Tesis sobre el tema "NRAP"
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Inder, Kerry y n/a. "The Functional Role of NRAP in the Nucleolus". Griffith University. School of Biomolecular and Biomedical Science, 2006. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20070201.133347.
Texto completoInder, Kerry. "The Functional Role of NRAP in the Nucleolus". Thesis, Griffith University, 2006. http://hdl.handle.net/10072/367738.
Texto completoThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
Full Text
Utama, B. "Isolation and characterization of Nrap, a novel nucleolar protein /". [St. Lucia, Qld.], 2001. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16281.pdf.
Texto completoMc, Grail Fernández Kimberley Anne. "Targeting NRAS mutant melanomas through metabolic stress". Doctoral thesis, Universitat Autònoma de Barcelona, 2021. http://hdl.handle.net/10803/673108.
Texto completoLos genes BRAF y NRAS presentan una mayor incidencia mutacional en melanoma cutáneo. Alteraciones en estos genes resultan en la activación constitutiva de la vía de RAS-ERK1/2, lo que contribuye activamente al desarrollo y la progresión tumoral del melanoma. Aunque ambas mutaciones dan lugar a alteraciones de la misma vía de señalización, ha sido ampliamente descrito que los tumores que se generan de las mismas, constituyen dos entidades diferentes tanto a nivel molecular como desde el punto de vista clínico. Una cuestión relevante reside en el hecho de que mientras los melanomas mutados en BRAF disponen de terapias específicas dirigidas contra el oncogén, los melanomas que presentan mutaciones en NRAS carecen de tratamientos específicos. Como consecuencia, estos pacientes son tratados con tratamientos antitumorales más genéricos, que desembocan en tasas de respuesta mucho menores y en una elevada toxicidad. En este contexto, el desenmascaramiento de las diferencias moleculares existentes entre los tumores con mutaciones en BRAF y en NRAS es esencial para el establecimiento de nuevas estrategias terapéuticas dirigidas a pacientes que presentan mutaciones en NRAS. Resultados obtenidos previamente en nuestro grupo de investigación, sumados a los de otras investigaciones, han confirmado la presencia de diferentes patrones metabólicos sujetos a la regulación por BRAFV600E. Sin embargo, apenas existe evidencia sobre el papel de las mutaciones en NRAS en la regulación metabólica. El establecimiento de características metabólicas específicas de melanomas con mutaciones en NRAS podría contribuir al desarrollo de nuevos enfoques terapéuticos dirigidos contra este tipo de tumor. Durante el desarrollo de este estudio hemos investigado las implicaciones moleculares derivadas de la falta de glucosa en células de melanoma mutadas en NRASQ61 y BRAFV600E, con el fin de establecer si la presencia de características metabólicas dependientes de NRAS podría ser explotada para el desarrollo de nuevas terapias contra este tipo de tumor. En este estudio, hemos demostrado la presencia de patrones metabólicos bajo el control de NRASQ61. Las células que presentan mutaciones en NRASQ61 muestran una respuesta diferencial al estrés metabólico, en comparación con las células mutadas en BRAFV600E, que desemboca en la hiperactivación de la vía de RAS-ERK1/2 y en la sensibilización de estas células al inhibidor multi-quinasa Sorafenib. PFKFB2, PFKFB3 y PFK-1 son elementos clave en la regulación de este proceso. Adicionalmente, proponemos una nueva aproximación terapéutica para el tratamiento dirigido de los melanomas mutados en NRASQ61, basada en la combinación de 2-deoxi-D-glucosa (2DG) y Sorafenib. Tras los resultados obtenidos, podemos concluir que los tumores que presentan mutaciones en NRAS y BRAF son entidades diferentes a distintos niveles, no solo a nivel clínico y molecular, sino también a nivel metabólico, lo que implica la existencia de nuevas ventanas terapéuticas para el tratamiento de tumores que presentan mutaciones en NRAS.
BRAF and NRAS are the most commonly found mutated genes in cutaneous melanoma. Alterations in these genes result in the constitutive activation of the RAS-ERK1/2 pathway, contributing to tumor development and progression. Beside both genes are consecutive located in the same signaling cascade, BRAF and NRAS mutated tumors are considered two different entities at clinical and molecular levels, resulting in distinct signaling patterns and different biological behavior. Furthermore, while there is a first line of treatment using targeted therapy against BRAF mutant melanomas, NRAS mutant tumors remain without specific line of treatment, showing low response rates and high toxicity to the currently applied therapies. Thus, the understanding of the molecular differences between BRAF and NRAS mutant tumors is essential to improve therapeutic opportunities for the treatment of patients carrying NRAS mutations. Previous results in our group, together with additional investigations, have highlighted the presence of different metabolic settings subjected to BRAFV600E oncogene regulation. However, little is known about the role of NRAS mutations in metabolic rewiring. Deciphering metabolic settings in NRAS mutant melanomas could provide new avenues for the establishment of specific therapeutic approaches against these, until now, untargetable tumors. In this study, we have investigated the molecular implications of glucose starvation in NRASQ61 and BRAFV600E mutant cells in order to establish whether the presence of NRAS-dependent metabolic settings can be exploited for the development of targeted therapies against NRAS mutant melanomas. Overall, in this study we have demonstrated the presence of NRASQ61 oncogene-dependent metabolic settings. NRASQ61 mutant cells show a differential response to metabolic stress when compared to BRAFV600E mutant cells, which results in the hyperactivation of the RAS-ERK1/2 pathway and the sensitization to the multikinase inhibitor Sorafenib. PFKFB2, PFKFB3 and PFK-1 are key players in the regulation of this process. We also propose a novel approach for the specific targeting of NRASQ61 mutant melanomas based on the combination of 2-deoxy-D-glucose (2DG) and Sorafenib. We conclude that NRAS and BRAF mutant tumors are different entities at different levels, not only at molecular and clinical levels but also at metabolic level and this fact provides a new therapeutic window for the targeting of NRAS mutant tumors.
Universitat Autònoma de Barcelona. Programa de Doctorat en Bioquímica, Biologia Molecular i Biomedicina
Mosigi, Wilson. "Role and procedures of natural resources accounting (NRA) : an NRA framework for Botswana". Master's thesis, University of Cape Town, 2000. http://hdl.handle.net/11427/5737.
Texto completoThis paper aims to show the role that NRA can play in environmental and economic accounting, and the procedures that need to be followed when carrying out natural resources accounting. The paper first reviews the SNA and its shortcomings regarding the treatment of the environment and natural capital. This is done by looking at the SNA classification of assets and examining how far environmental attributes are accounted for. Then the paper proposes the use of NRA to correct the deficiencies of the SNA Satellite accounts are suggested for resource based sectors in the Botswana economy, in order to augment national accounts. It is stressed that economic growth is only correctly reflected if the accounting prices used reflect full opportunity costs i.e. correct for externalities.
Filho, João Bosco de Oliveira. "Mutação em NRAS causa uma síndrome autoimune linfoproliferativa humana". Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5144/tde-04112008-174252/.
Texto completoThe p21 RAS subfamily of small GTPases, including KRAS, HRAS, and NRAS, regulates cell proliferation, cytoskeletal organization and other signaling networks, and is the most frequent target of activating mutations in cancer. Activating germline mutations of KRAS and HRAS cause severe developmental abnormalities leading to Noonan, cardio-facial-cutaneous and Costello syndrome, but activating germline mutations of NRAS have not been reported. Autoimmune lymphoproliferative syndrome (ALPS) is the most common genetic disease of lymphocyte apoptosis and causes autoimmunity as well as excessive lymphocyte accumulation, particularly of CD4-, CD8- ab T cells. Mutations in ALPS typically affect Fas-mediated apoptosis, but certain ALPS individuals have no such mutations. We show here that the salient features of ALPS as well as a predisposition to hematological malignancies can be caused by a heterozygous germline Gly13Asp activating mutation of the NRAS oncogene that does not impair Fas-mediated apoptosis. The increase in active, GTP-bound NRAS augmented RAF/MEK/ERK signaling which markedly decreased the pro-apoptotic protein BIM and attenuated intrinsic, nonreceptor-mediated mitochondrial apoptosis. Thus, germline activating mutations in NRAS differ from other p21 Ras oncoproteins by causing selective immune abnormalities without general developmental defects
Burge, Erin Jeffrey. "A Mycobacterium-inducible Nramp in striped bass Morone saxatilis". W&M ScholarWorks, 2003. https://scholarworks.wm.edu/etd/1539616588.
Texto completoLe, Thi Van Anh. "Characterization of poplar metal transporters to improve rehabilitation of metal polluted soils". Thesis, Paris 11, 2015. http://www.theses.fr/2015PA112004/document.
Texto completoPhytoremediation is the use of plants to clean up polluted soils. Previous approaches have mostly used native plants able to tolerate, degrade and accumulate environmental pollutants such as toxic metals, but transgenic plants may also be considered for phytoremediation in the future. Poplar is well adapted for phytoremediation and suitable for molecular genetic studies. However, high metal accumulation in poplar leaves limits phytoextraction due to toxic metal return to the soil after leaf abscission. In order to circumvent this problem, genetic engineering can be used to limit metal accumulation in leaves or direct metal accumulation in poplar trunks using relevant metal transporter genes under the control of tissue-specific promoters. This thesis focuses on the characterization of 3 candidate metal transporters potentially involved in metal tolerance and accumulation in poplar: PtIREG1, PtNRAMP3.1 and PtNRAMP3.2. Expression of PtIREG1 in yeast and in Arabidopsis thaliana indicated that it contributes to nickel tolerance. Transgenic poplars were generated in which PtIREG1is either ectopically overexpressed or expressed specifically in wood tissues. PtNRAMP3.1 and PtNRAMP3.2 transgenic plants were also generated during this thesis. Despite their high similarity, PtNRAMP3.1 and PtNRAMP3.2 displayed distinct localizations in poplar: PtNRAMP3.2 is targeted to the vacuolar membrane whereas PtNRAMP3.1 localizes in a compartment connected with the Golgi apparatus. Metal concentrations were modified in leaves of transgenic plants grown on metal-contaminated or non-contaminated soil. The results obtained will contribute to develop a biotechnological approach using transgenic plants for the rehabilitation in metal polluted soils
Najem, Ahmad. "Drug combination strategies to abrogate resistance in NRAS mutant melanoma". Doctoral thesis, Universite Libre de Bruxelles, 2017. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/258096.
Texto completoDoctorat en Sciences biomédicales et pharmaceutiques (Pharmacie)
info:eu-repo/semantics/nonPublished
Longvert, Christine. "Rôle de NRAS et PTEN au cours de la mélanomagenèse". Phd thesis, Université René Descartes - Paris V, 2012. http://tel.archives-ouvertes.fr/tel-00787304.
Texto completoVaughan, Russell John. "The Nramp family of transition metal transporters in Arabidopsis thaliana". Thesis, University of Southampton, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427450.
Texto completoChim, Florence Yi Ting. "Sindbis Virus Entry of Mosquito Midgut Epithelia...Is NRAMP Involved?" UNF Digital Commons, 2015. http://digitalcommons.unf.edu/etd/614.
Texto completoBane, Lukas. "Structural and Functional Studies Into Nramp Divalent Metal Transporter Mechanisms". Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845404.
Texto completoBiology, Molecular and Cellular
Picha, James Rothwell. "An accurate beam model for the NRAO 91 meter radio telescope". Thesis, University of British Columbia, 1986. http://hdl.handle.net/2429/26320.
Texto completoScience, Faculty of
Physics and Astronomy, Department of
Graduate
Gruenheid, Samantha. "Nramp genes : roles in resistance to infection and in iron metabolism". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0029/NQ64565.pdf.
Texto completoLam-Yuk-Tseung, Steven. "Nramp metal transporters : insights into their structure, function, and subcellular targeting". Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=102520.
Texto completoBraune, Jan [Verfasser] y Nikolas von [Akademischer Betreuer] Bubnoff. "Zirkulierende Tumor DNA erlaubt Therapiemonitoring in BRAF und NRAS mutiertem malignem Melanom". Freiburg : Universität, 2021. http://d-nb.info/1231232560/34.
Texto completoRemold, Anna [Verfasser] y Volker [Akademischer Betreuer] Heinemann. "NRAS und SMAD4 als Biomarker bei fortgeschrittenem Pankreaskarzinom / Anna Remold ; Betreuer: Volker Heinemann". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/116655953X/34.
Texto completoWhite, Jacqueline Katie. "Analysis of human NRAMP, IL8R and V1L1 genes (2q35) using yeast artificial chromosomes". Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.339595.
Texto completoAlmedom, Ruth [Verfasser], Alexander [Akademischer Betreuer] Gottschalk y Walter [Akademischer Betreuer] Volknandt. "Funktionelle Charakterisierung zweier Levamisolrezeptor-assozierter Proteine in C. elegans - NRA-2 und NRA-4 / Ruth Almedom. Gutachter: Alexander Gottschalk ; Walter Volknandt. Betreuer: Alexander Gottschalk". Frankfurt am Main : Univ.-Bibliothek Frankfurt am Main, 2013. http://d-nb.info/1043978232/34.
Texto completoKim, James [Verfasser] y Jochen Sven [Akademischer Betreuer] Utikal. "STAT3 – the switch of melanoma-associated NRAS mutations / James Kim ; Betreuer: Jochen Sven Utikal". Heidelberg : Universitätsbibliothek Heidelberg, 2021. http://nbn-resolving.de/urn:nbn:de:bsz:16-heidok-301399.
Texto completoDuggan, Megan C. "The Role of Novel NRAS Isoforms in Melanoma Disease Progression and BRAF Inhibitor Resistance". The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1491229758308229.
Texto completoCale, Jessica. "Functional analysis of a rare disease variant in human NRAS causing Noonan-Like syndrome". Thesis, Cale, Jessica (2016) Functional analysis of a rare disease variant in human NRAS causing Noonan-Like syndrome. Honours thesis, Murdoch University, 2016. https://researchrepository.murdoch.edu.au/id/eprint/35093/.
Texto completoCailliatte, Rémy. "Caractérisation physiologique et moléculaire de la famille de transporteurs de métaux NRAMP chez Arabidopsis thaliana". Montpellier SupAgro, 2009. http://www.theses.fr/2009NSAM0010.
Texto completoDuring my thesis I have undertaken the functional and physiological characterization of three members of the NRAMP family (for Natural Resistant-Associated Macrophage Protein) in Arabidopsis thaliana. The members of this gene family, occurring in organisms like bacteria, yeast or vertebrate, code for metal transporters. The NRAMP proteins are mainly involved in the uptake and distribution of iron in the cells. In plants, the mechanisms controlling Fe uptake are quite well characterized whereas the following steps of distribution between organs, cells and organelles are less understood. First, I have shown that the AtNRAMP6 gene is expressed in the vascular system of leaves, in the sepals, the septum of the silique and in the funiculus of the seeds. The heterologous expression of AtNRAMP6 in the yeast Saccharomyces cerevisiaeinduces an increased sensitivity to cadmium. The study of “knock out” and over expressor plants has shown that this gene is involved, in planta, in cadmium tolerance, probably by controlling intra-cellular pools of Cd. Second, through the complementation of the yeast mutant ∆smf2, I have shown that AtNRAMP2 encodes an intra-cellular manganese (Mn) transporter. In Arabidopsis thaliana, the “knock out” mutant nramp2-1 is disregulated in the Mn homeostasis, due to a defect in Mn targeting to the chloroplasts that eventually affects the photosynthetic activity. The AtNRAMP2 protein is not targeted to the chloroplasts but rather to intra-cellular organelles probably related to peroxysomes, and plays a crucial role in the targeting of Mn to chloroplasts. Finally, I have shown that the AtNRAMP1 gene, expressed in the root cortex, encodes a plasma membrane located protein. AtNRAMP1 can complement the ∆smf1 yeast mutant impaired in Mn acquisition from the growth medium. Influx experiments realized on roots from “knock out”, over-expressors and control plants have established that AtNRAMP1 controls the high affinity uptake of Mn in plants
Heux, Pauline. "Différenciation des cellules de la crête neurale lors de l'activation constitutive des protéines NRAS ou BRAF". Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0529/document.
Texto completoMelanocytes are the vertebrate cells that produce melanin, conferring color on skin, hair and eyes. They arise from a multipotent embryonic cell population called the neural crest, which also gives rise to the peripheral nervous system of the body and many other cell types. Abnormal proliferation of melanocyte precursors before birth can lead to human congenital melanocytic nevus (CMN). CMN are caused by prenatal somatic mutations in the NRAS or BRAF genes of the MAP-Kinase pathway, in one of these precursors. The largest CMN, covering entire segments of the body or head, are syndromic. They are sometimes associated with epileptogenic brain or meningeal malformations, tumors or melanocytosis, and they present a risk of about 5% in all these sites of becoming pediatric malignant melanoma. During my thesis, I explored mouse models expressing constitutively activated NRAS or BRAF proteins in neural crest cell lineages, from very early in embryogenesis. BrafV600E mutant embryos are embryonic lethal at mid-gestation, probably due to coinciding vascular and brain defects. In contrast, NrasG12D mice are viable, present extracutaneous melanocytosis in various sites as well as postnatal hyperpigmentation of the skin. This is associated with increased hair follicle density, and a deregulated hair cycle. Cell culture of mutant or wildtype mouse neural crest cells of both genotypes has permitted the comparison and discovery of molecular differences introduced by these mutations
Lanquar-Danon, Viviane. "Approches de génétique moléculaire et de protéomique pour l'analyse de l'homéostasie métallique chez Arabidopsis thaliana". Paris 11, 2007. http://www.theses.fr/2007PA112084.
Texto completoIn plants, metal transporters play major roles in intracellular metal homeostasis. Many metal transporters are able to transport essential metal as well as toxic metals. To understand the relationship between the transport of essential metals and the detoxification of noxious metals in Arabidopsis, we have used two strategies: a targeted approach with the aim to elucidate the function of NRAMP metal transporters and a global proteomic approach to identify novel plasma membrane proteins regulated under cadmium stress. NRAMP are able to transport a broad range of metals such as Fe, Mn and Cd. Using a combination of molecular genetic, cell biological and analytical approaches, we have shown that AtNRAMP3 and AtNRAMP4 are vacuolar membrane proteins with several redundant functions: during seed germination they are essential to mobilize vacuolar Fe stores while in adult plant they are required to recycle Mn from the vacuole. In addition, the nramp3nramp4 double mutant is also hypersensitive to the oxidative stress generated by cadmium and AtNRAMP3 and AtNRAMP4 accumulates after an oxidative stress. These proteins could be involved in the supply of metal cofactors to reactive oxygen species detoxifying enzymes. The plasma membrane is the first interface where Cd stress is perceived and where cadmium may be taken up or extruded from the cell. In order to characterize novel intrinsic proteins involved in these functions, we have developed a comparative proteomic strategy based on 15N metabolic labeling of Arabidopsis cell. Comparative analysis of the plasma membrane proteome is under way and we have already identified candidate proteins regulated by Cd
Petti, Carlotta. "Identification of molecular targets of oncogenic NRAs and BRAF involved in regulation of melanoma cell proliferation". Thesis, Open University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437808.
Texto completoDorard, Coralie. "Rôle des protéines RAF dans le développement du mélanome induit par NRas q61k chez la souris". Paris 7, 2014. http://www.theses.fr/2014PA077090.
Texto completoThe RAS/RAF/ERK pathway plays a key role in melanoma, with BRAF and NRAS mutations in 50% and 15% of cases, respectively. The development of chemical inhibitors specifically targeting mutated v600EBRAF represents a major breakthrough in the treatment of metastatic melanoma, although resistance often develops quickly following treatment. Furthermore, such compounds cannot be used to treat half of melanoma patients, especially those mutated on NRAS. In this study, we evaluated the contribution of BRAF and its closely related kinase CRAF downstream of NRAS during tumoral progression in mouse models. We developed NRASQ61K-induced mouse melanoma models in which single or compound ablation of BRAF and CRAF genes can be achieved in the melanocyte lineage upon tyrosinase promoter-driven Cre or CreERT2 expression. These models allowed us investigating the role of both RAF kinases at each step of tumoral progression, from tumor initiation to metastatic melanoma. Temporaly-controlled concomitant ablation of BRAF and CRAF abolished nevi formation and melanoma progression and maintenance, showing that RAF signaling is absolutely required for NRAS-induced melanoma development. However, we will present data showing that BRAF and CRAF play specific roles during the different steps of melanoma progression. In addition, using primary cultures of melanomas, we show that ablation of RAF kinases often lead to the emergence of resistant cells showing reactivation of ERK in the absence of BRAF and CRAF. Our results disclose specific and complementary functions for BRAF and CRAF in NRAS-induced mouse melanoma, and pave the road for further studies on treatment and resistance mechanisms
Rouillé, Thomas. "Modèles d'étude pour l'évaluation préclinique de thérapies ciblées dans le nævus congénital mélanocytaire humain Clonogenic Cell Subpopulations Maintain Congenital Melanocytic Nevi Varying proliferative and clonogenic potential in NRAS-mutated congenital melanocytic nevi according to size". Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS593.
Texto completoCongenital melanocytic nevi (CMN) are benign cutaneous tumors resulting from melanocytic proliferation during fetal development. CMN of more than 20cm in diameter are associated with socio-aesthetic issues and an increased risk of malignant transformation into melanoma. Most lesions are characterized by a single mutation affecting the oncogene NRAS, which leads to the expression of a constitutively active protein. For patients harboring CMN, the only validated treatment is surgical resection, though they are often incomplete and do not prevent the risk of melanoma emergence. Our objective was to characterize the molecular pathways deregulated downstream of NRAS, and to validate in vitro as well as in two innovative preclinical models of CMN (ex vivo CMN explants and xenografts on immunocompromised mice Rag2-/-) the effects of inhibitory molecules of those pathways. Fourteen patients harboring NRAS mutated CMN were prospectively included in our study. Our in vitro experiments reveal an overactivation of MAPK and PI3K-AKT signaling pathways in CMN cells. In vitro, MEK and AKT inhibitors (respectively Binimetinib and GSK690693) induce a decrease of proliferation and survival. Ex vivo and in vivo, inhibitors induce a decrease in nevocytic cells Sox10+ and Melan-A+ as well as a decrease in proliferative cells Ki67+, especially when combined. The associated goal of our study is to develop an intra-tumoral therapy, to be used as an adjuvant or neo-adjuvant therapy, and adapted to the genetic profile of these tumors, in order to decrease tumor volume and avoid repeated and mutilating surgeries, and potentially decrease the risk of malignant transformation
Liebscher, Steffi. "Die Bedeutung von VEGF-C und NRP-2 für die Strahlenresistenz im Prostatakarzinom". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-222372.
Texto completoBackground In addition to radical prostatectomy, radiotherapy is a standard therapy for the treatment of prostate tumours and leads to good results for local tumour control and survival. However, as with the resection, the risk of recurrence for advanced tumours is relatively high compared to tumours in earlier stages. Therefore, there is a high urgency to improve radiotherapy especially for advanced stages. One approach is the combination of irradiation with molecular therapies. The aim is to block certain target proteins to increase the radiosensitivity of the prostate carcinoma cells. A potential target could be the blockade of the VEGF-C/NRP-2/Akt signalling pathway (VEGF-C – vascular endothelial growth factor C; NRP-2 – neuropilin 2; Akt – protein kinase B). In prostate cancer the concentrations of VEGF-C and NRP-2 are increased compared to normal prostate cells. Studies have shown that both proteins have a progressive effect on tumourigenesis. In preliminary work Muders et al. (2009) also showed the activation of Akt via the VEGF-C/NRP-2 axis and a resistance to H2O2 induced oxidative stress. Akt also has a protective effect against irradiation in various tumour entities. It is assumed that this also applies to prostate carcinoma cells. Aim of the study Within the framework of this thesis, it was investigated whether and via which mechanism VEGF-C, NRP-2, and Akt affect the radioresistance in prostate carcinoma cell lines. Methods In vitro and in vivo experiments were performed in the human prostate carcinoma cell lines PC-3, DU145, LNCaP, as well as in PC-3 xenografts. The influence of VEGF-C and NRP-2 on the radioresistance was examined in vitro after knock down of the corresponding genes using siRNA or after supplementation with human recombinant VEGF-C in colony formation assays. In order to determine the influence of VEGF-C and NRP-2 on possible cell survival mechanisms, the autophagic flux was examined after the blockade of autophagy with bafilomycin A1 using western blot, the DNA double strand break repair by quantification of the γH2AX foci, and the cell cycle distribution by flow cytometry. The signal transduction of VEGF-C via Akt as well as, as a further possibility, the signal transduction via ERK1/2 were tested after siRNA transfection with and without irradiation using western blot. Further experiments on Akt were performed in vitro and in vivo with the PI3K/Akt inhibitor nelfinavir in PC-3 cells. The in vitro effect of nelfinavir on radioresistance was tested using a colony formation assay after treatment of the cells with 10 μM nelfinavir. In vivo, the effect of nelfinavir without and in combination with irradiation in PC-3 xenografts was investigated in nude mice. For the determination of the tumour growth time, the mice were treated with 80 mg nelfinavir/kg body weight 30 times within 6 weeks. In a further experiment, the local tumour control was determined with simultaneous fractionated irradiation with total doses of 30 to 120 Gy and a follow-up time of 180 days. Results The investigations on radioresistance via the VEGF-C/NRP-2/Akt signalling pathway showed that in the three prostate carcinoma cell lines PC-3, DU145, and LNCaP VEGF-C significantly mediates radioresistance. For NRP-2 however, it was found that, depending on the cell line, it either leads to radioresistance (DU145) or radiosensitization (PC-3). Further, it was shown that in PC-3 and DU145 VEGF-C does not mediate radioresistance via Akt or ERK1/2. The experiments on radioresistance mediating mechanisms revealed that VEGF-C promotes autophagy in untreated PC-3 cells, but NRP-2 does not. Under irradiation, an effect of VEGF-C and NRP-2 on autophagy could not be detected reproducibly. A further experiment has shown that in PC-3 autophagy has no influence on the clonogenic survival after irradiation. In addition, it was found that VEGF-C does not affect the DNA double strand break repair in PC-3. Furthermore, it was shown that a reduction in the VEGF-C content leads to a G2/M arrest in PC-3. However, no effect could be observed in DU145. In studies regarding the influence of Akt on radioresistance independent of VEGF-C and NRP-2, nelfinavir inhibited Akt phosphorylation at Ser473 and minimally affected the clonogenic survival of PC-3 cells. In PC-3 xenografts, nelfinavir did not lead to any tumour growth delay and did not have a radiosensitizing effect in vitro or in vivo. Conclusion In the experiments, it was shown that VEGF-C mediates radioresistance in prostate cancer cells. This finding could serve as a research approach for the development of a combined therapy of a VEGF-C blockade and irradiation. A potential mechanism by which VEGF-C mediates radioresistance is the reverse of the G2/M arrest, depending on the cell line. NRP-2 acts differently in the mediation of radioresistance or radiosensitivity, depending on the cell line. On this, further investigations should be carried out with regard to possible interactions within other signalling pathways with a radiosensitizing influence. Within the investigated signalling pathway, it was further shown that VEGF-C does not mediate radioresistance via Akt. The present work contains the first study examining the effect of nelfinavir in combination with irradiation on prostate cancer cell survival in vitro as well as on growth time and local tumour control in vivo. Herein no radiosensitizing effects of nelfinavir could be detected. Since nelfinavir radiosensitizes cells of other tumour entities and is also known to interfere with a series of signalling pathways that promote or inhibit cell survival, it should be clarified whether tumour cells with a particular genetic profile are more responsive to treatment with nelfinavir
Santos, Hellen Cristine dos. "Caracterização de espadas antigas por técnicas não destrutivas". Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/43/43134/tde-16102014-134346/.
Texto completoA set of physical techniques have been applied to characterize archaeological and art artifacts and contribute to its preservation and restoration. The application of these techniques are indicated because they are non invasive methods, preserving the material to be analyzed. In this work, we propose a procedure to investigate indirectly the hardness of ancient swords, by nondestructive techniques. With this aim, we decided to apply the techniques PIXE, NRA, XRD and RBS in the study of ancient swords, specially Indian (Damascus blade) and a Japanese (Wakizashi) swords. With PIXE we identified the major compounds in the blades and in their grips. In the Indian blade were identified the following elements: Cr, Mn, Fe, Ni, Cu, Zn e As. In the Japanese only iron was identified, although, with RBS we could identified a thin _lm of carbon on its surface. The grips were also analyzed and the results indicated to Indian were: Cr, Fe, Cu and Au; and to Japanese: Fe, Cu, As e Ag in the peace Habaki, and S, Cl, K, CA, Fe, As e Au in the peace Fuchi, those pieces are part of the grip. The XRD technique was applied to verify the crystalline structure which were formed during the forging process (hammering and quenching). These information can help to understand more about the quenching and hammering process. The crystalline phase in the surface of the blade was identified as iron. The surface is composed by crystallites oriented with grain size in order to 200_A, oriented as the result of hammering process. Also there is an amorphous phase in the Japanese blade, suggesting that in the forje process the temperature achieved was lower when compared with the Indian sword. The Damascus blade is famous due its hardness and ductility. An element that can improve these characteristics is the nitrogen. Its determination is possible using NRA technique, more specially the reaction 15N(p; _)12C. The nitrogen could been insert in the blade during the edge hardness process (in this process the blade was quenched into animal urine that its main compound are uric acid (C5H4N4O3) and urea (NH2)2CO, or in a brine). It was not possible to identify the presence of nitrogen within our limit of quantification.
Nunally, Michael Lee. "Website Design and Development for College and University Recreation Programs Accredited by the NRPA/AALR Council on Accreditation". TopSCHOLAR®, 2004. http://digitalcommons.wku.edu/theses/209.
Texto completoBaker, Anne-Marie. "Natural resistance-associated macrophage protein (Nramp) : genetic mapping around the locus on chromosome 1 and comparative sequence analysis". Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388368.
Texto completoPIMENTEL, Clebson Pantoja. "Investigação de ocorrência de alterações moleculares nos genes KRAS, HRAS, NRAS e BRAF em carcinoma papilífero da tireóide". Universidade Federal do Pará, 2018. http://repositorio.ufpa.br/jspui/handle/2011/9976.
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O tipo mais comum de câncer de tireoide é o Carcinoma Papilífero (PTC), que representa 80% de todos os casos de neoplasias que acometem essa glândula. O PTC é um tumor maligno, de evolução lenta, que ocorre em qualquer idade, com maior frequência entre 30 a 40 anos. A via metabólica MAPK é a via mais associada ao PTC. Dentre as muitas proteínas que atuam nessa via e que se encontram alteradas nos casos de PTC, destacam-se aquelas codificadas por genes pertencentes às famílias RAS e BRAF. Considerando que na Amazônia brasileira, os estudos genéticos e clínicos sobre o câncer de tireoide são raros, o presente trabalho teve como objetivo investigar possíveis alterações nos genes HRAS, NRAS, KRAS e BRAF em pacientes portadores de PTC oriundos de um hospital público da cidade de Belém (PA), e fazer a associação entre a mutação encontrada e os achados bioquímicos e clínicos. Para isso, foram utilizadas como ferramentas a Reação em Cadeia da Polimerase (PCR) e a técnica de sequenciamento automático direto. A análise estatística foi realizada pelo pacote de software SPSS versão 21.0. Os dados contínuos foram expressos em média e desvio padrão e os dados categóricos foram expressos em porcentagem. O teste t de Student foi utilizado para avaliar as variáveis contínuas e os testes exato de Fisher e Qui-quadrado foram usados para analisar as variáveis categóricas. Foi considerado p<0,05 como significativo em todas as análises. Como resultados, a análise por sequenciamento do gene BRAF revelou a presença da mutação BRAFV600E em 21 de 53 pacientes (16 mulheres e 5 homens, 39,6%), assim como uma mutação nova no códon 38 no gene K-RAS (p.D38E). Em relação aos dados clínicos, houve uma associação significativa entre a mutação BRAFV600E e rouquidão, assim como entre a mutação BRAFV600E e metástase linfonodal. Adicionalmente, a observação de uma nova mutação no gene K-RAS indica que o número de alterações gênicas envolvendo a via metabólica MAPK encontra-se ainda incompleto. Os dados obtidos podem ser utilizados para uma melhor avaliação pré-cirúrgica de tumores tireoidianos, com o objetivo de aumentar a sensibilidade para a detecção do câncer e evitar cirurgias desnecessárias de lesões erroneamente identificadas como malignas.
The most common cancer of the thyroid is the papillary carcinoma (PTC), which represents 80% of the cases of cancer affecting this gland. PTC is a malignant tumor, with slow evolution, found in any age, but with a higher occurrence in patients between 30-40 years old. The metabolic pathway MAPK is the most associated with PTC. Among the several proteins which have a role in this pathway, we highlight the ones encoded by the genes belonging to families RAS and BRAF. Considering that there are few clinical and genetic studies focusing on thyroid cancer from Brazilian Amazonian region, the aim of this study was to investigate the occurrence of alterations in genes HRAS, NRAS, KRAS and BRAF in patients with PTC treated in a public hospitals, from Belém (PA), seeking to make an association between the mutations found and the biochemical and clinical findings. To achieve this goal, polymerase chain reaction (PCR) and direct automatic sequencing were used. Statistical analyses were performed using the software SPSS version 21.0. Continuous data were expressed as means and standard deviation and categorical data were described in terms of percentages. Student t Test was used to evaluate the continuous variables, while Fisher exact test and Chi-square were used to analyze categorical variables. We considered p<0.05 as significant value in all the analyses. Our results showed that, among the analyzed genes, only BRAF showed a mutation, BRAFV600E, in 21 out of the 53 patients (16 female and 5 males, 39.6%). Additionally, a new mutation in codon 38 of gene K-RAS was found (p.D38E). Considering clinical data, we found a significant association between the BRAFV600E mutation and hoarseness, as well as between this mutation and lymph node metastasis. In addition, the observation of a new mutation in the K-RAS gene indicates that the number of gene changes involving the MAPK pathway is still incomplete. The data obtained can be used for a better pre-surgical evaluation of thyroid tumors, in order to increase the sensitivity for the detection of cancer and avoid unnecessary surgeries of lesions erroneously identified as malignant.
Tichauer, Ruth Elena. "In silico screening of NRas protein oncogenic mutations : new structural and physico-chemical insights into the catalytic activity". Electronic Thesis or Diss., Toulouse 3, 2019. http://www.theses.fr/2019TOU30028.
Texto completoRas subfamily of small GTPase proteins holds a key position in cell proliferation pathways. Indeed, the transmission of cell growth signals is controlled by proteins belonging to it. In their GTP-bound conformation, these proteins interact and activate downstream effectors of cell replication and differentiation. The hydrolysis reaction that takes place in their center, terminates these interactions, thereby leading to the GDP-bound inactive state. Point mutations of key residues lead to a hydrolysis rate drop that keeps Ras in a GTP-bound active state. Now, high concentrations of active Ras have been associated to abnormal cell proliferation, emblematic of cancerous tissues dissemination. With this into consideration, the elucidation of Ras mechanisms for accelerating GTP cleavage appears as a major step in the development of cancer targeted therapies that would consist in restoring the hydrolysing capabilities within oncogenic Ras to a wild-type rate. In an attempt to gain insight into Ras catalysing properties at the atomic level, unconstrained Molecular Dynamics (MD) simulations describing the G domain at different levels of theory (Molecular Mechanics (MM), Semi-empirical and Density Functional Theory (DFT)) were carried out for NRas member in its wild-type and Gln 61 mutated forms. These simulations were coupled to biomechanic characterisations of the complexes under inspection employing the static modes approach. The latter method, allows the identification of hot spots {\it i.e.} responsive residues of the biomolecule, that have a mechanical influence on the GTPase function of the protein. Hence, they could serve as suitable sites to host drug-like molecules containing specific chemical groups that would facilitate GTP hydrolysis. The obtained results show that water molecules positioning is crucial for efficiently catalysing the reaction that takes place in NRas center. Indeed, the precise positioning observed within the wild-type is lost within the mutants studied here. Furthermore, the active site structural modifications undergone upon Gln 61 substitutions, together with solvent distribution in it, impact directly GTP electronic density. The latter is accommodated to a GDP-like state within the wild-type protein only, as experimentally determined in previous investigations. Thus, oncogenic Gln 61 mutations impair this major catalysing effect. Among three engineered NRas proteins of the Q61R mutated form, proposed during this thesis, one is presented during the defence while the three are described in the manuscript. The chemical groups inserted at the identified site enable the recovery of water distribution as within the wild-type. To end, during the defence only, an alternative reaction pathway of the enzymatic reaction is proposed
Pearson, Michael John. "The management of a national environmental problem 'toxic cyanobacteria'". Thesis, University of Dundee, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311866.
Texto completoWONG, Miu Fai Tommy. "Fragmented authoritarianism and politics of hydropower in China : case studies of TGP & NRP". Digital Commons @ Lingnan University, 2010. https://commons.ln.edu.hk/pol_etd/4.
Texto completoRaveu, Gaëlle. "Optimisation de la fabrication par carbothermie de carbure d'uranium à teneur en oxygène maitrisée". Thesis, Orléans, 2014. http://www.theses.fr/2014ORLE2071/document.
Texto completoMixed carbides (U, Pu)C, are good fuel candidate for IVth generation reactors because of their high fissile atoms density and excellent thermal properties for economical (more compact and efficient cores) and safety reasons (high melting margin). UC can be imagine as a surrogate material ror R&D studies on (U,Pu)C fuel behavior, because of their similar structures. The carbothermic reaction was used because it is the most studied and now consider for industrial process. However, it involves powders manipulation : in air, carbide can strongly react at room temperature and under controlled atmosphere it can absorb impurities. An inerted installation under Ar, BàGCARA, was therefore used. Process improvements were carried out, including the sintering atmosphere in order to evaluate the impact on the sample purity (about oxygen content). The original method by ion bearn analysis was used to determine the surface composition (oxygen in-depth profiles in the first microns and stoichiometry). This oxygen analysis was set for the first time in carbonaceous materials. XRD analysis showed the formation of an intermediate compound during the carbothermic reaction and a better crystallization of the samples fabricated in BàGCARA. They also have a better microstructure, density, and visual appearance if compared to former samples. Vacuum sintering leads to a denser UC with fewer second phases if compared to Ar, Ar/H2 or controlled PC atmospheres. However, it was not possible to analyze carbides without air contact which may impact their lattice parameter and lead to their deterioration. When the carbide is initially free of oxygen, it oxidizes faster, more intensely and heterogeneously. The mechanical stress induced between the grains lead to fracturing the material, to corrosion cracking and then a debonding of the material. A study of oxidation mechanisms would be interesting to validate and understand the evolution of the material in contact with oxygen. A study of the mechanisms involved could be considered by coupling EBSD technique and ion beam analysis to check whether there is a link between a preferential oxidation of the grains and their crystallographic orientation
Seydou, Moumouni Allassane. "Etude expérimentale des effets hydrodynamiques des décharges nanosecondes répétitives pulsées (NRP) dans l'interaction plasma-flamme". Thesis, Chasseneuil-du-Poitou, Ecole nationale supérieure de mécanique et d'aérotechnique, 2016. http://www.theses.fr/2016ESMA0029/document.
Texto completoDifferent phenomena are involved in plasma-assisted ignition/combustion and result in a complex interaction of physico-chemical and hydrodynamic processes. However, in the literature, the influence of the hydrodynamic effects is often neglected and most of studies support chemical and thermal effects as the main mechanisms of interaction. The aim of this experimental study is to highlight the role of the hydrodynamic effects of NRP discharges for a better comprehension of the main mechanisms involved in plasma-flame interaction. PIV is performed to characterize the airflow and study plasma-inert flow interaction. This approach enabled highlight hydrodynamic effects of NRP discharges, namely a shock wave (1-30 μs) and a hot kernel (30-500μs). A constant volume combustion chamber is then used in reactive case to conduct single shot experiments of methane-air mixture ignition by NRP discharges in laminar and turbulent configurations. Simultaneous PLIF and chemiluminescence respectively on OH and OH* radicals are performed. An analysis based on apparent flame velocity of the reactive front is conducted in order to understand the ignition process as well as the observed flame front wrinkling as the number of discharges pulses is increased
Gong, Caifeng. "Intérêt de l’utilisation d’un peptidomimétique ciblant le récepteur NRP-1 pour le traitement du médulloblastome". Thesis, Université de Lorraine, 2018. http://www.theses.fr/2018LORR0115.
Texto completoMedulloblastoma (MB) is the most common malignant pediatric brain tumors which is the leading cause of cancer death in children. Despite the progress of new treatments, the risk of recurrence, morbidity, and death after treatment remain important. The neuropilin-1 receptor (NRP-1) has recently been implicated in tumor progression of MBs, which seems to play an important role in the phenotype of cancer stem cells (CSCs). Targeting this molecule could thus present an interesting therapeutic value in the treatment of MB. We have selected cancer stem like cells of MBs in the form of medullospheres (MSs) from 3 cell lines (DAOY, D283-Med and Med-D341). These models were characterized by expression of neuropilins (NRP-1 and NRP-2) and phenotypic markers (CD133, CD15 and NF-M). Results showed a significant increase of the expression of NRP-1 by our CSCs models cultured in MSs that confirms our targeting strategy. The impact of the treatment of these cells with an innovative compound specifically targeting NRP-1, MR438, was then evaluated in vitro alone and in association with radiotherapy, especially on the study of the capacity for self-renewal. A decrease of self-renewal capacity for MB stem cells after exposition of MR438 with an increase of radiosensitivity for the 3 cell models in vitro was demonstrated. In vivo, MR438 was evaluated on heterotopic xenograft models in nude mice and showed a significant augmentation of radiosensitivity for DAOY tumors with a tendency to decrease tumor progression for the other 2 cell lines. Interestingly, the compound MR438 induced a significant decrease in the number of stem cells for all of our models. The compound appeared to induce CSCs to a differentiated phenotype at least for the DAOY cells, although mechanisms could not be clearly elucidated. In conclusion, inhibition of NRP-1 via MR438 seems to stimulate the differentiation of CSCs that may eventually reduce the progression of MB and bring a benefit in association with radiotherapy. Evaluation of this compound on orthotopic models of MB would provide information on its effectiveness on models closer to the physiopathology taking into account its distribution at the cerebral level
Boespflug, Amélie. "Thérapies ciblées dans le mélanome : mécanismes impliqués dans les effets paradoxaux, les résistances et évaluation de nouvelles combinaisons". Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1187.
Texto completoTargeted therapies like RAF inhibitors (RAFi) and MEK inhibitors (MEKi) have completely changed the therapeutic landscape in metastatic melanome. RAFi offer increased survival in patients with BRAF V600 mutated metastatic melanoma but they are limited in their use as single agents by an hyperactivation of the MAPK signaling pathway in non BRAF mutated cells that is responsible for the developpement of treatment induced primary melanomas. In this work we show the differences in the transcriptomic modifications induced by RAF inhibitos in BRAF mutated melanoma cell lines and NRAS mutated cell lines and we identified potential genes implicated in the development of treatment induced melanomas. The anti-tumor efficacity of RAFi is also limited by the acquired resistances that appear after several months of treatment. We show that a high BRAF V600E mutant allelic burden is potentially associated with a good response to RAFi and that ZEB1 induced cell plasticity is responsible for resistance to RAFi. No targeted therapy is approuved for NRAS mutated melanoma. Innate and acquired resistances limit the developpment of MEKi in this setting. We show that NRAS amplification and a MEK P124L mutation are responsible for resistance in NRAS melanoma. Finally, we tested five targeted therapies in combination with trametinib in NRAS mutated PDXs to identify combinations that improve the anti-tumoral effect of MEKi in this setting
Takashima, Asami. "Protein kinase C δ is a potential therapeutic target in malignant melanoma with NRAS mutation or B-RAF inhibitor-resistance". Thesis, Boston University, 2013. https://hdl.handle.net/2144/12236.
Texto completoMetastatic melanoma is the major cause of skin cancer death, and the annual incidence of melanoma continues to increase. Despite the impressively high rates of response to BRAF inhibitors in patients with melanomas harboring BRAF mutations, most of these patients eventually relapse after developing resistance to the drug, due in part to secondary mutations in NRAS. Although NRAS mutation is the second most common genetic mutation in melanoma patients (after BRAF mutation), there is currently no treatment option that targets NRAS-mutated melanomas. Previous reports have demonstrated the sensitivity of cancer cell lines carrying RAS mutations to apoptosis initiated by inhibition of protein kinase C delta (PKCδ), suggesting the possible association between RAS mutational status and sensitivity to PKCδ inhibition. I therefore hypothesized that PKCδ inhibitors might also be cytotoxic in melanomas with primary or acquired NRAS mutations. In this project, the effect of PKCδ inhibition, and the efficacy of a new PKCcS inhibitor, BJE6-106 (B106), in melanoma were investigated. Inhibition of PKCδ inhibited the growth of multiple human melanoma cell lines carrying NRAS mutations, and induced apoptosis mediated by terminal caspase activation. Analysis of the molecular mechanisms demonstrated activation of the JNK pathway after PKCδ inhibition, leading to the activation (phosphorylation) of H2AX, a histone H2A variant. Activation of H2AX was attenuated when JNK1/2 levels were repressed, indicating that H2AX activation is mediated by the JNK pathway in response to PKCδ inhibition. Consistent with recent reports on the apoptotic role of phospho-H2AX, knockdown of H2AX prior to PKCδ inhibition mitigated the induction of caspase-dependent apoptosis. To explore the potential of B106 further, melanoma cell lines harboring BRAF mutations that had evolved resistance to a BRAF inhibitor, PLX4032 (vemurafenib), were developed. B106 effectively induced cytotoxicity in these cells, suggesting the potential clinical application of targeting PKCδ in patients who have relapsed following treatment with PLX4032. Taken together, this work suggests that inhibition of PKCδ causes caspase-dependent apoptosis in melanomas with NRAS mutations and in PLX4032-resistant BRAF mutant melanomas. This apoptosis is mediated via activation of the JNK-H2AX pathway, which involves a novel role for phospho-H2AX in the execution of apoptosis.
Kaufmann, Ivan Rodrigo. "Estabilização de filmes finos de óxido de germânio por incorporação de nitrogênio visando aplicações em nanoeletrônica". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/83676.
Texto completoIn order to improve the performance of Metal-Oxide-Semiconductor Field Effect Transistor (MOSFET), germanium is a good candidate to replace silicon as semiconductor due to its higher charge carrier mobility. However, the germanium dioxide (GeO2) film over Ge is water soluble and produces poor electrical characteristics. In this way, this Master dissertation proposes thermal oxinitridation of the GeO2 films in nitric oxide (15NO) atmosphere in order to improve its electrical and physico-chemical characteristics. Samples were first cleaned using a mixture of hydrogen peroxide (H2O2) and hydrogen chloride + water (HCl + H2O, 4:1). GeO2 films were thermally grown on Ge using oxygen enriched in 97% in the isotope of mass 18, which generated ~5 nm thick film. Oxinitridation was performed in a rapid thermal furnace under 15NO atmosphere, at the 400-600°C temperature range, and 1-5 minutes time range. The goal was to form a germanium oxinitride film (GeOxNy) with physico-chemical properties that are satisfactory for microelectronics industry. We also performed thermal annealing in inert atmosphere to test the thermal stability of GeOxNy films. Nuclear Reaction Analysis (NRA) and Rutherford Backscattering Spectrometry in channeled geometry (RBS-c) were used to quantify the total amount of oxygen 18O and 16O, respectively. NRP was also performed to determine the 18O and 15N depth distribution. In order to investigate the chemical composition of the samples, X-ray Photoelectron Spectroscopy (XPS) was performed. RBS and NRA analysis showed isotopic exchange between 18O and 16O for all temperatures investigated. This result corroborates previous literature studies. Samples oxynitrided in 5 minutes at 500°C and all the samples oxinitrided at 550-600°C showed complete isotopic exchange. We also observed by NRP that nitrogen incorporation occurs more superficially until 550°C. XPS results indicate more formation of GeOxNy near the surface of the samples and for higher temperatures and/or time of oxinitredation. Thermal stability results indicated that the nitrogen incorporation near the sample surface inhibit the GeO desorption. On the other hand, samples that were not oxynitrided have almost all the GeO2 desorbed when thermal annealing is performed.
Bernard, Elodie. "Comportement du deutérium dans les matériaux d’intérêt pour la fusion thermonucléaire". Thesis, Paris 11, 2012. http://www.theses.fr/2012PA112250/document.
Texto completoPlasma-wall interactions play an important part while choosing materials for the first wall in future fusion reactors. Moreover, the use of tritium as a fuel will impose safety limits regarding the total amount present in the tokamak. Previous analyses of first-wall samples exposed to fusion plasma highlighted an in-bulk migration of deuterium (used as an analog to tritium) in carbon materials. Despite its limited value, this retention is problematic: contrary to co-deposited layers, it seems very unlikely to recover easily the deuterium retained in such a way. Because of the difficult access to in situ samples, most published studies on the subject were carried out using post-mortem sample analysis.In order to access to the dynamic of the phenomenon and come apart potential element redistribution during storage, we set up a bench intended for simultaneous low energy ion implantation, reproducing the deuterium interaction with first-wall materials, and high energy microbeam analysis. Nuclear reaction analysis performed at the micrometric scale (µNRA) allows characterizing deuterium repartition profiles in situ. This analysis technique was checked to be non-perturbative.We observed from the experimental data set that the material surface (depth 0-1 µm) displays a high and nearly constant deuterium content, with a uniform distribution. On the contrary, in-bulk deuterium (1-11 µm) localizes in preferential trapping sites related to the material microstructure. In-bulk deuterium inventory seems to increase with the incident fluence, in spite of the wide data scattering attributed to the structure variation of studied regions. Deuterium saturation at the surface as well as in-depth migration is instantaneous; in-vacuum storage leads only to a small deuterium global desorption.Observations made via µNRA were combined with results from other characterization techniques. X-ray µtomography allowed identifying porosities as the preferential trapping sites for in-depth deuterium retention. Raman µspectrometry disclosed the formation of an amorphous layer at the surface, very thin (~30 nm) and deuterium saturated, following deuterium irradiation.At last, we confronted the experimental characterization obtained with existing models for deuterium behaviour in carbon materials and proposed a simple and original one. Considering that in-depth retention is due to deuterium implantation and Coulombian diffusion at the open porosity surfaces, it allows reproducing qualitatively the observed experimental profiles
Naccache, Mayss. "Genetic analysis of the effect of «Nramp 1» on the host and pathogen genomes in the context of chronic «Salmonella» infection". Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=40687.
Texto completoLes infections à salmonelles regroupent différentes maladies dont la salmonellose et la fièvre typhoïde. Le portage asymptomatique des salmonelles est fréquent et contribue à la dissémination de la maladie. En utilisant une approche de criblage génomique par locus, nous avons identifié dix loci (Ses1-Ses10) affectant la persistance de Salmonella chez la souris. Un locus majeur, Ses1, a été validé en utilisant des souris congéniques. Nramp1 demeure un gène candidat de choix pour Ses1 quoiqu’un test d’interaction Ses1/Nramp1-/- se soit avéré non significatif. Le modèle proposé de portage de Salmonella incluant des interactions entre les loci Ses1/Ses4 et Ses1/Ses5 sera exploré par la création de nouvelles lignées congéniques combinatoires qui ont été créées durant la préparation de cette thèse. L'influence de Nramp1 sur le transcriptome de Salmonella a été étudiée au niveau des mécanismes bactériens de virulence. En particulier, nous avons observé une expression différentielle de phoP, et par conséquent l’expression différentielle de gène dont l’expression est contrôlée par PhoP, en présence de Nramp1. Nos résultats confirment l'importance des interactions hôte-pathogène dans l’issue de l'infection à salmonelles.
Niekraszewicz, Liana Appel Boufleur. "Microanálise com feixes de íons : caracterização de elementos leves em materiais via micro-NRA e micro-PIXE". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2014. http://hdl.handle.net/10183/108537.
Texto completoA couple of years ago, the Ion Implantation Laboratory (LII) at IF- UFRGS installed a microprobe station and ever since it has been under development. This is the first and unique ion microprobe station installed in Brazil and therefore it is of great interest to make it efficient and available to the scientific community. Some techniques are well developed in the microbeam station: micro-PIXE, STIM and proton beam writing. A wide variety of techniques based on broad ion beams stimulates further work for the implementation of such techniques for the case where the beam spot size is of the order of few micrometers. The study of the micro-NRA technique (Nuclear Reaction Analysis) is important since it can be used for the detection of light elements that are not detected with the techniques already in operation at the microprobe station. Such elements, such as carbon, nitrogen and oxygen are the major constituents of most materials under study in LII. In this study, we present the experimental parameters as well as the analytical results obtained with the micro-NRA technique. A preliminary assessment suggests that the technique has a great potential for the characterization and mapping of carbon, while the results for oxygen and nitrogen indicate the need for a complementary technique. Additionally, the results obtained with micro-NRA were compared with the results from measurements with micro-PIXE obtained with a SDD detector with ultra-thin window. An evaluation of the elemental maps obtained by the two techniques indicates that the measurements made with micro-PIXE provide results with better statistics and elemental maps with higher quality.
Vilhena, António. "Método de avaliação do estado de conservação de edifícios. Análise e contributos para o seu aperfeiçoamento e alargamento do âmbito". Doctoral thesis, Instituto Superior Técnico, 2011. http://hdl.handle.net/10174/4728.
Texto completoWeyler, Christian [Verfasser] y Elmar [Akademischer Betreuer] Heinzle. "Synthesis of UDP-glucose, UDP-glucuronic acid and NRP luminmide using permeabilized cells / Christian Weyler. Betreuer: Elmar Heinzle". Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2016. http://d-nb.info/1088400132/34.
Texto completoRichard, Mylène. "Les exo-glycals activés pour la synthèse de dérivés saccharidiques complexes : application à la préparation de glycoamino acides et de peptidomimétiques". Thesis, Université de Lorraine, 2015. http://www.theses.fr/2015LORR0133/document.
Texto completoThis work is focused on the development of new synthetic pathways for exo-glycals functionalization and synthesis of bioactive compounds. The first part of this manuscript describes the efficient preparation of new tertiary S-glycosides and γ-glycoamino acids via Michael addition of thiols derivatives and carbanions on anomeric carbon of exo-glycals. The obtained γ-glycoamino acids were then incorporated in α/γ mixed peptides and their structural properties were studied by NMR, IR, CD and molecular modelling studies. Furthermore, cyclic multivalent platforms were built by intramolecular cyclization of these entities. The second part of the manuscript concerns the elaboration of peptidomimetics targeting neuropilin-1 receptor, implicated in tumor angiogenesis. Based on molecular modeling studies, some compounds showed interesting binding affinity for NRP-1 receptor and one of them displayed promising properties toward inhibition of tubule formation
Edlundh-Rose, Esther. "Molecular Signatures of Cancer". Doctoral thesis, Stockholm, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-3954.
Texto completo