated.
The characterization results showed that metals were incorporated into the catalyst
structure successfully. However, surface area results showed that loaded metals
blocked the pores of MCM-41 and decreased the surface area of the catalysts. Effects
of zirconium (Zr) metal with different weight ratios were also investigated. Results
showed that Zr loading increased the surface area of the catalyst.
A high pressure fixed bed flow reactor was built and the catalyst testing
experiments were performed between the temperature range of 200-400°C, at 50 bars. The activity results of the catalyst synthesized by impregnation method showed that no DME was formed over this catalyst
however it showed promising results for production of methanol and ethanol. Selectivity values of these alcohols were between 0.35 and 0.2. Formation of methane and CO2 indicated the occurrence of reverse dry reforming reaction. Incorporation of Zr into the catalyst structure at neutral synthesis condition caused significant activity enhancement, giving CO conversion values of about 40% at 400°
C. Product distribution obtained with this catalyst indicated the formation of DME, ethanol, methanol as well as CH4 and CO2. Highest DME selectivity (60%) was observed with the catalyst prepared by physical mixing of commercial methanol reforming catalyst with silicotungstic acid incorporated methanol dehydration catalyst having W/Si ratio of 0.4.
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Narang, Monica Ajoo. « Expression of the human myotonic dystrophy kinase (DMK) gene in transgenic mice ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq26136.pdf.
Texte intégral
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Rajendran, Jaikishan. « DME/P critical area determination and its implementation on message-passing processor ». Ohio : Ohio University, 1992. http://www.ohiolink.edu/etd/view.cgi?ohiou1172867327.
Texte intégral
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Gerber, James B. « A cost benefit analysis of radio frequency identification (RFID) implementation at the Defense Microelectronics Activity (DMEA) ». Monterey, California. Naval Postgraduate School, 2011. http://hdl.handle.net/10945/10609.
Texte intégralRésumé :
This thesis focuses on the Defense Microelectronics Activity (DMEA) and its need to reduce its budget through becoming more efficient. There are many means for becoming more efficient; this report will analyze the adoption of radio frequency identification (RFID) technology as one way in which DMEA can achieve cost savings. The goal was to construct a working model to simulate factory conditions at electronics manufacturers' facilities, regardless of the size or breadth of production. The end state was to identify all major variables associated with the costs of RFID implementation, and the derived annual benefits, thereby giving decision makers an idea of the relative financial attractiveness of RFID.
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Lakshminarayanan, Sowmya. « A FRET based high content screen identifies DMPK as a novel tether of ER and mitochondria ». Doctoral thesis, Università degli studi di Padova, 2016. http://hdl.handle.net/11577/3424456.
Texte intégralRésumé :
Inter-organelle communication is a key feature of basic eukaryotic cells functions and of numerous cell signaling events (Bravo-Sagua et al., 2014). One of the best-characterized interorganelle cross talk is that between Endoplasmic Reticulum (ER) and mitochondria(Lopez-Crisosto et al., 2015). Also referred to as mitochondria associated ER-membranes (MAMs), the existence of mitochondria-ER contacts was uncovered 50 years ago through electron microscopic studies(Copeland and Dalton, 1959). The 90s saw the first break-through in functional significance of the MAMs, when Vance and Rizzuto et al., showed that exchange of phospholipids and calcium transfer occurs between the two organelles(Rizzuto et al., 1998; Vance, 1990). Despite the importance of the tether in metabolism and disease(Cali et al., 2013; Giorgi et al., 2015; Vance, 2014), only few proteins have so far been described to maintain the structural integrity of the tether in mammals (Lopez-Crisosto et al., 2015). MFN2was the firststructural tether to be identified. ER localized MFN2 forms homo and heterotypic interactions with mitochondrialMFN2 and MFN1, thus tethering the two organelles. As residual juxtapositionexist in Mfn2-/-cells, yet to be discovered tethersmust exist (de Brito and Scorrano, 2008). Hence, we set out to perform a genome wide screening to identify the structural components of the tether in mouse embryonic fibroblasts (MEFs). In order to perform the genome wide screening, we capitalized on the FRET based biosensor developed by Csordas et al., where CFP fused with FRB domain and YFP fused with FKBP domain were targeted to ER
(by a Sac 1 signaling sequence) and mitochondria (by an Akap signaling sequence) respectively (Csordas et al., 2010). We modified this biosensor by driving expression of both fluorescent molecules from a single mRNA, introducing between their cDNAs a self-cleaving Tav2A peptide(Luke et al., 2008). This modification allows expressing equimolar level of the proteins.
Thanks to FKBP and FRB binding domain, which interacts upon addition of rapamycin, we were able to study the basal and maximal level of juxtaposition between the two organelles. We then utilized this modified biosensor to perform a high content screen to identify molecules that either tether or space ER and mitochondria. We termed them as tethers and spacers respectively. We analyzed raw images from the screen and calculated the maximum number of contacts possible for every gene. Following automated image analysisand statistical analysis using R programming in cellHTS2 package of the primary screen performed on ~10,000 genes, we identified 14.4% genes as ER-mitochondria tethers (i.e., genes that once ablated increase the distance between the two organelles) and 5.3% genes as spacers (i.e., genes that once ablated decrease the distance between the two organelles). Pathway analysis using reactome and Panther predicted both existing and new pathways that are yet to explored in terms of ERmitochondria communication. Subcellular localization analysis of the tethers revealed eight proteins predicted to be present in both ER and outer mitochondrial membrane (OMM). One of the eight is myotonic dystrophy protein kinase (DMPK) and we have further characterized how DMPK tethers ER and mitochondria. DMPK is mutated in myotonic dystrophy 1 (DM1) (Cho and Tapscott, 2007). Having six known isoforms based on alternate splicing in humans and mouse (Wansink et al., 2003), DMPK’s role in myotonic dystrophy is not yet understood completely since the KO model of this gene developed late onset of myopathy and cardiac contractile dysfunction (Reddy et al., 1996). The subcellular localization either to ER or to mitochondria of the isoforms have been identified, although very less emphasis has been given to the functional relevance of different sub-cellular localizations. In conclusion, we have developed a new method to assess the proximity of ER and mitochondria and we have utilized this technology in a high content screen to identify novel structural components of the tether. The data from the screen has also spanned several existing pathways where ER-mitochondria junction has been implicated but not completely understood. Hence, the molecules identified from our screen, will help in unraveling the molecular players in these cellular pathways.La comunicazione tra organelli cellulari è una delle principali funzioni delle cellule eucariotiche e di numerosi processi di segnalazione (Bravo-Sagua et al., 2014). Uno dei cross-talk intracellulari maggiormente caratterizzati è quello tra reticolo endoplasmatico (ER) e mitocondri (Lopez-Crisosto et al., 2015). Definiti anche come “Membrane ER Associate ai Mitocondri” (MAMs), l’esistenza dei contatti tra mitocondri ed ER è stata scoperta più di 50 anni fa tramite studi di microscopia elettronica (Copeland and Dalton, 1959). Gli anni 90 videro poi il primo punto di svolta per la comprensione del significato funzionale dei MAMs quando Vance e Rizzuto et al., dimostrarono che lo scambio di fosfolipidi ed il trasferimento di ioni calcio avviene proprio nei punti di giunzione tra questi due organelli. Malgrado l’importanza di questi contatti nei processi metabolici e patologici, finora solo per poche proteine è stata descritta la funzione di mantenimentodell’integrità strutturale dei MAMsnei mammiferi (Lopez-Crisosto et al., 2015). MFN2 è stato il primo componente strutturale dei MAMs ad essere identificato. La componente di Mfn2 localizzata sulla membrana dell’ER è in grado di formare interazioni omo- ed eterotipiche con molecole di MFN2 e MFN1 presenti nella membrana mitocondriale, formando così un ponte tra i due organelli. Poiché una residua giustapposizione tra mitocondri ed ER è stata osservata anche in cellule Mfn2-/-, ne consegue che devono esistere altre molecoleancora da scoprire coinvolte nella modulazione dei contatti tra i due organelli. Abbiamo quindi voluto eseguire uno screening genomico su larga scala per identificare i componenti strutturali delle giunzioni tra mitocondri ed ER in fibroblasti embrionali murini (MEF). Per fare ciò, abbiamo sfruttato al meglio un biosensore basato sulla FRET sviluppato da Csordas et al., in cui la proteina CFP è fusa con il dominio funzionale FRB, e la proteina YFP con il dominio funzionale FKBP. Queste proteine andranno a legarsi rispettivamente all’ER (tramite la sequenza di localizzazione Sac1) ed ai mitocondri (tramite la sequenza di localizzazione Akap) (Csordas et al., 2010). Abbiamo modificato questo biosensore affinchéentrambe le molecole fluorescenti si trovassero su unico mRNA e la loro espressione fosse guidata da un singolo promotore, tramitel’introduzione tra i loro cDNA del peptide auto-catalitico Tav2a (Luke et al., 2008). Grazie ai domini di legame FKBP e FRB, che interagiscono dopo l’aggiunta di rapamicina, siamo stati in grado di misurare sia il livello basale sia il massimo livello di giustapposizione tra i due organelli. Abbiamo poi utilizzato questo biosensore così modificato per seguire uno screening genetico su larga scala in modo da identificare le molecole che avvicinano o allontanano ER e mitocondri, definite rispettivamente come “tethers” e “spacers”. Abbiamo analizzato le immagini non processate ottenute tramite lo screening e calcolato per ogni gene il numero massimo di contatti possibili. A seguito dell’analisi automatizzata delle immagini e successivamente dell’analisi statistica, effettuata utilizzando il pacchetto cellHTS2 tramite la programmazione in R,dei dati dello screening primario effettuato su ~10000 geni, abbiamo classificato il 14.4% dei geni come tethers tra ER e mitocondri (i.e., geni che una volta rimossi aumentano la distanza tra i due organelli) e il 5.3% come spacers (i.e., geni che una volta rimossi diminuiscono la distanza tra i due organelli). L’analisi dei processi cellulari in cui questi geni risultano coinvolti tramite i programmi Reactome ePanther ha evidenziato sia pathways già noti sia altri che devono ancora essere esplorati in termini di comunicazione tra mitocondri ed ER. L’analisi della localizzazione subcellulare delle proteine classificate come “tethers” ha rivelato otto proteine per cui è stata predetta la localizzazione sia all’ER sia nella membrana mitocondriale esterna (OMM). Una di queste otto proteine è DMPK (myotonicdystrophyproteinkinase), abbiamo quindi ulteriormente caratterizzato come DMPK tether tra ER e mitocondri. DMPK risulta mutata nella distrofia miotonica 1 (DM1) (Cho and Tapscott, 2007). Questa proteina presenta sei isoforme note dovute asplicing alternativo sia nell’uomo sia nel topo (Wansink et al., 2003). Il ruolo di DMPK nella distrofia miotonica non è ancora completamente chiarito, in quanto il modello animale KO per questo gene sviluppa tardivamente miopatia e disfunzioni cardiache contrattili (Reddy et al., 1996). La localizzazione subcellulare delle varie isoformeè stata riportata ai mitocondri o all’ER, tuttavia molta meno enfasi è stata data alla sua rilevanza funzionale. In conclusione, abbiamo sviluppato un nuovo metodo per determinare la prossimità tra ER e mitocondri ed abbiamo utilizzato questa tecnologia in uno screening genetico su larga scala per identificare nuovi componenti strutturali che regolano i contatti tra i due organelli. I dati ricavati da questo screening mettono in evidenza anche molti processi cellulari in cui le giunzioni tra mitocondri ed ER erano state implicate, ma il loro ruolo non è stato ancora completamente compreso. Le molecole identificate tramite il nostro screen aiuteranno quindi a svelare i componenti molecolari in questi pathways cellulari.
30
Rodrigues, Luiza Paulsen. « Identificação e avaliação da distribuição alélica de repetições do trinucleotídeo CTG no gene DMPK em indivíduos saudáveis e em pacientes com distrofia miotônica tipo 1 ». reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/158225.
Texte intégralRésumé :
O gene DMPK (Dystrophia Myotonica-Protein Kinase) humano está localizado no locus 19q13.3, sendo dividido em 15 éxons, com uma região polimórfica de repetições CTG em sua região 3’ não traduzida. Indivíduos normais apresentam de 5 a 34 repetições CTG. Indivíduos com alelos com mais de 50 repetições CTG apresentam distrofia miotônica tipo 1 (DM1), uma doença multissistêmica de herança autossômica dominante. Os sintomas incluem miotonia, fraqueza muscular progressiva, hipogonadismo, entre outros. Neste trabalho, a distribuição dos alelos do gene DMPK em indivíduos controles foi estabelecida em duas populações (brasileira e peruana), por meio de PCR convencional utilizando iniciadores fluorescentes e repeat-primed PCR. O protocolo confirmou 93 casos não relacionados de DM1 (76 brasileiros e 17 peruanos) após a análise de 224 amostras com suspeita clínica. A distribuição e as frequências dos alelos normais foram estabelecidas em ambas as populações e os alelos mais frequentes foram 5 (frequência = 0,326) e 13 (frequência = 0,545) repetições de CTG em brasileiros e peruanos, respectivamente. A frequência de alelos normais grandes (aqueles com mais de 45 repetições CTGs) foi de 9% e 4% em brasileiros e peruanos, respectivamente. Neste trabalho é descrita a análise molecular de DM1 na maior coorte brasileira até o momento e é o primeiro trabalho em que foi analisada a população peruana. A distribuição e a frequência de alelos normais também foram estabelecidas e alelos mutáveis foram detectados entre os indivíduos controles.The human DMPK (Dystrophia Myotonica-Protein Kinase) gene is located at 19q13.3 locus, being organized into 15 exons, with a polymorphic tract of CTG repeats in its 3' untranslated region. Normal individuals have 5-34 CTG repeats. Individuals carrying alleles with more than 50 CTG repeats have myotonic dystrophy type 1 (DM1), a multisystemic disease of autosomal dominant inheritance. Symptoms include myotonia, progressive muscle weakness, hypogonadism, among others. Disease prevalence is variable among populations and may be related to the frequency of large normal alleles (those with more than 18 CTG repeats). Here we determined here the distribution of alleles of DMPK gene in healthy and DM1 patients in Brazilian and Peruvian populations, through conventional PCR using fluorescent primers and repeat-primed PCR. This protocol confirmed 93 unrelated cases of DM1 (76 Brazilians and 17 Peruvians) following the analysis of 224 samples with clinical suspicion. Distribution and frequencies of normal alleles were also established in both populations and the most frequent alleles were 5 (frequency of 0.326) and 13 (frequency of 0.545) CTG repeats in Brazilians and Peruvians, respectively. Frequency of large normal alleles (those with more than 45 CTG repeats) was established to be 9% and 4% in Brazilians and Peruvians, respectively. This report describes molecular analysis of DM1 in the largest Brazilian cohort so far, and is the first to report any data in the Peruvian population. Distribution and frequency of normal alleles were also established and mutable alleles were detected among controls.
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O'Reilly, Sean W. P. « RNAi Screening of the Kinome Identifies PACT as a Novel Genetic Modifier of Foci Integrity in Myotonic Dystrophy type 1 ». Thèse, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/30639.
Texte intégralRésumé :
Myotonic Dystrophy type 1 (DM1), the most common form of adult muscular dystrophy (~1:8000) currently has no effective treatment. In DM1, expansion of a tri-nucleotide repeat in the 3' UTR of the DMPK gene results in DMPK mRNA hairpin structures, aggregating as insoluble ribonuclear foci. The resulting mis-regulation of important splicing factors, causes the inclusion of fetal exons in dozens of transcripts that contribute to the disease phenotype. In order to identify novel gene targets and kinase signalling pathways for potential therapeutics we have performed a high-throughput RNAi. RNA foci were visualized and quantified by in-situ hybridization. From our screen, we have identified a novel gene, PACT, as a modulator of foci integrity and that PACT knockdown can induce MBNL1 protein levels. The identified signalling complex represents a valid target for DM1 therapeutics. Our data further emphasizes the utility of RNAi screens in identifying disease-associated genes.
32
Chen, Mingqing. « Interactions between multi-kinase inhibitors and solute carrier transporters ». The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1585741410361704.
Texte intégral
33
Krejčí, Jan. « Optimalizace sítě pozemních radionavigačních prostředků zabezpečení RNAV ve FIR Praha ». Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2014. http://www.nusl.cz/ntk/nusl-231086.
Texte intégralRésumé :
This diploma thesis concerns with creating of study which deals with the optimization of the ground network infrastructure of radio navigation aids for RNAV in FIR Praha. The thesis contains an analysis of concept of development of Czech navigation environment and introduces DEMETER software, in which the optimization analyses are realized. The thesis describes DME/DME navigation system from the perspective of individual components and parameters. The actual study deals with an optimization of the ground network infrastructure of the radio navigation aids and includes the definition of network performance requirements, creation of general methodology of optimization of navigation performance analysis and a procedure of choosing a suitable placement of radio navigation aid. The integral parts of the study are analyses of current state of navigation performance and analyses of possible improvement of radio navigation infrastructure.
34
Seo, Kangwoo. « Experimental investigation of DME assisted gasoline CAI combustion with re-breathing valve strategy ». Thesis, Brunel University, 2015. http://bura.brunel.ac.uk/handle/2438/12194.
Texte intégralRésumé :
Controlled auto-ignition (CAI), also known as HCCI combustion in a gasoline engine has been extensively researched due to their potential of improved engine efficiency and low NOx emission. However, the combustion timing and the phasing of conventional CAI combustion depend on the in-cylinder condition, such as temperature and combustible mixture strength and thus cannot be directly controlled. In this study, direct DME (Dimethyl Ether) injection was adopted to increase the ignitability of premixed gasoline/air charge and to trigger the auto ignition of premixed charge. Re-breathing valve strategies were used to obtain hot internal EGR to eliminate a need of intake heating. Firstly, the pilot valve opening event, including its opening and closing timing, valve lift and dwell duration between the main valve event, was analysed by the WAVE simulation. Based on the analysis a re-breathing cam lobe was manufactured and installed on a Ricardo E6 engine to achieve the intake rebreathing and exhaust rebreathing operations. The intake re-breathing was realised by the pilot intake valve opening during the exhaust stroke and the exhaust re-breathing was achieved by the secondary exhaust valve opening during the intake stroke. Effects of the pilot intake valve open timing, 2nd DME injection timing, split DME injection ratio, air/fuel ratio and compression ratio were examined during the intake rebreathing operation. Then the performance and emission characteristics of DME assisted gasoline CAI combustion were examined during the exhaust re-breathing operation. Finally, results of the intake and exhaust re-rebreathing operations were compared to the conventional SI operation. The experimental study found that both the intake and the exhaust re-breathing operations provided enough heat to initiate DME assisted gasoline CAI combustion. The direct DME injection enabled to control the start of combustion and phasing. The quantity of the first DME injection showed greater effect than its timing, whereas the injection timing of 2nd DME injection had more dominant effect than its quantity. The exhaust re-breathing strategy provided stratified and hotter internal EGR that does not impact negatively on the volumetric efficiency because exhaust gas was re-breathed from the exhaust port during the intake stroke. High load of both CAI and SI baseline operations were limited by knocking combustion and their low load were limited by incomplete combustion. Exhaust re-breathing operation extended substantially the operational range of the DME assisted gasoline CAI combustion. Extremely low NOx emissions were obtained by DME/gasoline CAI operations. Most importantly, the exhaust rebreathing method produced dramatically improved overall efficiency of 43% compared to 28% of SI operation at a typical part-load operation of 4.0-5.0bar IMEP. It was also found that slightly improved efficiency and the extended operation range could be obtained by 33%:67% split DME injection ratio at higher load, while 67%:33% split DME injection ratio at lower load.
35
Dhakal, Pashupati. « Angular Magnetoresistance Oscillations in the Molecular Organic Conductor (DMET)2I3 : Experiment and Calculation ». Thesis, Boston College, 2010. http://hdl.handle.net/2345/1566.
Texte intégralRésumé :
Thesis advisor: Michael J. NaughtonQuasi-one dimensional (Q1D) molecular organic conductors are among the most exciting materials in condensed matter physics, exhibiting nearly every known ground state. They are highly anisotropic, structurally and electronically, and show large oscillatory phenomena in conductivity for magnetic field rotated in different crystalline planes. Several theoretical works have been published to explain these angular magnetoresistance oscillation (AMRO) effects, but the underlying physics remains illunderstood. Here, we present measurements and calculations of magnetotransport in the molecular organic (super)conductor (DMET)2I3 which detect and simulate all known AMRO phenomena for Q1D systems. Employing, for the first time, the true triclinic crystal structure in the calculations, these results address the mystery of the putative vanishing of the primary AMRO phenomenon, the Lebed magic angle effect, for orientations in which it is expected to be strongest. They also show a common origin for Lebed and so-called "Lee-Naughton" oscillations, and confirm the generalized nature of AMRO in Q1D systems. Furthermore, we report the temperature dependence of the upper critical magnetic field in (DMET)2I3, for magnetic field applied along the intrachain, interchain, and interplane directions. The upper critical field exhibits orbital saturation at low temperature for field in all directions, implying that superconductivity in (DMET)2I3 is conventional spin singlet
Thesis (PhD) — Boston College, 2010
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Physics
36
García, Trenco Andrés. « Desarrollo de catalizadores híbridos CuZnOAl2O3/zeolita para el proceso de síntesis directa de DME ». Doctoral thesis, Universitat Politècnica de València, 2014. http://hdl.handle.net/10251/34781.
Texte intégralRésumé :
El plan de investigación se centra en el estudio y diseño de catalizadores híbridos para el proceso de síntesis directa de dimetil éter (DME) a partir de gas de síntesis, también conocido en la literatura como "Syngas-To-DME o STD process" [1].
Para llevar a cabo el proceso de síntesis directa de DME se emplean catalizadores híbridos constituidos por mezclas físicas del componente de síntesis de metanol (catalizador basado en Cu) y el componente ácido que lleva a cabo la deshidratación de metanol para dar lugar al DME (zeolita) [1].
De manera general, las labores en las que se centra el plan de investigación persiguen lograr un mayor entendimiento de las propiedades del catalizador híbrido que determinan su comportamiento en el proceso de síntesis directa de DME (STD), prestando especial atención al componente zeolítico con el cual están asociadas la mayoría de controversias en la literatura científica.García Trenco, A. (2013). Desarrollo de catalizadores híbridos CuZnOAl2O3/zeolita para el proceso de síntesis directa de DME [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/34781
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Ahmad, Ruaa [Verfasser], et Manfred [Akademischer Betreuer] Döring. « Katalysatorsynthese umd -optimierung für die DME-Direktsynthese aus CO-reichem Synthesegas / Ruaa Ahmad ; Betreuer : Manfred Döring ». Heidelberg : Universitätsbibliothek Heidelberg, 2014. http://d-nb.info/1177811383/34.
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Photinon, Kanokorn. « DEVELOPMENT OF DIMETHYL ETHER (DME) AND CARBON DIOXIDE SENSORS USING PLATINUM NANOPARTICLES AND THICK FILM TECHNOLOGY ». Case Western Reserve University School of Graduate Studies / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1164899809.
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Jiang, Qian. « Direct dimethyl ether synthesis from CO2/H2 ». Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAF041/document.
Texte intégralRésumé :
DME est un carburant propre qui contribue à diminuer les émissions de gaz à effet de serre; il est aussi une molécule plate-forme pour le stockage d'énergie. L'objectif de la thèse est le développement de matériaux catalytiques bifonctionnels pour la synthèse directe de DME à partir de CO2/H2 à partir de Cu/ZnO/ZrO2 comme le catalyseur de la synthèse de méthanol à partir de CO2/H2 et Al-TUD-1 comme le catalyseur de déshydratation du méthanol en DME. Dans cette thèse, Al-TUD-1 a été étudiée comme un catalyseur de la déshydratation du méthanol en DME pour la première fois. Son activité en déshydratation du méthanol en DME augmente avec la diminution du rapport Si/Al. Les catalyseurs bifonctionnels ont été préparés par un procédé de dépôt par co-précipitation. Le SMSI a été démontré et était bénéfique pour la dispersion de cuivre métallique, la surface de cuivre métallique augmente avec le rapport Si/Al. Dans le même temps, on a observé le blocage des sites acides d'Al-TUD-1 par le cuivre. Afin d'exposer les sites acides d'Al-TUD-1, la méthode de « core-shell » a été adoptée pour préparer le catalyseur bifonctionnel. Elle aide à libérer la fonction acide en empêchant son blocage par le cuivre. Cette méthode de synthèse a été bénéfique pour la stabilité des particules de cuivre métalliques, mais des faibles conversions de CO2/H2 ont été observées en raison de l'inaccessibilité du noyau. Un autre catalyseur bifonctionnel a été préparé par une méthode de mélange physique pour comparaison. L'optimisation du catalyseur bifonctionnel Cu/ZnO/ZrO2@Al-TUD-1 pour la synthèse directe de DME à partir de CO2/H2 a permis d'éclairer les principaux paramètres affectant le contact intime de deux fonctions catalytiques: surface et dispersion du cuivre, les propriétés acide et basic, la présence d'eau et l'accessibilité des sites actifs pour les réactifsDME is a clean fuel that helps to diminish the emissions of green house gases; it is as well a platform molecule for the energy storage. The objective of the thesis is the development of bifunctional catalytic materials for the direct DME synthesis from CO2/H2 based on Cu/ZnO/ZrO2 as the methanol synthesis from CO2/H2 catalyst and Al-TUD-1 as the methanol dehydration to DME catalyst. In this thesis, Al-TUD-1 was investigated as the methanol dehydration to DME catalyst for the first time. The methanol dehydration to DME performance increases with the decrease of Si/Al ratio. The bifunctional catalysts were prepared by co-precipitation deposition method. The SMSI was demonstrated and was beneficial for the metallic copper dispersion, the metallic copper surface area increases with the Si/Al ratio. In the same time the blockage of acid sites of Al-TUD-1 by copper was observed. In order to expose the acid sites of Al-TUD-1, the core shell method was adopted to prepare the bifunctional catalyst. It helps to free the acid function preventing its blockage by copper. This method of synthesis was beneficial for the stability of metallic copper particles, but performed low conversions of CO2/H2 due to the inaccessibility of the core. Another bifunctional catalyst was prepared by physically mixing method for comparison. The optimization of the bifunctional Cu/ZnO/ZrO2@Al-TUD-1 catalyst for the direct DME synthesis from CO2/H2 allowed enlightening the main parameters that affect the intimate contact of two catalytic functions: copper surface area and dispersion, acid and basic properties, water presence and the accessibility of the active sites for the reactants
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Ding, Hao. « Facility separation criteria development and enhancement for directive Distance Measuring Equipment (DME) in the national airspace system ». Ohio University / OhioLINK, 1998. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1176835681.
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Godavarthi, Bhavya Sree. « A Computational Study on the Effect of Injection Strategy on Emissions in a DME Fueled CI Engine ». University of Akron / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=akron1449077797.
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Lee, Seungcheol [Verfasser], et R. [Akademischer Betreuer] Dittmeyer. « Novel bifunctional double-layer catalysts for application in microreactors for direct DME synthesis / Seungcheol Lee. Betreuer : R. Dittmeyer ». Karlsruhe : KIT-Bibliothek, 2016. http://d-nb.info/1082294624/34.
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Kakourou, G. « Protocol development for analysis of the DMPK repeat in preimplantation genetic diagnosis and the investigation of gene expression in human oocytes and blastocysts ». Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/18763/.
Texte intégralRésumé :
Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder caused by expansion of an unstable CTG repeat within the 3’UTR of the DMPK gene, which expands further in length during transmission from generation to generation. Prenatal diagnosis is available, although the decision for pregnancy termination can be difficult due to the variable phenotypic expression of DM1. In vitro fertilisation with preimplantation genetic diagnosis (PGD), offer another reproductive option for affected couples, which involves genetic analysis and selection of an unaffected embryo to establish a pregnancy. These technologies have also provided access to human gametes and preimplantation embryos and encouraged research aimed at understanding the molecular pathways controlling human preimplantation development. The first part of this study focused on the improvement of existing techniques for PGD and the development of universal multiplex fluorescent PCR PGD protocols for the efficient and accurate diagnosis of DM1. The second part of the study involved followup analysis of DM1 affected and unaffected embryos donated for research with the aim to investigate transmission of the CTG repeat from the affected and unaffected parent to the preimplantation embryo. The final objective was to obtain a global gene expression profile by microarray analysis of human oocytes and blastocysts, with a focus on important functional pathways. The protocols developed achieved high efficiency and accuracy of diagnosis, reduced the genetic work-up time, overall supporting PGD for DM1 as an effective and practical alternative to prenatal diagnosis. This study also adds to current evidence regarding CTG repeat transmission and provides information on repeat expansion and embryo quality in DM1. A comparison of expression in the healthy oocyte and blastocyst is presented, including the identification of oocyte-unique and blastocyst-unique genes. The microarray data from this study will guide experiments to identify cases where normal gene expression is disrupted.
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Kruger, Stephan J. « Validation of the precision distance measuring equipment (DME/P) module of the baseline microwave landing system (MLS) mathematical model ». Ohio : Ohio University, 1993. http://www.ohiolink.edu/etd/view.cgi?ohiou1175711926.
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Haubeil, J. Jeffrey. « Operational viability of a directive distance measuring equipment (DME) antenna in a national airspace system (NAS) approach and landing environment ». Ohio : Ohio University, 1996. http://www.ohiolink.edu/etd/view.cgi?ohiou1178311788.
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Merten, Charlotte Caroline [Verfasser]. « Analyse der Genexpression von humanen Stro-1-positiven Zahnkeim- und Beckenkammzellen in DME-Medium und osteogenem Differenzierungsmedium / Charlotte Caroline Merten ». Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2020. http://d-nb.info/1217062726/34.
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Ziat, Esma. « Emery-Dreifuss muscular dystrophy-associated FHL1 gene mutations : study of molecular and functional consequences in skeletal muscle ». Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066455.
Texte intégralRésumé :
La dystrophie musculaire d'Emery-Dreifuss (EDMD) est caractérisée par des retractions précoces, une faiblesse et atrophie musculaire lentement progressive, et une atteinte cardiaque. Les mutations des gènes EMD et LMNA sont respectivement responsables de formes liées à l'X et de formes autosomiques de l'EDMD. Ces deux gènes codent pour des protéines de l'enveloppe nucléaire, l'émerine et les lamines A/C. Les mutations du gène FHL1 ont été impliquées dans d'autres cas d'EDMD liée à l'X. FHL1 codent pour FHL1A, FHL1B et FHL1C, protéines jamais décrites comme localisées à l'enveloppe nucléaire. Nous avons cherché à enrichir les connaissances sur la distribution subcellulaire des différentes isoformes de FHL1 dans les muscles squelettiques humains sains et malades. Nous avons mis en évidence que les isoformes FHL1 présentent à la fois une localisation cytoplasmique et nucléaire dans les myoblastes humains. Au noyau, FHL1B est fortement accumulé au niveau de l'enveloppe nucléaire où il interagit avec les lamines A/C et l'émerine. Cette localisation à l'enveloppe nucléaire est indépendante de l'expression de l'émerine ou des lamines A/C. La différenciation des myoblastes entraîne une forte réduction de l'expression de FHL1B et de son exclusion progressive du noyau, n'impliquant pas la protéine CRM-1. Nous avons mis en évidence l'augmentation de l'expression de FHL1B dans les myoblastes de deux patients atteints d'EDMD, l'un porteur d'une mutation dans le gène LMNA, l'autre dans le gène FHL1. En conclusion, la localisation spécifique de FHL1B et sa modulation dans les myoblastes de patients confirment les cas d'EDMD liés à FHL1 comme des pathologies de l'enveloppe nucléaireEmery-Dreifuss muscular dystrophy (EDMD) is characterized by the triad of early contractures, slowly progressive muscle wasting and weakness, and cardiac disease. Mutations in EMD and LMNA, encoding for the nuclear envelope (NE) proteins emerin and lamin A/C, are associated with X-linked and autosomal form of EDMD, respectively. The discovery that FHL, encoding FHL1A, FHL1B and FHL1C, is implicated in the pathogenesis of EDMD, raises the question of how a non-NE protein can be linked to emerin and lamin A/C. We aimed to provide knowledge of the subcellular distribution and expression of the various FHL1 isoforms in healthy and diseased human skeletal muscle. We found that FHL1 isoforms display a dual cytoplasmic and nuclear localization in human myoblasts. In addition, FHL1B strongly accumulated at the NE where it interacted with both lamin A/C and emerin. NE localization of FHL1B was independent of emerin and lamin A/C expression. Myoblast differentiation resulted in greatly reduced FHL1B protein expression and in the progressive nuclear exclusion of FHL1 protein isoforms. We have shown that chromosome region maintenance 1 (CRM1)-mediated nuclear export was not involved in the progressive decrease of nucleoplasmic FHL1B. Finally, we detected increased FHL1B protein levels in myoblasts of two patients with LMNA- and FHL1-related EDMD. Altogether, the specific localization of FHL1B and its modulation in disease-patient’s myoblasts confirmed FHL1-related EDMD as a NE disease
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Neji, Najett. « Etude de la compatibilité radioélectrique du futur système de communication aéronautique en bande L ». Phd thesis, Supélec, 2011. http://tel.archives-ouvertes.fr/tel-00825251.
Texte intégralRésumé :
Au début des années 2000, les instances aéronautiques ont exprimé le besoin de développer un nouveau système de radiocommunication aéronautique du fait de l'augmentation du trafic aérien et de la saturation croissante des capacités de communication radio entre les aéronefs et les stations de contrôle aérien. L'une des composantes de ce système, nommée L-DACS (" L-band Digital Aeronautical Communication System "), devrait opérer dans la bande L-aéronautique (960-1164 MHz), dans laquelle fonctionnent également de nombreux autres systèmes radioélectriques. La compatibilité radioélectrique (CRE) de L-DACS avec ces systèmes est un des facteurs principaux à prendre en considération dans le développement d'un tel système.L'objectif principal de cette thèse est d'identifier les principaux problèmes reliés à la CRE et d'en étudier les cas critiques. Ces travaux sont fondamentaux en aéronautique, puisque tout dysfonctionnement dans la communication ou dans les systèmes de radionavigation peut mettre en danger la sécurité du vol. Les conclusions de cette thèse contribueront à la normalisation du système L-DACS et à la finalisation de ses spécifications.Dans une première étape, on étudie l'état de l'art dans les communications aéronautiques et en CRE. On analyse en particulier les dernières spécifications des deux systèmes candidats L-DACS. Ensuite, on propose un algorithme de calcul de brouillage dans le but d'étudier la CRE dans le domaine fréquentiel, d'en identifier et d'en traiter les cas critiques. L'analyse fréquentielle étant insuffisante dans plusieurs cas, on propose alors une approche temporelle d'étude de CRE. Après en avoir présenté les avantages, on présente un exemple d'étude de l'effet d'un système L-DACS sur un récepteur DME (" Distance Measuring Equipment ") à l'aide d'un banc de test CRE aéronautique.Cette thèse a été réalisée en collaboration avec la Direction Générale de l'Aviation Civile (DGAC), qui est un acteur principal pour la réglementation des communications et un affectataire de fréquence pour le spectre aéronautique en France. La thèse contribue aux études menées par la DGAC à l'échelle nationale et internationale.Dans les perspectives, on propose la poursuite de cette étude par une approche temporelle plus générale pour étudier la CRE entre des systèmes radioélectriques quelconques en tenant compte de paramètres supplémentaires liés à la dynamique des systèmes et aux propriétés de leurs technologies.
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Schedin, Niclas. « Alternativa Drivmedel som Enhetsdrivmedel ». Thesis, Försvarshögskolan, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:fhs:diva-3982.
Texte intégralRésumé :
Fossila drivmedel står idag för en överlägsen majoritet av den totala användningen av drivmedel som dagligen förburkas. Alternativ till de fossila drivmedlen krävs för att säkerställa tillgång i framtiden. Försvarsmakten har fått uppdrag från regeringen att utforska möjligheten att övergå till att driva sina fordon på förnyelsebara bränslen.Militära organisationer strävar efter ett enhetsdrivmedel, alltså ett gemensamt drivmedel som driver samtliga fordon och enheter. Största anledningen är den förenklade logistik som kan uppnås om endast ett drivmedel används.Detta arbete har sökt efter ett alternativt drivmedel som skulle kunna användas som enhetsdrivmedel inom Försvarsmakten. Detta för att lösa problematiken med att både byta till ett förnyelsebart drivmedel och ett enhetsdrivmedel i samma fas.Slutsatserna som dragit i detta arbete är att FT-bränslen har potential att användas som enhetsdrivmedel ur ett tekniskt perspektiv. Den höga flampunkt som FT-bränslen har skulle kunna innebära att även sjöfarkoster kan använda samma drivmedel som mark- och luftfarkoster. Dock saknas i dagsläget tillräcklig tillgänglighet och framställningen är i utvecklingsfasen.Fossil fuels currently account for the vast majority of the total amount of fuel that isconsumed globally every day. Alternatives to fossil fuels are needed to ensuresufficient supply in the future. The Swedish Armed Forces have been tasked by theGovernment to investigate and examine the possibility of operating their vehicles onrenewable fuels.Military organizations strive for the use of a single fuel concept. A single fuel conceptmeans that only one kind of fuel is used in all vehicles and machines. The majorreason for this is the simplified logistics that can be achieved if only one fuel is used.This paper has sought an alternative fuel that can also be used as a single fuel in theSwedish Armed Forces. In order to solve the problem of changing to a renewable andto a single fuel in one single step.The main conclusion drawn in this paper is that Fischer-Tropsch fuels have thepotential to be a single fuel from a technical perspective. The high flashpoint ofFischer-Tropsch fuels could mean that they might also be used in navy vessels.However, there is currently insufficient availability and production is in thedevelopment stages.
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Ginai, Maaria. « Incorporating primary human renal proximal tubule cells into a hollow fibre bioreactor in the development of an in vitro model for pharmaceutical research ». Thesis, Loughborough University, 2015. https://dspace.lboro.ac.uk/2134/20110.
Texte intégralRésumé :
Current in vitro cellular methods utilised in drug metabolism and pharmacokinetic (DMPK) studies during drug development do not provide the 3D structure and functions of organs found in vivo, such that resulting in vitro-in vivo extrapolation (IVIVE) may not always accurately reflect clinical outcome. This highlights the need for the development of new dynamic in vitro cell models to aid improvement of IVIVE. The aim of this project was to incorporate characterised primary renal cells within a hollow fibre bioreactor for use in DMPK studies investigating renal clearance. Fluorescence based assays were developed to assess the functionality of three drug transporters involved in the renal transport of pharmaceutical compounds: P-gp, BCRP and OCT2. The developed assays were then applied alongside transporter visualisation and genetic expression assays to characterise primary human proximal tubule cells over a series of population doublings. Cells at a population doubling of 5 demonstrated the best transporter activity whilst allowing cells to be expanded in vitro. Polysulfone (PSF) based membranes, which are widely used in dialysis components were developed by blending additives to improve renal cell attachment and culture. The membranes exhibited a characteristic porous internal structure with smooth skin layers on the surface, and were able to be sterilised via autoclaving due to their high thermal stability. PSF blended with polyvinylpyrrolidone (PVP) was the most hydrophilic with cell metabolic activity similar to standard tissue culture plastic. The production of hollow fibres of varying thicknesses and properties from the PSF and PVP blend yielded a marked difference in renal cell attachment and long term viability. Fibres incorporated into glass casings to produce the single hollow fibre bioreactors (HFBs) were able to be sterilised by autoclaving whilst remaining intact. Due to the variation of fibre integrity within the batch, many fibres exhibited tears within the HFBs. This ultimately led to cell depletion within the fibre over the culture period; however, intact fibres demonstrated an increase in cell growth towards the end of the culture period under flow conditions. These results demonstrate the progress made towards a small scale in vitro renal model incorporating characterised primary renal cells to aid the improvement of IVIVE in DMPK research.