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1
Germaud, Nathalie. "Polymorphisme du gène NCR3/NKp30 et variabilité de la fonction des cellules Natural Killer humaines." Phd thesis, Université René Descartes - Paris V, 2012. http://tel.archives-ouvertes.fr/tel-00789417.
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Les cellules Natural Killer (NK) sont non, seulement de précieux effecteurs cytotoxiques de la réponse immunitaire innée dirigée contre les tumeurs et les infections, mais aussi d'importants immunorégulateurs. Leur activation dépend d'une balance complexe entre des signaux émanant de multiples récepteurs, tantôt inhibiteurs, tantôt activateurs. Parmi les récepteurs activateurs, NCR3 représente un acteur important de la lyse tumorale et de l'interaction avec les cellules dendritiques. Dans le but de caractériser la variabilité interindividuelle de la réponse NK et d'établir une référence pour des études ultérieures dans un contexte pathologique, nous avons examiné, dans un échantillon de 43 donneurs sains, les corrélations entre la variabilité fonctionnelle des cellules NK en réponse à la stimulation de leur récepteur NKp30 et le niveau d'expression des transcrits de NCR3 ainsi que celui de la protéine correspondante, au regard du polymorphisme génomique. Nous avons mis en évidence une étroite corrélation entre l'expression membranaire de NKp30 et NKp46 et la fonction cytotoxique NK, mais pas avec la sécrétion de cytokines. Nous avons retrouvé l'effet déjà connu du variant rs986475 sur l'expression de l'un des transcrits alternatifs de NCR3, T3. Nous avons également identifié un autre variant, rs11575836, influençant le niveau de transcrits T1, en relation avec la cytotoxicité induite par la signalisation NKp30. Cette étude pointe le doigt sur la spécificité des voies de signalisation des fonctions NK et le réseau complexe de gènes impliqués dans leur régulation. Nous avons par ailleurs évalué la variabilité génétique de NCR3 dans la myasthénie auto-immune où les cellules NK pourraient jouer un rôle. Le re-séquençage du gène NCR3 n'a pas révélé d'association avec un polymorphisme commun mais a permis d'identifier deux mutations rares, " faux-sens ", retrouvées uniquement chez des patients myasthéniques. L'une d'elle, L19R, est non-conservative et représente un candidat particulièrement intéressant à examiner en détail du fait de sa localisation dans une région très conservée dans la phylogénie. Même si de nombreux points restent à élucider, ces résultats indiquent qu'il devrait être possible de relier de façon globale et intégrative le polymorphisme de l'ADN, ainsi que l'expression des transcrits et des protéines, à la réponse fonctionnelle des cellules NK
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Baaklini, Sabrina. "Compréhension de la résistance humaine au paludisme : des études génétiques aux approches fonctionnelles." Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0384/document.
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La sévérité du paludisme est influencée par des interactions complexes entre de nombreux facteurs dont la génétique de l’hôte. Plusieurs études de liaison génétique menées dans différentes ethnies africaines ont montré une liaison entre le locus 6p21 et le paludisme simple. De plus, différents variants au sein des gènes TNF et NCR3, retrouvés dans ce locus, ont été indépendamment associés à ce phénotype au Burkina Faso.Ainsi, nous nous sommes tout d’abord intéressés aux polymorphismes du TNF. Nos résultats montrent que les variants TNF-308, TNF-244, et TNF-238 sont associés à la parasitémie maximale ou aux accès simples au Congo. Les approches moléculaires indiquent que le TNF-244 a un effet cis-régulateur avec une activité promotrice réduite en présence du variant A ainsi qu’une fixation altérée de protéines nucléaires en présence de ce même variant. Enfin, nos analyses bio-informatiques suggèrent que le TNF-244 et le TNF-238 agissent en synergie pour modifier le site de fixation d’au moins un facteur de transcription.Nous avons ensuite confirmé l’association du NCR3-412 avec le paludisme simple et le nombre d’accès fébrile au Congo. Les analyses fonctionnelles montrent que ce SNP a aussi un effet cis-régulateur avec une activité promotrice accrue en présence de l’allèle G et une liaison altérée de deux complexes protéiques en présence de l’allèle C. Les approches in silico et in vitro indiquent que les facteurs STAT4 et RUNX3 sont ceux dont la fixation est altérée.NCR3-412 altérant la résistance à la forme simple du paludisme, nous avons souhaité déterminer s’il est aussi impliqué dans la résistance au paludisme sévère mais nous n’avons détecté aucune associationThe severity of malaria is influenced by complex interactions between many factors including host genetics. Numerous genetic studies conducted in different African ethnic groups have shown a significant linkage between the 6p21 locus and mild malaria attack. In addition to their linkage, several polymorphisms found under the linkage peak, and more precisely within TNF and NCR3, were also independently associated with different sub-phenotypes of mild malaria in Burkina Faso.Thus, we first focused on TNF polymorphisms. Among the 4 polymorphisms analyzed, we found associations between TNF-238, TNF-244, TNF-308 and either mild malaria attack or maximum parasitemia. Molecular approaches showed that TNF-244 has a cis-regulatory effect. Indeed, we observe a decreased promoter activity and an altered binding of nuclear proteins in the presence of the A variant. In addition, our bioinformatics analyses suggested a cooperative effect of TNF-244 and TNF-238 in modifying the binding of at least one transcription factor.We then confirmed the association of NCR3-412 with both mild malaria and the number of febrile episodes in Congo. Functional analyses have shown that this SNP has also a cis-regulatory effect with a decreased promoter activity and an altered binding of two nuclear protein complexes in the presence of the C allele. Finally, in silico and in vitro approaches indicated that STAT4 and RUNX3 are the two transcription factors affected.As NCR3-412 is associated with resistance to mild malaria, we therefore investigated whether this SNP is also involved in severe malaria resistance, but we did not detect any association neither with severe anemia nor with cerebral malaria
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Semeraro, Michaela. "Neuroblastoma and gastrointestinal stromal tumor as a target for natural killer lymphocytes : the role of ncr3/nkp30." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T045/document.
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Depuis la formulation de la théorie de l’immuno-surveillance en 1957 par Burnet et Thomas, le monde scientifique s’est efforcé d’identifier les cellules immunitaires impliquées dans ce processus. Les lymphocytes Natural Killer (NK) constituent une composant majeure de l’immuno-surveillance innée dans plusieurs cancers hématologiques et solides. L’activité des lymphocytes NK passe principalement par une grande variété de récepteurs avec un rôle activateur ou inhibiteur. Parmi les récepteurs activateurs présents à la surface des lymphocytes NK, le récepteur NCR3/NKp30 a un rôle majeur dans la toxicité directe contre la cellule cible et dans l’activation des cellules dendritiques.Les tumeurs stromales gastrointestinales (GIST) et le Neuroblastome (NB) sont deux tumeurs sensibles à l’immuno-surveillance par les lymphocytes NK. Dans une étude récente notre équipe a démontré que l’épissage alternatif du gène NCR3/NKp30 peut être déterminant dans la fonction NK et dans la survie des patients atteints de GIST.Afin de caractériser les lymphocytes infiltrant le GIST, nous avons effectué une recherche visant à analyser l’infiltrat des lymphocytes CD3+, des lymphocytes T régulateurs (Treg) et des lymphocytes NK dans des tumeurs GIST localisés, et corréler ces résultats à la survie des patients. Nous avons mis en évidence que, avant traitement, les lymphocytes NK sont surtout localisés au niveau des fibres trabéculaires qui entourent la tumeur, alors que les lymphocytes T sont localisé à l’intérieur de la tumeur en contact avec les cellules tumorales qui expriment HLA-I.Nous avons aussi observé que les cellules NK ont un phénotype plutôt CD56bright et migrent à l’intérieur de la tumeur après traitement par Imatinib. L’analyse de survie a mis en évidence que les lymphocytes NK et T peuvent prédire la survie sans progression (PFS). Ces résultats mettent en évidence l’importance de l’infiltrat immunitaire dans la prédiction du risque de rechute dans le GIST et surlignent l’importance de viser une réponse immunitaire dans les protocoles thérapeutiques.Nous avons ensuite déterminé la proportion de lymphocytes NK dans le sang périphérique et dans la moelle dans une cohorte de Neuroblastome (NB) localisé et métastatique : une infiltration plus important par les NK CD56bright a été observé chez les patients présentant une maladie métastatique et chez les patients avec une réponse mineure au traitement d’induction. De plus, les NK présents dans les échantillons de moelle osseuse infiltrés par les neuroblastes, présentaient une expression plus basse du récepteur NKp30. L’expression du ligand de NKp30, B7-H6, a été mise en évidence sur les neuroblastes infiltrant la moelle osseuse, et sa forme soluble, sB7-H6, a été retrouvée être positivement corrélée à l’extension de maladie et inversement à la réponse au traitement d’induction. L’analyse de l’épissage alternatif du gène NCR3/NKp30 a permis de mettre en évidence l’impact des isoformes NKp30 sur la survie sans progression chez les patients atteints de NB de haut risque en maladie minimale résiduelle après chimiothérapie d’induction. En particulier, les patients présentant un taux élevé de l’isoforme pro-inflammatoire (NKp30b) par rapport à l’isoforme immunosuppressive (NKp30c), présentent une meilleure survie sans évènement. Nous avons aussi démontré le rôle des monocytes dans l’amplification de la réponse NKp30 dépendant. Les résultats de notre recherche dans le GIST et dans le NB, deux maladies différentes mais toutes les deux sensibles aux lymphocytes NK, surlignent l’importance d’intégrer de nouvelles options thérapeutiques aptes à cibler le système immunitaireSince Burnet and Thomas formulated in 1957 the cancer immunosurveillance theory, the scientific world has made tremendous progress to identify the immune cells involved in this process. Natural Killer (NK) cells have emerged as a major component of the innate immunosurveillance of several hematological and solid malignancies. The activity of NK-cells is mainly mediated through their wide variety of receptors with activating and inhibitory functions. Among the versatile receptors present on NK cells, the activating receptor NCR3/NKp30 is a major receptor involved in both direct killing of target cells and mutual NK and dendritic cell activation.Gastrointestinal stromal tumors (GIST) and Neuroblastoma (NB) are known to be tumors sensitive to NK immunosurveillance. In a recent study we showed that alternative splicing of NCR3/NKp30 gene can affect NK cell function and GIST patient’s outcome.In order to better characterize the GIST tumor-infiltrating lymphocytes, we analyzed the CD3+, T regulatory (Treg) and NK lymphocytes infiltration within primary localized GIST tumors and we determined their prognostic value. We described that, before treatment, NK cells are mainly localized in fibrous trabeculae while T lymphocytes are in the tumor nests in HLA-I positive tumor cells contact. Moreover infiltrating NK cells displayed a secreting CD56bright phenotype, and accumulate in tumor nests after Imatinib (IM) treatment. Importantly CD3+ and NK lymphocytes independently predicted progression free survival (PFS). These results highlight the importance of the immune infiltrate in re-define the GIST risk stratification and allow enhancing the immune response in the therapeutic decisions.We next investigated the proportions of NK cells in blood and bone marrow (BM) in a cohort of localized and metastatic NB; a high proportion of CD56bright NK cells was associated with metastatic NB and with poor response to induction treatment within the metastatic NB. Moreover, infiltrated BM presented NKp30 down regulation. The expression of the NKp30 ligand, B7-H6, was found on BM neuroblasts, while the soluble protein, sB7-H6 correlated with resistance to treatment. Furthermore the transcriptional status of NKp30/NCR3 dictated the event-free survival rates of HR-NBs with minimal residual disease post-induction chemotherapy: in particular patients presenting a high proportion of the immunosuppressive isoform (NKp30c) compared to the pro-inflammatory isoform (NKp30b), presented a worse outcome. We further demonstrated the significant role of monocytes to amplify the NKp30 activation response.These researches in GIST and NB, two different but at the meantime NK-sensitive diseases support the effort to define new immunological therapeutic approaches and to determine their optimal use
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Nguyen, Thy Ngoc. "Prédisposition génétique au paludisme à Plasmodium falciparum : études d'association et analyses fonctionnelles de variants génétiques candidats situés dans des régions liées génétiquement au paludisme." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM4116.
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Dans cette thèse, nous avons étudié l'influence de plusieurs variants génétiques situés dans les régions chromosomiques 5q31-q33, 6p21, et 17p12, pour lesquelles une liaison génétique avec des phénotypes de paludisme a été montrée.Les gènes NCR3 et TNF, qui sont situés dans la région chromosomique 6p21, ont été associés au paludisme dans une population vivant au Burkina Faso. Nous avons répliqué ces études dans une population congolaise afin deconfirmer les associations des polymorphismes avec les accès palustres simples et la parasitémie symptomatique. Nos résultats montrent que le polymorphismeNCR3-412 est associé avec les accès palustres simples au Congo, et que les polymorphismes TNF-308, TNF-244, et TNF-238 sont associés avec les accès palustres simples ou la parasitémie symptomatique. En outre, nos analyses bioinformatiques suggèrent que les polymorphismes TNF-244 et TNF-238 agissent en synergie pour modifier le site de fixation pour au moins un facteur de transcription.Les deux gènes HS3ST3A1 et HS3ST3B1, qui sont situés dans la région chromosomique 17p12, sont impliqués dans la biosynthèse des heparanes sulfates. Dans cette étude, nous avons étudié l'association d’un polymorphisme situé dans le promoteur de HS3ST3A1 avec les accès palustres simples et la parasitémie symptomatique, et n’avons détecté aucune association. Nous avons étudié en outre le gène NDST1, situé dans la région chromosomique 5q31-q33, et qui code également pour une enzyme impliquée dans la voie héparane sulfate. Des résultats préliminaires encourageants soutiennent l'hypothèse que la variation génétique de NDST1 influence la parasitémie asymptomatiqueIn this thesis, we investigated the influence of some genetic variants located within chromosomes 5q31-q33, 6p21, and 17p12, which have been shown to be linked to malaria phenotypes. The genes NCR3 and TNF, which are located in the chromosomal region 6p21, have been reported to be associated with malaria in Burkina Faso population. We have replicated those studies in Congolese population to evaluate the associations of the SNPs in those genes with mild malaria attack and Plasmodium parasitemia. The results showed that the variant NCR3-412 is associated with mild malaria in Congo, and TNF-308, TNF-244, and TNF-238 are associated with mild malaria attack, maximum parasitemia, or both. In addition, bioinformatic studies suggest that TNF-244 and TNF-238 synergise to alter the binding of transcription factors.The two genes HS3ST3A1 and HS3ST3B1, which are located in chromosomal regions 17p12, are involved in the heparan sulfate proteoglycan biosynthesis. In this study, we further investigated the association of the polymorphisms in these genes with mild malaria attack and maximum parasitemia. However no association was found. We further studied the NDST1 gene, which is located within chromosome 5q31-q33, and which encodes the bifunctional enzyme N-deacetylase/ N-sulfotransferase 1, and also participates in the heparan sulfate synthesis . Encouraging results support the hypothesis that NDST1 variation influence controlling parasitemia. Further association and functional studies are needed to validate the role of NDST1 in malaria infection. More generally, the enzymes involved in the heparan sulfate pathway might play a key role in controlling malaria infection
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Sanka, Michel. "Compréhension des mécanismes moléculaires et des facteurs génétiques impliqués dans le paludisme sévère : analyse des profils transcriptomiques et processus biologiques caractéristiques du neuropaludisme et méta-analyse sur des gènes associés à la résistance au paludisme." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0615/document.
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Le paludisme est l'une des maladies infectieuses les plus dévastatrices qui a affecté environ 214 millions de personnes dans le monde. Elle est causée par l'infection par le parasite plasmodium, dont P. falciparum et P. vivax sont les plus représentés. Le développement asexué du parasite dans le sang provoque la physiopathologie de la maladie dont l'évolution passe du paludisme simple au paludisme grave, notamment le neuropaludisme. Nos travaux ont d'abord porté sur l'analyse du transcriptome, par la technologie des microarrays, des cellules sanguines d'une cohorte constituée au Sénégal. L'analyse des résultats a permis d'identifier un ensemble de gènes dont l'expression permettait de distinguer le profil transcriptomique du neuropaludisme de ceux du paludisme simple et des autres formes de paludisme grave. Ces gènes sont enrichis en voies biologiques impliquées dans l'activation des récepteurs des lymphocytes B et T mais aussi des TLR et des récepteurs Fcgamma. On y trouve aussi plusieurs gènes candidats qui ont déjà été testés pour leur résistance au paludisme, dont RNASE3 et IL18R. Nous avons aussi réalisé, avec une partie de cette même cohorte sénégalaise, une étude d’association cas-contrôles qui n’a pas permis de détecter d’association entre le polymorphisme NCR3-412 et le paludisme sévère. Enfin l’approche basée sur une métaanalyse a permis de confirmer son implication dans le paludisme simple, ainsi que celle du polymorphisme LTA+252 dans le paludisme sévère, contrairement au LTA+80, au TNF-238 et au TNF-308. L’ensemble des travaux contribuent à une meilleure compréhension des facteurs génétiques et génomiques impliqués dans la résistance de l’hôte au paludismeMalaria is one of the most devastating infectious diseases that has affected an estimated 214 million people worldwide and caused nearly 600,000 deaths in 2015. It is caused by infection with the plasmodium parasite, P. falciparum and P. vivax are the most represented. The asexual development of the parasite in the blood causes the pathophysiology of the disease which can evolve from mild malaria to severe malaria, including cerebral malaria. Our work first focused on the analysis of the microarray transcriptome of blood cells of a cohort composed in Senegal. The analysis of the results allow to identify a set of genes whose expression permit to distinguish the transcriptomic profile of cerebral malaria from those of mild malaria and other forms of severe malaria. These genes are enriched in biological pathways involved in the activation of B and T lymphocyte receptors also TLRs and Fcgamma receptors. These genes also include several candidate proteins that have already been tested for resistance to malaria, including RNASE3 and IL1RN
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Afridi, Sarwat. "Influence de variants génétiques candidats sur des phenotypes liés au paludisme à Plasmodium falciparum et effet fonctionnel du polymorphisme NCR3-412 associés au paludisme." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4037.
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Le paludisme est une cause majeure de morbidité et de mortalité, plus particulièrement en Afrique sub-saharienne. De très nombreuses observations sont en faveur de l'existence de facteurs génétiques contrôlant le devenir de l'infection palustre. Il est très probable que certains variants génétiques de gènes candidats du paludisme affectent la résistance du paludisme à travers leur effet sur la réponse immunitaire acquise. Afin de vérifier cette hypothèse, nous avons étudié, dans une population vivant au Burkina Faso, des variants génétiques de HBB, IL4, IL12B, TNF, LTA, FCGR2A et NCR3 dont l'association avec des phénotypes liés à la résistance au paludisme a été publiée; nous avons évalué leur influence sur les niveaux d'IgG dirigés contre les antigènes de Plasmodium falciparum en utilisant un test d'association basé sur les familles. Ainsi, nous avons détecté, l'effet de l'hémoglobine C, FCGR2A-H131, le TNF-857T, et TNF1304A sur les niveaux des sous-classes d'IgG anti-P. falciparum. Ces résultats constituent une base utile pour des études ultérieures du contrôle génétique de la réponse immunitaire chez des individus vivant dans une zone d'endémie. Un autre projet a porté sur l'étude fonctionnelle du polymorphisme NCR3-412, dont nous avions montré l'association avec les accès palustres simples. Nos résultats basés sur des techniques moléculaires montrent l'effet de ce polymorphisme situé dans le promoteur sur la liaison de protéines nucléairesMalaria is the major cause of morbidity and mortality especially in the Sub-Saharan Africa. There is a growing body of evidence for genetic factors controlling the outcome of malaria infection. It is thought that some genetic variants of malaria candidate genes affect malaria resistance through their effect on the acquired immune response. In order to verify this hypothesis, we worked on genetic variants of HBB, IL4, IL12B, TNF, LTA, FCGR2A and NCR3, which have been associated with malaria resistance phenotypes, to determine their influence on levels of anti-P. falciparum IgG in urban population of Burkina Faso. Using family-based association analysis, we detected the effect of Hemoglobin C, FCGR2A-H131, TNF-857T, and TNF1304A on the levels of anti-P. falciparum IgG. This study can pave the way towards further comprehension of genetic control of an individual's immune response against malaria. Another project focused on functional study of polymorphism NCR3-412, which has already been associated to mild malaria. We investigated the functional effect of this polymorphism located in the promoter by using molecular techniques and showed the effect of this polymorphism on the binding of nuclear proteins
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Pedro, Liliana Cristina Galhofa. "Ativos biológicos: aplicação da NCRF 17 numa empresa vitivinícola." Master's thesis, Instituto Politécnico de Setúbal. Escola Superior de Ciências Empresariais, 2016. http://hdl.handle.net/10400.26/11163.
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Dissertação apresentada para cumprimento dos requisitos necessários à obtenção do grau de
Mestre em Contabilidade e Finanaçassetor agrícola é um setor muito especifico, sendo seu objeto os ativos biológicos e a sua base a transformação dos mesmos. As fases do nascimento, crescimento, produção, entre outras, geram dúvidas no reconhecimento contabilístico destes ativos. O International Accounting Standards Board (IASB) em dezembro de 2000 emitiu o primeiro normativo dirigido à atividade agrícola a International Accounting Standard (IAS) 41 - Agricultura. No dia 1 de janeiro de 2010 entrou em vigor o Sistema de Normalização Contabilística (SNC) que inclui a Norma Contabilística e de Relato Financeiro (NCRF) 17 - Agricultura. Passou, assim, a existir um normativo para as entidades portuguesas não cotadas em bolsa que desenvolvem esta atividade. A NCRF 17 tem como objetivo o tratamento contabilístico, a apresentação das demonstrações financeiras e as divulgações relativas à atividade agrícola. Introduz novos conceitos e preocupações a ter com o tratamento dos ativos biológicos, como o reconhecimento e mensuração pelo justo valor. Este estudo tem como objetivo uma reflexão sobre a problemática dos ativos biológicos e sua mensuração; reconhecimento; tratamento contabilístico; apresentação de demonstrações financeiras; e divulgações relativas à atividade agrícola. Segue-se os métodos bibliográfico, documental e de estudo de caso exploratório e descritivo e usa-se a entrevista como técnica para a recolha de dados. Recorre-se, ainda, a relatórios e contas e outros documentos emitidos pela empresa objeto do estudo ou com ela relacionados. Efetua-se uma revisão de literatura em que se apresenta a contabilidade aplicada ao setor em questão e um levantamento e análise de estudos empíricos sobre o tema. Depois, efetua-se um estudo de caso em que se analisa a aplicação da NCRF 17 numa empresa do Baixo Alentejo. Constatou-se que a empresa elabora e divulga a sua informação sobre ativos biológicos e subsídios governamentais em conformidade com a NCRF 17.
Abstract: The agricultural sector is a very specific sector, being its main object the biological assets and its base their transformation. Births, growth, production, among other phases, generate doubts in the accounting recognition of these assets. The International Accounting Standards Board (IASB) on December 2000 has emitted the first normative directed to the agricultural activity the International Standard Accounting (IAS) 41 - Agriculture. The Sistema de Normalização Contabilística (SNC) is applied since January the1st 2010. It includes the Norma Contabilística e de Relato Financeiro (NCRF) 17 - Agricultura. From then on a standard for non listed Portuguese entities that develop this activity became to exist. NCRF 17 has as its main objective the accounting treatment, the financial statements presentation and disclosures about the agricultural activity. It introduces new concepts and concerns to have with biological assets treatment, as fair value recognition and measurement. The aim of this study is to perform a reflection on the problematic of biological assets and their measurement; recognition; accounting treatment; presentation of financial statements; and disclosures connected to the agricultural activity. We follow bibliographical, documentary and exploitive and descriptive case study methods and use the interview as a technique for data collection. We have used, as well, annual accounts and other documents emitted or related with the company object of this study. We have developed a literature review in which we present accounting applied to the sector in question and the collection and analysis of empirical studies on the subject. Later, a case study was, also, developed in order to analyse the application of NCRF 17 by a company situated in Baixo Alentejo. We have observed that the company elaborates and discloses its information on biological assets and governmental subsidies in compliance with NCRF 17.
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Carvalheiro, Ana Raquel da Silva. "Activos fixos tangíveis : NCRF 7 : relatório de estágio curricular." Master's thesis, FEUC, 2010. http://hdl.handle.net/10316/13085.
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Barroca, Célia Antunes. "Subsídios do governo no âmbito do SNC - NCRF 22." Master's thesis, Universidade de Aveiro, 2011. http://hdl.handle.net/10773/5995.
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Mestrado em Contabilidade - AuditoriaA globalização dos mercados, articulada com a abertura das fronteiras dentro da UE, e com a diversidade de sistemas contabilísticos, acentuou a necessidade de criar um único sistema contabilístico que fosse aceite internacionalmente e, ao mesmo tempo, que facilitasse o acesso aos mercados de capitais internacionais. Em Portugal, a normalização contabilística, sob a forma de um plano de contabilidade, iniciou-se em Portugal há mais de 30 anos, coma aprovação em 1977 do primeiro Plano Oficial de Contabilidade, que viria a ser reformulado em 1989, 1991, 1995 e 2005, culminando em 2010 com a sua total substituição por um novo Sistema de Normalização Contabilístico. Constata-se que os procedimentos contabilísticos impostos pelo SNC, no caso particular da NCRF 22 - Contabilização dos Subsídios do Governo e Divulgação de Apoios do Governo, são mais exigentes e pormenorizados do que os previstos no anterior sistema normativo nacional, em vigor até 31/12/2009. Apresentando um relato financeiro mais moderno e internacional e que melhora a informação financeira prestada a quem dela necessita, a aplicação da NCRF 22 permite, às entidades nacionais, evidenciar indicadores financeiros efectivamente equivalentes aos que são apresentados por outras entidades, de outros países, tais como Espanha, França e Bélgica, onde o tratamento contabilístico dos subsídios relacionados com activos não segue o preconizado na actual IAS 20 - Contabilização dos Subsídios do Governo e Divulgação de Apoios do Governo, possibilitando assim, a nível europeu e internacional, um melhor e maior acesso, quer a financiamentos, quer a concursos, bem como, potenciar o aumento da competitividade das empresas portuguesas, no que concerne à capacidade de reporte das suas demonstrações financeiras, em ambiente de concorrência, para uma melhor captação de fontes de financiamento internacionais.
The globalization of markets together with the opening of frontiers inside the EC and the diversity of accounting systems have enhanced the necessity for the creation of only one accounting system which would be internationally accepted and, at the same time, would facilitate the access to international capital markets. In Portugal, the accounting standards process took the form of a chart of accounts and appeared more than thirty years ago when in 1977 the first Official Chart of Accounts was approved; it would be reformulated in 1989, 1991, 1995 and 2005 when it was finally entirely substituted by a new Accounting Standards System (SNC). It can be observed that the accounting procedures imposed by SNC, particularly concerning NCRF 22 – Accounting for Government Grants and Disclosure of Government Assistance – are more demanding and detailed than those prescribed by the former national standards system in force until 31st December 2009. NCRF 22 offers a more modern and international financial report and provides more precise financial information; in addition, its application allows national entities the ability to highlight financial indicators accurately equivalent to the ones presented by entities from other countries such as Spain, France and Belgium, where accounting treatment of subsidies related to assets does not follow what is advised in the current IAS-20 – Accounting for Government Grants and Disclosure of Government Assistance, therefore permitting at an European and international level a better and wider access either to financing or to tenders, as well as to assistance in the increase of competiveness of Portuguese companies concerning their capacity to carry forward their financial reports through international financing sources in a highly competitive environment.
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Martins, Helder José Almeida. "Cumprimento dos requisitos de divulgação da NCRF 18: inventários." Master's thesis, Universidade de Aveiro, 2013. http://hdl.handle.net/10773/12149.
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Mestrado em Contabilidade - AuditoriaO anexo às demonstrações financeiras assumiu principal primazia aquando da entrada em vigor do Sistema de Normalização Contabilística. A divulgação da informação contabilística e a sua comparabilidade e harmonização a nível internacional são fatores críticos numa organização, fruto de uma exigência progressiva por parte dos stakeholders empresariais. Neste contexto, o presente estudo examina o grau de cumprimento das divulgações da Norma Contabilística e de Relato Financeiro (NCRF) 18 – Inventários por parte de uma amostra composta por 31 empresas com valores não cotados para os anos de 2010 e 2011. Este estudo tenciona igualmente fornecer provas dos fatores associados ao cumprimento. A realização desta investigação permitiu-nos concluir que as empresas cumprem os requisitos de divulgação exigidos na NCRF 18 em 80,4% e 81% nos anos de 2010 e 2011, respetivamente. Aferiu-se ainda que as empresas com maior antiguidade, maior liquidez e menor rendibilidade são as que apresentam maior índice de divulgação.
The annex to the financial statements became a priority upon entry into force of Accounting Normalization System. The disclosure of accounting information and its international comparability and harmonization are critical factors within an organization, resulting from a gradual demand by the business stakeholders. It is in this context that this study examines the level of disclosure compliance with the Accounting Standard and Financial Reporting (NCRF) 18 - Inventories from a sample made up of 31 unquoted companies for the years 2010 and 2011. This study also intends to provide evidence of the factors related to compliance. The conduction of this research allowed us to conclude that companies fulfill the disclosure requirements of NCRF 18 in 80.4% and 81% in 2010 and 2011, respectively. We could also conclude that older companies with more liquidity and lower profitability present the highest disclosure index.
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Ferreira, Helena Maria dos Santos. "Impacto da adoção da NCRF 6 "Ativos Intangíveis" do SNC." Master's thesis, Universidade de Aveiro, 2011. http://hdl.handle.net/10773/8769.
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Mestrado em Contabilidade - AuditoriaNa linha do processo de harmonização contabilística europeia, a 1 de janeiro de 2010 entrou em vigor em Portugal o Sistema de Normalização Contabilística (SNC), revogando o Plano Oficial de Contabilidade (POC) e legislação complementar. A presente dissertação tem como objetivo analisar o impacto da transição do POC para o SNC no que se refere aos ativos intangíveis, através de um estudo de caso múltiplo, tendo por base as demonstrações financeiras (DF) de um conjunto de seis empresas que até ao exercício de 2009 elaboraram e apresentaram as suas DF individuais de acordo com o POC e que, por força da transição de normativos, a partir de janeiro de 2010 viram-se obrigadas a apresentar as mesmas em conformidade com o SNC. Com esta investigação pretende-se averiguar o efeito da aplicação da NCRF 6 – Ativos intangíveis (NCRF 6) do SNC no valor dos ativos intangíveis, na posição financeira e no desempenho destas empresas, bem como nos seus indicadores económico financeiros. Da análise efetuada à informação do período de 2009 preparada segundo os dois normativos, verificou-se que a aplicação da NCRF 6 originou valores distintos em determinadas componentes do balanço e da demonstração dos resultados e, consequentemente, em determinados indicadores económico financeiros dessas empresas. Observou-se que os impactos da adoção da NCRF 6 nas empresas em estudo estão relacionados, fundamentalmente, com as diferenças entre os dois normativos relativamente ao reconhecimento das despesas de instalação e das despesas de investigação (que com a adoção da NCRF 6 deixaram de ser reconhecidas como ativos) e à valorização subsequente do goodwill (que deixa de ser amortizado, ficando apenas sujeito a testes de imparidade). O estudo revela, assim, que a adoção da NCRF 6 teve um impacto significativo no valor dos ativos intangiveis das empresas analisadas, tendo afetado ligeiramente a posição financeira (de forma negativa e positiva em três e duas das empresas, respetivamente), à exceção de um caso onde não ocorreu qualquer alteração. Por outro lado, a adoção da norma afetou significativamente o resultado líquido do exercício de duas das empresas em estudo (uma de forma negativa e outra de forma positiva), não tendo sido detetados impactos significativos em outras duas empresas. Quanto às duas restantes empresas verificou-se que a aplicação da norma não provocou qualquer alteração nos seus resultados.
In line with European accounting harmonization process, on January the 1st 2010 the Sistema de Normalização Contasbilística (SNC) began, replacing the Plano Oficial de Contabilidade (POC) and its complementary legislation. This dissertation aims to analyze the impact of the transition from POC to SNC in relation to intangible assets, through a multiple case study, based on the financial statements of a group of six companies that prepared and presented its financial statements in accordance with the POC till 2009 and, due to the change of rules and regulations, from January 2010, found themselves required to submit the same in accordance with the SNC. This investigation intends to ascertain the effect of applying NCFR 6 – Ativos intangíveis (NCRF 6) of the SNC on the value of intangible assets, on the financial position and performance of these companies, as well as on their economic financial indicators. From the analysis of the information of the period of 2009 prepared according to two standards, it was found that the application of NCRF 6 originated distinct values in certain components of the balance sheet and in income statement and therefore in certain economic financial indicators of these companies. It was observed that the impact of the adoption of NCRF 6 in the companies being studied are primarily related to differences between the two standards in the recognition of the installing costs and research expenditure (that with the adoption of NCRF 6 are no longer recognized as assets) and the subsequent valuation of goodwill (which is no longer amortized, and only subjected to impairment tests). The study thus reveals that the adoption of NCRF 6 had a significant impact on the value of intangible assets of the companies surveyed, and slightly affected the financial position (negatively in three and positively in two of the companies), except for one case where there was no change. On the other hand, the adoption of the standard significantly affect the net profit of two firms under study (one negatively and the other positively), but no significant impacts were detected in two other companies. As for the two last companies it was found that the application of the standard did not cause any change in their results.
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Vasconcelos, Sandra Cristina Santos. "Adoção da NCRF 17 - estudo de caso no setor leiteiro." Master's thesis, Universidade de Aveiro, 2012. http://hdl.handle.net/10773/9711.
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Mestrado em Contabilidade - AuditoriaA adoção do Sistema de Normalização Contabilístico a 1 de janeiro 2010 trouxe alterações profundas na mensuração dos ativos biológicos e produtos agrícolas. O normativo contabilístico português contempla pela primeira vez, a mensuração ao justo valor. No presente estudo pretendemos aferir a forma como as explorações leiteiras portuguesas estão a mensurar o seu efetivo leiteiro, através de um estudo de caso múltiplo. Os dados foram obtidos através da realização de inquéritos aos respetivos técnicos oficiais de contas. Os resultados obtidos mostram que os valores de mercado para os animais de produção leiteira são inconsistentes, reduzindo a comparabilidade da informação financeira.Com o intuito de contornarmos as falhas identificadas, elaboramos um modelo para o cálculo do justo valor do efetivo leiteiro tendo por base a atualização dos benefícios económicos futuros.
The adoption of Sistema de Normalização Contabilística on January 1st 2010 has caused substantial changes in the measurement of biological assets and agricultural products. The Portuguese accounting standards address the measuring of the fair value for the first time. This study intends to determine the way Portuguese dairy farms are measuring their dairy herd through a multiple case study. Data was collected by surveys submitted to chartered accountants. The results demonstrate that market values for dairy cattle production are inconsistent, reducing the comparability of financial information. With the purpose of overcoming the identified weaknesses, a model was developed in order to calculate the fair value of the dairy herd having as base the updating of future economic benefits.
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Bianchi, Maria Teresa Teixeira de Carvalho Marinho. "Processo Preparatório de Transição POC para NCRF/SNC: Motivações e Impactes." Dissertação, Faculdade de Economia da Universidade do Porto, 2008. http://hdl.handle.net/10216/20605.
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Melo, Liliana Ferreira de. "Benefícios dos empregados: impactos da adoção da NCRF 28 e divulgações." Master's thesis, Universidade de veiro, 2013. http://hdl.handle.net/10773/12139.
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Mestrado em Contabilidade - AuditoriaEm 1 de janeiro de 2010 entrou em vigor o Sistema de Normalização Contabilística (SNC), revogando o Plano Oficial de Contabilidade (POC) e legislação complementar. Por força da adoção das Normas Contabilísticas e de Relato Financeiro (NCRF), verifica-se diversas diferenças no tratamento contabilístico de diversas rubricas, de entre as quais os benefícios dos empregados. A presente dissertação analisa o nível de cumprimento das divulgações exigidas pela NCRF 28 e os impactos da adoção do SNC nos benefícios dos empregados, identificando as principais alterações no respetivo tratamento contabilístico. É também objetivo deste estudo caracterizar o tipo de benefícios dos empregados das empresas da amostra. A metodologia utilizada no estudo empírico consistiu na análise de conteúdo dos relatórios e contas de uma amostra de empresas portuguesas que adotam o SNC, nos períodos de 2010 e 2011. Da análise efetuada concluímos que a rubrica de benefícios dos empregados que tem maior peso na estrutura de gastos são as remunerações ao pessoal, e que os planos de benefícios definidos são os benefícios pós-emprego mais concedidos. Ao nível dos impactos da transição do POC para o SNC, constatámos que não se registaram impactos significativos relacionados com os benefícios dos empregados. Quanto aos requisitos de divulgação dos benefícios dos empregados concluímos que as empresas apresentam um elevado nível de cumprimento na maioria dos indicadores analisados.
On January 1, 2010 the Accounting Standards System (SNC) entered into force, repealing the Official Accounting Plan (POC) and complementary legislation. By virtue of the adoption of Accounting Standards and Financial Reporting Standards (IFRS), there are several differences in the accounting treatment of various items, among which the employee benefits. This dissertation analyzes the level of compliance with the disclosures required by NCRF 28 and the impacts of the SNC in employee benefits, identifying the main changes on the appropriate accounting treatment. It is also an objective of this study to characterize the type of employee benefits of sampled firms. The methodology used in the empirical study consisted in a content analysis of annual reports of a Portuguese companies sample that adopt the SNC, in the periods of 2010 and 2011. The analysis performed we conclude that the heading of employee benefits that have greater weight in the structure of expenditures are salaries to staff, and that defined benefit plans are the most awarded post-employment benefits . In terms of how the transition from the POC to the SNC, we found that there were no significant impacts related to employee benefits. Regarding disclosure requirements for employee benefits we conclude that companies show a high degree of compliment on most of indicators have been analyzed.
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Bianchi, Maria Teresa Teixeira de Carvalho Marinho. "Processo Preparatório de Transição POC para NCRF/SNC: Motivações e Impactes." Master's thesis, Faculdade de Economia da Universidade do Porto, 2008. http://hdl.handle.net/10216/20605.
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Lai, Chieh Min. "Transcription regulation of two natural killer cell activating receptors, NKG2D and NCR1." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/42212.
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Natural Killer (NK) immune lymphocytes are mainly known to eliminate cancerous and virus infected cells. When they encounter another host cell, they utilize surface receptors to scan the target cell for telltale disease-associated ligands. Therefore, these receptors play a central role in regulating NK cell effector functions that include direct cytotoxicity and cytokine release. NKG2D and NCR1 are among the most studied NK receptors identified to date. NKG2D binds a range of stress induced MHC class I like ligands while NCR1 binds the viral protein, haemagglutinin, as well as unidentified tumour ligands. Knockout mouse models have highlighted the importance of these receptors in combating tumorigenesis, virus infections, and in the development of autoimmune disorders. The expression of these receptors is specific: NKG2D is expressed only on NK cells and a minority of T cell subsets while NCR1 is even more restricted to the NK lineage. Yet the basis behind the transcriptional regulation of NKG2D and NCR1 has remained a mystery. I have found genetic and epigenetic mechanisms that control the expression of the receptors, including involvement of a retrotransposon in regulation of the mouse Nkg2d gene. Luciferase assays were used to delineate crucial DNA elements such as promoters and enhancers. Bioinformatic and RNA expression techniques have led to the discovery of GABP, RUNX3 and RUNX1 as regulators of NKG2D and NCR1. The role of these transcription factors were verified using gel shift, chromatin immunoprecipitation, knockdown, dominant negative and overexpression experiments. My results shed light on transcription regulation of crucial NK receptors. At the same time, it allows me to make inferences on the NK genetic regulatory program.
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Neves, Bruno Ferreira das. "Instrumentos de cobertura e o seu reconhecimento no âmbito da NCRF 27." Master's thesis, FEUC, 2010. http://hdl.handle.net/10316/14029.
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Oliveira, Marta José Ferreira. "A adoção da NCRF 17 no setor da cortiça: efeitos da transição." Master's thesis, Universidade de Aveiro, 2012. http://hdl.handle.net/10773/11023.
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Mestrado em Contabilidade - FiscalidadeCom a entrada em vigor do SNC, verificou-se uma alteração na mensuração dos ativos biológicos e produtos agrícolas passando a adotar o critério valorimétrico do justo valor. Neste novo paradigma, a agricultura é um dos setores que mais mutação evidencia no procedimento contabilístico, por imposição da NCRF 17 – “Agricultura”. Esta Dissertação tem como objetivo analisar o impacto da adoção da NCRF 17 no setor corticeiro, assim como analisar o nível de conservadorismo do novo normativo. Dos resultados obtidos concluiu-se, que durante o período de transição as demonstrações financeiras não espelharam uma imagem coerente da aplicação da primeira vez das NCRF. No entanto apurou-se que no ano seguinte as demonstrações financeiras mostraram um esforço evidente de ajustamento à realidade do novo normativo. Perante a aplicação dos índices de Gray (1980) demonstrou-se que o SNC é menos conservador que o anterior normativo.
The SNC adoption brought massive changes in the measurement of biological assets and farm products, basically related to the adoption of fair value valuation criteria. In this new paradigm, agriculture is one of the sectors with greater changes in the accounting policies by the imposition of NCRF 17 - "Agriculture". This thesis aims to analyze the impact of the adoption of NCRF 17 in the cork industry, as well as analyzing the level of its conservatism in comparison with previous accounting frame of reference. Results indicate that during the transition period financial statements did not express a coherent picture of the first time adoption of NCRF. However, it was found that in the following year financial statements have shown an obvious effort of adjustment to the new accounting frame of reference. Gray’s (1980) indexes have shown that SNC is less conservative than the previous accounting frame of reference.
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Silva, Marisa Alexandra Cotrim. "Análise apriorística do impacto da adoção da NCRF 8 do novo SNC." Master's thesis, Universidade de Aveiro, 2011. http://hdl.handle.net/10773/8800.
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Mestrado em Contabilidade - AuditoriaA harmonização contabilística reveste-se de grande importância para a análise e comparabilidade da informação financeira a nível internacional. Em Portugal, o novo SNC foi um dos passos mais importantes no sentido da harmonização contabilística internacional. A NCRF 8 – ativos não correntes detidos para venda e unidades operacionais descontinuadas é uma das novidades do SNC, uma vez que no normativo POC e DC o tratamento dos ativos detidos para alienação não era feito de forma autónoma. No entanto, atualmente os ativos detidos para alienação são classificados, reconhecidos, mensurados, apresentados e divulgados de forma diferente e separadamente dos outros ativos nas demonstrações financeiras. A apresentação e divulgação das unidades operacionais descontinuadas é também uma novidade do SNC. No caso de estudo realizado, procurou-se analisar qual poderá vir a ser a aplicabilidade da NCRF 8 no âmbito do novo SNC. Dado ainda não existirem dados disponíveis suficientes para se efetuar uma análise prática deste tema nas empresas nacionais abrangidas pela NCRF 8, e sabendo que as empresas com valores mobiliários admitidos à cotação na Bolsa de Valores adotam as IAS/IFRS desde 2005, optou-se por analisar as empresas do PSI 20 no contexto do paralelismo possível entre a NCRF 8 e a IFRS 5.
The accounting harmonization is of great importance for the analysis and comparability of financial information internationally. In Portugal, the new SNC was one of the most important steps towards international harmonization of accounting. The NCRF 8 - non-current assets held for sale and discontinued operations is one of the novelties of the SNC, since the POC and DC treatment of assets held for sale was not made independently. However, current assets held for sale are classified, recognized, measured, presented and disclosed differently and separately from other assets in the financial statements. The presentation and disclosure of discontinued operations is also a novelty of the SNC. In the case of study, we tried to analyze what could be the applicability of NCRF 8 under the new SNC. As yet there are insufficient data available to make a practical analysis of this issue in national companies covered by NCRF 8, and knowing that companies with securities admitted to listing on the Stock Exchange adopt IAS / IFRS since 2005, it was decided to analyze the PSI 20 companies in the context of possible parallelism between the NCRF 8 and IFRS 5.
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Correia, Ana Isabel Franco. "Activos intangíveis numa empresa de prestação de serviços - transição do POC para SNS." Master's thesis, Instituto Superior de Economia e Gestão, 2011. http://hdl.handle.net/10400.5/3414.
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Mestrado em Contabilidade, Fiscalidade e Finanças EmpresariaisO Sistema de Normalização Contabilística (SNC) enquadra-se na estratégia da União Europeia e na necessidade de procurar a harmonização contabilística que promova uma maior integração no mercado único europeu. Neste trabalho de projecto pretende-se analisar as principais diferenças qualitativas e quantitativas entre o novo sistema de normalização contabilística e o plano oficial de contabilidade (POC) no tocante aos activos intangíveis de uma empresa de serviços. Em termos qualitativos, a transição para o novo sistema contabilístico reflectiu-se em mudanças significativas na definição, reconhecimento, mensuração e divulgação dos activos intangíveis. O impacto de adopção do novo sistema contabilístico aos activos intangíveis da empresa estudada, concretamente nas carteiras de clientes adquiridas, foi sobretudo no cálculo da vida útil estimada, que deverá passar de 5 para 12 anos. Este ajustamento, conjuntamente com o desreconhecimento de cerca de 38 % dos contratos de manutenção em elevadores, teve um impacto de 2.790.307,92 euros no valor total do activo intangível e cerca de 741.410,65 euros no capital próprio.
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Sokolow, Sophie. "Les souris déficientes pour les échangeurs sodium-calcium (NCX1 et NCX3): deux modèles murins pour l'étude de leurs rôles pysiologiques in vivo ;Implication de NCX3 dans la fonction neuromusculaire." Doctoral thesis, Universite Libre de Bruxelles, 2004. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211196.
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Nous avons généré des souris déficientes pour les gènes codant pour les échangeurs Na/Ca de type I (NCX1) et de type III (NCX3) afin d'étudier, in vivo, le rôle de ces deux protéines.L‘analyse phénotypique des souris adultes totalement déficientes pour le gène Ncx1 (Ncx1-/-) n'a pu être menée étant donné que ces souris décèdent au cours du développement embryonnaire.
Les souris déficientes pour le gène Ncx3 (Ncx3-/-) sont viables et fertiles. Nous avons analysé l'effet de l'inactivation du gène Ncx3 dans le muscle squelettique et plus particulièrement au niveau de la jonction neuromusculaire.
L'analyse histologique des muscles squelettiques de souris Ncx3-/- a révélé des altérations des fibres musculaires caractérisées par la présence de foyers de fibres nécrotiques et d'infiltrats de cellules mononuclées.
L'analyse électromyographique classique a montré un électromyogramme anormal du muscle gastrocnémien de souris Ncx3-/-, révélant une affection neuromusculaire pré- et post-synaptique caractérisée par (i) la petitesse de l'amplitude de la réponse M au repos, (ii) le décrément après stimulation répétitive à basse fréquence, (iii) l'incrément après stimulation répétitive à haute fréquence et (iv) la facilitation post-exercice. L'électromyographie à fibre unique a révélé une MCD élevée et des blocages anormaux de la transmission neuromusculaire, reflétant une atteinte post-synaptique de la jonction neuromusculaire chez les souris Ncx3-/-. L'ensemble de ces anomalies électromyographiques sont les caractéristiques du syndrome myasthénique de Lambert-Eaton.
Finalement, pour déterminer les conséquences de l'inactivation du gène Ncx3 sur l'activité physique des souris Ncx3-/-, nous avons réalisé des tests comportementaux sur ces souris. Ces tests ont permis de détecter un épuisement et une faiblesse musculaire accrus à l'effort chez ces souris.
En conclusion, nos observations montrent que les souris Ncx3-/- présentent des anomalies électromyographiques similaires à celles du syndrome myasthénique de Lambert-Eaton. Ces résultats suggèrent que l'échangeur NCX3 est peut-être impliqué dans la pathogenèse de certaines formes de cette maladie.
Des études supplémentaires afin de confirmer notre hypothèse devront donc être réalisées.
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We produced and analyzed mice deficient for Na/Ca exchanger 3 (NCX3), a protein which mediates cellular Ca2+ efflux (forward mode) or Ca2+ influx (reverse mode) and thus controls intracellular Ca2+ concentration. NCX3-deficient mice (Ncx3-/-) present a skeletal muscle fiber necrosis and a defective neuromuscular transmission, reflecting the absence of NCX3 in the sarcolemma of the muscle fibers and at the neuromuscular junction. The defective neuromuscular transmission is characterized by the presence of electromyographic abnormalities including low compound muscle action potential amplitude, a decremental response at low frequency nerve stimulation, an incremental response and a prominent post-exercise facilitation at high frequency nerve stimulation as well as neuromuscular blocks. The analysis of quantal transmitter release in Ncx3-/- neuromuscular junctions revealed an important facilitation superimposed on the depression of synaptic responses and an elevated delayed release during high frequency nerve stimulation. It is suggested that Ca2+ entering nerve terminals is cleared relatively slowly in the absence of NCX3, thereby enhancing residual Ca2+ and evoked and delayed quantal transmitter release during repetitive nerve stimulation. Our findings indicate that NCX3 plays an important role in vivo in the control of Ca2+ concentrations in the skeletal muscle fibers and at the neuromuscular junction.
Doctorat en sciences biomédicales
info:eu-repo/semantics/nonPublished
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Pantazi, Eirini. "Defining the role of NCR- ILC3s in chronic colitis." Thesis, King's College London (University of London), 2018. https://kclpure.kcl.ac.uk/portal/en/theses/defining-the-role-of-ncr-ilc3s-in-chronic-colitis(5bbf74d6-2bd2-4933-8ec2-5c24f63addee).html.
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Innate lymphoid cells (ILCs) are relatively newly identified cells that have a lymphoid-like morphology, but lack antigen specific receptors. Similarly to T cells, they can be divided into three main groups (1, 2 and 3), which produce distinct combinations of cytokines to mediate their functions, and whose development depends on different transcriptional factors. Group 3 ILCs (ILC3s) are enriched at mucosal surfaces, where they act as key effector cells. They can be further subdivided into lymphoid tissue inducer (LTi) cells, and NCR+ or NCR- ILC3s based on whether or not they express natural cytotoxicity receptors. NCR- ILC3s, which co-produce IL-22 and IL-17A, remain poorly understood, especially with regards to their function in the colon. In this thesis it was shown that NCR- ILC3s were the dominant ILC3 subset in the healthy colon, as well as during colonic inflammation, and that NCR- ILC3s drived colitis in Tbx21-/- x Rag2-/- Ulcerative Colitis (TRUC) mice with IL-22 being their effector cytokine. NCR- ILC3 derived IL-22 triggered endoplasmic reticulum (ER) stress in colonic epithelial cells and induced CXCL1 and CXCL5 secretion that subsequently led to neutrophil recruitment to the inflamed colon. These pro-inflammatory actions of IL-22 were augmented by IL-17A, another cytokine produced by NCR- ILC3s that is strongly implicated in inflammatory bowel disease (IBD) pathogenesis. Whole transcriptome analysis of colonic biopsies from patients with Ulcerative colitis (UC) and healthy individuals revealed compelling evidence that these pro-inflammatory, IL-22 dependent pathways may be relevant in human disease. Taken all together these data shed more light into TRUC disease, and possibly provides new insights into the immunopathology of chronic colitis. Targeting the pro-inflammatory pathways mediated by NCR- ILC3s may represent a novel therapeutic approach for IBD.
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Saint-Marcel, Christophe. "Traçabilité et réutilisation des spécifications comportementales d'objet : le modèle NCR." Université Joseph Fourier (Grenoble), 1999. http://www.theses.fr/1999GRE10273.
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Parmi l'ensemble des modeles couramment utilises lors des developpements orientes objet, les diagrammes de classes et d'etats sont souvent presentes comme les piliers de la modelisation. Si on sait aujourd'hui utiliser et reutiliser des sous-systemes de classes sous la forme de patrons, frameworks, etc, les diagrammes d'etats restent sous-employes. En effet l'expression complete et coherente d'un statechart est un exercice de modelisation qui comporte certaines limites. Elle est difficile des lors qu'il s'agit d'exprimer l'evolution d'objets complexes et co-occurrents. Elle est peu reutilisable dans la mesure ou un statechart decrit le comportement des objets d'une seule classe et finalement peu exploitable du fait d'une integration souvent jugee difficile et repoussee a l'etape d'implantation. En partant de ce constat, nous proposons dans cette these une nouvelle structuration de l'espace de modelisation en trois dimensions : structurelle, comportementale et phenomenale. Les deux premieres sont destinees a l'ingenierie de composants reutilisables, la troisieme est dediee aux developpements de systemes d'information par reutilisation. Nous montrons comment une telle architecture peut influer sur l'utilisation et la reutilisation conjointe de classes et de statecharts. Notre solution repose sur le modele ncr. Ce dernier organise la modelisation des objets en trois parties distinctes. La notion correspond au concept usuel de classe et permet de modeliser les proprietes structurelles des objets du systeme. Le comportement est une description graphique d'evolutions generiques qui utilise les statecharts. Le role decrit la connexion entre les proprietes d'une notion et les evolutions d'un comportement ; il en assure la coherence. La clarte des specifications obtenues constitue un des apports de cette approche. Nous autorisons l'integration conceptuelle des diagrammes de classes et d'etats, offrant par la meme l'assurance d'une tracabilite complete de ces specifications ainsi que leur reutilisation dans des contextes multiples. Le modele propose encourage les concepteurs d'applications a integrer de tels diagrammes dans le processus de developpement logiciel.
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Pina, Fátima Patrícia Coelho da Costa Rodrigues. "As funções e a relação do contabilista certificado com o acompanhamento e tratamento contabilístico de projetos subsidiados." Master's thesis, Instituto Politécnico de Setúbal. Escola Superior de Ciências Empresariais, 2018. http://hdl.handle.net/10400.26/20751.
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Dissertação/Trabalho de Projeto/Relatório de Estágio
submetida como requisito parcial para obtenção do
grau de Mestre em Contabilidade e FinançasO presente trabalho insere-se num relatório de estágio no âmbito da conclusão do mestrado, tendo sido proposto como objetivo descrever as funções do contabilista certificado no acompanhamento de projetos apoiados por subsídios comunitários, incluindo a responsabilidade que o mesmo tem sobre todo o processo de contabilização. A maioria dos apoios destinam-se a PME, as quais por falta de conhecimento recorrem a consultores, sendo o contabilista um interveniente especializado, e um garante de qualidade ao longo de todo o processo de candidatura, incluindo a execução do projeto. Assim, tendo por base um estudo de caso, assente num projeto financiado ao abrigo do SI-Qualificação e Internacionalização, são descritos os procedimentos a ter em conta em cada fase, bem como os principais aspetos contabilísticos dos diferentes tipos de subsídios, tendo por base a NCRF 22. Constatou-se que a complexidade de um processo destes é elevada e que o contabilista pode fazer a diferença para o sucesso do mesmo.
The present work is part of an internship report in the scope of the conclusion of the master's degree, and it was proposed as an objective to describe the functions of the certified accountant in the follow-up of projects supported by community subsidies, including the responsibility that it has over the entire accounting process. Most of Government grants are for SMEs, which due to the lack of knowledge use the expertise of consultants. Thus, the accountant being a specialized player is a quality guarantor throughout the application process, including the execution of the project. Based on a case study of a project funded under the grants for Qualification and Internationalization, we describe the procedures to be taken into account at each stage, as well as the main accounting aspects of the different types of subsidies under the application of NCRF 22. It was found that the complexity of such process is high and that the accountant can make a difference to the success of the same.
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Sieber, Matthias. "Modulatoren des Calcineurin-NFATc-Signalweges in humanen TH-Zellen." Phd thesis, Universität Potsdam, 2010. http://opus.kobv.de/ubp/volltexte/2010/4467/.
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Die Ca2+/Calmodulin-aktivierte Serin/Threonin-Phosphatase Calcineurin ist ein Schlüsselmolekül des T-Zell-Rezeptorabhängigen Signalnetzwerkes. Calcineurin aktiviert die Transkriptionsfaktoren der NFATc-Familie durch Dephosphorylierung und reguliert darüber die Expression wichtiger Zytokine und Oberflächenproteine. Die Aktivität von Calcineurin wird durch zahlreiche endogene Proteine moduliert und ist Angriffspunkt der immunsuppressiven Substanzen Cyclosporin A und FK506.
In dieser Arbeit wurde der alternative niedermolekulare Calcineurin-NFATc-Inhibitor NCI3 hinsichtlich seiner Effekte auf T-Zell-Rezeptor-abhängige Signalwege charakterisiert. Die Ergebnisse zeigen, daß das Pyrazolopyrimidinderivat NCI3 nichttoxisch und zellmembranpermeabel ist. In T-Zell-Rezeptor-stimulierten primären humanen TH-Zellen unterdrückt NCI3 die Proliferation und IL-2-Produktion (IC50-Wert ~4 µM), da die Dephosphorylierung von NFATc und die anschließende nukleäre Translokation gehemmt wird. NCI3 inhibiert die calcineurinabhängige NFAT- und NF-κB-, aber nicht die AP-1-kontrollierte Reprtergenexpression, in mikromolaren Konzentrationen (IC50-Werte 2 bzw. 7 µM). Im Gegensatz zu Cyclosporin A stört NCI3 nicht die Phosphataseaktivität von Calcineurin, sondern interferiert mit der Calcineurin-NFATc-Bindung.
Ein wichtiges endogenes Modulatorprotein für die Calcineurinaktivität ist RCAN1, das vermutlich den Calcineurin-NFATc-Signalweg über einen negativen Rückkopplungsmechanismus reguliert.
Hier wurde gezeigt, daß RCAN1 in humanen TH-Zellen exprimiert wird. Die Spleißvariante RCAN1-1 ist in ruhenden T-Zellen basal exprimiert und wird nicht durch T-Zell-Rezeptor-Stimulierung in seiner Expression verändert. RCAN1-4 dagegen ist in ruhenden Zellen kaum zu detektieren und wird stimulierungsabhängig induziert. Durch die Verwendung Calcineurin-NFATc-spezifischer Inhibitoren wie NCI3 wurde gezeigt, daß die RCAN1-4-Induktion durch diesen Signalweg limitiert ist.
Die in dieser Arbeit gewonnenen Daten und Erkenntnisse tragen dazu bei, das Verständnis der Funktion und Regulation von Calcineurin in T-Zellen zu vertiefen.The Ca2+/calmodulin dependent serine/threonine phosphatase calcineurin is a key molecule in the T cell receptor dependent signalling network. Calcineurin dephosphorylates and thereby activates the transcription factors of the NFATc family that, among others, control the expression of important cytokines and cell surface molecules. The activity of Calcineurin is modulated by several endogenous proteins and is inhibited by the immunosuppressants cyclosporine A and FK506. Here, the novel low molecular weight inhibitor NCI3 was characterized in respect to its effects on T cell receptor dependent signalling. The results of this work show, that the pyrazolopyrimidine derivate NCI3 is nontoxic and permeates the cell membrane. Upon TCR stimulation NCI3 suppresses T cell proliferation and IL-2 production of primary human TH cells with IC50 values of ~4 µM by blocking the dephosphorylation and subsequent nuclear translocation of NFATc. NCI3 conse-quently inhibits calcineurin dependent NFAT- and NF-κB-, but not AP-1-controlled reporter gene expression, in micromolar concentrations (IC50 values 2 and 7 µM, respectively). In opposite to cyclosporine A and FK506, NCI3 does not interfere with the phosphatase activity of calcineurin but rather disturbs the calcineurin-NFATc interaction. A major endogenous modulator of calcineurin is the protein RCAN1, which is supposed to regulate calcineurin-NFATc signalling in a negative feedback loop. The presented data show that RCAN1 is expressed in human TH cells. The splice variant RCAN1-1 is basally expressed in resting T cells, and its expression levels are not changed by T cell receptor stimulation. Expression of RCAN1-4, on the other hand, is nearly undetectable in resting TH cells and is induced upon cell stimulation. By using calcineurin-NFATc specific inhibitors such as NCI3 it could be shown that RCAN1-4 induction is limited by this pathway. This work provides a comprehensive characterization of the novel inhibitor NCI3 and insights into the regulation of calcineurin by RCAN1 in human TH cells.
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Silva, Adriano Torres da. "Impacto nas Demonstrações Financeiras da Adopção da NCRF 17 - Agricultura, um exemplo de animais vivos." Dissertação, Faculdade de Economia da Universidade do Porto, 2009. http://hdl.handle.net/10216/54311.
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Silva, Adriano Torres da. "Impacto nas Demonstrações Financeiras da Adopção da NCRF 17 - Agricultura, um exemplo de animais vivos." Master's thesis, Faculdade de Economia da Universidade do Porto, 2009. http://hdl.handle.net/10216/54311.
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Lansdale, Jackie Courntey. "NCR vs DRO: Evaluation of Effectiveness, Teacher Preference, and Fidelity of Implementation." Scholar Commons, 2012. http://scholarcommons.usf.edu/etd/4355.
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Abstract
Previous research has demonstrated that non-contingent reinforcement (NCR) and differential reinforcement of other behaviors (DRO) are effective procedures in reducing problem behavior of children both in and out of the classroom. However, few studies have assessed which procedure is most socially acceptable among teachers. In addition, studies have not recorded data on fidelity of implementation among teachers. A non-concurrent multiple baseline across teachers design was used to (a) demonstrate the effect of NCR and DRO on the problem behaviors of school aged children with no identified developmental disability, and (b) assess implementation fidelity of each procedure by the teacher. This study further assessed which procedure was preferred by teachers by the addition of questionnaires and a choice phase in which teachers ultimately chose which procedure to implement. Results showed that both procedures significantly reduced problem behavior across all participants, with the DRO procedure having the greatest effect. The procedure that was preferred most by teachers varied across participants. One of the three participants preferred the NCR procedure, one preferred the DRO procedure and the last participant gave mixed results between the procedure she said she preferred in the surveys and the procedure she chose to implement in the final choice phase.
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Ribeiro, Irina Raquel Pinheiro. "Impacto das Normas Contabilísticas e de Relato Financeiro nas Empresas Portuguesas, de acordo com a percepção dos TOC's." Master's thesis, Instituto Superior de Economia e Gestão, 2010. http://hdl.handle.net/10400.5/2927.
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Mestrado em Contabilidade, Fiscalidade e Finanças EmpresariaisEsta dissertação pretende analisar e avaliar os potenciais impactos da aplicação das Normas Contabilísticas e de Relato Financeiro (NCRF), que se encontram em vigor desde Janeiro de 2010, nas empresas portuguesas, na perspectiva dos Técnicos Oficiais de Contas (TOC's). Assim, foi realizado um questionário aos TOC's a fim de avaliar o nível de preparação das empresas para adoptarem as NCRF; analisar e avaliar os potenciais impactos das NCRF nas empresas portuguesas; e avaliar a percepção que os utilizadores da informação têm da aplicação das NCRF e do seu impacto na qualidade das Demonstrações Financeiras. Os principais resultados indicam que as NCRF têm um impacto elevado nas empresas portuguesas, principalmente na qualidade das suas Demonstrações Financeiras e no valor do Capital Próprio. Adicionalmente, constatou-se que a aplicação das normas tem impacto ao nível da divulgação da informação, pois exige um maior número de informações a divulgar, e na mensuração dos elementos, devido à aplicação do justo valor que provoca uma maior volatilidade destes. No que se refere ao nível de preparação dos TOC's e das empresas, concluiu-se que estes se encontram razoavelmente preparados para aplicarem e adoptarem as NCRF.
The purpose of this dissertation is to analyze and evaluate the potential impacts of Normas Contabilísticas e de Relato Financeiro (NCRF) application, effective since January of 2010, on portuguese companies, from the perspective of the professionals accountants (TOC's). Therefore, a survey has been answered by Accountants in order to evaluate the preparation level of the companies in adopting the NCRF; to analyze and evaluate the potential impacts of NCRF on portuguese companies, and also to evaluate the user's knowledge in applying NCRF and its impact on financial reports quality. The results indicate that NCRF has a high impact on the portuguese companies, mainly in financial reports quality and in the Equity value. Additionally, the study suggests that the application of the NCRF impacts significantly in financial reports disclosures, due to the quantity of information demanded and fair value application in measuring accounting elements, leading to their volatility. Concerning the preparation level of accounting professionals and portuguese companies, the study concludes that both are reasonably prepared to apply and implement the NCRF.
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Tang, Han, and Han Tang. "The Importance of Prior Geologic Information on Hydraulic Tomography Analysis at the North Campus Research Site (NCRS)." Thesis, The University of Arizona, 2016. http://hdl.handle.net/10150/621836.
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The purpose of this study is to investigate the importance of prior information about hydraulic conductivity (K) by Kriging, using point K data and/or residual covariance, on improvements of K estimates at the North Campus Research Site (NCRS). Among many methods that can characterize the mean or detail distribution of hydraulic conductivity (K), the Cooper-Jacob straight line solution, Kriging using point K data, single-well pumping tests inversion and Hydraulic Tomography (HT) have been compared in this study, using the head data collected from 15 cross-hole pumping tests collected at NCRS, where 9 existing wells were installed with packer system and the pressure responses at different intervals in different wells were monitored with transducers. It is found that the HT method, which fuse all the available pumping test data, yields more accurate and consistent results. However, many studies have indicated that the hydraulic data combined with geologic investigation will improve the HT estimates. Thus, in this study, hard data of K obtained by permeameter (227 data points) are brought in using Kriging and combined with HT to yield better estimate K field. Moreover, the validations of unused tests indicate that the estimated K obtained using collected K information makes more accurate predictions.
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Ferreira, Sónia Patrícia da Cruz. "Impacto das NCRF de acordo com a percepção dos TOC´s : dois anos após a sua aplicação." Master's thesis, Instituto Superior de Economia e Gestão, 2012. http://hdl.handle.net/10400.5/10328.
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Mestrado em Contabilidade, Fiscalidade e Finanças EmpresariaisEste Trabalho Final de Mestrado pretende analisar e avaliar o impacto da aplicação das Normas Contabilísticas e de Relato Financeiro (NCRF), segundo a perspetiva dos Técnicos Oficiais de Contas (TOC's). Assim, foi realizado um questionário aos TOC's com vista a apurar o nível de preparação das empresas e dos profissionais de contabilidade para aplicarem as NCRF; analisar e avaliar o impacto das NCRF nas empresas portuguesas; verificar qual o nível de perceção que os utilizadores da informação possuem da aplicação das NCRF e do impacto destas na qualidade das Demonstrações Financeiras. Os principais resultados indicam que a maioria dos TOC's concorda com a adoção das NCRF, mesmo para os que atualmente exercem funções. No entanto são os TOC's com idade inferior a 36 anos, os que têm mais consenso nas suas respostas. Relativamente ao nível de preparação para as NCRF, conclui-se que os TOC's e as empresas se encontravam razoavelmente preparadas. O impacto das NCRF é positivo, principalmente na qualidade das Demonstrações Financeiras e no valor do Capital Próprio das empresas portuguesas. Relativamente às fases do processo contabilístico, a divulgação e a mensuração foram as mais afetadas, devido ao maior nível de divulgação exigido e à aplicação do justo valor.
The goal of this study is to analyze and evaluate the impact of the application of Normas Contabilísticas e de Relato Financeiro (NCRF), according to the perspective of professional accountants (TOC's). Thus, we conducted a survey to TOC's in order to ascertain the level of preparation of companies and accounting professionals to adopt the NCRF, analyze and evaluate the impact of NCRF in Portuguese companies, verify the level of information users perception of the application of NCRF and the impact on the quality of financial reports. The main results indicate that most TOC's agree with the adoption of NCRF, even those who currently do exercise functions. However are the TOC's with less than 36 years old the ones with more consistent answers. The results also suggest that the TOC's and the companies were reasonably prepared. The impact of the NCRF is positive, particularly in the quality of financial reports and the equity value in Portuguese companies. In terms of accounting process, the disclosure and the measurement phases are the most affected due to the higher level of disclosure required and the application of fair value.
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Chitren, Ann M. "Immediate and subsequent effects of matched and unmatched NCR as treatment for stereotypy /." Available to subscribers only, 2006. http://proquest.umi.com/pqdweb?did=1240699441&sid=5&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Pires, Jorge Manuel Rodrigues. "SNC - interligação entre a contabilidade e as finanças empresariais." Master's thesis, Universidade de Évora, 2013. http://hdl.handle.net/10174/12116.
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O sistema de Normalização Contabilística (SNC) entrou em vigor no dia 1de janeiro de 2010, revogando o POC e legislação complementar. 0 novo modelo contabilístico configura uma adaptação em Portugal das IAS/IFRS emitidas pelo IASB, tai como adotadas pela União Europeia, harmonizando a prática contabilística nacional corn as normas internacionais de contabilidade, permitindo a comparabilidade das demonstrações financeiras à escala universal, e diferencia-se do anterior pela introdução de dois novas paradigmas que são o reporting e o justo valor. 0 presente trabalho de projeto visa elencar os conceitos métodos e técnicas que constituem as melhores práticas ao nível das finanças empresariais, ilustrando a sua aplicação no seio das normas contabilísticas e de relato financeiro (NCRF), disponibilizando aos preparadores e stakeholders da informação financeira as ferramentas necessárias para produzir e analisar demonstrações financeiras de finalidades gerais, que passam a ser vistas como um referencial único e comum, onde a contabilidade e as finanças empresariais estão cada vez mais próximas e interdependentes; ### Abstract: The Accounting Standards System (SNC) entered into force on January 1,2010, revoking the POC and complementary legislation. The new accounting model in Portugal configures an adaptation of IAS/IFRS issued by the IASB,as adopted by the European Union by harmonizing national accounting practice with international accounting standards, allowing comparability of financial statements to a universal scale, and differs from the previous by introducing two new paradigms are reporting and fair value. This research project aims to list the concepts methods and techniques that constitute best practices in terms of corporate finance, illustrating its application within the accounting standards and financial reporting (NCRF), providing preparers and stakeholders of financial reporting tools needed to produce and analyze general purpose financial statements, which come to be seen as a single, common reference, where accounting and corporate finance are increasingly close and interdependent.
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Fonseca, Raquel Ribeiro da. "Impactos do SNC na contabilidade do sector agrícola em Portugal." Master's thesis, FEUC, 2011. http://hdl.handle.net/10316/17745.
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Relatório estágio do mestrado em Gestão, apresentada á Faculdade de Economia da Universidade de Coimbra sob a orientação de Susana Jorge.Este relatório tem por base o estágio curricular efectuado na empresa ―Moneris Douro e Beiras‖, que opera, maioritariamente, na área da contabilidade. As tarefas desenvolvidas no estágio correspondem às práticas contabilísticas efectuadas na empresa, e serão desenvolvidas na primeira parte do trabalho. Na segunda parte deste relatório, caracteriza-se, brevemente, a agricultura em Portugal e como esta tem sido um factor de desenvolvimento económico. Ainda nesta parte, efectua-se a apresentação da IAS 41 e da NCRF 17, normativos que regulam a contabilidade do sector agrícola, desde a passagem do POC para o SNC em 2010. Por último, apresenta-se um projecto, no âmbito dos Projectos PRODER, à luz da norma contabilística portuguesa da agricultura, verificando-se que trouxe alterações importantes para a contabilidade das operações deste sector.
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Jeffs, Graham J. "The effect of sodium/calcium exchanger 3 (NCX3) knockout on neuronal survival following global cerebral ischaemia in mice." University of Western Australia. School of Biomedical, Biomolecular and Chemical Sciences, 2007. http://theses.library.uwa.edu.au/adt-WU2008.0063.
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Cerebral ischaemia is a leading cause of disability and death world-wide. The only effective treatments are thrombolytic therapy (plasminogen activator; tPA) and hypothermia (33?C). However, tPA has limited clinical application due to its short therapeutic time window and its specific application in thrombo-embolic stroke. Moderate hypothermia (33?C) is only being used following cardiac arrest in comatose survivors. Hence more treatments are urgently required. The first step in developing new treatments is the identification and characterisation of a potential therapeutic target. Since brain damage following cerebral ischaemia is associated with disturbances in intracellular calcium homeostasis, the sodium-calcium exchanger (NCX) is a potential therapeutic target due to its ability to regulate intracellular calcium. Currently, however there is uncertainty as to whether the plasma membrane NCX has a neuroprotective or neurodamaging role following cerebral ischemia. To address this issue I compared hippocampal neuronal injury in NCX3 knockout mice (Ncx3-/-) and wild-type mice (Ncx3+/+) following global cerebral ischaemia. In order to perform this study I first established a bilateral common carotid occlusion (BCCAO) model of global ischaemia in wild-type C57/BlHsnD mice using controlled ventilation. After trials of several ischaemic time points, 17 minutes was established as the optimum duration of ischaemia to produce selective hippocampal CA1 neuronal loss in the wild-type mice. I then subjected NCX3 knockout and wild-type mice to 17 minutes of ischaemia. Following the 17 minute period of ischaemia, wild-type mice exhibited 80% CA1 neuronal loss and 40% CA2 neuronal loss. In contrast, NCX3 knockout mice displayed > 95% CA1 neuronal loss and 95% CA2 neuronal loss. Following experiments using a 17 minute duration of global ischaemia, a 15 minute duration of ischaemia was also evaluated. Wild-type mice exposed to a 15 minute period of ischaemia, did not exhibit any significant hippocampal neuronal loss. In contrast, NCX3 knockout mice displayed 45% CA1 neuronal loss and 25% CA2 neuronal loss. The results clearly demonstrate that mice deficient for the NCX3 protein are more susceptible to global cerebral ischaemia than wild-type mice. My findings showing a neuroprotective role for NCX3 following ischaemia, suggest that the exchanger has a positive role in maintaining neuronal intracellular calcium homeostasis. When this function is disrupted, neurons are more susceptible to calcium deregulation, with resultant cell death via calcium mediated pathways. Therefore, improving NCX activity following cerebral ischaemia may provide a therapeutic strategy to reduce neuronal death.
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Van, der Merwe George K. (George Karel)1968. "NCR-sensitive gene expression and regulation of nitrogen interconversion by VID30 in Saccharomyces cerevisiae." Thesis, Stellenbosch : Stellenbosch University, 2002. http://hdl.handle.net/10019.1/52952.
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Dissertation (PhD)--University of Stellenbosch, 2002.ENGLISH ABSTRACT: Saccharomyces cerevisiae uses the nitrogenous compounds in its environment selectively. The basis of this phenomenon is the transcriptional regulation of genes whose products are required for nitrogen catabolism. A rich nitrogen source represses the expression of genes required for the degradation of poor nitrogen sources via the action of the target of rapamyein (TOR) signaling cascade. If only a poor nitrogen source is available, these genes are derepressed. This process is known as nitrogen catabolite repression (NCR) or nitrogen regulation. The DALI and DAL4 genes of S. cerevisiae are transcribed divergently from the 829 bp intergenic region. The five known UASNTR elements (GATAI-5) were mutated in the full context of the intergenic promoter. All five elements are required for the transcriptional activation of DAL4. The two elements most proximal to DAL4 (GATA4 and GATA5) contributed the most and the one most distal (GATAI) contributed the least to its expression. In contrast, three of the five elements (GATA2-4) are required for DALI activation. In addition, analyses revealed that no single element is shared equally between these two genes. Predictions as to the function of known nitrogen-regulating elements based on their sequence and location proved to be inaccurate in some cases. Mutation analyses of the three UISALL elements present in the intergenic promoter region revealed that UIS8, which does not share a high degree of homology with the consensus UISALL sequence, is required the most for transcriptional induction of both DALI and DAL4. Also, UIS7, which shares the most similarity with the UISALL consensus sequence, has the phenotype of a repressor-like element when mutated. These observations therefore portray the opposite phenotypes of what was expected. We identified a regulator, Vid30p, which is required for the transcriptional response of S. cerevisiae in low ammonia conditions. Genetic analyses of the vid30/j, mutant indicate that Vid30p functions by regulating the expression of genes required for the production and degradation of glutamate. The transcription of VID30 is NCR-sensitive, highly induced by low concentrations of ammonia, and rapamycin-sensitive. In addition, the vid30/j, mutant is hypersensitive to rapamycin, indicating that this protein is, directly or indirectly, controlled by the TOR signaling pathway.
AFRIKAANSE OPSOMMING: Saccharomyces cerevisiae het die vermoeë om stikstofbronne vanuit die omgewing selektief te benut. Die basis van hierdie verskynsel is die transkripsionele regulering van gene wat vir proteïene kodeer wat stikstof katabolisme bemiddel. 'n Goeie stikstofbron onderdruk die transkripsie van gene wat met die degradering van swak stikstofbronne gemoeid is. Hierdie onderdrukking word deur die teiken-van-rapamisien (TVR)-seintransduksiepad bewerkstellig. Wanneer slegs 'n swak stikstofbron beskikbaar is, word hierdie gene geaktiveer. Hierdie verskynsel staan as stikstofkatabolietonderdrukking (SKR) of stikstofregulering bekend. Die DALI- en DAL4-gene van S. cerevisiae word divergent vanaf 'n 829 bp intergeniese area getranskribeer. Vyf UASNTR-elemente (GATAI-5) is in die volle konteks van die intergeniese promotor gemuteer. Al vyf elemente word vir DAL4 transkripsionele aktivering benodig. Die twee elemente mees proksimaal tot DAL4 (GATA4 en GATA5) lewer die grootste bydrae tot DAL4-geenuitdrukking, terwyl die mees distale element (GATAI) die kleinste bydrae lewer. In teenstelling hiermee lewer slegs drie van die vyf elemente (GATA2-4) 'n noemenswaardige bydrae tot DALI se uitdrukking. Nie een van die vyf elemente lewer 'n gelykwaardige bydrae tot die uitdrukking van DALI en DAL4 nie. Voorspellings betreffende die bydrae van die onderskeie UASNTR-elemente tot die uitdrukking van die DALI- en DAL4-gene, gebaseer op die sekwens en die posisie van die element in die promotor, was meestal onakkuraat. Die drie U/SALL-elemente in die intergeniese area is gemuteer en toon dat U/S8, wat nie 'n groot mate van homologie met die U/SALL konsensus sekwens deel nie, die mees kritiese element vir transkripsionele induksie van beide DALI en DAL4 is. UIS7, wat 'n hoër mate van homologie met die UISALL konsensus sekwens deel, toon die fenotipe van 'n onderdrukkingselement wanner dit gemuteer word. Hierdie waarnemings is dus die teenoorgestelde van wat verwag is. Ons het 'n reguleerder, Vid30p, geïdentifiseer wat benodig word VIr die transkripsionele response van stikstofgereguleerde gene in lae konsentrasie ammonium. Genetiese analises van die vid3011 mutant toon dat Vid30p funksioneer deur die transkripsie van gene gemoeid met die vorming en degradering van glutamaat te reguleer. Die transkripsie van V/D30 is SKO-sensitief, word sterk deur lae konsentrasies ammonium geïnduseer, en is rapamisien-sensitief. Die vid30t!. mutant is ook hipersensitief vir rapamisien, wat aandui dat Vid30p, direk of indirek, deur die TVR-seintransduksiepad gereguleer word.
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Martins, Paulo Fernando. "Imparidade de activos e o papel da auditoria interna." Master's thesis, Universidade de Aveiro, 2010. http://hdl.handle.net/10773/3538.
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Mestrado em Contabilidade - Ramo AuditoriaEste estudo propõe divulgar os possíveis riscos inerentes à adopção da NCRF 12 e o papel que o auditor interno pode desempenhar no processo de conversão para o SNC e na gestão de riscos dos seus impactos. Analisamos os impactos da adopção do SNC e da NCRF 12, através das contas das entidades cotadas em bolsa. Apresentamos as metodologias de gestão de riscos adoptadas pelos Auditores Internos, como forma a acautelar os riscos desses impactos. Comprovamos a utilidade deste estudo através dos resultados obtidos, pois os impactos foram significativos e os riscos destes impactos potenciam a intervenção dos Auditores Internos.
This study proposes to disclose the possible inherent risks related with the adoption of NCRF 12 and the role that the internal auditor can play in the conversion process to the SNC and the risk management of their impacts. We have analyzed the impacts of the adoption of the SNC and NCRF 12, through the financial accounts of traded listed companies. We have presented the risk management methodologies adopted by the Internal Auditors, as a way to prevent the risks of these impacts. We have demonstrated the utility of this study through the results, because the impacts were significant and the risks of these potential impacts enhance the intervention of Internal Auditors.
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Oliveira, Emanuel Vaz. "A percepção dos TOCs sobre o normativo contabilístico das Entidades do Setor Não Lucrativo." Master's thesis, Instituto Superior de Economia e Gestão, 2014. http://hdl.handle.net/10400.5/8118.
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Mestrado em Contabilidade, Fiscalidade e Finanças EmpresariaisA Norma Contabilística e de Relato Financeiro para as Entidades do Setor Não Lucrativo (NCRF-ESNL), encontra-se em vigor desde Janeiro de 2012. Esta dissertação tem como objetivos principais, a análise das principais diferenças entre o antigo e o novo normativo do Setor Não Lucrativo, e a análise do impacto do novo normativo segundo a perceção dos TOC´s. Foi realizado um questionário aos TOC´s e os principais resultados indicam que a NCRF-ESNL teve impactos significativos em alguns elementos da contabilidade do SNL. O estudo revelou que os utilizadores da informação contabilista confiam mais nas instituições depois da adoção do novo normativo.
The Accounting Standard and Financial Reporting for non-profit sector entities (NCRF-ESNL), is in force since January 2012. This work has as main objectives, the analysis of the main differences between the ancient normative SNL and the new, and the analysis of the impact of the new standards according to the perception of accountants. The survey to TOC´s been done and the main results indicate that the NCRF-ESNL had significant impacts on some elements of SNL accounting. The study found that users of accounting information have more trust on institutions after the adoption of the new standards.
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Dallon, Emma Kay. "Exploration of Antimicrobial Activity in Natural Peptides and High-Throughput Discovery of Synthetic Peptides." BYU ScholarsArchive, 2018. https://scholarsarchive.byu.edu/etd/7468.
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Despite many medical advances, antibiotic resistant bacteria increasingly plague the modern world, necessitating discovery of new antibiotics. One area of nature that can provide inspiration for antibiotics is antimicrobial peptides. Many of these peptides exist in nature, with some classes that have not been studied or characterized well. One such class is the defensin-like peptides generated by the plant Medicago truncatula as part of their symbiotic relationship with Sinorhizobium meliloti. Nodule-specific Cysteine Rich (NCR) peptides are defined by the presence of multiple cysteines, and regulate the growth of S. meliloti within plant cells. While some of these NCR peptides have been shown to have antimicrobial properties, hundreds of peptides remain uncharacterized. We have developed an assay for further characterization of these peptides in E. coli. Of the seven peptides that have been tested using this assay, three have exhibited definitive antimicrobial properties against both E. coli and S. meliloti. Additionally, we have developed a system for discovering novel antimicrobial peptides. This platform, called PepSeq, uses the expression of random peptides in E. coli combined with deep sequencing to detect antimicrobial activity. This technology is capable of screening through millions of peptide molecules simultaneously. Using this platform, we have discovered and confirmed six novel antimicrobial peptides, with hundreds of additional predicted antimicrobial peptides. In addition to the peptides we have analyzed using PepSeq, additional peptide scaffolds could be used to discover more potent antimicrobial peptides.
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Barrière, Quentin. "Analyse fonctionnelle de BclA, un transporteur de peptides antimicrobiens impliqué dans la différenciation des bactéroïdes au cours de la symbiose Aeschynomene/Bradyrhizobium." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS460.
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Les plantes de la famille des légumineuses ont acquis la capacité d’accueillir au sein d’organes symbiotiques, les nodosités, des bactéries fixatrices d’azote appelées bactéroïdes. Cette symbiose permet aux plantes hôtes de satisfaire leurs besoins en azote. Certaines légumineuses produisent au sein des nodosités une grande famille de peptides antimicrobiens particuliers, les NCR (Nodule-specific Cysteine-Rich). Ils permettent à l’hôte de contrôler la population bactérienne intracellulaire via leurs activités antimicrobiennes, mais aussi d’imposer aux rhizobia une différenciation terminale des bactéroïdes. Durant ma thèse, j’ai participé à l’identification et à la caractérisation de la protéine bactérienne BclA. Ce transporteur ABC est nécessaire pour la formation de bactéroïdes différenciés lors de la symbiose Aeschynomene-Bradyrhizobium. Pour mieux comprendre sa fonction symbiotique, j’ai étudié la relation entre BclA et une enzyme de modification du peptidoglycane, la DD-carboxypeptidase 1. J’ai pu montrer que ces deux facteurs agissent de manière indépendante dans la mise en place de bactéroïdes différenciés. Une analyse fonctionnelle de BclA et une expérience d’évolution expérimentale avec le mutant bacA de Sinorhizobium, un orthologue de bclA, apportent une meilleure compréhension du rôle de ces transporteurs in vivo. L’ensemble des résultats obtenus pendant ma thèse suggère que BclA et BacA assurent la résistance bactérienne face aux NCR in planta, comme un prérequis pour la suite du processus, mais ne sont pas nécessaires à la différenciation per se. De plus, leurs activités d’import des NCR ne semblent pas être le mécanisme sous-jacent du processus de résistancePlants of the legume family have acquired the ability to host in specific symbiotic organs, the roots nodules, nitrogen fixing bacteria, called bacteroids. This symbiosis allows plants to fulfill all their nitrogen requirements. Some legume plants produce in their nodules a large family of antimicrobials peptides called the NCRs (Nodule-specific Cysteine-Rich). Their antimicrobial activities allow the host plant to control the intracellular bacterial population. NCRs peptides also govern terminal differentiation of the bacteroids. During my PhD work, I participated in the identification and characterization of BclA. This bacterial ABC transporter is involved in bacteroid differentiation during the Aeschynomene- Bradyrhizobium symbiosis. In order to better understand its symbiotic function, I studied the link between BclA and a peptidoglycan-modifying enzyme, the DD-carboxypeptidase 1. I was able to show that these two factors act in an independent manner in the establishment of bacteroid differentiation. A functional analysis of BclA and an experimental evolution on Sinorhizobium bacA mutant, an orthologue of bclA, conferred a better understanding of the in vivo role of these transporters. The results obtained during my thesis suggest that the BclA and BacA function is to ensure bacterial resistance to NCRs, as a prerequisite for the bacterial differentiation process, but is not needed for differentiation per se. Furthermore, their NCR uptake activities do not seem to be the mechanism underlying the resistance
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Nguyen, Van Phuong. "Plant and bacterial functions required for morphological bacteroid differentiation in the Aeschynomene-Bradyrhizobium model." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT158/document.
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Les légumineuses sont capables de développer des organes symbiotiques, les nodules, qui hébergent des bactéries du sol appelées rhizobia. Au sein des nodules les rhizobia intracellulaires se différencient en bactéroïdes capables de réduire l'azote atmosphérique en ammonium au bénéfice de la plante. En contrepartie, la plante alimente la bactérie en sources de carbone. Des études récentes sur le modèle symbiotique Medicago/Sinorhizobium ont montré dans les nodules la forte présence d'une grande diversité de peptides appelés NCR qui sont similaires aux peptides antimicrobiens (AMP) impliqués dans l'immunité innée. Ces NCR sont responsables du maintien de l'homéostasie entre les cellules hôtes et la forte population bactérienne qu'elles contiennent. Bien que certains NCR sont de vrais AMP, capable de tuer des bactéries in vitro, dans les nodules ils induisent plutôt une différenciation terminale caractérisée par une élongation cellulaire, une amplification du génome, une perméabilité membranaire et une perte des capacités de division de la bactérie. Néanmoins le mode d'action des NCR reste à élucider. Au cours de ma thèse j'ai participé à la caractérisation des processus de différenciation dans le modèle Aeschynomene, une légumineuse tropicale, Bradyrhizobium.Dans un premier temps, une nouvelle classe de NCR a été identifiée chez différentes espèces d'Aeschynomene. Ces NCR sont responsables de la différenciation des Bradyrhizobium via un processus similaire à celui décrit chez Medicago. Ces résultats suggèrent une évolution convergente des processus de différenciation chez les Dalbergioïdes (Aeschynomene) et le clade des IRLC (Medicago).Ensuite, pour identifier les fonctions bactériennes requises lors de la différenciation, j'ai criblé 53 mutants Tn5 d'Aeschynomene indica fix- . Huit gènes bactériens dont la mutation inhibe ou affecte le processus de différenciation ont été identifiés. Parmi eux, je me suis focalisé sur la DD-CPase une enzyme de modification du peptidoglycane et sur 2 gènes impliqués dans l'homéostasie du phosphate.La caractérisation du gène DD-CPase1 a permis de démontrer que le remodelage du peptidoglycane est requis pour une différenciation correcte des bactéroïdes chez les plantes hôtes qui produisent des NCR, en général, et chez Aeschynomene en particulier. Ces résultats suggèrent une interaction possible entre DD-CPase1 et des NCR conduisant à l'endoréplication des bactéroïdes.Enfin, j'ai étudié les propriétés physiologiques et symbiotiques des mutants pstC et pstB. Les mutants Tn5 des gènes pstC et pstB de la souche ORS285 de Bradyrhizobium sont sévèrement affectés par la carence en phosphate en culture pure et leurs propriétés symbiotiques (différenciation, réduction de l'azote) sont fortement réduites. Des analyses fonctionnelles plus approfondies de l'opéron Pst devraient permettre une meilleure compréhension du lien entre l'homéostasie du phosphate et l'efficience symbiotique dans l'interaction Aeschynomene-Bradyrhizobium.Mes travaux ont permis d'élargir nos connaissances sur l'évolution de la symbiose en montrant que le modus operandi impliquant des peptides dérivés de l'immunité innée utilisée par certaines légumineuses pour maintenir leur population bactérienne intracellulaire sous contrôle est plus répandue et ancienne qu'on ne le pensait et a été utilisée par l'évolution à plusieurs reprises. De plus différentes cibles bactériennes pouvant participer au processus de différenciation ont également été identifiéesThe legume species are able to form symbiotic organs, the nodules, that house soil bacteria called rhizobia. Within these nodules intracellular rhizobia differentiate into bacteroids, which are able to reduce atmospheric dinitrogen to ammonium for the benefit of the plants. In counterpart, the plants provide carbon sources to the bacteria. Recent studies on symbiotic model Medicago-Sinorhizobium showed that the nodules of M. truncatula produce a massive diversity of peptides called NCRs, which are similar to antimicrobial peptides (AMPs) of innate immune systems. These NCRs are responsible in maintaining the homeostasis between the host cells in the nodules and the large bacterial population they contain. Although many NCRs are genuine AMPs, which kill microbes in vitro, in nodule cells they do not kill the bacteria but induce them into the terminally differentiated bacteroids characterized by cell elongation, genome amplification, membrane permeability and loss of cell division capacity. However, the action mode of NCRs is still an open question. During my PhD thesis I focused on the identification of plant and bacterial functions required for bacteroid differentiation in the Aeschynomene-Bradyrhizobium model.Firstly, a new class of cysteine rich peptides (NCR-like) was identified in tropical aquatic legumes of the Aeschynomene genus, which belong to the Dalbergioid clade. These peptides govern terminal bacteroid differentiation of photosynthetic Bradyrhizobium spp. This mechanism is similar to the one previously described in Medicago suggesting that the endosymbiont differentiation in Dalbergioid and ILRC legumes is convergently evolved.Secondly, in order to identify the bacterial functions involved in bacteroid differentiation, I screened 53 fix- Tn5 mutants of the ORS278 strain on Aeschynomene indica. This screening allowed identify 8 bacterial genes, which inhibit or disorder the bacteroid differentiation. Among these identified genes, I focused on DD-CPase encoding a peptidoglycan-modifying enzyme and two genes pstC and pstB belonging to Pst-system.The characterization of DD-CPase gene demonstrated that the remodeling peptidoglycan enzyme, DD-CPase1, of Bradyrhizobium is required for normal bacteroid differentiation in host legumes that produce NCRs, in general, and in Aeschynomene spp., in particular. This prompts a possibility of direct interaction of DD-CPase1 with NCRs leading to endoreduplication of the bacteroids.Finally, I have investigated the physiological and symbiotic properties of different mutants of pstC and pstB genes. The Tn5 mutants of pstC and pstB genes of Bradyrhizobium sp. strain ORS278 severely affected symbiosis on A. indica and A. evenia. Further functional studies on pst-operon will provide deeper understanding the correlation between phosphate homeostasis and nitrogen fixation efficiency in Aeschynomene-Bradyrhizobium symbiosis.This study broadens our knowledge on the evolution of symbiosis by showing that the modus operandi involving peptides derived from innate immunity used by some legumes to keep their intracellular bacterial population under control is more widespread and ancient than previously thought and has been invented by evolution several times
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Ayrignac, Xavier. "Caractérisation des formes atypiques de maladies inflammatoires démyélinisantes et SEP atypiques : description clinico-radiologique et analyse de la fonction du récepteur Nkp46/NCR1." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT033.
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Aux côtés des formes dites classiques de Sclérose en plaques (SEP), un nombre important de patients présentent des caractéristiques atypiques qui vont être responsable d’une période, parfois longue, d’errance diagnostique. Certains de ces patients, malgré les atypies, font clairement partie du spectre de la SEP tandis-que d’autres présentent probablement des maladies inflammatoires démyélinisantes idiopathiques distinctes qui sont, à ce jour, toujours en attente d’individualisation.Les objectifs principaux de ce travail de thèse étaient de mieux caractériser ces formes atypiques de SEP et autres maladies inflammatoires démyélinisantes idiopathiques.Nous avons effectué un travail rétrospectif de caractérisation clinique et radiologique (sur les données d’IRM acquises en conditions de vie réelle) afin d’aider au diagnostic et à mieux définir le pronostic évolutif de ces patients. Nous avons également effectué une analyse anatomopathologique chez les patients présentant une lésion inflammatoire nécessitant une biopsie avec pour objectif de mieux positionner ces lésions au sein du spectre de la SEP et du spectre des Neuromyélites Optiques (NMOSD). Enfin nous avons effectué une caractérisation de l’expression astrocytaire du récepteur NKp46 au sein des lésions de SEP et des lésions inflammatoires démyélinisantes atypiques.Les principaux résultats sont :1) En l’absence d’autre lésion cérébrale évocatrice de SEP, le risque de développer une SEP cliniquement définie chez un patient présentant une lésion cérébrale inflammatoire démyélinisante isolée est faible.2) La SEP, notamment dans sa forme progressive, peut avoir des caractéristiques proches de celles rencontrées dans le cadre des léucoencéphalopathies héréditaires. Dans ces situations, l’analyse des lésions de la substance grise, de la topographie des lésions de la substance blanche et le caractère nodulaire (>3mm mais non diffus) sont en faveur du diagnostic de SEP.3) Les lésions inflammatoires démyélinisantes du système nerveux central sont extrêmement hétérogènes en IRM. Néanmoins, certaines caractéristiques leurs sont communes : liseré périphérique en hypersignal en diffusion, prise de contraste périphérique ouverte, respect de la substance grise. L’analyse anatomopathologique sur tissus provenant de biopsies réalisées pour incertitude diagnostique démontre une préservation quasi systématique du marquage AQP4.4) L’expression astrocytaire de NKp46, récepteur classiquement décrit comme spécifique des lymphocytes NK, est commune à de nombreuses conditions neuroinflammatoires et neurodégénératives y compris la SEP, les NMOSD et les autres maladies inflammatoires démyélinisantes. Nous n’avons, à ce jour, pas pu déterminer l’implication du récepteur NKp46 dans la réponse astrocytaire en conditions inflammatoires.En conclusion, l’étude de notre cohorte rétrospective multicentrique a permis de mieux préciser les caractéristiques clinique (y compris de suivi), anatomopathologiques et IRM de patients présentant des formes atypiques de SEP et de maladies inflammatoires démyélinisantes.L’identification de sous-types de SEP caractérisés par une atteinte extrêmement sévère tant sur le plan clinique que radiologique nous semble pouvoir être un modèle d’étude intéressant dans la recherche de biomarqueurs d’imagerie et biologiques de la maladieBeside classical multiple sclerosis (MS), a significant proportion of patients can present some atypical clinical or radiological characteristics that will lead to diagnostic uncertainties. On one side, some of these patients belong to MS spectrum whereas some other probably have yet unidentified inflammatory demyelinating disorders.Our objectives were to describe those patients with atypical MS and atypical idiopathic inflammatory demyelinating disorders.We retrospectively gathered clinical and radiological (in a real-life setting) data from patient to better delineate diagnostic clues and to better assess prognosis of these patients. Moreover, a neuropathological analysis of patients’ tissue collected for diagnostic uncertainties was performed to assess AQP4 staining in patients with acute atypical inflammatory demyelinating disease. Finally, we characterized the expression of the activating receptor NKp46 within astrocytes in MS and other inflammatory neurological diseases.Our main results were the following:1) in the absence of any other lesion suggestive of MS, the overall risk of MS diagnosis and typical MS relapse is low.2) MS, notably primary progressive or bout-onset MS, can share MRI characteristics with inherited leukoencephalopathies and leukodystrophies. In this context, a thorough analysis of deep and cortical gray matter, topography of white matter lesions and size (typically nodular > 3mm but not confluent) strongly argues in favor of MS.3) In spite of a marked heterogeneity of central nervous system inflammatory demyelinating lesions, some characteristics such as a peripheral B1000 hyperintensity with open rim gadolinium enhancement (with or without central enhancement) and gray matter sparing are common to all of these conditions. Moreover, neuropathological analysis of these lesions suggests a systematic normal/increased AQP4 staining.4) NKp46 astrocytic expression, a classical NK cells marker is common to several neuroinflammatory diseases including MS, NMOSD and other inflammatory demyelinating disorders. To date, we were not able to ascertain NKp46 involvement in the context of neuroinflammation.To conclude, our analysis enabled to refine clinical, neuropathological and MRI characteristics of patients with atypical MS and atypical inflammatory demyelinating disorders.The identification of “clusters” of atypical MS with dramatic disability progression and early evidence of neurodegeneration should allow us to identify promising MRI and/or biological biomarkers of disease progression
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Reich, Sabrina [Verfasser], and Bernhard [Akademischer Betreuer] Hauer. "Studies on variable surface loop regions of the ene reductase NCR from Zymomonas mobilis / Sabrina Reich. Betreuer: Bernhard Hauer." Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2014. http://d-nb.info/105162164X/34.
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Green, Lori Jean. "Decreasing Problematic Throwing Behavior in a Child with Autism Through Parent Delivered Fixed-time Schedules of Noncontengent Reinforcement (NCR)." OpenSIUC, 2015. https://opensiuc.lib.siu.edu/theses/1706.
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The purpose of this study was to examine the effects of parent delivered non-contingent reinforcement (NCR) on decreasing throwing behavior exhibited by a young child with autism. During the pretreatment phase of the experiment the participant went a functional analysis to determine the target behavior of throwing. Baseline data was collected followed by the intervention phase. During the intervention phase, the non-contingent reinforcement (NCR) procedures were conducted. Attention was given to the participant on a fixed-time schedule and was influenced based on the participant’s behavior. The schedule of reinforcement was slowly increase with the decrease or lack of throwing attempts. Furthermore, this study aimed to determine whether parent delivered fixed-time schedules of non-contingent reinforcement decrease the non-preferred activities of throwing objects.
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Remtoula, Natacha. "Caractérisation fonctionnelle des récepteurs NK à la surface des lymphocytes T CD4+ tumoraux et normaux." Thesis, Paris Est, 2009. http://www.theses.fr/2009PEST0034.
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Le syndrome de Sézary (SS) est un variant leucémique et érythrodermique de lymphomes T cutanés. Il est caractérisé par la présence d’une population clonale de LT CD4+, présentant un noyau cérébriforme atypique, dans la peau, les ganglions lymphatiques et le sang périphérique. Après un bilan clinique, le diagnostic de cette pathologie est confirmé par l’analyse immunohistochimique d'une biopsie cutanée. Néanmoins, la cytomorphologie des cellules de Sézary circulantes n’est pas uniquement associée au SS. Notre laboratoire a identifié CD158k comme marqueur membranaire spécifique des cellules de Sézary. Ce récepteur offre un intérêt dans le diagnostic du SS et dans le suivi de l’évolution de la pathologie. Ainsi, nos résultats montrent qu’un immuno-marquage CD3+ CD158k+, analysé en cytométrie en flux, est une technique spécifique et sensible de détection de la cellule de Sézary par rapport à la cytomorphologie. Alors que dans plus de 30% des cas le SS passe inaperçu durant l’examen cytomorphologique, une analyse en cytométrie en flux permet la mise en évidence de cellules tumorales résiduelles. La présence systématique de CD158k à la surface des cellules de Sézary nous a conduit à rechercher l’expression d’autres KIRs. Sur les lymphocytes tumoraux circulants d’un patient ainsi que sur la lignée cellulaire correspondante, l’expression des formes activatrices et inhibitrices des récepteurs CD158a/h et CD158b/j est détectée. A la différence des lymphocytes NK et T CD8+, le récepteur présentant une fonction inhibitrice (KIR-L) ne l’emporte pas sur celui ayant une fonction activatrice (KIR-S) dans la cellule de Sézary. En fait, les KIR-L, à l’exception de CD158k, sont trouvés non fonctionnels dans la cellule tumorale. Ainsi, l’engagement des formes activatrices CD158h ou CD158j permet une régulation positive de la voie de signalisation CD3-dépendante de JNK et de la prolifération tumorale. Une étude fonctionnelle de la population T CD4+ KIR+, équivalent normal de la cellule de Sézary, a aussi été réalisée. Nous avons mis en évidence une expression préférentielle de la forme activatrice ou inhibitrice des récepteurs KIR homologues, selon le donneur. D’autre part, les KIRs activateurs ou inhibiteurs, exprimés à la surface des LT CD4+, jouent un rôle de co-récepteur vis-à-vis du TCR. Ainsi, une régulation positive ou négative de la prolifération et de la voie de signalisation CD3-dépendante de ERK est observée en fonction du type de récepteur co-engagé. Il est bien établi que les KIR-S s’associent à la molécule adaptatrice KARAP/DAP12 pour la transduction d’un signal d’activation. Dans les cellules T CD4+ saines et tumorales, la protéine recrutée par ces récepteurs est encore non identifiée. Notre étude sur la population T CD4+ CD158j+ de sujets sains montre l’implication de la protéine HS1 dans la signalisation mise en place par le récepteur KIR activateur. La réalisation de ce travail a permis de mieux comprendre les mécanismes mis en place à partir des KIRs dans les cellules T CD4+. Ce travail ouvre de nouvelles perspectives concernant le rôle de ces récepteurs dans les mécanismes permettant l'expansion tumorale des cellules de SézarySézary syndrome (SS) is a leukemic and erythrodermic variant of cutaneous T-cell lymphomas. It is characterized by the presence of a clonal CD4+ T lymphocyte population in the skin, lymphnodes and peripheral blood. After clinical assessment, diagnosis of this disease is confirmed by immunohistochemistry analysis of a skin biopsy. However, the cytomorphology of circulating Sézary cells is not just associated to SS. Our laboratory has identified CD158k as a phenotypic marker for Sézary cells. This receptor can be used in the diagnosis of the SS and in monitoring the evolution of the disease. Our results show that the CD3/CD158k immunostaining, analysed by flow cytométrie, is more specific and sensitive than cytomorphology to detect atypical circulating cells. While more than 30% of the SS is misdiagnosed by the cytomorphologic identification, flow cytometry analysis allows the detection of residual tumor cells. Given the systemic expression of CD158k on Sézary cells, we next investigated the expression of additional KIRs. On circulating malignant lymphocytes from one patient and the corresponding cell line, the expression of inhibitory and activating forms of CD158a/h and CD158b/j receptors was detected. In contrast to NK cells and CD8+ T lymphocytes, the inhibitory receptor signaling (KIR-L) does not outweigh the activating receptor signaling (KIR-S) in the Sézary cell. In fact, KIR-L, except CD158k, are found not functional in the tumor cell. Thus, CD158h or CD158j engagement results in an enhanced CD3-induced cell proliferation and JNK activation. A functional study of CD4+ KIR+ T lymphocyte population, the normal equivalent of Sézary cells, was then performed. We observed an exclusive expression of the activating or the inhibitory form of KIR receptors, depending on the donor. Activating or inhibitory KIRs, expressed on the CD4+ T cell surface, act as coreceptors. Thus, a positive or negative regulation of the CD3-induced cell proliferation and ERK activation is observed by triggering the KIR-S or -L respectively. It is well known that stimulatory KIR initiates intracellular signals through their association with the adaptor protein KARAP/DAP12. However, in normal and malignant CD4+ T cells the protein recruited by these receptors is still not identified. Our study on CD4+ CD158j+ T lymphocyte population from healthy individuals showed the involvement of HS1 protein as a potential adaptor molecule in the activating KIR signaling pathway. This work has provided insight into the mechanisms of KIRs signaling in CD4+ T cells and opens new perspectives on the role of these receptors in proliferation of Sézary cells
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Pascoal, Maria Olímpia Alvarez de Sousa Fernandes. "A contabilização dos ativos biológicos: problemática da mensuração e reconhecimento." Master's thesis, Escola Superior de Ciências Empresariais, 2014. http://hdl.handle.net/10400.26/6240.
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Dissertação de Mestrado em Contabilidade e FinançasO International Accounting Standards Committee (IASC), introduziu a IAS 41 – Agricultura, a primeira norma direcionada ao sector agrícola. A comissão de Normalização Contabilística (CNC) criou o Sistema de Normalização Contabilística (SNC), que integra a NCRF 17 – Agricultura (2010), no sentido de harmonizar os princípios e conceitos contabilísticos, para que todas as entidades possam operar num contexto de globalização de mercados. A NCRF 17 vem introduzir o conceito de justo valor como base de mensuração dos ativos biológicos, em detrimento do custo histórico que era utilizado anteriormente pelo Plano Oficial de Contabilidade (POC). O sector agrícola é um sector muito específico, cuja atividade gera dúvidas e incertezas, uma vez que as transformações biológicas (crescimento, produção, procriação, etc.) vão alterar a substância do ativo biológico, o que torna difícil a sua contabilização baseada no custo histórico. Nesse sentido considera-se pertinente a abordagem deste tema por ser contemporâneo e pouco abordado na literatura portuguesa e pela expectativa da aplicabilidade do justo valor como base de mensuração no sector agrícola. Este estudo apresenta na primeira parte a revisão de literatura, procura-se fazer uma análise crítica e fundamentada com base em artigos publicados, por outros autores e na (IAS 41) e na NCRF 17, sobre os ativos biológicos, justo valor, reconhecimento e mensuração. A segunda parte consiste num estudo de caso em que se analisa a aplicação do justo valor em ativos biológicos numa empresa de atividade pecuária, A observação dos dados apresentados permitiu concluir que a empresa utilizava o justo valor, com base nas cotações do mercado (existência de mercado ativo), para a valorização dos seus ativos biológicos em todas as fases da vida dos animais, assim como utiliza o justo valor na mensuração de todos os ativos biológicos.
The International Accounting Standards Committee (IASC) introduced IAS 41 - Agriculture, the first standard directed to the agricultural sector. The Comissão de Normalização Contabilística (CNC) established the Sistema de Normalização Contabilística (SNC) which integrates NCRF 17 - Agriculture (2010), in order to harmonize the accounting principles and concepts, so that all entities can operate in a context of globalization of markets. The NCRF 17 introduces the concept of fair value as the measurement basis of biological assets, at the expense of historical cost that was previously used by the Official Plano Oficial de Contabilidade (POC). The agricultural sector is a very specific sector, whose activity creates doubt and uncertainty, since the biological changes (growth, production, reproduction, etc.) will alter the substance of the biological asset. Therefore, it turns out to be difficult to make the accounting recognition of the element at historical cost. In this sense we consider appropriate to approach this topic because it is contemporary and rarely addressed in the Portuguese literature and because of the expectation of the applicability of fair value as a basis of measurement in the agricultural sector. In the first part, this study shows a literature review. We try to make a critical and reasoned analysis based on articles published by other authors and IAS 41 and NCRF 17, about biological assets, fair value recognition and measurement. The second part is a case study which analyzes the application of fair value to biological assets in a cattle ranching company. The observation of the data showed that the company used fair value based on market prices (existence of an active market) , for the valuation of their biological assets at all stages of the animals life, and used fair value, as well, in the measurement of all biological assets.
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Erasmus, Daniel J. "Deletion analysis of the Ure2p in Saccharomyces cerevisiae and effect of NCR on the production of ethyl carbamate during wine fermentations." Thesis, Stellenbosch : Stellenbosch University, 2000. http://hdl.handle.net/10019.1/51671.
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Thesis (MSc)--University of Stellenbosch, 2000.ENGLISH ABSTRACT: The wine yeast Saccharomyces cerevisiae has the ability to utilize several different nitrogenous compounds to fulfill its metabolic requirements. Based upon different growth rates of the yeast in a particular nitrogen source, nitrogen compounds have been classified as either good or poor nitrogen sources. In an environment which contains different quality nitrogen sources, such as grape must, the yeast first utilizes good and then the poor nitrogen sources. This discrimination between good and poor nitrogen sources is referred to as nitrogen catabolite repression (NCR). Examples of good nitrogen sources are ammonia, glutamine and asparagine. Nitrogen sources such as allantoin, y-aminobutyrate (GABA), arginine and proline are poor quality nitrogen sources. Several regulatory proteins, Ure2p, Gln3p, Da180p,Gat1pand Deh1p, mediate NCR in S. cerevisiae. These trans-acting factors regulate transcription of NCR sensitive genes. All these proteins, except Ure2p, bind cis-acting elements in the promoters of genes that are responsible for degradation of poor nitrogen sources. Gln3p is an activator of NCR sensitive genes in the absence of good nitrogen sources. The predominant mechanism by which NCR functions is by using Ure2p to inactivate the activator Gln3p in the presence of a good nitrogen source. Several research groups have studied the Ure2p, mainly due to its prion-like characteristics. The Ure2p has two domains: a prion inducing domain located in the N-terminal region and a NCR regulatory domain located in the C-terminal domain. The aims of this study were (i) to determine the part of the C-terminal domain which is responsible for NCR, (ii) to establish if ure2 deletion mutants produce less ethyl carbamate during wine fermentations and (iii) if NCR functions in industrial yeast strains. Nested deletions of the URE2 gene revealed that the NCR regulatory domain resides in the last ten amino acids of the Ure2p. This was established by Northern blot analysis on the NCR sensitive genes DAL5, CAN1, and GAP1 genes. Ethyl carbamate in wine is produced by spontaneous chemical reaction between urea and ethanol in wine. Urea is produced by S. cerevisiae during the metabolism of arginine. Arginine is degraded to ornithine and urea by arginase, the product of the CAR1 gene. Degradation of urea by S. cerevisiae is accomplished by urea amidolyase, a bi-functional enzyme and product of the DUR1,2 gene which is subject to NCR. This study investigated if a ure2 mutant strain produced less ethyl carbamate during wine fermentations. Wine fermentations were conducted with diploid laboratory strains: a ure2 mutant strain and its isogenic wild type strain. GC/MS analysis of the wine revealed that the ure2 mutant produced less ethyl carbamate but more ethanol than the wild type strain when arginine, di-ammoniumphosphate, asparagine or glutamine were added as nitrogen sources, in combinations and separately. There was no significant difference between the wild type fermentation and the ure2 mutant fermentation when no nitrogen was added. It was found that a combination between the deletion of URE2 and the addition of a good nitrogen source resulted in lower levels of ethyl carbamate. High density micro array analysis done on an industrial strain wine yeast in Chardonnay grape must revealed that the GAP1, CAN1, CAR1 and DUR1,2 genes, responsible for transport and metabolism of arginine and degradation of urea, are NCR sensitive. These data strongly suggest that NCR functions in industrial yeast strains.
AFRIKAANSE OPSOMMING: Die wyngis Saccharomyces cerevisiae kan verskillende stikstofbronne gebruik om in sy stikstofbehoeftes te voldoen. Stikstofbronne word as goeie of swak stikstofbronne geklassifiseer op grond van die groeitempo van die gis op die betrokke stikstofbron. 'n Goeie stikstofbron laat die gis vinniger groei as wat dit op 'n swak stikstofbron sou groei. In omgewings soos druiwemos waar daar 'n verskeidenheid van stikstofbronne teenwoordig is, sal die gis eers die goeie bronne en daarna die swak bronne benut. Stikstofbronne soos ammonium, asparagien en glutamien word geklassifiseer as goeie bronne. Allantoïen, y-amino-butaraat (GABA), prolien en arginien word as swak stikstofbronne geklassifiseer. Die meganisme waarmee S. cerevisiae tussen die stikstofbronne onderskei, staan as stikstof kataboliet onderdrukking (NCR) bekend. Die proteïene wat vir verantwoordelik is NCR naamlik Ure2p, Gln3p, Gat1 p, Dal80p en Deh1 p, bind met die uitsondering van Ure2p, almal aan cis-werkende elemente in die promoters van NCR-sensitiewe gene. Die trans-werkende faktore reguleer die transkripsie van NCR-sensitiewe gene. NCR werk hoofsaaklik deur die inhibering van Gln3p deur Ure2p in die teenwoordigheid van 'n goeie stikstofbron. Die oorgrote meerderheid NCR-sensitiewe gene word deur Gln3p in die afwesigheid van 'n goeie stikstofbron geaktiveer. Heelwat navorsing is op die prionvormings vermoë van Ure2p gedoen. Ure2p het twee domeine: 'n N-terminale domein wat vir prionvorming verantwoordelik is en die C-terminale domein waar die NCR funksie van Ure2p gesetel is. Die doel van die studie was (i) om te bepaal waar in die C-terminale domein van Ure2p die NCR regulering geleë is, (ii) of ure2 delesie mutante minder etielkarbamaat tydens wynfermentasies produseer en (iii) of NCR in industriële gisrasse funksioneel is. Delesie analises van URE2 het getoon dat die NCR regulerings domein in die laaste tien aminosure gesetel is. Dit is vas gestel m.b.v. noordlike klad tegniek analises op die OALS, CAN1 en GAP1 gene.Etielkarbamaat in wyn word deur die spontane chemiese reaksie tussen ureum en alkohol geproduseer. Ureum word gedurende die metabolisme van arginien in S. cerevisiae geproduseer. Arginien word deur arginase, produk van die CAR1 geen, na ornitien en ureum afgebreek. Die bi-funksionele ureum amidoliase, gekodeer deur die DUR1,2 geen, breek ureum na CO2 en NH/ af. As gevolg van die NCRsensitiwiteit van dié gene is ondersoek ingestel na In ure2 mutant se vermoë om minder etielkarbamaat tydens wynfermentasies te produseer. Chardonnay druiwemos is met In diploiede laboratorium ras en die isogeniese ure2 mutant gefermenteer. GC/MS analise op die wyn het getoon dat die ure2 mutant minder etielkarbamaat, maar meer alkohol in vergelyking met die wilde tipe gis produseer, as arginien, di-ammoniumfosfaat, asparagien en glutamien, afsonderlik of gesamentlik byvoeg is. Daar was egter nie In merkwaardige verskil tussen die fermentasies waar geen stikstof bygevoeg is nie. Dit dui daarop dat In kombinasie van In URE2 delesie en die byvoeging van stikstof etielkarbamaat vlakke verlaag. Mikro-skyfie analise van In industriële gis in Chardonnay mos het getoon dat die GAP1, CAN1, CAR1 en DUR1,2 gene wat verantwoordelik is vir die transport en metabolisme van arginien en degradasie van ureum, wel NCR-sensitief is. Dit dui daarop dat NCRwel in industriële gisrasse funksioneel is.
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Haberstroh, Stacy L. ""The Sun Never Sets on National Cash Registers": The International Operations of the National Cash Register Company, 1885-1922." Miami University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=miami1375877485.
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Pritchett, Leah D. "Noncontingent Reinforcement and Decreasing Problem Behaviors with Students with Special Needs and Its Effect on Teacher Behavior." TopSCHOLAR®, 2017. http://digitalcommons.wku.edu/theses/1934.
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A pilot study of noncontingent reinforcement (NCR) was conducted using NCR statements to (a) decrease target behaviors, (b) increase unprompted praise statements from the teacher and decrease reprimands, and (c) increase proximity to the participants by the teacher implementing NCR. Data were collected using a single-subject research design on two participants and one teacher. The target behaviors were physical and verbal aggression and inappropriate gestures. Teacher behaviors targeted with this study were praise statements, reprimands, and proximity to students. The participants included were one 16-year-old student with an emotional behavior disability, one 18-year-old student identified with autism spectrum disorder (ASD) and an undergraduate student who was the teacher in this setting. The results were inconclusive regarding the students’ behavior due to confounding variables. However, regarding teacher behavior, the results demonstrated an increase in proximity and praise statements and a decrease in reprimands. This single-subject study provided empirical support that the NCR intervention positively altered teacher behavior.
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Nicoud, Quentin. "Study of terminal bacteroid differentiation features during the legume-rhizobium symbiosis Bradyrhizobium diazoefficiens USDA110 nodulation of Aeschynomene afraspera is associated with atypical terminal bacteroid differentiation and suboptimal symbiotic efficiency Sinorhizobium meliloti functions required for resistance to the antimicrobial NCR peptides and bacteroid differentiation." Thesis, université Paris-Saclay, 2021. http://www.theses.fr/2021UPASB007.
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La symbiose rhizobium-légumineuse est une intéraction étroite entre plante et bactérie. Au cours de cette symbiose, la bactérie est hébergée par la plante au sein d’organes symbiotiques où elle fixe l’azote atmosphérique pour la plante. Les espèces de légumineuses du groupe des IRLC et des Dalbergioïdes peuvent contrôler les rhizobia symbiotiques et induire un processus de différenciation particulier grâce à la production massive de peptides riches en cystéines (NCR) spécifiques aux nodosités. In vitro, les peptides NCR cationiques ont des activités de perméabilisation de la membrane sur de nombreuses bactéries. La manière dont les rhizobiums s'adaptent pour résister à ce stress intense reste encore aujourd’hui mal compris. Deux axes de recherche principaux ont été menés au cours de cette thèse, tous deux liés à la compréhension de la réponse des bactéries à la différenciation terminale imposée par les peptides NCR. D'un côté, nous avons analysé certaines fonctions bactériennes pour leur rôle dans la résistance à la NCR au cours de l'interaction modèle entre Medicago truncatula et Sinorhizobium meliloti. Dans ce travail, nous avons principalement évalué les fonctions membranaires telles que la synthèse du LPS, le système de réponse aux stress de l’enveloppe et des fonctions d'importation. Nous avons trouvé de nouvelles fonctions qui pourraient être impliquées dans la résistance à la NCR et la différenciation terminale des bactéroïdes.De l'autre côté, nous avons mené une approche multi-omique couplée à des techniques de biologie cellulaire pour caractériser l'interaction mal adaptée entre Bradyrhizobium diazoefficiens USDA110 et Aeschynomene afraspera. Nous avons découvert de nouvelles particularités dans cette interaction avec notamment une différenciation inhabituelleThe legume-rhizobia symbiosis is a close interaction between a plant and bacteria. During this symbiosis, bacteria are hosted by the plants in symbiotic organs called nodules and in which the symbionts fix atmospheric nitrogen for the plants. Legume species from IRLC and Dalbergioid can control symbiotic rhizobia and mediate a particular differentiation process through the massive production of nodule-specific cysteine-rich (NCR) peptides. In vitro, cationic NCR peptides have membrane-permeabilizing activities on many bacteria. How rhizobia adapt to resist this intense stress remains poorly understood. Two main research axes were driven during this thesis, both linked to the understanding of how bacteria react to terminal differentiation imposed by NCR peptides. On one side, we tried to functionally analyze bacterial functions for their role in NCR resistance during the model interaction between Medicago truncatula and Sinorhizobium meliloti. In this work, we mainly assessed membrane functions such as LPS synthesis, Envelope Stress Response, and import functions. We found novel functions that could be involved in NCR resistance and terminal bacteroid differentiation.On the other side, we conducted a multi-omics approach coupled with cell-biology techniques to characterize the ill-adapted interaction between Bradyrhizobium diazoefficiens USDA110 and Aeschynomene afraspera. We discovered new features in this interaction with an unusual differentiation