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Hansen, Lars-Petter Gunhildsberg, and Ivar Conradi Østhus. "NPT Online Broadband Test Tool." Thesis, Norwegian University of Science and Technology, Department of Telematics, 2009. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-8975.
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Many broadband subscribers suspect that they do not receive the data rate they are paying for. In order to verify that the broadband connection is compliant with the product purchased, subscribers can go on-line and choose between a myriad of available on-line broadband test tools with variable degree of precision. Today there exist no standardized methods to perform broadband evaluation for private subscribers. We review and benchmark a selection of the available broadband test tools to reveal their strengths and weaknesses. Different tools have different approaches in their evaluation of network performance. Our studies show that most of the tools achieve acceptable accuracy for common Internet access data rates in Norway today. But when the data rate is increasing, the results from the different tools start to deviate. This is apparent for the upload rates in particular. The test methodology and the implementation technology are crucial for high bandwidth measurements. The Norwegian Post and Telecommunications Authority will develop and release an on-line tool for evaluation of the end-users' Internet connections. We present the planned service and elaborate its possibilities and limitations. Network neutrality is a concept that is quite ambiguous, and there exist many different interpretations. Based on the principles of network neutrality, developed by the Norwegian Post and Telecommunications Authority, we evaluate if the planned service is able to reveal breaches of network neutrality. We conclude that this is not possible with the planned service, mainly because of the limitations in the planned architecture combined with the complexity of network neutrality. A broadband test tool should evaluate the quality of a broadband connection in context of its usage. We suggest a user profile scheme based on relevant services for different groups of users. Different services have requirements to different network characteristics, and this consequently determine what characteristics should be evaluated for each profile. Lastly, we make use of our gained knowledge and recommend possible extensions and future applications for broadband evaluation.
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Martinovová, Nikola. "NPM: Optimization of purchasing process." Master's thesis, Vysoká škola ekonomická v Praze, 2014. http://www.nusl.cz/ntk/nusl-192395.
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The theoretical part will be focused on presenting information within the process management. Some of the pieces of this theoretical information will be were slightly modified by internal Continental procedures and applied in the practical part of the thesis in order to redesign current purchasing process of non production material. The contents of the practical part of this thesis are the analysis of the current purchasing process of non-production material in the plant of Continental. The intention is to identify the waste and obstacles in the process. The main target is to improve the process in consideration of efficiency, lead time reduction and, if applicable, cost savings. Once the waste in the process is identified, the 100% value added ideal state is going to be developed, under consideration of implementing the improvements, which have been identified in the current state. Based on the differences between the current state and the ideal state of the process, the future state is going to be mapped.
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Boudra, Rafik. "Rôle de la Nucléophosmine (NPM1) dans la physiopathologie prostatique." Thesis, Clermont-Ferrand 2, 2015. http://www.theses.fr/2015CLF22598/document.
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La Nucléophosmine (NPM1/B23) est une petite chaperonne moléculaire impliquée dans de nombreux processus cellulaires, tels que la régulation de l’expression génique ou le contrôle du cycle cellulaire. De nombreuses études rapportent une surexpression de NPM1 dans divers types de tumeurs solides incluant les cancers de la prostate, et son rôle proH prolifératif dans des lignées cellulaires tumorales d’origines variées est bien établi. La première partie de notre travail s’est attaché à évaluer le potentiel oncogénique de NPM1 dans l’épithélium prostatique in vivo. Pour cela, nous avons généré un modèle de souris transgéniques qui surexpriment NPM1 spécifiquement dans l’épithélium de la prostate. Ces animaux présentent une hyperplasie prostatique associée à une augmentation de l’index prolifératif de l’épithélium. Nos expériences révèlent que NPM1 pourrait lever la quiescence des cellules épithéliales différenciées en dérégulant l’expression de gènes clés de la régulation du cycle cellulaire, comme la Cycline E ou p27kip1. Bien que ces souris ne développent pas de lésions néoplasiques, ces données suggèrent que NPM1 participe à la carcinogenèse prostatique en association avec d’autres lésions oncogéniques. La seconde partie du travail visait à comprendre la nature des mécanismes qui supportent la surexpression de NPM1 dans les tumeurs prostatiques. Des données récentes de la littérature indiquent un enrichissement de la protéine kinase mTOR au niveau du promoteur proximal de NPM1 dans des foies de souris. Pour déterminer s’il existe un lien fonctionnel entre mTOR et NPM1, nous avons tiré parti d’un modèle de fibroblastes embryonnaires de souris invalidés pour le suppresseur de tumeur PTEN dont l’inactivation mène à une hyperactivité de mTOR. Dans ce contexte, les taux d’ARNm et de protéines NPM1 sont augmentés par rapport aux cellules sauvages. Nos résultats montrent également que mTOR contrôle l’expression de NPM1 i) en se fixant sur son promoteur et en stimulant l’expression du gène et ii) en stabilisant l’ARNm de NPM1. Nous avons confirmé le lien entre NPM1 et mTOR in vivo grâce à notre modèle de souris invalidées pour PTEN dans l’épithélium prostatique. Enfin, nous avons montré que l’expression de NPM1 est nécessaire pour transduire les effets prolifératifs de la voie PI3K/AKT/mTOR. Ces données placent donc NPM1 comme nouvel effecteur en aval de cette voie de signalisation, faisant de cette protéine une potentielle cible thérapeutique dans les tumeurs présentant une perte de PTENNucleophosmin (NPM1/B23) is a small molecular chaperone involved in a large array of cellular processes, including the regulation of gene expression and the control of the cell cycle. Several studies have reported the overexpression of NPM1 in solid tumors from various histological origin, including prostate cancer, and its proliferative impact on several human cancer cell line is being well described. The first part of our work aimed at assessing the NPM1 oncogenic properties in the prostate gland in vivo. To do so, we generated a new transgenic mouse model that overexpresses NPM1 specifically in the prostatic epithelium. These mice harbor prostatic hyperplasia associated with an increase of the ki67 proliferative index. Our molecular investigations revealed that NPM1 could be an inhibitor of the quiescent state of epithelial cells through a dysregulation of key cell-cycle controlers such as Cyclin E or p27kip1. Although these mice do not develop neoplastic lesions, our data suggest that NPM1 overexpression accelerate prostate cancer progression when associated with other oncogenic alterations. The second part of the work aimed at understanding the mechanisms underlying NPM1 overexpression in prostate tumors. The serine/threonine Kinase mTOR was recently shown to bind to the proximal promoter of NPM1 in the mouse liver. In order to characterize a fonctionnal link between NPM1 and mTOR, we took advantage of murine embryonic fibroblast (MEF) deleted for PTEN, since these cells display a constitutive mTOR activity. In such cells, NPM1 protein and mRNA levels are increased compared to wild type MEF. We also demonstrated that mTOR controls NPM1 expression i) through its binding to NPM1 promoter, thus stimulating NPM1 gene expression and ii) by stabilizing NPM1 mRNA. We have confirmed the functional link between NPM1 and mTOR in vivo in a mouse model deleted for PTEN specifically in the prostatic epithelium. Finally, we have shown that NPM1 expression is necessary for the proliferation of PTEN knock-out MEF. These data set NPM1 as a new downstream effector of the PI3K/AKT/mTOR pathway, and suggest that it could be a new potential therapeutic target in PTEN negative human prostate cancer
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Goswami, Pronnoy. "Investigating the Reproducbility of NPM packages." Thesis, Virginia Tech, 2020. http://hdl.handle.net/10919/98491.
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The meteoric increase in the popularity of JavaScript and a large developer community has led to the emergence of a large ecosystem of third-party packages available via the Node Package Manager (NPM) repository which contains over one million published packages and witnesses a billion daily downloads. Most of the developers download these pre-compiled published packages from the NPM repository instead of building these packages from the available source code. Unfortunately, recent articles have revealed repackaging attacks to the NPM packages. To achieve such attacks the attackers primarily follow three steps – (1) download the source code of a highly depended upon NPM package, (2) inject malicious code, and (3) then publish the modified packages as either misnamed package (i.e., typo-squatting attack) or as the official package on the NPM repository using compromised maintainer credentials. These attacks highlight the need to verify the reproducibility of NPM packages. Reproducible Build is a concept that allows the verification of build artifacts for pre-compiled packages by re-building the packages using the same build environment configuration documented by the package maintainers. This motivates us to conduct an empirical study (1) to examine the reproducibility of NPM packages, (2) to assess the influence of any non-reproducible packages, and (3) to explore the reasons for non-reproducibility. Firstly, we downloaded all versions/releases of 226 most-depended upon NPM packages, and then built each version with the available source code on Github. Secondly, we applied diffoscope, a differencing tool to compare the versions we built against the version downloaded from the NPM repository. Finally, we did a systematic investigation of the reported differences. At least one version of 65 packages was found to be non-reproducible. Moreover, these non- reproducible packages have been downloaded millions of times per week which could impact a large number of users. Based on our manual inspection and static analysis, most reported differences were semantically equivalent but syntactically different. Such differences result due to non-deterministic factors in the build process. Also, we infer that semantic differences are introduced because of the shortcomings in the JavaScript uglifiers. Our research reveals challenges of verifying the reproducibility of NPM packages with existing tools, reveal the point of failures using case studies, and sheds light on future directions to develop better verification tools.Master of Science
Software packages are distributed as pre-compiled binaries to facilitate software development. There are various package repositories for various programming languages such as NPM (JavaScript), pip (Python), and Maven (Java). Developers install these pre-compiled packages in their projects to implement certain functionality. Additionally, these package repositories allow developers to publish new packages and help the developer community to reduce the delivery time and enhance the quality of the software product. Unfortunately, recent articles have revealed an increasing number of attacks on the package repositories. Moreover, developers trust the pre-compiled binaries, which often contain malicious code. To address this challenge, we conduct our empirical investigation to analyze the reproducibility of NPM packages for the JavaScript ecosystem. Reproducible Builds is a concept that allows any individual to verify the build artifacts by replicating the build process of software packages. For instance, if the developers could verify that the build artifacts of the pre-compiled software packages available in the NPM repository are identical to the ones generated when they individually build that specific package, they could mitigate and be aware of the vulnerabilities in the software packages. The build process is usually described in configuration files such as package.json and DOCKERFILE. We chose the NPM registry for our study because of three primary reasons – (1) it is the largest package repository, (2) JavaScript is the most widely used programming language, and (3) there is no prior dataset or investigation that has been conducted by researchers. We took a two-step approach in our study – (1) dataset collection, and (2) source-code differencing for each pair of software package versions. For the dataset collection phase, we downloaded all available releases/versions of 226 popularly used NPM packages and for the code-differencing phase, we used an off-the-shelf tool called diffoscope. We revealed some interesting findings. Firstly, at least one of the 65 packages as found to be non-reproducible, and these packages have millions of downloads per week. Secondly, we found 50 package-versions to have divergent program semantics which high- lights the potential vulnerabilities in the source-code and improper build practices. Thirdly, we found that the uglification of JavaScript code introduces non-determinism in the build process. Our research sheds light on the challenges of verifying the reproducibility of NPM packages with the current state-of-the-art tools and the need to develop better verification tools in the future. To conclude, we believe that our work is a step towards realizing the reproducibility of NPM packages and making the community aware of the implications of non-reproducible build artifacts.
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Liu, Hanwen. "Detecting code duplications in the NPM community." Thesis, Virginia Tech, 2021. http://hdl.handle.net/10919/104972.
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In the modern software development process, it has become a very mainstream practice to build software projects on top of third-party packages to simplify the development process. In this development method, it is quite common to copy existing code or files in other libraries instead of making regular calls. Although this approach can reduce the project's dependence on other libraries and make the project more streamlined, it also causes difficulties in maintenance and understanding. The ignorance of code duplication by third-party library community can even be exploited for malicious purpose, such as typo-squatting attack. This paper serves as a starting point to analyze the growing code duplication issues surrounding third-party open source packages, and what is the root cause of code duplication. In this paper, I conducted code duplication-related research based on some popular packages in the third-party open source packages community, the NPM community, by using the tokenizer tool and the code comparison tool to compute the code similarity, quantitatively analyzed the prevalence of code duplication in the NPM community, and did some related experiments based on this similarity. In the experiments, I found that code duplication is very common in NPM community: 17.1% of all the files have 1-93 similar file in other package when the threshold of similar file is set to 0.5. 29.3% of all the packages has at least one "similar package" when the threshold of similar package is set to 0.5. In all the 951 similar package pairs, 33.9% of them, 323 package pairs comes from the same domain. The ultimate goal of this paper is to promote the awareness of the commonness and the importance of code duplication in the third-party package community and the reasonable use of code duplication by developers in the project development.In the modern software development process, developers often call other people's completed code to build their own programs. There are generally two ways to do this: indirectly call other people's code through "import" or similar instructions in the program, or directly copy and paste other people's code and make slight modifications. The second method can make the program more independent and easy to use, but the code duplication problem caused by this method also has great security risks.This paper serves as a starting point to analyze the growing code duplication issues, and what is the root cause of code duplication. In this paper, I conducted code duplication-related research based on some popular code packages in the NPM community.I used some tools to compute a value to define how different codes are similar to each other, quantitatively analyzed the prevalence of code duplication in the NPM community, and did some related experiments based on this similarity. In the experiments, I found that code duplication is very common in the NPM community: 17.1% of all the files have 1-93 similar file in other package, and 29.3% of all the package have at least one "similar package", when the definition of similar files and packages are not that "strict".In all the 951 similar package pairs, 33.9% of them, 323 package pairs comes from the same domain. The ultimate goal of this paper is to promote the awareness of the commonness and the importance of code duplication in the third-party package community and the reasonable use of code duplication by developers in the project development.
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Neelagandan, Kalainanghi S. "Protein:protein interaction between Interferon Regulatory Factor (IRF-1) and necleophosmin (NPM1)." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25830.
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Interferon Regulatory Factor -1 (IRF-1) is a transcription factor that acts as a tumour suppressor in cancer cells. The inactivation or deletion of IRF-1 either in one or both allele has been frequently reported in leukaemia and myelodysplasia (MDS). On the other hand nucleophosmin (NPM), a nucleo-cytoplasmic shuttling phosphoprotein is also known to be aberrant in some form of leukaemia. NPM was first proposed as a binding partner of IRF-1 in 1997 and suggested to inactivate IRF-1 by inhibiting its DNA binding ability. No further researches on the interaction between IRF-1 and NPM1 was reported prior to the start of my PhD. In the research presented here the interaction and mechanism by which IRF-1 might be inactivated by NPM was studied. Under the context of both NPM and IRF-1 being frequently associated with leukaemia and MDS, the study was done to determine the role of NPM under its naïve condition and a most frequent mutated condition (NPMc+), where the C-terminal of NPM was frequently mutated to give rise to a cytoplasmic NPM in certain leukaemia. In this current research, the direct interaction between IRF1 and NPM was further confirmed both in vitro as well as within the cells. Following this, the effect of this interaction in respect to the leukaemic condition having NPMc+ mutation was done, by comparing the end results on AML2 (leukaemic cells with intact wild type NPM) and AML3 (leukaemic cells having a single NPM allele mutated to form NPMc+) cells. In this research, overexpression of wild type NPM (NPMwt) was found to increase IRF-1 transcriptional activity. On further analysis, the DNA binding activity of IRF-1 due to the presence of NPMwt or NPMc+ was not always inhibited, instead it shows a change in binding specificity, where NPMwt bound IRF-1, lacks DNA binding ability and DNA bound IRF-1 has a reduced binding towards NPM. This is being studied further in terms of NPM overexpression and increased IRF-1 transcriptional activity, as the order of addition (order of interaction in vivo) plays a major role in activating or deactivating IRF-1. This along with the increased transcriptional activity of IRF-1 suggests a novel function of NPM, where it could act in favour of IRF- 1 activity. Additionally, the NPM induced change in IRF-1 localisation was confirmed by the cytoplasmic localised IRF-1 in NPMc+ expressing cells and nucleolar sequestration in NPMwt overexpressing cells. This gives a novel mechanism by which NPM regulates IRF-1. Further, the NPMc+ specific colocalisation of IRF-1 urges to study the other proteins that may have been re-localised in AML cells due to the NPMc+ specific interaction. A mass spectrometric analysis on the cellular distribution of total proteins were analysed between AML2 (cells with NPMwt) and AML3 (cells containing NPMc+). Specific proteins related to cancer have been identified to be differentially distributed rather than being a random translocation. With this being said, a peptide phage display technology coupled with next generation sequencing was done to identify NPMwt binding peptides that can be used in drug discovery process or as small molecule inhibitors or activators. Three different peptides were selected at the end of the study that bind very effectively to NPMwt. These peptide can either aid or restrict NPM activity and need to be validated and studied in the future.
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Torchetti, Paolo. "Perceptive legitimacy : the NPT and it behavioural prescriptions." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=31145.
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Truths are illusions about which one has forgotten that this is what they are. - NietzscheOn March 5th 1970, a long process of international negotiation and power brokering culminated into the Nuclear Proliferation Treaty. As a result the 121 signatory states were legally subject to the norms, values, principles, and behavioural prescriptions of the nuclear proliferation regime. Twenty-nine years after the treaty's entrenchment, however, the nuclear proliferation regime and its enforcement agencies still face many of the same challenges that have plagued its implementation since its conception. The purpose of this analysis is to examine the causal relationship between the perception of the political legitimacy among the signatory members of the NPT, the likelihood of adherence to these behavioural prescriptions and to provide a framework to understand what would make for a legitimate treaty in the eyes of its members. This analysis will reveal that signatory members of the NPT who perceive the treaty as illegitimate are more likely to either defect or disobey the obligations of the treaty than those signatory members who perceive the NPT to be legitimate. (Abstract shortened by UMI.)
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Boman, Robin. "Innovationspolitikens styrning : Beskriven utifrån styrningsmodellerna NPM och govemance." Thesis, Mittuniversitetet, Institutionen för humaniora och samhällsvetenskap, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-35508.
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津崎, 直人. "NPTとアメリカ - NPT形成史の再検討による核不拡散の再考." 京都大学 (Kyoto University), 2009. http://hdl.handle.net/2433/124148.
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Lüker, Jakob [Verfasser]. "Nachweis von NPM1- und FLT3-Mutationen bei Patienten mit AML / Jakob Lüker." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2011. http://d-nb.info/1009752928/34.
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Nouri, Kazem [Verfasser]. "Biochemical Characterization of RHO GTPases-IQGAPs and NPM1-US11/Rev interactions / Kazem Nouri." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2017. http://d-nb.info/1139491148/34.
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Fawal, Mohamad-Ali. "The role of mRNA metaboism in NPM-ALK-mediated oncogenesis." Toulouse 3, 2009. http://thesesups.ups-tlse.fr/633/.
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Les lymphomes anaplasiques à grandes cellules (ALCLs) sont caractérisés par l'expression d'une protéine de fusion (X-ALK) dans laquelle le partenaire N-terminal (dans la majorité des cas la nucléophosmine NPM) est fusionné à la portion cytoplasmique de la protéine ALK (Anaplastic Lymphoma Kinase) contenant un domaine tyrosine kinase. L'expression constitutive de cette tyrosine kinase oncogénique provoque l'activation de nombreuses voies de signalisation responsables du caractère tumoral des cellules qui l'expriment. En découvrant que la protéine de liaison à l'ARN, AUF1, est un partenaire privilégié de NPM-ALK, nous avons émis l'hypothèse qu'outre son effet sur la transcription, la tyrosine kinase oncogénique pourrait également réguler l'expression des gènes au niveau post-transcriptionnel. En utilisant une combinaison d'approches biochimiques, nous avons mis en évidence une hyperphosphorylation de la protéine AUF1 dans les cellules murines NIH3T3 exprimant de manière stable la translocation NPM-ALK et une corrélation entre cette hyperphosphorylation et l'augmentation de la stabilité d'un certain nombre d'ARN contenant une ARE (c-myc, Cycline D1, A1, B2. . . ). En utilisant des expériences d'imagerie cellulaire, nous avons montré qu'AUF1, HuR (une autre AUBP) et NPM-ALK (ou d'autres fusions X-ALK) étaient concentrés dans des granules cytoplasmiques, que nous avons appelés AG, pour ALK Granules. Nous avons analysé par vidéo-microscopie la parenté entre les AG et d'autres granules cytoplasmiques, les processing bodies (PB) et les granules de stress (SG), qui jouent un rôle dans le tri, le stockage ou la dégradation des ARNm. Enfin, nous avons identifié le contenu protéique et ribonucléique (mRNA et miRNA) des AG. L'ensemble de nos résultats montrent que les AGs contribuent au contrôle du métabolisme des ARN dans les cellules et pourraient jouer un rôle majeur dans l'oncogénicité de NPM-ALKAnaplastic Large Cell Lymphomas (ALCLs) are characterized by the expression of a fusion protein (XALK), in which the N-terminal partner (in most cases the nuclephosmin NPM) is fused to the cytoplasmic portion of ALK (Anaplastic Lymphoma Kinase) containing a tyrosine kinase domain. The constitutive expression of this oncogenic tyrosine kinase causes activation of many signalling pathways responsible for malignant transformation of the cells that express it. Following the discovery that the RNA binding protein AUF1 to is a partner of NPM-ALK, we hypothesized that besides its effect on transcription, NPM-ALK may also regulate gene expression at the post-transcriptional level. In fact, AUF1belongs to the AUBP family that controls the stability and translation of many RNAs containing in their 3' non-coding region a region rich adenine and uridine (ARE). The majority of these mRNAs encode proteins involved in controlling cell proliferation, apoptosis, stress and immune response. Therefore, following its interaction with NPM-ALK, AUF1 activity could be modified resulting in deregulation of the expression of its RNA targets. Using a combination of biochemical approaches, we have shown that AUF1 is hyperphosphorylated in murine NIH3T3 cells stably expressing the NPM-ALK translocation and this hyperphosphorylation is correlated with an increased stability of a number of ARE containing RNAs (e. G. C-myc, cyclin D1, A1, B2. . . ). Using cell imaging experiments, we showed that AUF1, HuR (another AUBP) and NPM-ALK (or other fusion X-ALK proteins) were concentrated in cytoplasmic granules, which we called AG for ALK granules. We analyzed by video microscopy the relationship between AG and other cytoplasmic granules, the processing bodies (PBs) and stress granules (SGs), which play a role in sorting, storage or degradation of mRNA. Finally, we identified the protein and ribonucleic (mRNA and miRNA) of AG. All our results show that AGs contribute to the control of RNA metabolism in the cells and could play a major role in NPM-ALK mediated oncogenicity
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Henningsson, Mathilda, and Alisa Klokic. "Post-NPM i en svensk kontext : Tillitsbaserad styrning och ledning." Thesis, Linnéuniversitetet, Institutionen för ekonomistyrning och logistik (ELO), 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-105687.
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Inledning: New Public Management (NPM) har varit ett aktuellt ämne sedan 90-talet och det råder delade meningar kring NPMs status. Vissa menar att NPM leverkvar medan andra hävdar att NPM har dött ut. Andra forskare hävdar att NPM harkompletterats med post-NPM reforminitiativ där begrepp som samverkan,öppenhet och tillförlitlighet har fått ta större plats. Det som i svensk kontext kaninnefattas under post-NPM är tillitsbaserad styrning och ledning och dessframväxt och definition är det som fortsatt kommer att redogöras för i dennastudie utifrån Tillitsdelegationens arbete som grund. Syfte: Syftet med studien är att beskriva hur en styrningsidé inom ramen för postNPM i en svensk kontext kommit att utvecklas och definieras. Dels genom attstudera styrningsidéer som varit dominerande inom post-NPM, dels genom attstudera reformvågor och trender inom offentlig sektor. Studien syftar vidare tillatt bidra med kunskap om definitionen av tillitsbaserad styrning i Sverige genomen empirisk studie av Tillitsdelegationens arbete på uppdrag av regeringen i denså kallade tillitsreformen. Metod: Studien har utförts genom en kvalitativ innehållsanalys medkonventionellt tillvägagångssätt genom att studera Statens offentliga utredningaroch direktiv kopplade till Tillitsdelegationens arbete hämtade från regeringenshemsida. Slutats: Tillblivelsen av Tillitsbaserad styrning och ledning (TSL) baseras påkritik till tidigare styrning, att organisationer tar efter andra och ytterligarefaktorer som glömska och ignorans. TSL är en hybrid styrningsidé med influenserav NPM och post-NPM reformer där ambitionerna är att främja ett samarbetemellan olika aktörer, systemperspektiv och tillit, vilket liknar de andra post-NPMreformerna på många vis. Trots delegationens uppdrag i att skapa en nystyrningsidé föreslås snarare en ny ledarskapsfilosofi i TSL och uppdraget kandärför inte anses slutfört.
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Estêvão, Carlos Miguel da Silva Coelho Pinheiro. "O IDT, IP no contexto do NPM e do PRACE." Master's thesis, Universidade de Aveiro, 2013. http://hdl.handle.net/10773/12316.
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Mestrado em Administração e Gestão PúblicaO estudo reflete sobre o IDT,IP, organismo público que tinha como missão operacionalizar as políticas públicas de luta contra as drogas, lícitas e ilícitas, e as dependências. Neste sentido, o objetivo do trabalho visa avaliar os impactos que podem ser observados no IDT,IP resultantes das reformas administrativas influenciadas pelo NPM ocorridas na Administração Pública portuguesa, especificamente pelo PRACE, e pelas opções de Políticas Públicas de luta contra as drogas assumidas por Portugal ao longo da primeira década do século XXI. Tendo em conta o objetivo definido anteriormente optámos por realizar um estudo comparativo entre o IDT e o IDT,IP, investigando, para cada um deles, os impactos decorrentes das três dimensões mencionadas. Para isso foi necessário, previamente, contextualizar e fundamentar as três dimensões. No final da investigação concluímos que o IDT,IP é um organismo público onde os impactos decorrentes do paradigma do NPM, do PRACE e das opções de Política Pública das Drogas se evidenciam claramente.
The study reflects on the IDT,IP, a public structure whose mission was to operationalize public policies to combat drugs, licit and illicit, and dependencies. In this sense the purpose of the study is to evaluate the impacts that can be observed in the IDT,IP resulting from the administrative reforms influenced by NPM occurred in the Portuguese Administration, more specifically by the PRACE, and the Public Policy options assumed by Portugal throughout the first decade of the twenty-first century. Taking into account the obective of the investigation, we developed a comparative study between the IDT and the IDT,IP, analysing, for each of them, the impacts resulting from the three mentioned subjects. This required a previous contextualization and explanation of the three concepts. At the end of the investigation it is possible to understand that the IDT,IP is a public organisation where the impacts of the NPM paradigm, the PRACE and the Drugs Public Policy options is clearly evident.
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Robertsson, Caroline. "Har NPM påverkat kommunernas ledning? : En undersökning om Eskilstuna kommunkoncern." Thesis, Karlstads universitet, Centrum för de samhällsvetenskapliga ämnenas didaktik (from 2013), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-70847.
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Syftet med denna uppsats är att undersöka Eskilstuna kommuns styrning för att se om dem är påverkade av NPMs tankar om hur organisationer ska styras. För att undersöka detta använder jag mig av en kvalitativ innehållsanalys där jag undersöker kommunens policyer angående ledarskap. För att kunna applicera dessa på NPMs tankar har jag bland annat använt mig av Lena Agevall och Roland M. Almqvist definitioner av vad begreppen betyder. Slutsatsen av min undersökning var att Eskilstuna kommun är starkt influerad av NPMs tankar och att deras styrsätt bygger på NPM. För att forska vidare inom ämnet skulle det vara möjligt att jämför Eskilstuna kommun med en likande kommun antingen i Sverige eller internationellt för att de om deras styrning påverkats på samma sätt av NPM men istället för att göra en fallstudie skulle man gå kunna genomföra en jämförande analys.
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LIMA, Aleide Santos de Melo. "Estudo de alterações moleculares e sua relação com dados clínico-laboratoriais em pacientes adultos com leucemia mieloide aguda." Universidade Federal de Pernambuco, 2013. https://repositorio.ufpe.br/handle/123456789/13089.
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Marcadores moleculares, como mutações nos genes FLT3 e NPM1, são ferramentas úteis para a avaliação prognóstica de pacientes com leucemia mieloide aguda (LMA) e, até o momento, não tinham sido estudadas em pacientes com LMA no Estado de Pernambuco. Dessa forma, esse trabalho teve como objetivo caracterizar pacientes adultos com LMA diagnosticados na Fundação HEMOPE de acordo com achados clínico-laboratoriais e as mutações nos genes FLT3 e NPM1. Foram incluídos 115 pacientes com LMA de novo (15 com leucemia promielocítica aguda (LPA) e 100 com outros subtipos LMA). As frequências das mutações FLT3/ITD, FLT3/TKD e NPM1 nos pacientes não-LPA foram de 22%, 2% e 24%, respectivamente. Nos pacientes com LPA, a frequência foi de 40% e 6,7% para as mutações FLT3/ITD e NPM1, respectivamente, não sendo diagnosticado nenhum caso com mutação FLT3/TKD. As mutações FLT3/ITD e no NPM1 foram relacionadas com alta contagem de leucócitos (p=0,021; p=0,012) e mutações no NPM1 foram mais frequentes em pacientes com mais de 60 anos (p=0,01) e no grupo de cariótipo normal (p=0,008). Não foi observada diferença nas sobrevidas global (SG) e livre de doença (SLD) e nas taxas de remissão completa (TRC) e de recaída (TR) entre os grupos com e sem mutação FLT3/ITD e no NPM1 quando avaliados os pacientes não-LPA; entretanto, pacientes LPA com mutação FLT3/ITD apresentaram menores TRC, SG e SLD. Os resultados comprovam o valor preditivo da mutação FLT3/ITD para um curso clínico desfavorável na LPA do adulto, enquanto que, para os pacientes não-LPA, as mutações FLT3/ITD e no NPM1, aparentemente, não apresentaram o mesmo impacto prognóstico.
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Cajaleón, Figueroa Lisbeth, and Bernabé Rocío Vale Paucar. "Niveles de carnitina en pacientes que reciben nutrición parenteral total (NPT)." Universidad Nacional Mayor de San Marcos. Programa Cybertesis PERÚ, 2008. http://www.cybertesis.edu.pe/sisbib/2008/paucar_br/html/index-frames.html.
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En el Hospital Edgardo Rebagliati Martins, el aporte de lípidos en la Nutrición Parenteral Total (NPT), viene dándose por ácidos grasos de cadena larga. En el presente estudio se compararon los niveles plasmáticos de carnitina de pacientes que reciben NPT basada en TCL y los que reciben NPT basada en TCL/TCM por tiempo prolongado (≥7 días). Previamente se determinaron los niveles plasmáticos de carnitina en personas aparentemente sanas, pacientes con desnutrición severa y pacientes que reciben NPT por más de 20 días. Al final del estudio se hallaron los siguientes valores medios de carnitina plasmática, expresadas en µmol/L: personas aparentemente sanas 34,26; que se halla dentro de los valores normales, en pacientes con desnutrición severa 68,29; pacientes con NPT por más de 20 días 23,64; pacientes con NPT basada en TCL (≥7 días) 43,27; pacientes con NPT basada en TCL/ TCM (≥7 días) 26,68; hallándose sólo diferencia significativa al comparar los grupos que reciben NPT basada TCL y los que reciben NPT basada en TCL/TCM (≥7 días), p meno a 0.05. Palabras Clave: Carnitina, Ácidos grasos, Nutrición parenteral Total, LípidosAt the Edgardo Rebagliati Martins Hospital, the contribution of the lipids in Total Parenteral Nutrition (TPN) is given by long chain fatty acids (LCT). This study compared the plasma levels of carnitine in patients receiving TPN based on LCT and patients receiving TPN -based LCT/MCT (≥ 7 days). Previously, had been determinated the plasmatics levels of carnitine in apparently healthy people, severe malnutrition patients and patients receiving TPN for more than 20 days. At the end of this study, we found the next plasmatics carnitine medium values, showed in µmol/L: apparently healthy people 34,26; this is within the normal values, in severe malnutrition patients 68,29; and patients receiving TPN for more than 20 days 23,64; patients with TPN based on LCT (≥ 7 days) 43,27; patients with TPN based LCT/MCT (≥ 7 days) 26,68; We met only significant difference when comparing groups receiving TPN based LCT and patients receiving TPN-based TCM / TCL (≥ 7 days), p menor a 0.05. Key Words: Carnitine, Fatty acids, Total Parenteral Nutrition, Lipids
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Lee, W. H. "A model to study the function of NPM-MLF1 in myelodysplasia." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1324545/.
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Myelodysplastic syndromes (MDS) are bone marrow disorders characterized by ineffective haematopoiesis and peripheral cytopenias with frequent evolution to acute myeloid leukaemia (AML). Apoptosis is significantly deregulated in early MDS whereas advanced MDS is characterized by deregulation of the DNA damage response. As MDS proceeds to AML, the ratio of apoptosis to proliferation decreases, resulting in clonal outgrowth of abnormal cells. The t(3;5)(q25;q34) translocation, creating the NPM-MLF1 fusion, has been found as a sole cytogenetic abnormality in MDS/AML patients, although the sample numbers are limited. In these patients, inactivation of one functional NPM allele resulting from the t(3;5)(q25;q34) translocation may contribute to disease development. This concept is supported by the observations that Npm+/- mice exhibit disease phenotypes resembling human MDS (Grisendi, Bernardi et al. 2005). The t(3;5)(q25;q34) is recurrent, with poor prognosis, but the precise mechanism through which NPM-MLF1 induces malignant transformation remains unknown. We aimed to model this disease in vitro and in vivo by expressing NPM-MFL1 in mouse bone marrow hematopoietic stem/progenitor cells (HSPCs) and analyzing any changes in HSPC activity and response to DNA damage. The effect of NPM-MLF1 in vitro and in vivo was also examined in the Npm hemizygous context. Our data showed that NPM-MLF1 did not impair haematopoiesis in vitro and in vivo in wild-type HSPCs. FLT3/ITD is frequently associated with NPM mutations in AML patients. However, NPM-MLF1 did not show any collaboration with FLT3/ITD in our system. To recapitulate NPM hemizygosity in t(3;5)-MDS patients, we have expressed NPM-MLF1 in HSPCs derived from Npm+/- mice. A transient increase in the colony forming ability of the NPM-MLF1-expressing Npm+/- HSPCs was seen. Consistently, liquid culture experiments showed that NPM-MLF1-expressing Npm+/- HSPCs, but not NPM-MLF1-expressing Npm+/+ HSPCs, exhibited prolonged colony forming ability. This observation was accompanied by higher expression of the Meis1 gene in the NPM-MLF1-expressing Npm+/- HSPCs. Strikingly, expression of myeloid HPC-related genes, Hoxa9/10, which were undetectable in the NPM-MLF1-expressing Npm+/+ HSPCs, was maintained in the NPM-MLF1-expressing Npm+/- HSPCs. However, expansion of these cells was not seen in vivo. Such an effect was not seen in vivo, probably due to low reconstitution efficiency. In addition to prolonged myeloid HPC activity, NPMMLF1 was also found to alter radiation-induced H2AX phosphorylation, which is known to play a role in the DNA damage repair. Taken together, this study suggests that the ability of NPM-MLF1 to maintain HPC activity and interfere with DNA damage responses may favour the accumulation and outgrowth of the aberrant HSPCs. Secondary genetic abnormalities are most likely required to collaborate with NPM-MLF1 to transform the HSPCs, which may ultimately lead to overt AML. Thus, genome-wide analysis of MDS/AML patient samples harbouring NPM-MLF1 may uncover the mutations and/or genetic alterations crucial for disease development.
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Paucar, Bernabé Rocío Vale, and Figueroa Lisbeth Cajaleón. "Niveles de carnitina en pacientes que reciben nutrición parenteral total (NPT)." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2008. https://hdl.handle.net/20.500.12672/836.
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En el Hospital Edgardo Rebagliati Martins, el aporte de lípidos en la Nutrición Parenteral Total (NPT), viene dándose por ácidos grasos de cadena larga. En el presente estudio se compararon los niveles plasmáticos de carnitina de pacientes que reciben NPT basada en TCL y los que reciben NPT basada en TCL/TCM por tiempo prolongado (≥7 días). Previamente se determinaron los niveles plasmáticos de carnitina en personas aparentemente sanas, pacientes con desnutrición severa y pacientes que reciben NPT por más de 20 días. Al final del estudio se hallaron los siguientes valores medios de carnitina plasmática, expresadas en µmol/L: personas aparentemente sanas 34,26; que se halla dentro de los valores normales, en pacientes con desnutrición severa 68,29; pacientes con NPT por más de 20 días 23,64; pacientes con NPT basada en TCL (≥7 días) 43,27; pacientes con NPT basada en TCL/ TCM (≥7 días) 26,68; hallándose sólo diferencia significativa al comparar los grupos que reciben NPT basada TCL y los que reciben NPT basada en TCL/TCM (≥7 días), p meno a 0.05.
Palabras Clave: Carnitina, Ácidos grasos, Nutrición parenteral Total, Lípidos.-- At the Edgardo Rebagliati Martins Hospital, the contribution of the lipids in Total Parenteral Nutrition (TPN) is given by long chain fatty acids (LCT). This study compared the plasma levels of carnitine in patients receiving TPN based on LCT and patients receiving TPN -based LCT/MCT (≥ 7 days). Previously, had been determinated the plasmatics levels of carnitine in apparently healthy people, severe malnutrition patients and patients receiving TPN for more than 20 days. At the end of this study, we found the next plasmatics carnitine medium values, showed in µmol/L: apparently healthy people 34,26; this is within the normal values, in severe malnutrition patients 68,29; and patients receiving TPN for more than 20 days 23,64; patients with TPN based on LCT (≥ 7 days) 43,27; patients with TPN based LCT/MCT (≥ 7 days) 26,68; We met only significant difference when comparing groups receiving TPN based LCT and patients receiving TPN-based TCM / TCL (≥ 7 days), p menor a 0.05. Key Words: Carnitine, Fatty acids, Total Parenteral Nutrition, Lipids.
Tesis
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Schneider, Cédric. "Fonctionnalisation du noyau Pyrido[2,3-b]indole : synthèse d'inhibiteurs NPM-ALK." Lyon 1, 2008. http://www.theses.fr/2008LYO10304.
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Les lymphomes à grandes cellules anaplasiques ou ALCL (Anaplasic Large-Cell Lymphoma) sont des cancers appartenant à la famille des lymphomes de type non-Hodgkin. La majorité des ALCL est issue d’une translocation t(2;5)(p23;q35) donnant lieu à la formation d’une protéine de fusion appelée NPM-ALK. A ce jour, peu d’inhibiteurs présentent de bonnes activités contre cette protéine chimérique. A l’issue de criblages virtuels et de modélisations, réalisés en collaboration avec les équipes du Professeur Scapozza et du Professeur Gambacorti-Passerini, le noyau α-carboline a été défini comme structure de base pour la préparation d’inhibiteurs potentiels de la protéine oncogénique NPM-ALK. Par conséquent, les travaux de recherche réalisés lors de cette thèse ont concerné la synthèse d’inhibiteurs comportant le squelette pyrido[2,3-b]indole. A partir de ce motif, obtenu via une réaction de Graebe-Ullmann, des fonctionnalisations primaires ont été développées par des réactions de substitutions électrophiles aromatiques. Puis en présence d’α-carbolines chlorées sur le noyau pyridine, des réactions pallado-catalysées ont permis la formation de liaisons C(sp2)-C(sp2), C(sp2)-C(sp), C(sp2)-N et C(sp2)-O. Enfin, des réactions d’ortho-lithiation par l’intermédiaire de groupements ortho-directeurs ont été étudiées afin de fonctionnaliser la totalité de ce noyau tricyclique. Ces différentes voies de fonctionnalisation des α-carbolines ont conduit à la synthèse d’un panel de 135 molécules bioactives dont certaines possèdent une activité et une sélectivité très intéressante sur NPM-ALKAnaplasic Large-Cell Lymphoma (ALCL) is a type of cancer belonging to the non-Hodgkin family. The majority of ALCL arises from a translocation t(2;5) (p23;35) which leads to the formation of a fusion protein called NPM-ALK. Nowadays, few molecules are known to inhibit the activity of this chimeric protein. Computational studies and virtual screenings, realized in collaboration with Pr Scapozza and Pr Gambacorti-Passerini groups, showed that the –carboline moiety could be a starting point for the preparation of potential inhibitors of the NPM-ALK oncogenic protein. The aim of this PhD was to develop the synthesis of new inhibitors including the pyrido[2,3-b]indole scaffold. After a Graebe-Ullmann reaction to build the pyrido[2,3-b]indole moiety, initial functionalizations were developed via aromatic electrophilic substitution reactions. Then, the presence of a chloro group on the pyridine ring allowed the formation of C(sp2)-C(sp2), C(sp2)-C(sp), C(sp2)-N et C(sp2)-O bonds, using palladium-catalyzed couplings. Also, directed ortho-lithiations were used to complete the functionalization of the tricyclic moiety. These different methodologies afforded the synthesis of a library of 135 molecules. Some of them demonstrated good inhibitory activity and high selectivity against NPM-ALK
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Seibl, Marlene. "Quantifizierung von minimaler Resterkrankung bei akuter myeloischer Leukämie mit NPM1 Mutation mittels Real-Time-PCR." Diss., lmu, 2011. http://nbn-resolving.de/urn:nbn:de:bvb:19-126943.
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Leung, Siu-yung, and 梁小容. "NPM1 and FLT3-ITD mutations in cytogenetically normal acute myeloid leukaemia patients of Hong Kong." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44671143.
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Schmidt, Tracy E. "HIV-1 and the Nucleolus: A Role for Nucleophosmin/NPM1 in Viral Replication: A Dissertation." eScholarship@UMMS, 2013. https://escholarship.umassmed.edu/gsbs_diss/690.
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The nucleolus is a plurifunctional organelle with dynamic protein exchange involved in diverse aspects of cell biology. Additionally, the nucleolus has been shown to have a role in the replication of numerous viruses, which includes HIV-1. Several groups have reported HIV-1 vRNA localization within the nucleolus. Moreover, it has been demonstrated the HIV-1 Rev protein localizes to the nucleolus and interacts with nucleolar proteins, including NPM1. Despite evidence for a nucleolar involvement during replication, a functional link has not been demonstrated. I investigated whether introncontaining vRNAs have a Rev-mediated nucleolar localization step prior to export. Furthermore, I examined whether NPM1 mediates Rev nucleolar localization, participates in Rev function, and/or post-transcriptional events during viral replication. I used coupled RNA fluorescence in situhybridization and indirect immunofluorescence to visualize intron-containing vRNA relative to the nucleolus in the absence or presence of Rev expression. An RNAi-based approach was used to examine the role of NPM1 in Rev function and viral replication in cell lines and primary human macrophages. My research findings support a model for a Rev-independent nucleolar localization step of introncontaining vRNA prior to export. Intriguingly, my results also suggest NPM1 does not participate in Rev nucleolar localization or Rev-mediated vRNA export, as previously proposed. Rather, my findings support a novel role for NPM1, the cytoplasmic localization and utilization of a select class of Rev-dependent vRNAs. Collectively, my findings provide novel insight for a functional role of the nucleolus and NPM1 in HIV-1 replication, which enhances our current understanding of HIV-1 biology.
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Schmidt, Tracy E. "HIV-1 and the Nucleolus: A Role for Nucleophosmin/NPM1 in Viral Replication: A Dissertation." eScholarship@UMMS, 2008. http://escholarship.umassmed.edu/gsbs_diss/690.
Full textAbstract:
The nucleolus is a plurifunctional organelle with dynamic protein exchange involved in diverse aspects of cell biology. Additionally, the nucleolus has been shown to have a role in the replication of numerous viruses, which includes HIV-1. Several groups have reported HIV-1 vRNA localization within the nucleolus. Moreover, it has been demonstrated the HIV-1 Rev protein localizes to the nucleolus and interacts with nucleolar proteins, including NPM1. Despite evidence for a nucleolar involvement during replication, a functional link has not been demonstrated. I investigated whether introncontaining vRNAs have a Rev-mediated nucleolar localization step prior to export. Furthermore, I examined whether NPM1 mediates Rev nucleolar localization, participates in Rev function, and/or post-transcriptional events during viral replication. I used coupled RNA fluorescence in situhybridization and indirect immunofluorescence to visualize intron-containing vRNA relative to the nucleolus in the absence or presence of Rev expression. An RNAi-based approach was used to examine the role of NPM1 in Rev function and viral replication in cell lines and primary human macrophages. My research findings support a model for a Rev-independent nucleolar localization step of introncontaining vRNA prior to export. Intriguingly, my results also suggest NPM1 does not participate in Rev nucleolar localization or Rev-mediated vRNA export, as previously proposed. Rather, my findings support a novel role for NPM1, the cytoplasmic localization and utilization of a select class of Rev-dependent vRNAs. Collectively, my findings provide novel insight for a functional role of the nucleolus and NPM1 in HIV-1 replication, which enhances our current understanding of HIV-1 biology.
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Feuser, Paulo Emilio. "Encapsulamento simultâneo de nanopartículas magnéticas (NPMS) com ftalocianina de zinco (ZNPC) via polimerização em miniemulsão." reponame:Repositório Institucional da UFSC, 2012. https://repositorio.ufsc.br/xmlui/handle/123456789/122562.
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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós-Graduação em Engenharia Química, Florianópolis, 2012.Made available in DSpace on 2014-08-06T17:04:12Z (GMT). No. of bitstreams: 1 327717.pdf: 2405163 bytes, checksum: ded464e3384619c872511448eb58c9ac (MD5) Previous issue date: 2012
Uma das alternativas mais promissoras para o tratamento do câncer é a Terapia Fotodinâmica (TFD). A Ftalocianina de Zinco (ZnPc) é um fotossensibilizante de segunda geração com caráter hidrofóbico e necessita ser incorporado em um sistema de liberação adequado para ser injetado sistemicamente. Nanopartículas magnéticas, NPMs, constituída principalmente de magnetita (Fe3O4) apresentam alto valor de magnetização com grande potencial de aplicação no tratamento do câncer por hipertermia. O encapsulamento simultâneo de fármacos com NPMs tem sido reconhecido como uma técnica promissora para o tratamento do câncer por possibilitar a ação sinergética dos diferentes tipos de tratamento. O objetivo deste trabalho foi a síntese, caracterização e avaliação da toxicidade e fototoxicidade das NPMs, do encapsulamento da NPMs e ZnPc e o encapsulamento simultâneo de ZnPc com NPMs via polimerização em miniemulsão. As NPMs com ácido oléico (AO) foram preparadas pelo método de co-precipitação em meio aquoso e a análise de DRX mostrou picos característicos da magnetita (Fe3O4) com diâmetro médio de nanopartículas de 13nm. As NPMs apresentaram um alto valor de magnetização de saturação (Ms) (64 emu/g óxido de ferro). O encapsulamento das NPMs foi realizado via polimerização em miniemulsão com metacrilato de metila (MMA). As NPMs encapsuladas apresentaram um diâmetro aproximado de 100nm com valor de Ms de 34 emu/g de óxido de ferro. Para o encapsulamento da ZnPc utilizou-se duas técnicas de encapsulamento. A primeira foi a técnica de miniemulsão com auxílio da técnica de nanoprecipitação (PMMA/ZnPc)(FA)) e a segunda utilizou-se apenas a técnica de miniemulsão direta (PMMA/ZnPc(FO)). O teor de ZnPc nas nanopartículas poliméricas foi um pouco superior na amostra PMMA/ZnPc(FA) (3,7µg/mg) do que na amostra de PMMA/ZnPc(FO) (3,0 µg/mg). Ambas as técnicas resultaram em um tamanho médio de aproximadamente 100nm. Ao encapsular a ZnPc simultaneamente com as NPMs (PMMA/ZnPc/NPMs) não alteração em relação ao tamanho das nanopartículas (100nm), concentração de ZnPc (3,6 µg/mg) e propriedades magnéticas (31 emu/g de óxido de ferro) em relação ao encapsulamento em separado da ZnPc e NPMs. A liberação da ZnPc das nanopartículas poliméricas foi sustentada e lenta. Nas primeiras 20 horas cerca de 5-10% do ZnPc contida nas nanopartículas poliméricas foi liberada em todas as amostras. No ensaio de toxicidade (ausência de luz), as nanopartículas encapsuladas mostraram baixa toxicidade. No ensaio de atividade fotobiológica, observou-se, que a luz isoladamente (sem nanopartículas contendo ZnPc) não foi capaz de induzir efeito citotóxico sobre a cultura de células. Ao utilizar nanopartículas contendo ZnPc observou-se uma redução acentuada da viabilidade celular para 22% (PMMA/ZnPc(FA)) e 30% (PMMA/ZnPc/NPMs).
Abstract : Photodynamic therapy (TFD) is one of the most promising alternatives for the treatment of the cancer. Zinc phtalocyanine (ZnPc) is a second generation photosensitizer with hydrophobic character that should be incorporated in a suitable delivery system to be injected systemically. Magnetics nanoparticles (NPMs) consisting mainly of magnetite (Fe3O4) present high value of magnetization with great potential of application in the treatment of the cancer by hyperthermia. The simultaneous encapsulation of drugs with NPMs has been recognized as one promising technique for the treatment of the cancer making possible a synergetic action of the different types of treatment. The objective of this work was the synthesis, characterization and evaluation of the toxicity and phototoxicity of the NPMs, the encapsulation of the NPMs and ZnPc and the simultaneous encapsulation of ZnPc with NPMs by miniemulsion polymerization. The NPMs with oleic acid (AO) had been prepared by the co-precipitation method in aqueous solution. DRX analysis showed characteristic peaks of magnetite (Fe3O4) with average particle diameter of 13nm. The NPMs had presented high value of magnetization of saturation (Ms) (61 emu/g of iron oxide). The encapsulation of the NPMs was carried through methyl methacrylate (MMA) miniemulsion polymerization. The polymeric particles with NPMs encapsulated presented an average diameter of 100nm with value of Ms of 34 emu/g of iron oxide. Two techniques of encapsulation were employed for the encapsulation of ZnPc. The first one was the miniemulsion polymerization with the nanoprecipitation technique (PMMA/ZnPc) (FAN)) and second one used only the miniemulsion polymerization technique (PMMA/ZnPc (FO)). The amount of ZnPc in polymeric nanoparticles was higher in PMMA/ZnPc(FA) sample (3,7µg/mg) when compared to the sample of PMMA/ZnPc (FO) (3,0 µg/mg). Both techniques resulted in polymeric nanoparticles with an average diameter of approximately 100nm. The simultaneous encapsulation of ZnPc with NPMs (PMMA/ZnPc/NPMs) presented very similar values of average particle size (100nm), concentration of ZnPc (3,6 µg/mg) and magnetic properties (31 emu/g of iron oxide) when compared to the single encapsulation of ZnPc and NPMs. The release of the encapsulated ZnPc was supported and slow. In the first 20 hours approximately 5-10% of the encapsulated ZnPc was released in all samples. In the toxicity assay (light absence), the encapsulated nanoparticles had shown low toxicity. In the assay of phototoxicity activity, it was observed that the light (without polymeric nanoparticles containing ZnPc) was not able to induce cytotoxic effect on the culture of cells. When using polymeric nanoparticles with encapsulated ZnPc an accentuated reduction of the cellular viability of 22% (PMMA/ZnPc (FA)) and 30% (PMMA/ZnPc/NPMs) was observed.
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Hawborn, Maria, and Silva Jonsson Teresia Da. "Förekomst av smärta hos patienter som genomgår undertrycksbehandling." Thesis, Sophiahemmet Högskola, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:shh:diva-1870.
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SAMMANFATTNING Undertrycksbehandling eller den internationella benämningen NPWT (Negative pressure wound therapy) har under de senaste åren snabb ökat i användande då den har visat sig vara effektiv som behandlingsmetod vid svårläkta sår. Då det saknas kunskaper och erfarenheter kring patientens smärtupplevelse och undertrycksbehandling har syftet med denna studie varit att undersöka förekomsten av smärta hos dessa patienter. Utgångspunkten var fyra frågeställningar: patientens egna upplevelser av smärta, patientens smärtupplevelser utifrån vårdpersonalens perspektiv, vid vilka moment i sårbehandlingsprocessen upplever patienten smärta och hur smärtan påverkar livskvalitén och den psykiska hälsan. Som metod i den här studien har använts litteraturöversikt där datainsamlingen gjorts på ett systematiskt vis utifrån genomtänkta sökord med hjälp av PICO modellen. Femton artiklar valdes ut och analyserades för att samla in ett resultat som svarar på syftet. Dataanalysen genomfördes i sex olika steg. Där det plockades ut olika kodord som sedan kategoriserades. Huvudtema skapades utifrån dessa kategorier som sedan låg till grund för rubrikerna i resultatet vilka överensstämde med frågeställningarna i syftet. Till sist sammanställdes resultatet utifrån dessa rubriker. Resultatet visade på att patienter upplevde smärta i samband med NPWT. Vissa moment i behandlingen var dock mer smärtsamma än andra. Vid svampbaserad behandling mättes, med hjälp av VAS mer smärta än vid gasvävsbaserad. Nyanläggningen av förbandet upplevdes mer som ett pirrande obehag utifrån patienterna medan en del vårdpersonalen uppfattade det som ett smärtsamt moment. När det gällde applicering och borttagande av ytterförband var borttagandet mer smärtsamt än appliceringen utifrån patienternas uppfattning. Vid fysisk aktivitet eller vid infektioner kunde smärta också förekomma. Det var dock inte alltid smärtan som var det mest besvärliga för patienterna. Utan en del studier hade kommit fram till att det var smärtans påverkan på livskvalitén och den psykiska hälsan som gjorde patienterna stressade och begränsade dem mest. Slutsatsen som kunde dras utifrån denna studie var att trots förekomsten av smärta var patienternas inställning till NPWT positiv. De trodde att behandlingen hjälpte dem att läka deras sår både snabbare och effektivare. Patienterna upplevde dock ofta någon form av smärta under behandlingen. Det har framkommit i resultatet att bristande teknik vid förbandsbytet och nyanläggningen var en av orsakerna till smärta. Smärtan kunde också bidra till en begränsning av patientens sociala liv.
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Hoad, Bradley W. "Nucleophosmin and genomic stability." Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/96250/1/Bradley_Hoad_Thesis.pdf.
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Cancer is caused by a loss of genomic stability. Once cancer forms genomic instability allows it to adapt to the environment, metastasise and become resistant to therapeutics.
DNA damage poses a constant threat to genomic integrity with the action of nucleases, oxidation, ionising radiation and radio-mimetic chemicals causing an array of DNA lesions. NPM1 has recently been implicated in the processes of DNA repair. The data I present provides evidence of a novel role for NPM1 in DNA repair and specifically in the homologous repair pathway. NPM1 mutation is commonly associated with acute myeloid leukaemia. This thesis describes the deficient genomic stability mechanisms this form of leukaemia exploits to promote the progression of the disease, a novel discovery which may potentially change current treatment approaches.
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Blackburn, Douglas L. "The Chemical Weapons Convention verification regime a model for a new NPT? /." Thesis, Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 1993. http://handle.dtic.mil/100.2/ADA277976.
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Jönsson, Ebba. "Folkrätt och kärnvapen : Om tillämpningen av NPT som icke-spridning och nedrustningsavtal." Thesis, Örebro universitet, Akademin för juridik, psykologi och socialt arbete, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-17327.
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Gille, Christine [Verfasser], and Karsten [Akademischer Betreuer] Spiekermann. "MRD-Monitoring bei AML-Patienten mittels Hochdurchsatz-Amplikonsequenzierung (NPM1 Mutation A) / Christine Gille ; Betreuer: Karsten Spiekermann." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2021. http://d-nb.info/1229835466/34.
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Jensen, Kai-Ole [Verfasser]. "Monitoring minimaler Resterkrankung (MRD) bei der akuten myeloischen Leukämie (AML) mit NPM1 Mutation / Kai-Ole Jensen." Ulm : Universität Ulm, 2016. http://d-nb.info/1110969465/34.
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Qutob, Haitham. "DNA damage response and anti-apoptotic proteins expression in NPMc+ mutated cells in acute myeloid leukaemia." Thesis, University of Nottingham, 2014. http://eprints.nottingham.ac.uk/14209/.
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Nucleophosmin 1 (NPM1) is a multi-functional phosphoprotein, which shuttles between the nucleolus and the cytoplasm. It participates in many cellular processes including ribosome biogenesis and transport, centrosome duplication, and also contributes to the control of genomic stability. NPM1 interacts with many proteins including those that participate in DNA damage repair processes. C-terminal mutations in NPM1 occur in 35% of patients with acute myeloid leukaemia and are associated with a good prognosis. They are characterised by delocalisation of NPM1 into the cytoplasm. This may have a role in the sensitivity of mutant cells to chemotherapy via inactivation of the DNA damage response processes. Firstly, we aimed to identify potential differences in DNA repair in response to double-strand breaks (DSB) and alkylating inducers and then assess them through the comet assay in the wild-type and mutant NPM1 cell lines. The percentage and kinetics of DNA damage in both cell lines was identical, indicating that DNA lesions were repaired efficiently in both the wild-type and mutant cell lines. The γ-H2AX foci were also evaluated which increased to similar levels in mutant and wild-type cells lines after exposure to DNA damaging agents and decreased with similar rates when the cells were allowed 24 hours to repair the damage. Interestingly, following DNA damage, the amount of NPM1 increased significantly in NPMc+ cells, both in the nucleus and the cytoplasm, which was not seen in NPM1 wild-type cells. Next, we determined the subcellular localisation of APE1, which is a DNA repair enzyme in the base excision repair pathway and a transcriptional co-activator. APE1 has previously been shown to associate with NPM1. Using confocal microscopy, we found that the APE1 in both wild-type and NPMc+ mutant cell lines is predominately localised in the cytoplasm, while it is translocated into the nucleus after the cells were exposed to MMS, presumably to play a role in the DNA damage repair mechanism. As we could find no apparent difference in DNA repair between NPM1 mutated and wild type cells we went on to look at proteins involved in cell survival - BCL-2 and MCL-1. The NPMc+ mutant cell line expressed the highest level of mRNA BCL-2 and MCL-1 when compared to the NPM1 wild-type cell lines. The NPMc+ mutated cells have previously been shown to be sensitive to the effect of all-trans retinoic acid (ATRA). We looked to see whether ATRA has an effect on the anti-apoptotic proteins. The results demonstrate that the BCL-2 and MCL-1 levels were down-regulated to a greater level in the NPM1 mutant cell line than in the NPM1 wild-type cells. In patient samples, the BCL-2 and MCL-1 mRNA down-regulation was seen in 3/5 and 5/5 NPMc+ samples, respectively. Thus, these finding indicate that BCL-2 and MCL-1 mRNA expression is down-regulated following ATRA in NPMc+ mutant cells. Finally, siRNA was used to decrease levels of either total NPM1 or mutant NPM1 alone. Results showed that in the NPM1 mutant cells there was a down-regulation of BCL-2 mRNA, while in the NPM1 wild-type cells, no effect on the BCL-2 mRNA level was found. Furthermore, levels of P53 were up-regulated in the mutant NPM1 cells after knocking-down the total NPM1, whereas the wild-type cell line showed no change in the P53 level. These results provide evidence suggesting that down-regulation of NPM1 in the NPMc+ cell line increases total P53, possibly by interaction of ARF and HDM2, resulting in down-regulation of the BCL-2 in the mutated cells. In conclusion, perturbation of NPM1 subcellular localisation in NPMc+AML has no effect on the DNA repair mechanisms but we found differences in the anti-apoptotic proteins expression compared to NPM1 wild-type cells.
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Loubeau, Gaëlle. "Impact de la surexpression de la protéine nucléophosmine (NPM1) sur la progression des cancers de la prostate." Phd thesis, Université Blaise Pascal - Clermont-Ferrand II, 2012. http://tel.archives-ouvertes.fr/tel-00870415.
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La prolifération, la migration et l'invasion sont des processus cellulaires biologiques fondamentaux qui sont régulés par une multitude de signaux extracellulaires. L'intégration de ces stimuli au niveau de différentes voies de signalisation intracellulaires permet d'adapter les capacités des cellules à exercer ces fonctions aux conditions du milieu extérieur. Outre des évènements génétiques tels que les mutations ou les translocations chromosomiques, des dérégulations des capacités de prolifération, de migration et d'invasion des cellules sont retrouvées lors de la mise en place d'un processus tumoral. La protéine nucléophosmine (NPM1) est un acteur important dans le contrôle de la balance prolifération/apoptose. Initialement décrite pour son rôle dans la biogénèse des ribosomes, NPM1 participe à de multiples processus cellulaires comme la duplication des centrosomes, la progression du cycle cellulaire et la transcription génique. NPM1 est ainsi fréquemment surexprimée dans les tumeurs solides d'origines histologiques variées, parmi lesquelles les cancers du colon, du poumon ou encore les tumeurs ovariennes. Les travaux antérieurs de l'équipe ont mis également en évidence que la protéine NPM1 est surexprimée dans les tissus de carcinomes prostatiques en comparaison avec le tissu adjacent sain. Mon travail de thèse avait pour objectif d'étudier l'impact d'une surexpression de NPM1 dans la progression des cancers de la prostate. Nous avons dans un premier temps analysé, in vitro et in vivo, les capacités invasives de cellules caractéristiques d'un stade avancé de cancers de la prostate en fonction du niveau d'accumulation de NPM1. Les résultats obtenus suggèrent que la protéine NPM1 intervient dans le processus tumoral en activant des mécanismes prolifératifs, migratoires et invasifs des cellules tumorales de prostate. Dans un second temps, nous avons cherché à déterminer la nature des gènes dont la transcription était susceptible d'être affectée par l'expression de NPM1. L'analyse en qPCR array met en évidence que l'expression du facteur de croissance EGF est diminuée dans un contexte d'inhibition de NPM1, ainsi que l'activation de la voie de prolifération en aval ERK1/2. Enfin, l'activation constitutive de cette voie révèle que le rôle de NPM1 se situe en aval du récepteur EGFR et en amont de l'effecteur MEKK1, activateur de la voie ERK1/2. Ces données indiquent que NPM1 pourrait conférer un avantage prolifératif et invasif aux cellules tumorales de prostate. En revanche, cette protéine ne serait pas un initiateur de la tumorigénèse mais un potentialisateur de la progression des cancers de la prostate suite à des évènements génétiques initiateurs. Dans ce contexte et sur la base de nos travaux, nous proposons comme perspective que l'inhibition de l'accumulation de NPM1, protéine qui active la voie de survie ERK1/2 et qui agit parallèlement sur la disponibilité de contrôleurs du cycle cellulaire et de l'apoptose (e.g. P53), puisse potentialiser l'action d'agents thérapeutiques déjà utilisés comme des inhibiteurs de tyrosines kinases (gefitinib®).
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Marques, Fabiano do Prado. "O problema da mochila compartimentada e aplicações." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/55/55134/tde-07072015-155114/.
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Este trabalho aborda o Problema da Mochila Compartimentada que é uma variação do clássico problema da mochila e pode ser enunciado considerando-se a seguinte situação hipotética: um alpinista deve carregar sua mochila com possíveis itens de seu interesse. A cada item atribui-se o seu peso e um valor de utilidade (até aqui, o problema coincide com o clássico Problema da Mochila). Entretanto, os itens são de agrupamentos distintos (alimentos, medicamentos, utensílios, etc.) e devem estar em compartimentos separados na mochila. Os compartimentos da mochila são flexíveis e têm capacidades limitadas. A inclusão de um compartimento tem um custo fixo que depende do agrupamento com que foi preenchido, além de introduzir uma perda da capacidade da mochila. O problema consiste em determinar as capacidades adequadas de cada compartimento e como esses devem ser carregados, maximizando o valor de utilidade total, descontado o custo de incluir compartimentos. Neste trabalho propomos um modelo de otimização não linear inteiro para o problema e algumas heurísticas para sua resolução, para as quais apresentamos os resultados computacionais obtidos. Uma aplicação prática que surge no corte de bobinas de aço, sujeito à laminação é detalhada.This work approaches the Compartmentalized Knapsack Problem which is a variation of the classical knapsack problem and it can be stated as the following hypothetical situation: a climber must load his/her knapsack with a number of items. Two numbers, an weight and a utility value are given for each item (so far, the problem coincides with the classical integer Knapsack Problem). However, the items are of different classes (food, medicine, utensils, etc.) and they have to be packed in separate compartments inside the knapsack. The compartments are flexible and have limited capacities. Each compartment has a fixed cost that depends on the class of items chosen to load it and, in addition, each new compartment introduces a loss of capacity of the knapsack. The Compartmentalized Knapsack Problem consists of determining suitable capacities of each compartment and how these compartments should be packed. The objective is to maximize a total utility value paid off the cost of the compartments. The problem can be modeled as an integer non-linear optimization problem and we have designed some heuristic methods for its solution, for which we present a computational study. A practical application arises in cutting steel rolls subject to a lamination process.
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Graul, Katja [Verfasser]. "Untersuchungen von NPM1-Mutationen bei Patienten mit akuter myeloischer Leukämie bei Diagnosestellung und im Verlauf / Katja Graul." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1057869686/34.
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Asplund, Kajsa. "NPM i svenskt bistånd : Resultatstyrningens utveckling på Sida och dess påverkan på biståndsinsatserna." Thesis, Umeå universitet, Statsvetenskapliga institutionen, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-141626.
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This essay investigates how employees on the Swedish international development cooperation agency (Sida) perceives that the new public management (NPM) reform, result based management (RBM), have affected the international aid. And also, how the employees think that managing based on results works together with a holistic approach to aid. The material for the study was collected through qualitative interviews with five senior employees on Sida, mostly people that today sits on leading positions in the agency. The interviews had a reflective character where the respondents looked back on the twenty-year period that the agency have managed via results. What became evident in the study was that RBM have looked very different over the years, with different effect on the international aid as a result. There have been waves of result based management, and an oscillation between quantitative and qualitative results. The Swedish international aid through Sida has changed over time, some changes can be attributed to RBM, while others are due to political priorities, a changing world, and trends in the international aid. RBM effects the aid, primarily as it is supposed to. For example, the best performing organisations and actors in a sector gets the aid. But it also affects the aid in a manner perceived negative by the respondents. This when the focus lies on quantitative results. The focus on results have oscillated over the years between a quantitative and qualitative focus, with consequences for which aid-projects that get support from Sida. When focus lies on quantitative results, easily quantifiable, concrete projects gains ground to the disadvantage of non-quantifiable projects, and for example big reform processes. The respondents do not think that there are any discrepancies between a holistic approach to aid and result based management, if the focus on results are balanced and leaning towards easily quantifiable results. When the focus tips over towards quantifiability, a holistic view on aid is hard to maintain.
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Malcolm, Timothy Ian Mark. "Investigating the origin and pathogenesis of NPM-ALK driven anaplastic large cell lymphoma." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648739.
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Villalva, Grégoire Claire. "Profil d'expression génique dans les lymphomes anaplasiques à grandes cellules NPM-ALK positifs." Toulouse 3, 2004. http://www.theses.fr/2004TOU30201.
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Dans les lymphomes anaplasiques à grandes cellules, la translocation t(2;5)(p23;q35) conduit à l'expression aberrante de la protéine NPM-ALK (Nucléophosmine-Anaplastic Lymphoma Kinase). Nous avons voulu étudier les gènes dérégulés dans ces lymphomes par la technique de SSH (Subtractive Suppressive Hybridization). La première étape est la reverse-transcription des ARNm. Nous avons montré que le rendement de cette étape pouvait être augmenté en ajoutant la protéine T4 gene 32. La SSH a été effectuée à partir d'une lignée de lymphome anaplasique portant la translocation comparée à des cellules d'un patient porteur de la tumeur sans translocation. Nous avons obtenu 92 clones et le séquençage nous a permis d'identifier 31 gènes sur-exprimés dans la lignée t(2;5) positive. Le profil d'expression se caractérise par des gènes de survie cellulaire. Certains sont impliqués dans la signalisation médiée par la PI-3 kinase décrite comme effectrice de la voie médiée par NPM-ALK.
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Eriksson, Linus, and Emil Bertilsson. "Styrning eller störning : En kvalitativ studie inom den offentliga sektorn." Thesis, Karlstads universitet, Handelshögskolan (from 2013), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-70980.
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Syfte Studien syftar till att med hjälp av sjuksköterskor vid Landstingen i Värmland och Dalarna bidra till forskningen om hur sjuksköterskorna själva uppfattar att dagens NPM-influerade styrning inom vården påverkar deras förutsättningar att skapa värde. Frågeställningar • Vad är det som sjuksköterskorna själva uppfattar styr deras arbete? • Vilka områden upplever sjuksköterskorna påverkas av styrningen? • Vilka brister inom styrningen har sjuksköterskorna uppmärksammat och ser de några potentiella lösningar? • Hur anser sjuksköterskorna att förutsättningarna för värdeskapande påverkas av styrningen? Metod För att svara på studiens syfte har en kvalitativ ansats tagits. Det har utförts sjutton personliga intervjuer med sjuksköterskor på olika kirurgavdelningar inom Värmlands och Dalarnas Landsting. Resultat Studien visar att den NPM-influerade styrningen har en mestadels negativ påverkan på sjuksköterskornas möjlighet att skapa värde. Avdelningschefens styrning hade en positiv påverkan på sjuksköterskornas arbete. Sjuksköterskorna upplevde ett orimligt krav på produktivitet där hög genomströmning av patienterna efterfrågades, ofta i konflikt med vårdkvalitet. Bristande kommunikation mellan ledning och sjuksköterskor medför också onödig irritation och missnöje från sjuksköterskor. Slutsats Den hierarkiska maktstrukturen som idag finns inom sjukvården påverkar sjuksköterskorna på kirurgavdelningarna på landstinget i Värmland och Dalarna negativt när det kommer till deras möjlighet att skapa värde. Problemen rörande krav på produktivitet och dokumentation från ledningen har förvärrats av den hierarkiska strukturen och att sjuksköterskorna inte får vara med och påverka sitt eget arbete i den mån de önskar.Purpose The aim of the paper is to research how today's NPM-influenced methods of control affects the nurse’s ability to create value from the nurses point of view. Problem • According to the nurses, what controls their work? • Which areas are affected by the management control according to the nurses? • What flaws in the management control have the nurses noticed and do they see any potential solutions? • How do nurses consider the conditions for value creation to be influenced by management control? Methodology In order to answer the purpose of the study has a qualitative approach been used. Seventeen interviews were conducted with nurses at different surgeon sections in Värmland and Dalarna county. Results The study shows that the NPM-influenced governance has a negative impact on the nurses' ability to create value. The management control from the head of the department had a positive impact on nurse’s work. The nurses experienced an unreasonable demand for efficiency, where high flow of patients was requested, often in conflict with the safety of the patient. A lack of communication between management and nurses also causes unnecessary irritation and dissatisfaction from nurses. Conclusion The hierarchical power structure that exists today in the healthcare negatively affects the nurses on the surgeon sections in the county of Värmland and Dalarna when it comes to their ability to create value. The problems regarding the demands of productivity and documentation has been worsened by the hierarchical structure and the fact that the nurses cannot influence their own work to the extent they wish.
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Sundberg, Johan, and Gustaf Billing. "NPM och sjuksystern : En fallstudie kring New Public Managements påverkan på sjuksköterskans profession och yrkesgemenskap." Thesis, Uppsala universitet, Företagsekonomiska institutionen, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-169082.
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Lindblad, Malin. "Kommunala verksamheters pris : Hur valet av värderingsmodell har påverkat den kommunala verksamhetens slutliga pris i samband med avknoppning." Thesis, Linnéuniversitetet, Institutionen för ekonomistyrning och logistik (ELO), 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-26769.
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Bakgrund och problem: Avknoppning av kommunala verksamheter blir allt mer vanligt i och med att det i vissa fall kan vara mer effektivt att kommunen hyr tjänsten av kommunan-ställda som har tagit över driften av en kommunal verksamhet. Det har uppstått en viss pro-blematik i samband med värderingarna, vilket ledde till att avknoppningarna som genomför-des under år 2007/2008, många fall var felaktiga eftersom de inte inkluderade alla värden i företaget. En del hävdar att det finns skillnader mellan offentliga verksamheter och privata verksamheter och att det därmed inte går att tillämpa traditionella värderingsprinciper efter-som de inte tar hänsyn till ett flertal aspekter och effekter som inte syns i värderingen men som påverkar värdet på det kommunala bolaget. Andra hävdar att det inte finns några skillna-der mellan verksamheter från de olika sektorerna utan att värderingsprinciperna ska gå att tillämpa och ska leda fram till en korrekt värdering. Syfte: Syftet med denna studie är att studera hur värderingen av kommunala verksamheter i samband med avknoppningar har genomförts under perioden år 2007-2012 i Stockholmsregi-onen. Det kommer att identifieras vilka värderingsmodeller som har använts och vilka effekter som valen har lett fram till. Det kommer sedan ske en jämförelse med värderingsteorier för skapa kunskaper om varför vissa värderingsmodeller har valts framför andra, hur valet påver-kar hela värderingsprocessen och vilka effekter traditionella värderingsmodeller ger på den slutliga värderingen av offentliga verksamheter. Studien kommer leda fram till rekommenda-tioner över vilka värderingsmodeller som ska tillämpas i samband med avknoppningar av kommunala verksamheter. Metod: Metodavsnittet beskriver vilka metodlogiska val som har gjorts i arbetet med studien. Här motiveras valet av forskningsansats, urval av data, hur data har analyserats samt vilken kritik det kan finnas mot de källor som används i studien. Det motiveras även varför viss data och teori har använts och hur de tillhörande modeller används i analysdelen för att kunna leda fram till studiens slutsatser. Slutsats: Kommunerna har använt sig av traditionella värderingsprinciper och deras val av modell har styrts av faktorer som även påverkar valet av värderingsmodell inom den privata sektorn. Det finns stora likheter mellan sektorerna i hur deras värderingsprocess ser ut och vilka effekter modellvalen har gett på det slutliga priset för verksamheten. Valet av modell har stora effekter på det slutliga priset eftersom modellvalet styr vilka värden som ska inkluderas i värderingen och därmed vilket värde som värderingen leder fram till. Värdet utgör en stor del i arbetet med att prissätta verksamheten och det gör att valet av värderingsmodell har en på-verkan på det slutliga priset. Det gör att valet av modell måste göras noggrant för att rätt pris ska sättas på verksamheten. Det finns två modeller som rekommenderas i värderingen av kommunala verksamheter i samband med avknoppningar eftersom de ger en låg risk för fel-värderingar och uppfyller de rättsliga krav som finns på företagsvärderingar.
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Tschürtz, Florian [Verfasser]. "Monitoring der Minimalen Resterkrankung in der NPM1 mutierten Akuten Myeloischen Leukämie mittels quantitativer Real-Time PCR / Florian Tschürtz." Ulm : Universität Ulm. Medizinische Fakultät, 2014. http://d-nb.info/1052269842/34.
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Maag, Daniel. "New public Management (NPM) im Gesundheitswesen : ein Überblick über die Ansätze in den Kantonen /." Muri/Schweiz : Zentralsekretariat SGGP, 2000. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=008932365&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
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Müller, Wolfgang. "Centrelink als Multi-Service-Agentur zur Optimierung von Basiseinheiten im Rahmen NPM-typischer Verwaltungsmodernisierungen /." [S.l. : s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975584715.
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Garland, Gavin David. "Investigating the contribution of NPM-ALK to epigenetic regulation in anaplastic large cell lymphoma." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708607.
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Maquaire, Sabrina. "Rôle de la protéine nucléophosmine (NPM1/B23) dans la physiologie des tissus sensibles aux androgènes et la physiopathologie prostatique." Thesis, Clermont-Ferrand 2, 2011. http://www.theses.fr/2011CLF22162.
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Ribeiro, Erliney Ângelo do Espirito Santo. "Fatores criticos para o sucesso da NPM nos países em desenvolvimento: o caso da ENAPORT." Master's thesis, Instituto Superior de Economia e Gestão, 2016. http://hdl.handle.net/10400.5/12951.
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Mestrado em Contabilidade, Fiscalidade e Finanças EmpresariaisEste trabalho pretende analisar o impacto e as principais dificuldades na implementação da NPM nas empresas públicas dos países em desenvolvimento. Para o efeito, foi realizado um estudo de caso numa empresa estatal santomense do sector portuário, denominada ENAPORT. A NPM mudou o conceito de gestão nas empresas públicas, a utilização de ferramentas comuns às empresas privadas, foi fundamental para torná-las mais competitivas. Mas a adoção desta metodologia nos países em desenvolvimento não tem sido fácil. As principais conclusões do estudo desenvolvido na ENAPORT apontam para uma grande proximidade entre a política e a gestão, com repercussão ao nível do custo com o pessoal e do número de funcionários, ambos elevados. Também foi possível concluir que a empresa carece de procedimentos claros para avaliação de desempenho e que as ferramentas da contabilidade de gestão poderiam proporcionar uma visão orientada para o lucro e uma melhor gestão dos custos.
This work intends to analyze the impact and the main difficulties in the implementation of the NPM in the public companies, of the developing countries. For effect, a study of a case was conducted in a state-owned company from São Tome and the port sector, called ENAPORT. A NPM changed the concept of management in the public companies, the use of common tools at private companies, was fundamental to make them more competitive. But the adoption of this methodology in the developing countries hasn't been easy. The main conclusions of the developed study in the ENAPORT point for a big proximity between the politics and management, with the consequence at the level of the cost with the people and the number of workers both high. Was also possible to conclude that the company requires clear conducts for the assessment of performance and that the tools of accountancy of management could provide an oriented vision for profit and a better cost management.
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Boahen, Philip Adu. "Evaluating the impact of new public management (NPM) reforms in Ghana : the privatisation of water." Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/12949/.
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New public management (NPM) reforms have been promoted into the public administration domain during the past twenty to thirty years amidst growing concerns about performance problems in public sector organisations. NPM was based on the assumption that market principles could address performance problems in public instititions. Critics, though, cautioned against NPM reforms and pointed particularly toward their negative effects on employees and consumers. Although NPM was originally conceived in the OECD countries in the west to address specific socio-economic challenges such as unemployment and benefit crises, its principles have spread across countries in developed and emerging economies of the Sub-Saharan African region, including Ghana. In Ghana, NPM reforms have been carried out across a wide range of public sector organisations, and have included the privatisation (public-private partnership) of the Ghanaian WaterOrg in the form of a management contract. This study aims to draw on institutionalist and culturalist accounts to explain the impact of New Public Management (NPM) reforms on a range of stakeholders in the African context through case study research in the Ghanaian water sector. To achieve this overall aim, its key objectives are to: • Critically evaluate the intellectual origins and assumptions of NPM, and consider its applicability to the Sub-Saharan African context; • Identify the main reasons and counter arguments for using NPM reforms in the Ghanaian water sector, including those associated with post-colonialism, socio-economic and culturalist accounts; • Explore the extent of implementation of NPM reforms in the WaterOrg, including the use of privatisation and public-private partnerships and the forms of consultation used; • Identify and describe the critical success factors for a range of stakeholders (including employees and consumers) and then evaluate and explain the extent to which they have been achieved; • Assess the potential transferability of this study’s findings to other social contexts; and • Consider the potential implications of the study’s findings for effective public management in the case study organisation and other public sector organisations in Sub-Saharan Africa. This research takes a neo-empiricist approach and utilises methods associated with qualitative research such as semi structured interviews, observation and documentary materials to explore the rationale for privatising the Ghanaian WaterOrg. It also critically evaluates the process of implementation of the management contract, and its potential implications for employees of the WaterOrg and users of public services. This research reveals that privatisation did not achieve its prime objective of improving water accessibility for the vast majority of Ghanaian members of the public. This was primarily because of a complex range of inter-related institutional, socio-cultural and political factors that underpinned the management of the Ghanaian water sector. The PrivateCo’s management approach was also perceived to be divisive and favoured some employees (junior officers) over their senior counterparts on a range of issues. This was because the PrivateCo’s management team lacked proper understanding of the Ghanaian culture which was a reflection of the management structure of the WaterOrg. There were however, some improvements in ‘non-critical’ areas, including information technology through computerisation and customer services, particularly in terms of complaint reporting and payment of bills. This study thus reinforces the argument that understanding the socio-cultural context is fundamental for effective public management reforms, particularly in emerging economies, rather than adhering to principles that are based on theoretical assumptions and or universal claims of ‘what works well’. It thus calls for caution and a thorough review of how policies and programmes designed to address specific issues in the west are transferred to emerging and developing economies that have problems with capacity and weak institutional arrangements.
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Coronas, Sophie. "Rôle potentiel du phosphatidylinositol 5-phosphate dans l'oncogenèse associée à NPM-ALK : implication de PIKfyve." Toulouse 3, 2008. http://thesesups.ups-tlse.fr/321/.
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Les Lymphomes Anaplasiques à Grandes Cellules (ALCL) sont caractérisés par la translocation chromosomique t(2;5)(p23;q35) conduisant à l'expression de la protéine chimérique NPM-ALK. Le pouvoir transformant de cette chimère se fait via l'activation de voies telles que PI 3-kinase/Akt, STAT3/STAT5, pp60c-scr et PLC-gamma. Les phosphoinositides (PIs) régulent des voies de signalisation contrôlant la prolifération, le trafic vésiculaire, la motilité. Dans ce travail, nous avons étudié le rôle du phosphatidylinositol 5-phosphate (PtdIns5P), un nouveau second messager lipidique dans l'oncogenèse liée à NPM-ALK. Nos travaux montrent des taux élevés de PtdIns5P dans les lignées surexprimant NPM-ALK. La synthèse de PtdIns5P est dûe à l'action de PIKfyve, une enzyme contrôlant l'homéostasie vésiculaire. Nous montrons que NPM-ALK et PIKfyve s'associent dans un complexe moléculaire faisant intervenir la PI 3-kinase et que NPM-ALK régule l'activité lipide kinase de PIKfyve via son activité tyrosine kinase. De plus, le PtdIns5P se localise dans des extensions membranaires, sites actifs du remodelage du cytosquelette d'actine, suggérant que ce PI pourrait avoir un rôle dans le contrôle de ce processus. Enfin, nous montrons que PIKfyve est nécessaire aux processus invasifs et migratoires des cellules NPM-ALK. Ce travail met en évidence le rôle de PIKfyve et du PtdIns5P dans les phénomènes transformants induits par l'oncogène NPM-ALK, en particulier en ce qui concerne les mécanismes invasifs et migratoires. Cette étude dévoile pour la première fois un lien entre un processus oncogénique et le détournement des voies de trafic intracellulaire qui pourrait être généralisé à d'autres oncogènesAnaplastic large cell lymphomas (ALCL) are often associated with the chromosomic translocation, t(2;5)(p23;q35) leading to the expression of a constitutive active chimeric NPM-ALK protein in tumoral cells which strongly activates proliferative and anti-apoptotic pathways such as PLC-gamma, STAT3 and STAT5, pp60c-scr and the PI 3-kinase/Akt pathway. Phosphoinositides (PI) are keys regulators of signalling pathway involved in cytoskeleton reorganization, proliferation and vesicular trafficking. ) In this work, we focused on the potential role of the last PI characterized, phosphatidylinositol 5-phosphate (PtdIns5P) in NPM-ALK-dependant oncogenesis. We found higher levels of PtdIns5P in ALCL and NPM-ALK-transfected cells. This PtdIns5P increase is dependant on PIKfyve, an enzyme know for its role in membrane trafficking and homeostasis. We show that NPM-ALK and PIKfyve are indirectly associated within a complex via the PI 3-kinase. We provide evidence that the tyrosine kinase activity of NPM-ALK regulates the activity of PIKfyve. Moreover, we show that in NPM-ALK-expressing NIH3T3 cells, PtdIns5P is localized in the membrane extensions characteristic of NPM-ALK-transformed cells, which are dynamic actin remodeling sites, suggesting that the lipid could play a role in this process. Finally, we show that PIKfyve regulate the migration and the invasion of NPM-ALK-positive cells. This work provides evidence for the important role of PIKfyve and PtdIns5P in oncogenesis induced by NPM-ALK, particularly in migration and invasion. Overall, in addition to providing a new pharmacological target, this work reveals a link between vesicular trafficking and oncogenesis
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Guillonneau, Maëva. "Étude de la nucléophosmine NPM dans la réponse de l'endothélium à un stress oxydant majeur." Doctoral thesis, Université Laval, 2016. http://hdl.handle.net/20.500.11794/26990.
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Le compartiment microvasculaire est une cible importante du stress oxydant qui est un facteur majeur de la dysfonction endothéliale, notamment au cours d’exposition aux rayonnements ionisants. L’altération de l’endothélium induite par le stress oxydant est impliquée dans la toxicité radio-induite des tissus sains. Limiter les dysfonctions endothéliales est donc un enjeu important des traitements radiothérapeutiques actuels. Cet objectif nécessite une meilleure caractérisation de la signalisation du stress oxydant dans les cellules endothéliales. La voie p38 MAPK est incontournable dans la réponse au stress oxydant mais reste encore insuffisamment caractérisée. Par une approche protéomique, nous avons identifié la nucléophosmine (NPM) comme nouveau partenaire de p38 dans le cytoplasme des cellules endothéliales. La phosphatase PP2a est aussi associée à ce complexe NPM/p38. Nos travaux montrent que le stress oxydant (H2O2, 500μM) régule la déphosphorylation de NPM via PP2a, entraine sa dissociation rapide du complexe et favorise sa translocation vers le noyau. De plus, nous montrons que la présence de NPM déphosphorylée au noyau altère la réponse des cellules aux dommages à l’ADN induits par le stress oxydant. Le céramide sphingolipide membranaire est également un facteur important des voies de stress, particulièrement dans les cellules endothéliales. Notre étude aborde donc l’implication de ce sphingolipide dans la régulation de la voie NPM/p38. Une meilleure caractérisation de la voie p38 et de ses acteurs permettra d’identifier de potentielles cibles afin de limiter les dysfonctions endothéliales et leurs conséquences délétères sur les tissus environnants.The microvascular compartment is a significant target of oxidative stress that is a major factor in endothelial dysfunction, especially during exposure to ionizing radiation. The alteration of endothelium induced by oxidative stress is involved in radiation-induced toxicity of normal tissues. Limiting endothelial dysfunction is therefore an important issue of current radiotherapeutic treatments. This objective requires a better characterization of oxidative stress signaling in endothelial cells. p38 MAPK pathway is essential in oxidative stress response but still insufficiently characterized. By using a proteomic approach, we identified nucleophosmin (NPM) as a new partner of p38 in the cytoplasm of endothelial cells. PP2a phosphatase is also associated with the NPM/p38 complex. Our work shows that oxidative stress (H2O2, 500μM) regulates the NPM dephosphorylation via PP2a, causes a rapid dissociation of the complex, and promotes its translocation to the nucleus. In addition, we show that the presence of NPM dephosphorylated at T199 in the nucleus alters the cellular response to DNA damage induced by oxidative stress. The membrane sphingolipid ceramide is also an important factor in stress pathways, particularly in endothelial cells. Our study describes the involvement of this sphingolipid in the regulation of NPM/p38 pathway. A better characterization of the p38 pathway and its actors provided by our study will identify potential targets in order to limit endothelial dysfunction and its deleterious effect on surrounding tissues.