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Добірка наукової літератури з теми "NPMT"

Автор: Grafiati

Опубліковано: 10 січня 2023

Оновлено: 28 січня 2023

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Статті в журналах з теми "NPMT"

Amusan, Lere, and Oluwayemisi Adebola Oyekunle. "Conceptualizing innovation management development through organizational learning in the public service: any lessons for developing states?" Problems and Perspectives in Management 14, no. 3 (September 6, 2016): 266–75. http://dx.doi.org/10.21511/ppm.14(3-1).2016.13.

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The present economic realities, the effects of globalization, the thirst for innovation and the public’s demand for improved services have led many developing states to review their approaches to service delivery. Most public service managers and professionals spend most of their time dealing with the day-to-day pressures of delivering services, operating and reporting to senior managers, legislators and agencies. They have little or no time to think about innovation, which would ease the pressures and burdens of service delivery. The intention of this paper is to point out the fact that capacity building is the bedrock of new public management development. This paper proposes that innovation management could be used as a form of organizational learning capability in challenging the maze of diplomacy and negotiation with experienced multinational extractive industries for the benefit of developing states. This could be achieved through excellent public investments and nurturing capability, from which they execute effective innovation processes, leading to new service innovations and processes, and superior service performance results. To achieve this objective, extensive literature on innovation management and organizational learning was consulted and the need for future research. In trying to unpack the discussion in the paper, the New Public Management Theory (NPMT), which is a pro-private sectors human resources management is proposed, though other available theoretical positions are explored taking into consideration the lapses entrenched in NPMT. Keywords: innovation, NPMT, learning culture, public management, developing states, development. JEL Classification: O10

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Chou, Wen-Chien, Shiu-Huey Chou, Ji-Shain Chiou, Bor-Sheng Ko, Shu-Wha Lin, Yueh-Chwen Hsu, and Hwei-Fang Tien. "A “canonical” Npm1 mutation Knock-in Mouse Model Revealed Subtle but Definitive Myeloid Expansion with Poor HSC Niche Interaction." Blood 118, no. 21 (November 18, 2011): 762. http://dx.doi.org/10.1182/blood.v118.21.762.762.

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Abstract Abstract 762 Nucleophosmin (NPM1) is a ubiquitous multifunctional phosphoprotein, which has nucleocytoplasmic shuttling activity. Somatic mutations in NPM1 gene result in cytoplasmic dislocation of NPM1 (NPM1c) and are frequently associated with acute myeloid leukemia (AML). The pathogenetic effects of mutated NPM1 protein have been explored by animal models including transgenic or “humanized” knock-in mouse models. Here, we demonstrate the first “canonical” mouse Npm1 mutant knock-in model. Different from the previously report of humanized NPM1 mutant knock-in model, we inserted TCTG after nucleotide c.857 of murine Npm1 coding sequence (c.854–857dupTCTG), a pattern identical to human NPM1 mutation, without any “humanized” sequence. This mutation caused a shift of peptide sequence from WQWRKSL* (amino acid 286–292) to LCLAVEEISLRKGFKQFEIFCLHFCNS* (amino acid 285 to 311), a pattern mildly different from the change in human NPM1 mutation, but is still predicted to generate a nuclear export signal. NPM1c+ genotype and protein accumulation in cytoplasm were confirmed with PCR and immunocytochemistry, respectively. We found that the homozygous NPM mutant (NPMc+/c+) mice were embryonic lethal before E10.5 day, while hetrozygote (NPMwt/c+) mice survived and were fertile, and born with Mendelian ratio. Most NPMwt/c+ mice had normal hematologic parameters and remained disease-free, however, these mice developed a delayed-onset aberration on the distribution of granulocyte-monocye progenitors (GMP), monocytes, and B lymphocytes in blood, spleen, and bone marrow. Colony forming unit assay showed normal hematopoietic development of marrow hematopoietic stem cells (HSC), but poor cobblestone formation while HSCs contacted with stroma microenvironment in NPMwt/c+ mice, suggesting the NPMc mutant may affect the ability of HSCs on contact signal expression. Three (12.5%) of 24 NPMwt/c+ mice developed leukocytosis and splenomegaly mimicking myeloproliferative neoplasm of human. Microscopic examination showed panmyelosis of the bone marrow and existence of hematopoiesis in the spleen. In addition, the immune activities of NPMwt/c+ mice's splenocytes and thymocytes with mitogen stimulation were decreased. In summary, our “canonical” NPMwt/c+ mouse model demonstrated subtle but definitive phenotypes in hematopoietic cells and provided insight into the pathogenesis of NPM1 mutation in human acute myeloid leukemia. A second hit may be necessary for the development of AML in NPMwt/c+ mice since no AML was detected in these mice till 20 months of age. Disclosures: No relevant conflicts of interest to declare.

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Manspeizer, H., E. J. Heyer, K. Lee, L. Mongero, B. Esrig, and C. R. Smith. "NPMT performance after coronary artery bypass grafting: cardiopulmonary bypass versus off-pump coronary artery bypass." Annals of Thoracic Surgery 70, no. 5 (November 2000): 1788. http://dx.doi.org/10.1016/s0003-4975(00)02079-8.

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Lukoyanov, A. V., A. O. Shorikov, and V. I. Anisimov. "Electronic structure of the NpMT 5 (M = Fe, Co, Ni; T = Ga, In) series of neptunium compounds." Physics of the Solid State 58, no. 3 (March 2016): 438–43. http://dx.doi.org/10.1134/s1063783416030215.

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Huang, Min, Xinran Li, and Beverly S. Mitchell. "Cysteine 288 Regulates NPMc+ Cytoplasmic Localization and Sensitizes Leukemic Cells to Bortezomib-Induced Apoptosis Through a Redox-Sensitive Mechanism." Blood 120, no. 21 (November 16, 2012): 532. http://dx.doi.org/10.1182/blood.v120.21.532.532.

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Abstract Abstract 532 Increasing evidence points to NPM1 mutations in exon 12 of the NPM1 gene (NPMc+) as a founder genetic event that defines a distinct leukemia entity accounting for approximately one-third of all AML. Unlike wild type NPM1, which resides predominantly in the nucleoli, NPMc+ mutants localize aberrantly in the leukemic-cell cytoplasm due to mutations at the C-terminus of NPM1. We have found that expression of NPMc+ in K562 and 32D cells sensitizes these cells to Bortezomib-induced apoptosis. Conversely, inducible small interfering RNA (shRNA)-induced knockdown of NPM1 in OCI-AML3 cell line, an AML cell line carrying the NPMc+ mutation, and in K562 cells over-expressing NPMc+ markedly reduced the ability of Bortezomib to induce apoptosis in both cell lines. Bortezomib-induced apoptosis in both OCI-AML3 and K562 cells was reversed with N-acetyl-1-cysteine (NAC), a ROS scavenger, suggesting that activation of ROS pathway plays an essential role in Bortezomib-induced apoptosis. Further studies showed that the cytoplasmic localization of NPMc+ in OCI-AML3 and 32D cells expressing NPMc+ increased in response to ROS activators such as diamide, hydrogen peroxide, and Bortezomib, but was reduced by NAC. These results prompted us to explore ROS-sensitive elements that might differentiate NPMc+ from wt-NPM1. We discovered that tryptophan 288 in wt-NPM1 is mutated to cysteine 288 in the majority of NPMc+ C-terminal mutants identified to date. Strikingly, mutagenesis of C288 to alanine re-localized NPMc+ completely to nucleolus, whereas mutagenesis of C21 and C104, the only two cysteines that exist in wt-NPM1, failed to alter the cytoplasmic localization of NPMc+. Unexpectedly, we also found that NPM1 oligomerization is disrupted in C21A+C104A mutants of both wt-NPM1 and NPMc+, indicating that C21 and C104 are essential for the oligomerization of NPM1. In addition, the proportion of cytoplasmic-localized endogenous wt-NPM1 also increased in response to ROS generation in K562 cells over-expressing NPMc+ or C21A+C104A-NPMc+, indicating that C288-NPMc+ partially relocates wt-NPM1 to the cytoplasm upon ROS activation through disulfide bond formation between C288-NPMc+ and C21 or C104 of wt-NPM1. Finally, we established the importance of C288-NPM1c+ as a sensitizing factor in Bortezomib-induced apoptosis by demonstrating that the sensitizing effects of NPMc+ to Bortezomib was significantly attenuated in K562 and 32D cells expressing C288A-NPMc+. In contrast, expression of C21A+C104A-NPMc+ sensitized K562 and 32D cells to Bortezomib-induced apoptosis to the same extent as NPMc+. We conclude that the mutation of tryptophan 288 to cysteine that is present in the great majority of NPM1c+ leukemic cells is the essential event that mediates the cytoplasmic localization of NPMc+ and that sensitizes leukemia cells to Bortezomib-induced apoptosis regardless of the oligomerization status of NPMc+. We also conclude that the intracellular redox level is an additional major factor that regulates the distribution of NPMc+ in the cytoplasm as opposed to the nucleolus in AML cells. Disclosures: No relevant conflicts of interest to declare.

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Bolli, Niccolò, Elspeth M. Payne, Clemens Grabher, Jeong-Soo Lee, Adam B. Johnston, Brunangelo Falini, John P. Kanki, and A. Thomas Look. "Expression of the cytoplasmic NPM1 mutant (NPMc+) causes the expansion of hematopoietic cells in zebrafish." Blood 115, no. 16 (April 22, 2010): 3329–40. http://dx.doi.org/10.1182/blood-2009-02-207225.

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AbstractMutations in the human nucleophosmin (NPM1) gene are the most frequent genetic alteration in adult acute myeloid leukemias (AMLs) and result in aberrant cytoplasmic translocation of this nucleolar phosphoprotein (NPMc+). However, underlying mechanisms leading to leukemogenesis remain unknown. To address this issue, we took advantage of the zebrafish model organism, which expresses 2 genes orthologous to human NPM1, referred to as npm1a and npm1b. Both genes are ubiquitously expressed, and their knockdown produces a reduction in myeloid cell numbers that is specifically rescued by NPM1 expression. In zebrafish, wild-type human NPM1 is nucleolar while NPMc+ is cytoplasmic, as in human AML, and both interact with endogenous zebrafish Npm1a and Npm1b. Forced NPMc+ expression in zebrafish causes an increase in pu.1+ primitive early myeloid cells. A more marked perturbation of myelopoiesis occurs in p53m/m embryos expressing NPMc+, where mpx+ and csf1r+ cell numbers are also expanded. Importantly, NPMc+ expression results in increased numbers of definitive hematopoietic cells, including erythromyeloid progenitors in the posterior blood island and c-myb/cd41+ cells in the ventral wall of the aorta. These results are likely to be relevant to human NPMc+ AML, where the observed NPMc+ multilineage expression pattern implies transformation of a multipotent stem or progenitor cell.

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Xu, Jie, Wu Zhang, Xiaojing Yan, Chen Zhao, Jiang Zhu, Zhu Chen, Sai-Juan Chen, and Jiong Hu. "NPM1 Mutation Contributes to Hematological Dysfunction By Disrupting H3K79 Methylation." Blood 128, no. 22 (December 2, 2016): 2702. http://dx.doi.org/10.1182/blood.v128.22.2702.2702.

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Abstract NPM1 is one of the most frequent acquired mutated genes in acute myeloid leukemia (AML). Previous studies have shown that NPM1 mutation (NPMc+) established the distinctive gene expression signatures, which were associated with mixed lineage leukemia (MLL)-target genes, like MEIS1 and HOXA cluster. In AML carrying MLL fusion-oncoproteins, DOT1L-mediated histone 3 lysine 79 (H3K79) methylation is implicated in the regulation of MLL-target genes. Compared with MLL abnormalities, NPM1 variants preserve the similar transcriptional characteristics. However, whether NPM1 mutation could affect the histone modification of H3K79 methylation is unknown. In this study, we showed that NPM1 mutation dysregulated the homeostasis of hematopoietic stem and progenitor cells and resulted in ageing-related myeloproliferation in NPMc+ transgenic mouse model. Interestingly, through scanning the chromatin modification related gene profiling, di- and tri- methylated H3K79 were significantly elevated in bone marrow (BM) Lin-Sca-1+c-Kit+ cells (LSKs) of NPMc+ mice comparing to wild type (WT). Meanwhile, in the leukemia cell lines and AML primary BM samples, we confirmed that NPM1 mutated cells expressed the higher level of H3K79 methylation. In vitro assays also indicated that the decrease or increase of methylated H3K79 could be regulated respectively by knockdown or overexpression of NPM1 mutant but not WT. Importantly, with DOT1L inhibitor treatment, reduced di- and tri- methylated H3K79 was observed in OCI-AML3 (NPMc+) strains but not OCI-AML2 (NPM1 WT) cells. In contrast with OCI-AML2, DOT1L inhibitor significantly promoted the cell apoptosis and restrained the cell cycle of OCI-AML3. Moreover, by the means of murine BM colony formation assay, DOT1L inhibitor obviously weakened myeloid cell proliferation in NPMc+ mice, while colony number in WT group did not change. Also, leukemia development was repressed in OCI-AML3-xenografted NOD/SCID mice with the treatment of DOT1L inhibitor. Taken together, NPM1 mutation contributes to hematological dysfunction by disrupting H3K79 methylation, which could be largely attenuated by DOT1L inhibitor. Disclosures No relevant conflicts of interest to declare.

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Sportoletti, Paolo, Emanuela Varasano, Roberta Rossi, Oxana Bereshchenko, Debora Cecchini, Ilaria Gionfriddo, Niccolò Bolli, et al. "The human NPM1 mutation A perturbs megakaryopoiesis in a conditional mouse model." Blood 121, no. 17 (April 25, 2013): 3447–58. http://dx.doi.org/10.1182/blood-2012-08-449553.

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Okuwaki, M., A. Sumi, M. Hisaoka, A. Saotome-Nakamura, S. Akashi, Y. Nishimura, and K. Nagata. "Function of homo- and hetero-oligomers of human nucleoplasmin/nucleophosmin family proteins NPM1, NPM2 and NPM3 during sperm chromatin remodeling." Nucleic Acids Research 40, no. 11 (February 22, 2012): 4861–78. http://dx.doi.org/10.1093/nar/gks162.

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Martelli, M. P., V. Pettirossi, N. Manes, A. Liso, F. Mezzasoma, F. Cecchetti, M. F. De Marco, et al. "Selective Silencing of the NPM1 Mutant Protein and Apoptosis Induction upon ATRA In Vitro Treatment of AML Cells Carrying NPM1 Mutations." Blood 110, no. 11 (November 16, 2007): 868. http://dx.doi.org/10.1182/blood.v110.11.868.868.

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Abstract We previously identified a new AML category carrying NPM1 mutations which lead to aberrant cytoplasmic expression of the nucleolar protein NPM1, hence the term NPMc+ AML[Falini et al, NEJM 2005]. This leukemia accounts for about one-third of adult AML and shows distinctive biological and clinical features[Falini et al, Blood 2007]. Notably, AML carrying NPM1 mutations in the absence of FLT3-ITD are characterized by a favourable prognosis. However, still a proportion of NPMc+ AML cannot be cured by conventional treatments and new therapeutic strategies need to be explored. We previously identified OCI/AML3 as the only human AML cell line carrying cytoplasmic mutated NPM (type A) in the absence of FLT3-ITD[Quentmeier et al, Leukemia 2005]. Because of these features and the ability to engraft in NOD/SCID mice, the OCI-AML3 represents a remarkable tool for the study of NPMc+ AML. Previous findings that ATRA exerts growth inhibitory effects on the OCI/AML3 prompt us to investigate the molecular mechanisms underlying the response to ATRA, with focus on the NPM mutant protein. As cellular model for our studies, we also used primary leukemia cells originated from a patient with NPMc+ AML (mutation A) bearing FLT3-ITD (Mont1) that have been propagated in NOD/SCID mice for 5 years without loss of initial characteristics. Early cell cycle arrest and proapoptotic effects of pharmacological doses of ATRA were confirmed in both cellular models in vitro. Morphological signs of differentiation were not evident. Western blot analysis using specific antibodies showed marked downregulation of the leukemic NPM1 mutant protein upon ATRA treatment, preceding apoptosis activation. On the other hand, wild-type NPM1 protein levels remained unchanged, leading to a condition of NPM1 haploinsufficiency. Semi-quantitative RT-PCR for NPM mutant A showed no change in mRNA expression following treatment, suggesting a regulation of the NPM mutant protein expression at post-transcriptional level. Indeed, concomitant treatment with proteasome-inhibitors partly reverted this effect. Downregulation of NPM mutant protein preceded activation of caspase-8 and caspase-3, PARP-cleavage and Bax activation. No NF-kB activation was observed upon ATRA treatment. Activation of the p53-dependent pathway was a later event, as expected in conditions of NPM1 haploinsufficiency. Importantly, these results were confirmed in the primary NPMc+ AML cells from patient Mont1. Activation of caspase-8 suggests that the response to ATRA in NPMc+ AML cells may be mediated through the death receptor pathway. Although protein levels of TRAIL, TRAIL receptors and TNF-alpha receptors seem to be unaffected, it might be possible that the NPM1 mutant protein modulates the signalling through death cell receptors. Analysis of ATRA-induced transcriptome and proteome modifications in NPMc+ AML is ongoing and will be also presented, as well as further pre-clinical studies on patients’ primary AML cells and in NOD/SCID mice. In conclusion, our data suggest that NPM mutant protein might be involved in the in vitro response to ATRA in AML cells carrying NPM1 mutations. Figure Figure

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Більше джерел

Дисертації з теми "NPMT"

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 PTEN
Nucleophosmin (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. - Nietzsche
On 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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Книги з теми "NPMT"

Regehr, Ernie. Rebuilding confidence in the NPT: Resolving the NATO-NPT contradiction. Waterloo, Ont: Project Ploughshares, 2005.

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Canadian Institut For International Peace and Security. Non-proliferation treaty (NPT). S.l: s.n, 1989.

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Kwan-bong, Kim. NPT wa Pukhan haek. Sŏul-si: Yejin, 1995.

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Akiyama, Nobumasa. NPT: Kaku no gurōbaru gabanansu. Tōkyō-to Chiyoda-ku: Iwanami Shoten, 2015.

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NPT ch'eje wa haek anbo. Sŏul T'ŭkpyŏlsi: T'ongil Yŏn'guwŏn, 2010.

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Sokolski, Henry D. Reviewing the Nuclear Nonproliferation Treaty (NPT). Carlisle, PA: Strategic Studies Institute, U.S. Army War College, 2010.

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Sokolski, Henry D. Reviewing the Nuclear Nonproliferation Treaty (NPT). Edited by Army War College (U.S.). Strategic Studies Institute. Carlisle, PA: Strategic Studies Institute, U.S. Army War College, 2010.

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Army War College (U.S.). Strategic Studies Institute, ed. Reviewing the Nuclear Nonproliferation Treaty (NPT). Carlisle, PA: Strategic Studies Institute, U.S. Army War College, 2010.

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Kŭllobŏl amaketton: Haek mugi wa NPT. Sŏul-si: Ch'aek Sesang, 2010.

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(Japan), Jichitai Mondai Kenkyūjo, ed. NPM no kenshō: NIhon to Yōroppa. Shinjuku-ku [Tokyo]: Jichitai Kenkyūsha, 2005.

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Частини книг з теми "NPMT"

Balusu, Ramesh, Warren Fiskus, and Kapil N. Bhalla. "Nucleophosmin (NPM1)." In Targeted Therapy of Acute Myeloid Leukemia, 251–73. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-1393-0_13.

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Fischer, R. X., and W. H. Baur. "NPT." In Zeolite-Type Crystal Structures and their Chemistry. 41 New Framework Type Codes, 357–63. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-642-41452-7_36.

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Runzheimer, Bodo. "Netzplantechnik (NPT)." In Operations Research I, 159–215. Wiesbaden: Gabler Verlag, 1986. http://dx.doi.org/10.1007/978-3-663-19689-1_3.

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Runzheimer, Bodo. "Netzplantechnik (NPT)." In Operations Research, 180–243. Wiesbaden: Gabler Verlag, 1999. http://dx.doi.org/10.1007/978-3-322-94495-5_3.

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Runzheimer, Bodo. "Netzplantechnik (NPT)." In Lineare Planungsrechnung und Netzplantechnik, 159–215. Wiesbaden: Gabler Verlag, 1987. http://dx.doi.org/10.1007/978-3-663-13200-4_3.

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Runzheimer, Bodo, Thomas Cleff, and Wolfgang Schäfer. "Netzplantechnik (NPT)." In Operations Research 1, 143–205. Wiesbaden: Gabler Verlag, 2005. http://dx.doi.org/10.1007/978-3-322-82917-7_3.

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Doglio, Fernando. "No More NPM." In Introducing Deno, 79–94. Berkeley, CA: Apress, 2020. http://dx.doi.org/10.1007/978-1-4842-6197-2_4.

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Butler, Richard. "Beyond the NPT." In Beyond 1995, 65–71. Boston, MA: Springer US, 1990. http://dx.doi.org/10.1007/978-1-4684-1315-1_7.

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Ramjit, Ruan T., and Charles E. Hill. "Acute Myeloid Leukemia: FLT3/NPM1." In Diagnostic Molecular Pathology in Practice, 133–39. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-19677-5_17.

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Antonini, Rachele, Letizia Cirillo, Linda Rossato, and Ira Torresi. "Chapter 1. Introducing NPIT studies." In Non-professional Interpreting and Translation, 2–26. Amsterdam: John Benjamins Publishing Company, 2017. http://dx.doi.org/10.1075/btl.129.01ant.

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Тези доповідей конференцій з теми "NPMT"

Mehranfar, Mahsa, Juan Mejia, Sherif Hassanien, and James Martin. "Integrity Mitigation Prioritization Using Multi-Criteria Decision-Making." In ASME 2019 Pressure Vessels & Piping Conference. American Society of Mechanical Engineers, 2019. http://dx.doi.org/10.1115/pvp2019-93621.

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Abstract In-line Inspection (ILI) tools are regularly used for inspecting transmission pipelines. However, it is challenging to use such technology for a large portion of pipes; e.g. terminals and pumping stations, because of diameter changes, tight turns, or other pipe/inspection characteristics. Non-contact pipeline magnetic testing (NPMT) is a well-suited technique to inspect potentially non-ILI pipes. This paper presents a new framework for selecting and prioritizing digs-based LSM high severity features. A multi-criteria decision-making approach was developed using pair-wise comparisons which stems from the Analytical Hierarchy Process (AHP). AHP is a structured technique for organizing and analyzing complex decisions to help the decision maker set priorities and make the best decision given available information. In addition to the application of AHP, a cost benefit analysis and evaluation of risk have been conducted in order to support a risk-informed decision-making for selecting the top priority digs. Pipe properties, LSM tool reported data and Subject Matter Expert (SME) opinion were utilized in order to efficiently render a decision regarding prioritization of dig sites. The developed approach can be used as a regular process to prioritize similar dig programs. This method is capable of ranking different dig sites based on SME opinion as well as construction information and LSM reported data.

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Chatzidimitriou, Kyriakos C., Michail D. Papamichail, Themistoklis Diamantopoulos, Michail Tsapanos, and Andreas L. Symeonidis. "npm-miner." In ICSE '18: 40th International Conference on Software Engineering. New York, NY, USA: ACM, 2018. http://dx.doi.org/10.1145/3196398.3196465.

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Arteca, Ellen, and Alexi Turcotte. "npm-filter." In MSR '22: 19th International Conference on Mining Software Repositories. New York, NY, USA: ACM, 2022. http://dx.doi.org/10.1145/3524842.3528501.

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Marciniak, Malgorzata, and Agnieszka Mykowiecka. "NPMI Driven Recognition of Nested Terms." In Proceedings of the 4th International Workshop on Computational Terminology (Computerm). Stroudsburg, PA, USA: Association for Computational Linguistics and Dublin City University, 2014. http://dx.doi.org/10.3115/v1/w14-4805.

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Homburg, Vincent. "E-government and NPM." In the 6th international conference. New York, New York, USA: ACM Press, 2004. http://dx.doi.org/10.1145/1052220.1052289.

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Meta, E., and E. Manske. "D6.1 Topography Analysis in the NPMM-200." In SMSI 2021. AMA Service GmbH, Von-Münchhausen-Str. 49, 31515 Wunstorf, Germany, 2021. http://dx.doi.org/10.5162/smsi2021/d6.1.

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Moraru, Dan Cristian, Radu-Cezar Doru, Ilan Marcovici, Valentin Bejan, Laura Iulia Bozomitu, Camelia Tamas, Bogdan Mihnea Ciuntu, et al. "Negative Pressure Wound Therapy (NPWT) – Performance and Limitations." In 2019 E-Health and Bioengineering Conference (EHB). IEEE, 2019. http://dx.doi.org/10.1109/ehb47216.2019.8969976.

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Qutob, Haitham, Amina Abdul-Aziz, Amy Proudfoot, Martin Grundy, Nigel H. Russell, Monica Pallis, and Claire H. Seedhouse. "Abstract 331: Targeting MCL1 in NPM1-mutant AML." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-331.

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McGarry, Ray, and Peyman Moghaddam. "NPML boundary conditions for second‐order wave equations." In SEG Technical Program Expanded Abstracts 2009. Society of Exploration Geophysicists, 2009. http://dx.doi.org/10.1190/1.3255611.

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Palafox, Pablo, Aljaz Bozic, Justus Thies, Matthias Niesner, and Angela Dai. "NPMs: Neural Parametric Models for 3D Deformable Shapes." In 2021 IEEE/CVF International Conference on Computer Vision (ICCV). IEEE, 2021. http://dx.doi.org/10.1109/iccv48922.2021.01246.

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Звіти організацій з теми "NPMT"

Pilat, J. F. Rethinking the NPT. Office of Scientific and Technical Information (OSTI), February 1995. http://dx.doi.org/10.2172/10120276.

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Gilligan, Kimberly V., J. Michael Whitaker, John A. Oakberg, and Catherine Snow. Best Practices for NPT Transit Matching. Office of Scientific and Technical Information (OSTI), September 2016. http://dx.doi.org/10.2172/1327679.

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Burk S. Challenges to the 2015 NPT Review Conference. Office of Scientific and Technical Information (OSTI), May 2013. http://dx.doi.org/10.2172/1089831.

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Scott, Andrew. Development of Simulation Software for NPT-MD. Fort Belvoir, VA: Defense Technical Information Center, November 2004. http://dx.doi.org/10.21236/ada429450.

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Heinonen, Olli. IAEA Mechanisms to Ensure Compliance with NPT Safeguards. The United Nations Institute for Disarmament Research, March 2020. http://dx.doi.org/10.37559/wmd/19/wmdce2.

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Swan, R. THE FUTURE OF THE NPT: REVCON AND BEYOND. Office of Scientific and Technical Information (OSTI), December 2020. http://dx.doi.org/10.2172/1734616.

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Miller, Karen. The Global Nonproliferation Regime: The NPT and Beyond. Office of Scientific and Technical Information (OSTI), September 2021. http://dx.doi.org/10.2172/1821358.

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Saunders, E. Case Study: Iran, Islam, the NPT, and the Bomb. Office of Scientific and Technical Information (OSTI), April 2011. http://dx.doi.org/10.2172/1022875.

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Wan, Wilfred. Nuclear Risk Reduction: Engaging the Non-NPT Nuclear-Armed States. UNIDIR, February 2021. http://dx.doi.org/10.37559/wmd/21/nrr/01.

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Davis, Scott. The NPT and Iran: A Case of Domestic and Bureaucratic Politics. Fort Belvoir, VA: Defense Technical Information Center, January 1996. http://dx.doi.org/10.21236/ada441432.

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