Relevant bibliographies by topics / NNMT

Academic literature on the topic 'NNMT'

Author: Grafiati
Published: 10 December 2022
Last updated: 11 September 2023

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Journal articles on the topic "NNMT"

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Thomas, Martin G., Davide Sartini, Monica Emanuelli, Matthijs J. van Haren, Nathaniel I. Martin, David M. Mountford, David J. Barlow, et al. "Nicotinamide N-methyltransferase catalyses the N-methylation of the endogenous β-carboline norharman: evidence for a novel detoxification pathway." Biochemical Journal 473, no. 19 (September 27, 2016): 3253–67. http://dx.doi.org/10.1042/bcj20160219.

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Nicotinamide N-methyltransferase (NNMT) is responsible for the N-methylation of nicotinamide to 1-methylnicotinamide. Our recent studies have demonstrated that NNMT regulates cellular processes fundamental to the correct functioning and survival of the cell. It has been proposed that NNMT may possess β-carboline (BC) N-methyltransferase activity, endogenously and exogenously produced pyridine-containing compounds which, when N-methylated, are potent inhibitors of Complex I and have been proposed to have a role in the pathogenesis of Parkinson's disease. We have investigated the ability of recombinant NNMT to N-methylate norharman (NH) to 2-N-methylnorharman (MeNH). In addition, we have investigated the toxicity of the BC NH, its precursor 1,2,3,4-tetrahydronorharman (THNH) and its N-methylated metabolite MeNH, using our in vitro SH-SY5Y NNMT expression model. Recombinant NNMT demonstrated NH 2N-methyltransferase activity, with a Km of 90 ± 20 µM, a kcat of 3 × 10−4 ± 2 × 10−5 s−1 and a specificity constant (kcat/Km) of 3 ± 1 s−1 M−1. THNH was the least toxic of all three compounds investigated, whereas NH demonstrated the greatest, with no difference observed in terms of cell viability and cell death between NNMT-expressing and non-expressing cells. In NNMT-expressing cells, MeNH increased cell viability and cellular ATP concentration in a dose-dependent manner after 72 and 120 h incubation, an effect that was not observed after 24 h incubation or in non-NNNT-expressing cells at any time point. Taken together, these results suggest that NNMT may be a detoxification pathway for BCs such as NH.
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Yu, Tao, Yong-Tao Wang, Pan Chen, Yu-Hua Li, Yi-Xin Chen, Hang Zeng, Ai-Ming Yu, Min Huang, and Hui-Chang Bi. "Effects of Nicotinamide N-Methyltransferase on PANC-1 Cells Proliferation, Metastatic Potential and Survival Under Metabolic Stress." Cellular Physiology and Biochemistry 35, no. 2 (2015): 710–21. http://dx.doi.org/10.1159/000369731.

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Background: Aberrant expression of Nicotinamide N-methyltransferase (NNMT) has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress. Methods: Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress. Results: NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking. Conclusions: These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress.
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Liu, Wenxiu, Meng Zhu, Xiaoming Li, Limian Er, and Shengmian Li. "NNMT Is an Immune-Related Prognostic Biomarker That Modulates the Tumor Microenvironment in Pan-Cancer." Disease Markers 2023 (February 9, 2023): 1–17. http://dx.doi.org/10.1155/2023/9226712.

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Emerging evidence has revealed the significant roles of nicotinamide n-methyltransferase (NNMT) in cancer initiation, development, and progression; however, a pan-cancer analysis of NNMT has not been conducted. In this study, we first thoroughly investigated the expression and prognostic significance of NNMT and the relationship between NNMT and the tumor microenvironment using bioinformatic analysis. NNMT was significantly increased and associated with poor prognosis in many common cancers. NNMT expression correlated with the infiltration levels of cancer-associated fibroblasts and macrophages in pan-cancer. Function enrichment analysis discovered that NNMT related to cancer-promoting and immune pathways in various common cancers, such as colon adenocarcinoma, head and neck squamous cell carcinoma, ovarian serous cystadenocarcinoma, and stomach adenocarcinoma. NNMT expression was positively correlated with tumor-associated macrophages (TAMs), especially M2-like TAMs. The results suggest that NNMT might be a new biomarker for immune infiltration and poor prognosis in cancers, providing new direction on therapeutics of cancers.
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Sun, Wei, Yongxiang Zou, Zheng Cai, Jinxiang Huang, Xinjie Hong, Qiang Liang, and Weilin Jin. "Overexpression of NNMT in Glioma Aggravates Tumor Cell Progression: An Emerging Therapeutic Target." Cancers 14, no. 14 (July 21, 2022): 3538. http://dx.doi.org/10.3390/cancers14143538.

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Purpose: Increasing evidence has revealed that nicotinamide N-methyltransferase (NNMT) is a key factor influencing the prognosis of tumors. The present study aimed to investigate the role of NNMT in glioma and to elucidate the associated functional mechanisms. Methods: Clinical samples were analyzed by immunohistochemical staining and Western blotting to evaluate NNMT expression in glioma and normal brain tissues. The correlation between NNMT expression and glioma was analyzed using the Cancer Genome Atlas (TCGA) database. Additionally, NNMT was knocked down in two types of glioma cells, U87 and U251, to evaluate the invasive ability of these cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate NNMT knockdown in the cells. Furthermore, ELISA was used to determine the balance between nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide hydrogen (NAD/NADH ratio), which verified the altered methylation patterns in the cells. The glioma xenograft mouse models were used to verify the regulatory role of NNMT, GAP43, and SIRT1. Results: Analysis based on our clinical glioma samples and TCGA database revealed that overexpression of NNMT was associated with poor prognosis of patients. Knockdown of NNMT reduced the invasive ability of glioma cells, and downregulation of its downstream protein GAP43 occurred due to altered cellular methylation caused by NNMT overexpression. Gene Set Enrichment Analysis confirmed that NNMT modulated the NAD-related signaling pathway and showed a negative association between NNMT and SIRT1. Moreover, the regulatory roles of NNMT, GAP43, and SIRT1 were confirmed in glioma xenograft mouse models. Conclusion: Overexpression of NNMT causes abnormal DNA methylation through regulation of the NAD/NADH ratio, which in turn leads to the downregulation of GAP43 and SIRT1, eventually altering the biological behavior of tumor cells.
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Parsons, Richard B., Shylesh Aravindan, Anusha Kadampeswaran, Emily A. Evans, Kanwaljeet K. Sandhu, Elizabeth R. Levy, Martin G. Thomas, Brian M. Austen, and David B. Ramsden. "The expression of nicotinamide N-methyltransferase increases ATP synthesis and protects SH-SY5Y neuroblastoma cells against the toxicity of Complex I inhibitors." Biochemical Journal 436, no. 1 (April 27, 2011): 145–55. http://dx.doi.org/10.1042/bj20101685.

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NNMT (nicotinamide N-methyltransferase, E.C. 2.1.1.1) catalyses the N-methylation of nicotinamide to 1-methylnicotinamide. NNMT expression is significantly elevated in a number of cancers, and we have previously demonstrated that NNMT expression is significantly increased in the brains of patients who have died of Parkinson's disease. To investigate the cellular effects of NNMT overexpression, we overexpressed NNMT in the SH-SY5Y cell line, a tumour-derived human dopaminergic neuroblastoma cell line with no endogenous expression of NNMT. NNMT expression significantly decreased SH-SY5Y cell death, which correlated with increased intracellular ATP content, ATP/ADP ratio and Complex I activity, and a reduction in the degradation of the NDUFS3 [NADH dehydrogenase (ubiquinone) iron–sulfur protein 3] subunit of Complex I. These effects were replicated by incubation of SH-SY5Y cells with 1-methylnicotinamide, suggesting that 1-methylnicotinamide mediates the cellular effects of NNMT. Both NNMT expression and 1-methylnicotinamide protected SH-SY5Y cells from the toxicity of the Complex I inhibitors MPP+ (1-methyl-4-phenylpyridinium ion) and rotenone by reversing their effects upon ATP synthesis, the ATP/ADP ratio, Complex I activity and the NDUFS3 subunit. The results of the present study raise the possibility that the increase in NNMT expression that we observed in vivo may be a stress response of the cell to the underlying pathogenic process. Furthermore, the results of the present study also raise the possibility of using inhibitors of NNMT for the treatment of cancer.
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Zhang, Weixian, Yue Jing, Shuai Wang, Yan Wu, Yawei Sun, Jia Zhuang, Xiaofeng Huang, et al. "Identification of Biological Functions and Prognostic Value of NNMT in Oral Squamous Cell Carcinoma." Biomolecules 12, no. 10 (October 15, 2022): 1487. http://dx.doi.org/10.3390/biom12101487.

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Background: Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme that catalyzes the methylation of nicotinamide (NAM) to generate 1-methyl nicotinamide (MNAM). Although previous studies have shown that NNMT is frequently dysregulated to promote the onset and progression of many malignancies, its expression profile, prognostic value and function in oral squamous cell carcinoma (OSCC) are still unknown. Methods: We used untargeted metabolomics based on mass spectrometry to analyze potential metabolite differences between tumors and matched adjacent normal tissues in 40 OSCC patients. Immunohistochemistry (IHC) was used to analyze the NNMT expression profile in OSCC, and the diagnostic and prognostic values of NNMT were evaluated. Next, qPCR and Western blot were used to compare the expression of NNMT in five OSCC cell lines. Stable transfected cell lines were constructed, and functional experiments were carried out to elucidate the effects of NNMT on the proliferation and migration of OSCC cells. Finally, gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) data to investigate the potential functional mechanisms of NNMT in OSCC. Results: We found that the nicotinamide metabolic pathway was abnormally activated in OSCC tumor tissues compared with normal tissues. NNMT was expressed ubiquitously in tumor cells (TCs) and fibroblast-like cells (FLCs) but was absent in tumor-infiltrating lymphocytes (TILs). OSCC patients with highly expressed NNMT in TCs had higher risk of lymph node metastasis and showed a worse pattern of invasion (POI). Moreover, patients with highly expressed NNMT were also susceptible to postoperative recurrence. Highly expressed NNMT can independently predict shorter disease-free survival and recurrence-free survival. Functionally, we demonstrated that the ectopic expression of NNMT promoted OSCC tumor cell proliferation and migration in vitro. Conversely, silencing exerted significantly opposite effects in vitro. In addition, GSEA showed that highly expressed NNMT was mainly enriched in the epithelial–mesenchymal transformation (EMT) pathway, which displayed a significant positive correlation with the six classic EMT markers. Conclusions: Our study uncovered that NNMT may be a critical regulator of EMT in OSCC and may serve as a prognostic biomarker for OSCC patients. These findings might provide novel insights for future research in NNMT-targeted OSCC metastasis and recurrence therapy.
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Parsons, Richard B., and Paul D. Facey. "Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution." Biomolecules 11, no. 10 (September 28, 2021): 1418. http://dx.doi.org/10.3390/biom11101418.

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Nicotinamide N-methyltransferase (NNMT) has progressed from being considered merely a Phase II metabolic enzyme to one with a central role in cell function and energy metabolism. Over the last three decades, a significant body of evidence has accumulated which clearly demonstrates a central role for NNMT in cancer survival, metastasis, and drug resistance. In this review, we discuss the evidence supporting a role for NNMT in the progression of the cancer phenotype and how it achieves this by driving the activity of pro-oncogenic NAD+-consuming enzymes. We also describe how increased NNMT activity supports the Warburg effect and how it promotes oncogenic changes in gene expression. We discuss the regulation of NNMT activity in cancer cells by both post-translational modification of the enzyme and transcription factor binding to the NNMT gene, and describe for the first time three long non-coding RNAs which may play a role in the regulation of NNMT transcription. We complete the review by discussing the development of novel anti-cancer therapeutics which target NNMT and provide insight into how NNMT-based therapies may be best employed clinically.
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Liu, Jie-Ru, Zhao-Hui Deng, Xiao-Juan Zhu, Yu-Rong Zeng, Xiang-Xiang Guan, and Jiang-Hua Li. "Roles of Nicotinamide N-Methyltransferase in Obesity and Type 2 Diabetes." BioMed Research International 2021 (July 27, 2021): 1–8. http://dx.doi.org/10.1155/2021/9924314.

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Type 2 diabetes (T2D) is thought to be a complication of metabolic syndrome caused by disorders of energy utilization and storage and characterized by insulin resistance or deficiency of insulin secretion. Though the mechanism linking obesity to the development of T2D is complex and unintelligible, it is known that abnormal lipid metabolism and adipose tissue accumulation possibly play important roles in this process. Recently, nicotinamide N-methyltransferase (NNMT) has been emerging as a new mechanism-of-action target in treating obesity and associated T2D. Evidence has shown that NNMT is associated with obesity and T2D. NNMT inhibition or NNMT knockdown significantly increases energy expenditure, reduces body weight and white adipose mass, improves insulin sensitivity, and normalizes glucose tolerance and fasting blood glucose levels. Additionally, trials of oligonucleotide therapeutics and experiments with some small-molecule NNMT inhibitors in vitro and in preclinical animal models have validated NNMT as a promising therapeutic target to prevent or treat obesity and associated T2D. However, the exact mechanisms underlying these phenomena are not yet fully understood and clinical trials targeting NNMT have not been reported until now. Therefore, more researches are necessary to reveal the acting mechanism of NNMT in obesity and T2D and to develop therapeutics targeting NNMT.
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Griffiths, Alexandra, Jun Wang, Qing Song, Iredia D. Iyamu, Lifeng Liu, Jooman Park, Yuwei Jiang, Rong Huang, and Zhenyuan Song. "Nicotinamide N-methyltransferase upregulation via the mTORC1-ATF4 pathway activation contributes to palmitate-induced lipotoxicity in hepatocytes." American Journal of Physiology-Cell Physiology 321, no. 3 (September 1, 2021): C585—C595. http://dx.doi.org/10.1152/ajpcell.00195.2021.

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Defined as the dysfunction and/or cell death caused by toxic lipids accumulation in hepatocytes, hepatic lipotoxicity plays a pathological role in nonalcoholic fatty liver disease. The cellular and molecular mechanisms underlying lipotoxicity remain to be elucidated. In this study, using AML12 cells, a nontransformed murine hepatocyte cell line, exposed to palmitate (a 16-C saturated fatty acid) as an experimental model, we investigated the role and mechanisms of nicotinamide N-methyltransferase (NNMT), a methyltransferase catalyzing nicotinamide methylation and degradation, in hepatic lipotoxicity. We initially identified activating transcription factor 4 (ATF4) as a major transcription factor for hepatic NNMT expression. Here, we demonstrated that palmitate upregulates NNMT expression via activating ATF4 in a mechanistic target of rapamycin complex 1 (mTORC1)-dependent mechanism in that mTORC1 inhibition by both Torin1 and rapamycin attenuated ATF4 activation and NNMT upregulation. We further demonstrated that the mTORC1-dependent ATF4 activation is an integral signaling event of unfolded protein response (UPR) as both ATF4 activation and NNMT upregulation by tunicamycin, a well-documented endoplasmic reticulum (ER) stress inducer, are blunted when hepatocytes were pretreated with Torin1. Importantly, our data uncovered that NNMT upregulation contributes to palmitate-induced hepatotoxicity as NNMT inhibition, via either pharmacological (NNMT inhibitors) or genetic approach (siRNA transfection), provided protection against palmitate lipotoxicity. Our further mechanistic exploration identified protein kinase A (PKA) activation to contribute, at least, partially to the protective effect of NNMT inhibition against lipotoxicity. Collectively, our data demonstrated that NNMT upregulation by the mTORC1-ATF4 pathway activation contributes to the development of lipotoxicity in hepatocytes.
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Li, Guoli, Sining Fang, Xiao Shao, Yejia Li, Qingchao Tong, Beibei Kong, Lifen Chen, et al. "Curcumin Reverses NNMT-Induced 5-Fluorouracil Resistance via Increasing ROS and Cell Cycle Arrest in Colorectal Cancer Cells." Biomolecules 11, no. 9 (August 31, 2021): 1295. http://dx.doi.org/10.3390/biom11091295.

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Nicotinamide N-methyltransferase (NNMT) plays multiple roles in improving the aggressiveness of colorectal cancer (CRC) and enhancing resistance to 5-Fluorouracil (5-FU), making it an attractive therapeutic target. Curcumin (Cur) is a promising natural compound, exhibiting multiple antitumor effects and potentiating the effect of 5-FU. The aim of the present study is to explore the effect of Cur on attenuating NNMT-induced resistance to 5-FU in CRC. A panel of CRC cell lines with different NNMT expressions are used to characterize the effect of Cur. Herein, it is observed that Cur can depress the expression of NNMT and p-STAT3 in CRC cells. Furthermore, Cur can induce inhibition of cell proliferation, G2/M phase cell cycle arrest, and reactive oxygen species (ROS) generation, especially in high-NNMT-expression CRC cell lines. Cur can also re-sensitize high-NNMT-expression CRC cells to 5-FU both in vitro and in vivo. In summary, it is proposed that Cur can reverse NNMT-induced cell proliferation and 5-FU resistance through ROS generation and cell cycle arrest. Given that Cur has long been used, we suppose that Cur is a promising anticancer drug candidate with minimal side effects for human CRC therapy and can attenuate NNMT-induced resistance to 5-FU.
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Dissertations / Theses on the topic "NNMT"

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Giuliante, Rachela. "Caratterizzazione di cellule staminali tumorali ottenute da linee cellulari di carcinoma della laringe e di carcinoma della vescica." Doctoral thesis, Università Politecnica delle Marche, 2016. http://hdl.handle.net/11566/243113.

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Secondo la teoria delle cellule staminali tumorali, lo sviluppo del tumore sarebbe sostenuto dalla presenza di una distinta sottopopolazione di cellule tumorali, denominate cancer stem cells (CSCs), dotate della capacità di autorigenerarsi e di una spiccata resistenza agli agenti chemioterapici. Nel presente studio, è stato messo a punto un protocollo di crescita volto all’arricchimento in CSCs, mediante formazione di sfere, delle linee cellulari Hep-2 (carcinoma della laringe), T24 (carcinoma della vescica), MG63 (osteosarcoma), CaCo-2 (carcinoma del colon-retto) e A549 (carcinoma polmonare). Successivamente è stata effettuata un caratterizzazione molecolare e fenotipica delle popolazioni arricchite in CSCs, mediante rispettivamente l’analisi di espressione di markers di staminalità e la valutazione in vivo del potenziale tumorigenico. Inoltre, a carico delle CSCs e delle cellule di controllo, sono stati analizzati i livelli dell’enzima nicotinamide N-metiltrasferasi (NNMT). L’analisi immunocitochimica e mediante Real-Time PCR hanno evidenziato elevati livelli di espressione dei markers di staminalità nelle popolazioni cellulari arricchite in CSCs rispetto ai controlli. In seguito all’inoculo in topi atimici delle cellule relative alla linea Hep-2, la popolazione arricchita in CSCs dava luogo a masse tumorali di dimensioni maggiori rispetto a quelle originatesi dalle cellule di controllo, evidenza che suggerisce la spiccata capacità da parte delle CSCs di indurre la formazione in vivo di tumori. Le analisi condotte a carico dell’NNMT mostrano un’overespressione dell’enzima nelle popolazioni arricchite in CSCs rispetto ai controlli. In considerazione dell’importante ruolo svolto dalle CSCs nello sviluppo di recidive e nella diffusione metastatica, i risultati riportati in questo lavoro potrebbero contribuire allo sviluppo di nuove strategie terapeutiche per il trattamento del cancro e suggeriscono il significativo coinvolgimento dell’NNMT nel metabolismo della cellula neoplastica.
According to cancer stem cells theory, tumor development would be maintained by a distinct subpopulation of tumor cells, termed cancer stem cells (CSCs), that have the ability to self-renew and to resist to chemotherapeutic agents. In the present study, we setup a culture system to enrich CSCs from Hep-2 (laryngeal cancer), T24 (bladder cancer), MG63 (osteosarcoma), CaCo-2 (colorectal cancer) and A549 (lung cancer) cancer cell lines, through sphere formation. We further performed molecular and phenotypic characterization of CSC-enriched cell populations, by exploring the expression levels of stem markers and in vivo evaluating their tumorigenic potential, respectively. Moreover, we investigated the expression levels of the enzyme nicotinamide N-methyltransferase (NNMT) in CSCs and parental cells. Real-Time PCR and immunocytochemistry revealed that CSC-enriched populations showed increased expression levels of stem markers compared with controls. After subcutaneous injection of Hep-2 cells into immunocompromised mice, CSC-enriched population yielded tumors of a much larger size compared with those generated by parental cells, suggesting the strong ability of CSCs to form tumors in vivo. NNMT expression analysis revealed enzyme upregulation in CSC-enriched populations compared to parental counterpart. Considering the fundamental role of CSCs in tumor relapse and onset of metastases, findings reported in this work could contribute to the development of new therapeutic strategies for cancer treatment and suggest an important involvement of NNMT in cancer cell metabolism.
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Pozzi, Valentina. "L'enzima nicotinamide N-Metiltrasferasi: un nuovo marker diagnostico e target terapeutico nel carcinoma orale." Doctoral thesis, Università Politecnica delle Marche, 2011. http://hdl.handle.net/11566/241870.

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Il carcinoma squamocellulare (OSCC) rappresenta la lesione neoplastica più frequente nella cavità orale. Nonostante i progressi effettuati in campo sia chirurgico sia terapeutico, la sopravvivenza media a 5 anni si mantiene ancora al di sotto del 50%. La ricerca di marcatori molecolari coinvolti nella progressione neoplastica risulta essere quindi di primaria importanza. In relazione a studi precedentemente condotti, che hanno portato all’identificazione dell’enzima Nicotinamide N-metiltrasferasi (NNMT) quale potenziale marker di alcune tipologie di tumore, è risultato interessante intraprendere uno studio dell’espressione dell’NNMT nel carcinoma orale squamocellulare. Tale analisi è stata condotta su campioni di tessuto orale sano e canceroso relativi a pazienti affetti da OSCC, affrontando uno studio sia a carico del mRNA mediante RT-PCR e Real-Time PCR, sia a carico della proteina mediante Western blot, analisi immunoistochimiche e saggio di attività enzimatica. Allo scopo di esplorare il coinvolgimento dell’NNMT nel metabolismo della cellula tumorale, sono stati successivamente effettuati esperimenti di silenziamento dell’enzima in una linea cellulare di carcinoma orale; le cellule trasfettate e quelle di controllo sono state in seguito inoculate in topi nudi. I risultati ottenuti hanno consentito di osservare un aumento significativo dell’espressione dell’NNMT (tessuto tumorale vs mucosa sana) nella maggior parte dei soggetti privi di metastasi, mentre nei casi che presentavano metastasi linfonodali l’NNMT non sembrava subire marcate alterazioni della sua espressione. L’analisi immunoistochimica ha confermato l’overespressione della proteina nei campioni di OSCC rispetto ai campioni di mucosa sana dove il segnale era quasi o del tutto assente. Inoltre l’aumento di espressione dell’NNMT risultava più marcato nei campioni di tumore moderatamente o ben differenziato rispetto ai campioni di tumore indifferenziato. I risultati ottenuti mediante saggio di attività catalitica hanno indicato un aumento dei livelli di attività dell’enzima nel tessuto tumorale nella quasi totalità dei campioni esaminati. Il silenziamento dell’NNMT effettuato su cellule di carcinoma orale ha comportato una diminuzione della crescita cellulare e della capacità di formare colonie in assenza di adesione al substrato. Gli esperimenti condotti sui topi atimici hanno mostrato come l’inoculo delle cellule trasfettate nelle quali il gene NNMT era stato silenziato determinava la formazione di masse tumorali di dimensioni marcatamente ridotte rispetto a quelle ottenute in seguito all’inoculo delle cellule di controllo. L’elevata espressione dell’NNMT nel carcinoma squamocellulare sembrerebbe indicare che l’enzima possa svolgere una funzione importante nel processo di oncogenesi orale. L’esistenza di una correlazione inversa tra i livelli di espressione dell’NNMT in OSCC (tumore versus mucosa sana) e la presenza di metastasi supporta l’ipotesi secondo la quale l’enzima possa svolgere un importante ruolo nell’invasione neoplastica, candidandolo a potenziale marcatore prognostico di tale neoplasia. L’identificazione di una correlazione inversa tra i livelli di espressione dell’NNMT e il grado istologico suggerisce un possibile ruolo dell’enzima nelle fasi iniziali dell’oncogenesi. I risultati delle analisi di attività enzimatica consentono inoltre di candidare l’NNMT quale possibile marcatore diagnostico di tale tipologia neoplastica. I risultati ottenuti in seguito agli esperimenti di silenziamento ed analisi in vivo evidenziano un coinvolgimento dell’enzima NNMT nella proliferazione cellulare. Il silenziamento di tale enzima comporta infatti una riduzione della capacità proliferativa e del potenziale tumorigenico della cellula neoplastica; la sua inibizione potrebbe quindi rappresentare un possibile approccio molecolare alla terapia del carcinoma orale.
Oral squamous cell carcinoma (OSCC) is the most common malignancy of oral cavity. In recent 50 years, despite the advances in surgery and adjuvant therapies, the 5-year mortality rate of oral cancer is about 50% around the world. Up to now, reliable biomarkers for OSCC are still lacking. Therefore, it is necessary to identify target molecules for effective therapy and for early diagnosis of OSCC. In the present study, we focused on the expression of Nicotinamide N-Methyltransferase (NNMT), which catalyses the N-methylation of nicotinamide, pyridines and other structural analogs, playing an important role in the biotransformation and detoxification of many xenobiotics. Several tumours have been associated with abnormal NNMT expression. However its role in tumour development remains largely unknown. To explore the involvement of NNMT in OSCC, we analysed the enzyme expression in tumour and non-tumour oral tissues obtained at surgery by RT-PCR, Real-Time PCR, Western blot, immunoistochemical analysis and catalytic activity assay. We also evaluated the effect of shRNA-mediated inhibition of NNMT on the proliferative potential of an oral cancer cell line. Transfected and normal oral cells were injected into athymic mices in order to evaluated the effect of NNMT silencing on tumour growth. The results showed a significant increase of NNMT expression (tumour tissue vs normal mucosa) in most of the favourable OSCCs (N0), while no marked NNMT expression alteration between tumour and normal mucosa was detected in most of metastatic tissues (N+). Immunohistochemical analyses performed on paraffin-embedded samples of oral cancer and normal mucosa indicated a significant NNMT upregulation in the examined OSCCs, that was more evident in well- and moderately-differentiated cases than in undifferentiated ones. Consistent with the results of immunoistochemistry, NNMT specific activity values were significantly higher in OSCCs than in control samples. ShRNA vectors targeted against NNMT efficiently suppressed gene expression, showing an inhibition rates around 70%, observed at both the mRNA and protein levels. Down-regulation of NNMT significantly inhibited cell proliferation and decreased colony formation ability on soft agar. In athymic mices NNMT silencing effectively induced a drastic reduction in tumour volume, suggesting the involvement of the enzyme in cancer development. The present data support the hypothesis that NNMT plays a role in oral carcinogenesis and represents a highly promising marker for early detection of oral cancer. The results obtained from silencing and in vivo experiments seem to suggest that NNMT is involved in cell proliferation and its inhibition could represent a possible molecular approach to the treatment of oral cancer.
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SETA, RICCARDO. "Overexpression and silencing of nicotinamide N-methyltransferase in human cancer cell lines." Doctoral thesis, Università Politecnica delle Marche, 2017. http://hdl.handle.net/11566/245439.

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Il carcinoma polmonare rappresenta la principale causa di morte per cancro a livello mondiale. Il carcinoma orale rappresenta l’undicesima neoplasia più diffusa nel mondo. Nonostante i progressi effettuati in campo terapeutico, il tasso di sopravvivenza dei pazienti affetti da tali patologie rimane scarsa. Pertanto, risulta di fondamentale importanza l’identificazione di biomarcatori per una diagnosi precoce di tali neoplasie. Oggetto del presente lavoro di ricerca è l’enzima nicotinamide N-metiltrasferasi (NNMT). Al fine di esplorare il ruolo svolto dall’enzima nel metabolismo della cellula tumorale, i livelli di espressione dell’NNMT sono stati esaminati nella linea cellulare di carcinoma polmonare A549 ed è stato valutato l’effetto del silenziamento dell’enzima sulla tumorigenicità mediante il saggio MTT ed il saggio in soft-agar. Successivamente, è stato esaminato l’effetto dell’upregolazione dell’enzima sulla proliferazione cellulare nella linea cellulare di carcinoma orale HSC-2. Inoltre, è stato esplorato l’effetto dell’overespressione dell’NNMT sui livelli di espressione di geni coinvolti nel controllo del ciclo cellulare e dell’apoptosi, quali la β-catenina, Ki-67 e la survivina. Il silenziamento dell’NNMT nelle cellule A549 ha portato ad una significativa inibizione della proliferazione cellulare e della capacità di formare colonie in soft-agar, mentre l’overespressione dell’enzima nelle cellule HSC-2 ha determinato un significativo aumento della crescita cellulare. Inoltre, l’isoforma ΔEx3 della survivina è risultata significativamente upregolata nelle cellule HSC-2 overesprimenti l’NNMT. I risultati ottenuti hanno dimostrato il coinvolgimento dell’NNMT nella proliferazione della cellula tumorale, candidando l’enzima quale interessante bersaglio per una terapia antineoplastica. Inoltre, la correlazione osservata tra i livelli di espressione dell’NNMT e dell’isoforma ΔEx3 della survivina sembra suggerire un potenziale ruolo dell’NNMT nell’apoptosi.
Lung cancer is the leading cause of tumor-related death worldwide. As the majority of patients are diagnosed at a late stage, current therapeutic strategies have limited effectiveness and the prognosis remains poor. Oral cancer is the 11th most common tumor in the world. Despite advances in cancer therapy, the 5-year survival rate has not improved in the last three decades. Therefore, the identification of biomarkers for early diagnosis and treatment of these neoplasms are needed. The present study is focused on the enzyme nicotinamide N-methyltransferase (NNMT). To explore the role of the enzyme in cancer cell metabolism, we first examined NNMT expression levels in the human lung cancer cell line A549 by Real-Time PCR, Western blot and catalytic activity assay, and evaluated the in vitro effect of NNMT knockdown on tumorigenesis by MTT and soft agar colony formation assays. Subsequently, the effect of enzyme upregulation on cell proliferation was explored in the human oral cancer cell line HSC-2. Moreover, apoptosis and cell proliferation were investigated at molecular level, by evaluating the effect of NNMT overexpression on β-catenin, survivin isoforms, and Ki-67 expression. NNMT knockdown in A549 cells led to a significant inhibition of cell proliferation and colony formation ability on soft agar, while upregulation of the enzyme in HSC-2 cells significantly increased cell growth. Moreover, a positive correlation between NNMT and survivin-ΔEx3 isoform expression levels was found in HSC-2 cells. Results obtained demonstrated a potential involvement of NNMT in proliferation and tumorigenic capacity of both lung and oral cancer cells, thus representing an interesting molecular target for an effective anti-cancer therapy. Moreover, the possible correlation observed between NNMT and survivin-ΔEx3 expression levels seems to suggest a potential role of the enzyme in the regulation of apoptosis.
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Morganti, Stefano. "Identificazione dell'enzima Nicotinamide N-Metiltrasferasi quale marker molecolare del carcinoma polmonare non a piccole cellule." Doctoral thesis, Università Politecnica delle Marche, 2014. http://hdl.handle.net/11566/242767.

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Il carcinoma polmonare rappresenta la neoplasia più diffusa a livello mondiale e la principale causa di morte per cancro. L’aumento del tasso di sopravvivenza dei pazienti affetti da tale patologia è affidato ai progressi compiuti in campo chirurgico e terapeutico, nonché all’identificazione di nuovi marcatori per una diagnosi precoce. Oggetto del presente lavoro di ricerca è l’enzima nicotinamide N-metiltrasferasi (NNMT). I livelli di espressione dell’NNMT sono stati valutati nel tessuto polmonare tumorale e nel tessuto peritumorale prossimo e lontano, rispetto al margine della neoplasia, di 36 pazienti affetti da carcinoma polmonare non a piccole cellule (NSCLC) mediante Real-Time PCR, Western blot, analisi immunoistochimica e saggio di attività catalitica. Allo scopo di esplorare il coinvolgimento dell’NNMT nel metabolismo della cellula tumorale, è stato effettuato il silenziamento dell’NNMT mediante l’impiego di plasmidi codificanti shRNA ed è stato valutato l’effetto di tale downregolazione sulla proliferazione cellulare e sul potenziale tumorigenico della linea cellulare di carcinoma polmonare A549. I risultati ottenuti evidenziano un aumento dell’espressione dell’NNMT (mRNA e proteina) nel tessuto tumorale rispetto al tessuto peritumorale prossimo e lontano dal margine della neoplasia. Inoltre, il tessuto tumorale mostra livelli di attività specifica significativamente più elevati rispetto al tessuto peritumorale prossimo e lontano dalla neoplasia. In particolare, il tessuto polmonare peritumorale, sia prossimo che lontano dal margine della neoplasia dei casi sfavorevoli (N+), mostra livelli di attività nicotinamide N-metiltrasferasica più elevati rispetto a quelli rilevabili a carico degli stessi tessuti relativi ai casi favorevoli (N0), suggerendo che a livello molecolare il tessuto peritumorale dei casi sfavorevoli (N+) si trova in una fase, seppur estremamente precoce, della trasformazione neoplastica. Il silenziamento dell’NNMT ha determinato una diminuzione significativa della proliferazione cellulare e della capacità di formare colonie in assenza di adesione al substrato. I dati riportati nel presente lavoro indicano che l’NNMT rappresenta un marcatore molecolare del carcinoma polmonare non a piccole cellule e supportano l’ipotesi secondo la quale esso possa svolgere un ruolo importante nella crescita del tumore e nell’invasione neoplastica. Successivi studi saranno rivolti a chiarire se l’NNMT possa rappresentare un potenziale bersaglio di una terapia antineoplastica.
Lung cancer is the most common neoplasm worldwide and the leading cause of tumor death. Improvements in surgery and therapy, as well as the discovery of new and effective markers for an early diagnosis, are necessary to increase the overall survival rate. This study is focused on the enzyme nicotinamide N-methyltransferase (NNMT). NNMT expression levels were evaluated in tumor, tumor-adjacent and surrounding tissue samples of 36 patients with non-small cell lung carcinoma (NSCLC) by Real-Time PCR, Western blot analysis, catalytic activity assay and immunohistochemical analysis. To explore the involvement of NNMT in tumor cell metabolism, we evaluated the effect of shRNA-mediated inhibition of NNMT on cell proliferation and tumorigenic potential of A549 lung cancer cell line. Results obtained showed NNMT upregulation (mRNA and protein) in tumor compared with both tumor-adjacent and surrounding tissue. Moreover, NSCLC displayed significantly higher activity levels than those determined in both tumor-adjacent and surrounding tissue. Interestingly, both tumor-adjacent and surrounding tissue samples of unfavorable cases (N+) seem to display higher activity levels than those of favorable NSCLCs (N0), suggesting that normal-looking tissue of unfavorable cases seems to change toward cancer. NNMT downregulation significantly inhibited cell proliferation and reduced colony formation ability on soft agar. Reported data indicate that NNMT represents a molecular marker for non-small cell lung carcinoma and support the hypothesis that it could play an important role in tumor growth and invasion. Further studies may establish whether NNMT could represent a target for an effective anti-cancer therapy.
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CAMPAGNA, ROBERTO. "Nicotinamide N-Methyltransferase Inhibition in Endothelium: Effect on Cell Viability and Respiration." Doctoral thesis, Università Politecnica delle Marche, 2019. http://hdl.handle.net/11566/263472.

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An impairment of the vascular endothelium plays a role, either as a primary cause or as a result of organ damage, in most of human diseases. Despite intensive research, molecular mechanisms underlying endothelial dysfunction remain unclear. Potential factors affecting normal endothelial functions could be nicotinamide N-methyltransferase (NNMT) and 1-Methylnicotinamide (MNA). The aim of this work was to explore the role of NNMT in endothelial cells subjected to different types (models) of stressors. Experiments were performed with the use of endothelial cells EA.hy926 in which the NNMT expression was silenced. For EA.hy926 stable transfection, it was used a set of pLKO.1 vectors containing stem-loop cassettes encoding short hairpin RNA (shRNA) targeted to human NNMT. NNMT silenced cells were incubated with increasing concentrations of menadione, ONOO- and H2O2 for 24h and data obtained showed a significant decrease of cell viability in NNMT silenced cell lines compared to controls. Subsequently, metabolic function was evaluated through the Seahorse technology. Surprisingly, NNMT silenced lines showed reduced levels of mitochondrial respiration parameters compared to control line EAhy.926. In the second part of the work, results obtained were confirmed by using Human Aortic Endothelial Cells (HAEC) primary line, in which the MNA production was repressed by novel NNMT inhibitors 5-Amino-1-methylquinoline and 6-Methoxynicotinamide N-methylated. Consistently with data obtained on NNMT silenced EAhy.926 cells, menadione-treated HAECs incubated with NNMT inhibitors showed a significant decrease of cell viability compared to controls. Experiments of Seahorse technology revealed reduced levels of mitochondrial respiration parameters in HAECs treated with NNMT inhibitors compared to control. Taken together, data obtained suggest a possible involvement of NNMT in the bioenergetic regulation of endothelial cells and confirm the protective role of the enzyme in the endothelium.
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Kiohara, Valéria de Oliveira. "Estudo teórico dos aglomerados NnMm (N; M = Si, Ge, Al,Ga; n+m ? 4)." Instituto Tecnológico de Aeronáutica, 2013. http://www.bd.bibl.ita.br/tde_busca/arquivo.php?codArquivo=2754.

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Os materiais formados pelos elementos do grupo 13 e 14 da tabela periódica são de grande importância na construção de componentes eletrônicos como diodos e transistores. Por meio da deposição por vapor químico, quantidades controladas de átomos (boro, por exemplo) são introduzidas para modificar a estrutura eletrônica de aglomerados formados por outros elementos (o silício, por exemplo). Neste trabalho, foram realizados estudos para os aglomerados NnMm (N,M = Si, Ge, B, Al, Ga), com n + m ? 4, utilizando o método da teoria da perturbação de Møller-Plesset em segunda ordem (MP2), o método coupled cluster com excitações simples e duplas e triplas conectadas (CCSD(T)) e o método B3LYP baseado na teoria do funcional da densidade com os conjuntos de base cc-pVTZ e cc-pVQZ. Os resultados CCSD(T) foram extrapolados para o limite do conjunto de base completo (CBS, do inglês complete basis set). Os resultados CCSD(T)/CBS estão de acordo com os valores experimentais encontrados. Vários aglomerados foram estudados pela primeira vez. Para os aglomerados contendo apenas alumínio, verificou-se um caráter multiconfiguracional moderado, enquanto os funcionais com maior porcentagem de correlação Hartree-Fock apresentaram bom desempenho comparados aos valores CCSD(T)/CBS e em concordância com os resultados experimentais existentes.
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Mak, Rachel Y. C. "Reducing Complexity| A Regularized Non-negative Matrix Approximation (NNMA) Approach to X-ray Spectromicroscopy Analysis." Thesis, Northwestern University, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3669280.

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X-ray absorption spectromicroscopy combines microscopy and spectroscopy to provide rich information about the chemical organization of materials down to the nanoscale. But with richness also comes complexity: natural materials such as biological or environmental science specimens can be composed of complex spectroscopic mixtures of different materials. The challenge becomes how we could meaningfully simplify and interpret this information. Approaches such as principal component analysis and cluster analysis have been used in previous studies, but with some limitations that we will describe. This leads us to develop a new approach based on a development of non-negative matrix approximation (NNMA) analysis with both sparseness and spectra similarity regularizations. We apply this new technique to simulated spectromicroscopy datasets as well as a preliminary study of the large-scale biochemical organization of a human sperm cell. NNMA analysis is able to select major features of the sperm cell without the physically erroneous negative weightings or thicknesses in the calculated image which appeared in previous approaches.

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Vignoli, Benedetto Gabriele. "Optimization of the Security Incident Management plan of NNIT A/s via the Integration of the Vulnerability Reports Creator." Thesis, KTH, Skolan för informations- och kommunikationsteknik (ICT), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-190116.

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Modern IT companies manage security of their customers'networks following particular models, processes and procedures. In this thesis are presented the most important and widespread guidelines on Security Incident Response Plans as well as the implementation of a software for an IT danish company called NNIT. In particular, this software aims to improve NNIT's Security Incident Management Process generating automatic reports of vulnerabilities found in NNIT clients networks. Enhancing this process reducing its execution time is directly translated into a proactive response where vulnerabilities are tackled and patched before an attacker could exploit them. The software developed and described in this thesis is called VRC and thanks to a particular algorithm analyzes the database of vulnerabilities found by the vulnerability scanner and produces customizable reports. In the reports, the list of vulnerabilities is ordered by severity and number of machines a ected in order to present the most urgent vulnerabilities that should be xed. Finally, an evaluation of the VRC performance and usefulness is also included.
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Bodoni, Aline Faccioli. "Estresse oxidativo mitocondrial e deficiência familiar de glicocorticoide: caracterização fenotípica e funcional da nova variante p.G866D no gene Nicotinamide Nucleotide Transidrogenase (NNT)." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/17/17144/tde-23032018-131353/.

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Introdução: a proteína mitocondrial codificada pelo gene Nicotinamide Nucleotide Transidrogenase (NNT) regula o processo intramitocondrial de desintoxicação de espécies reativas de oxigênio (EROs). Defeitos na homeostase desse sistema (sistema Redox) podem comprometer a esteroidogênese adrenal. Objetivo: caracterizar o impacto funcional da nova variante missense NNT p.G866D (c.2597G>A) e sua associação com o fenótipo de deficiência familiar de glicocorticoide (DFG). Indivíduos e Métodos: Caso índice: lactente com DFG diagnosticada aos 18 meses, seus pais e irmão assintomáticos e controles saudáveis. O ácido desoxirribonucleico (DNA) genômico do caso índice foi submetido a sequenciamento exômico que revelou, entre algumas variantes gênicas-candidatas, a variante (c.2597G> A; p.G866D) em homozigose no exon 17 do gene NNT. Avaliou-se a segregação familiar dessa variante com o fenótipo de DFG. A análise funcional in vitro dessa variante foi realizada em cultura transitória de células mononucleares sanguíneas do paciente, heterozigotos e controles em condição basal e após a indução do estresse oxidativo com 100?m de H2O2 por cinco horas. A expressão do RNAm do gene NNT nessas células foi realizada por meio de qPCR. Os parâmetros mitocondriais avaliados foram: a produção intracelular de espécies reativas de oxigênio (EROS) detectadas por CMDCFDA, a concentração de glutationa reduzida (GSH) e ATP celular medidos ensaios luminescentes, , além da massa e potencial de membrana mitocondrial avaliados com o probe MitoTracker. Resultados: A análise de segregação familiar confirmou a segregação desta variante em homozigose com o fenótipo de DFG. A expressão do NNT RNAm foi semelhante entre paciente, heterozigotos e controles. Em homozigose a variante p.G866D no gene NNT causa aumento na produção de EROs, diminuição de GSH e diminuição da massa e potencial de membrana mitocondrial, tanto em condições basais, quanto após a indução de estresse oxidativo. Após a indução de estresse oxidativo as concentrações de ATP foram menores no homozigoto NNT p.G866D do que nos controles. Conclusão: este estudo confirma a associação da variante NNT em homozigose com o fenótipo de DFG Tipo quatro. In vitro o mutante homozigoto NNT p.G866D reduz significativamente os mecanismos de defesas antioxidantes, comprometendo o sistema da glutationa redutase, levando ao acúmulo de EROs.
Background: mitochondrial Nicotinamide Nucleotide Transidrogenase (NNT) is essential in the intracellular reactive oxygen species (ROS) detox process. Defects in this system may impair adrenal steroidogenesis by yet not fully understood mechanism. Aim: we sought to characterize the functional impact of the new NNT p.G866D (c.2597G>A) variant and its association with familial glucocorticoid deficiency (FGD). Subjects and Methods: evaluated subjects included the index case diagnosed with FGD at the age of 18 months, his asymptomatic parents and young brother and healthy controls. The Index case genomic DNA was evaluated by whole exome sequencing, which revealed several potential candidate variants, including the homozygous NNT p.G866D. We then analyzed the family pedigree to confirm the segregation of this variant with FDG phenotype. To prove the genotype-phenotype association, this new variant was comprehensive evaluated in vitro. Transient mononuclear cell cultures from the patient, family members and controls were performed both in basal conditions and after oxidative stress induced by 5-hours treatment with 100?m de H2O2. We analyzed NNT RNAm expression by qPCR and mitochondrial parameters including ROS intracellular production by 20, 70-diacetate dichlorodihydrofluorescein, reduced glutathione (GSH) and cellular ATP levels by luminescence, and mitochondrial mass and mitochondrial membrane potential by Mitotraker Probe system. Results: family pedigree analysis confirmed the segregation of the homozygous NNT p.G866D variant with FGD. In vitro, no differences in RNAm expression was found among patients, heterozygous carriers and healthy controls. Both in basal and under stress conditions, the homozygous p.G866D NNT variant exhibited significantly increased ROS production, decreased GSH levels and decreased mitochondrial parameters. In addition, under H2O2 oxidative stress, the homozygous p.G866D NNT also leaded in decreased ATP intracellular . Conclusion: this study clearly confirms the association of the homozygous NNT p.G866D variant with the phenotype of FGD. In vitro, this variant significantly impairs anti-oxidants mechanisms and affects the glutathione reductase systems resulting in increased ROS accumulation.
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Villarreal, Carlo Arlan. "An analysis of the reliability and validity of the Naglieri Nonverbal Ability Test (NNAT) with English language Learner (ELL) Mexican American children." Texas A&M University, 2003. http://hdl.handle.net/1969.1/3850.

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The purpose of this study was to investigate the reliability and validity of the results of the Naglieri Nonverbal Ability Test (NNAT; Naglieri, 1997a) with a sample of English Language Learner (ELL) Mexican American children and to compare the performance on the NNAT of 122 ELL Mexican American children with children from the standardization sample. The rationale for conducting this study was the need to identify culturally sensitive and technically adequate nonverbal measures of ability for the fastest growing minority group within America’s public schools today, Mexican American children. The NNAT was administered to participants with parental consent. Statistical analyses of the scores did yield positive evidence of internal consistency for the Nonverbal Ability Index (NAI) total score of the NNAT. However, when individual clusters were analyzed, Pattern Completion, Reasoning by Analogy, and Serial Reasoning did not yield positive evidence of internal consistency. Only Spatial Visualization approached the reliability standard deemed acceptable for tests of cognitive ability. The mean differences of the NNAT scores between two independent groups were also assessed in the present study. Results of the statistical analyses did not yield statistically significant differences across age and grade factors between the scores of the ELL Mexican American sample and the standardization sample. Finally, the proposed factor structure of the NNAT was compared with the factor structure found with the ELL Mexican American sample. Goodness-of-fit test statistics indicate that the proposed four-factor structure does not fit well with the data obtained from this sample of ELL Mexican American students. Furthermore, although the NNAT is considered to be a unidimensional test of general ability, nine factors were extracted upon analysis, providing evidence that the items on each of the four clusters do not function together as four distinct dimensions with this ELL Mexican American sample. Given that the individual clusters that collectively combine to yield the NAI total score are not based on any particular model of intelligence, interpretation of specific strengths and weaknesses should be discouraged. Finally, the NNAT’s overall score should be interpreted with caution and may best be used in conjunction with multidimensional ability and/or intelligence measures.
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Books on the topic "NNMT"

1

María Esther del Moral Pérez. Reflexiones sobre NNTT y educación. [Spain]: Universidad de Oviedo, Servicio de Publicaciones, 1998.

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National Naval Medical Center (U.S.), ed. Sharing the vision: "innovations in care", NNMC Transformation 2000. [Washington, D.C.?]: National Naval Medical Center, 2000.

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Inc, ebrary, ed. HP Network Node Manager 9: Getting started : manage your network effectively with NNMi. Birmingham, U.K: Packt Enterprise, 2011.

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Hansel, Troy. Nakai-Nam Theun Conservation Project, phase 2: NNT NBCA staff training and capacity building on extension techniques for participatory conservation. [Viangchan]: IUCN, 1998.

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NNAT Grade 3 NNAT 3 Level D : NNAT Practice Test 1: NNAT3 Grade 3 Level DC Test Prep Book for the Naglieri Nonverbal Ability Test. Gifted & Talented NNAT Test Prep Team, 2019.

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LLC, Math-Knots. NNAT - Grade 1 - VOL - 2 - TESTS - 3 & 4. Math-Knots LLC, 2020.

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Resources, Gateway Gifted. Gifted and Talented NNAT Test Prep: Gifted test prep book for the NNAT; Workbook for children in preschool and kindergarten. Gateway Gifted Resoures, 2016.

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Gifted and Talented NNAT Test Prep Team and Origins Publications. 2 Practice Tests for the NNAT Grade 1 NNAT 3 Level B : Practice Tests 1 and 2: NNAT 3 Grade 1 Level B Test Prep Book for the Naglieri Nonverbal Ability Test. Origins Tutoring, 2019.

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LLC, Math-Knots. NNAT - Grade 1 - VOL - 1 - TESTS - 1 And 2. Math-Knots LLC, 2020.

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Practice Test for the Naglieri Nonverbal Ability Test® (NNAT®) Level D. Mercer Publishing, 2008.

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Book chapters on the topic "NNMT"

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Andrews, Anne M., Greg A. Gerhardt, Lynette C. Daws, Mohammed Shoaib, Barbara J. Mason, Charles J. Heyser, Luis De Lecea, et al. "NNT." In Encyclopedia of Psychopharmacology, 901. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_4421.

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Ewing, Jan, Ron Estes, and Brandon Like. "Narrative Neurotherapy (NNT)." In Collaborative Therapy and Neurobiology, 87–99. New York, NY : Routledge, 2017: Routledge, 2017. http://dx.doi.org/10.4324/9781315622484-8.

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Saxén, Björn, and Henrik Saxén. "NNDT — A Neural Network Development Tool." In Artificial Neural Nets and Genetic Algorithms, 325–28. Vienna: Springer Vienna, 1995. http://dx.doi.org/10.1007/978-3-7091-7535-4_85.

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Brunetti, Jacopo, Walter D’Ambrogio, Annalisa Fregolent, and Francesco Latini. "Substructuring Using NNMs of Nonlinear Connecting Elements." In Lecture Notes in Mechanical Engineering, 1426–40. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-41057-5_116.

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Skitalinskaya, Gabriella, and John Cardiff. "Multilabel Text Classification of Unbalanced Datasets: Two-Pass NNMF." In Computational Linguistics and Intelligent Text Processing, 275–86. Cham: Springer Nature Switzerland, 2023. http://dx.doi.org/10.1007/978-3-031-23804-8_22.

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Jerschl, Martin, Dominik Süß, and Kai Willner. "Studies of a Geometrical Nonlinear Friction Damped System Using NNMs." In Dynamics of Coupled Structures, Volume 4, 341–48. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-29763-7_33.

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VanDamme, Christopher I., and Matthew S. Allen. "Using NNMs to Evaluate Reduced Order Models of Curved Beam." In Rotating Machinery, Hybrid Test Methods, Vibro-Acoustics & Laser Vibrometry, Volume 8, 457–69. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-30084-9_42.

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Jarman, Lucas M., Chris VanDamme, and Mathew S. Allen. "Nonlinear Dynamic Analysis of a Thermally Buckled Aircraft Panel Using NNMs." In Shock & Vibration, Aircraft/Aerospace, Energy Harvesting, Acoustics & Optics, Volume 9, 59–69. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-54735-0_7.

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Ecard, V. C., L. L. Menegaldo, and L. F. Oliveira. "NNMF Analysis to Individual Identification of Fingers Movements Using Force Feedback and HD-EMG." In XXVII Brazilian Congress on Biomedical Engineering, 477–83. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-70601-2_74.

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Monteverde Videla, Alessandro H. A., Luigi Osmieri, and Stefania Specchia. "Non-noble Metal (NNM) Catalysts for Fuel Cells: Tuning the Activity by a Rational Step-by-Step Single Variable Evolution." In Electrochemistry of N4 Macrocyclic Metal Complexes, 69–101. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-31172-2_3.

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Conference papers on the topic "NNMT"

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Eckert, Mark A., Fabian Coscia, Shawn Pan, Samantha M. Tienda, Agnieszka A. Chryplewicz, Chun-Yi Chiang, Anthony Montag, S. Diane Yamada, Matthias Mann, and Ernst R. Lengyel. "Abstract 5899: Compartment-resolved proteomics reveal NNMT as a master metabolic regulator of cancer associated fibroblasts." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-5899.

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Kaul, Kumud, and Pravir Kumar. "Fate of Jeratinine E as a potential compound to target NNMT protein in countering Parkinson’s disease." In 2023 2nd International Conference on Smart Technologies and Systems for Next Generation Computing (ICSTSN). IEEE, 2023. http://dx.doi.org/10.1109/icstsn57873.2023.10151586.

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Dolcen, Deniz N., Bryan Harada, Chuan He, and Suzanne D. Conzen. "Abstract 1290: Role of NNMT-regulated m6A mRNA modification in triple-negative breast cancer oncogenic gene expression." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-1290.

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Kanska, Justyna, Barbie Taylor-Harding, Paul-Joseph Aspuria, Beth Y. Karlan, Simon Gayther, and W. Ruprecht Wiedemeyer. "Abstract TMEM-026: ZEB1–MEDIATED NNMT EXPRESSION ELICITS PHENOTYPIC AND METABOLIC PLASTICITY OF OVARIAN CANCER CELLS UNDER NUTRITIONAL STRESS." In Abstracts: 11th Biennial Ovarian Cancer Research Symposium; September 12-13, 2016; Seattle, WA. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1557-3265.ovcasymp16-tmem-026.

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5

Zhang, Xinhua. "On the Resonant Nonlinear Normal Modes." In ASME 2009 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. ASMEDC, 2009. http://dx.doi.org/10.1115/detc2009-86706.

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The resonant nonlinear normal modes (NNMs) of a 2-dof conservative vibratory system is investigated in this paper. Three different approaches, the modified Adomian decomposition method, the variational method and the numerical NNM determination method are exploited respectively for constructing the NNM manifolds. Being different from the results reported in the literatures, new resonant NNM is obtained via these methods and for the 2-dof vibratory system considered herein, there is no NNM bifurcation, the number of the NNMs of this system is always equal to two.
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6

Panunzio, Alfonso M., Loïc Salles, Christoph Schwingshackl, and Muzio Gola. "Asymptotic Numerical Method and Polynomial Chaos Expansion for the Study of Stochastic Non-Linear Normal Modes." In ASME Turbo Expo 2015: Turbine Technical Conference and Exposition. American Society of Mechanical Engineers, 2015. http://dx.doi.org/10.1115/gt2015-43560.

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Nonlinear normal mode (NNM) analysis is one emerging technique to analyse the nonlinear vibration of bladed-disk. It links the resonance frequency to the energy present in the system, and allows a simple identification of internal resonances in the structure. Non-linear vibration analysis is traditionally carried out under the assumption that the mechanical properties and forcing function are deterministic. Since every mechanical system is by nature uncertain a truly accurate nonlinear dynamic analysis requires the inclusion of random variables in the response predictions. The propagation of random input uncertainties in a NNM analysis is the main aim of the presented work. The Asymptotic Numerical Method (ANM) will be used to calculate the NNMs for a contact problem in a computationally efficient way. The stochastic NNM permits to quantify the effect of uncertainties on the resonance frequency and the change in mode shape due to non-linearities, leading to the calculation of uncertain internal resonances. The proposed method is initially applied to a simple spring-mass system to demonstrate the effects of uncertainty on the NNM predictions. In a second step a blade-casing interaction with localized contact non-linearity is investigated with a real geometry. The resulting NNMs show the presence of internal resonance for both cases.
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7

Kuether, Robert J., and Matthew S. Allen. "Computing Nonlinear Normal Modes Using Numerical Continuation and Force Appropriation." In ASME 2012 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/detc2012-71257.

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Many structures can behave nonlinearly, exhibiting behavior that is not captured by linear vibration theory such as localization and frequency-energy dependence. The nonlinear normal mode (NNM) concept, developed over the last few decades, can be quite helpful in characterizing a structure’s nonlinear response. In the definition of interest, an NNM is a periodic solution to the conservative nonlinear equations of motion. Several approaches have been suggested for computing NNMs and some have been quite successful even for systems with hundreds of degrees of freedom. However, existing methods are still too expensive to employ on realistic nonlinear finite element models, especially when the Jacobian of the equations of motion is not available analytically. This work presents a new approach for numerically calculating nonlinear normal modes by combining force appropriation, numerical integration and continuation techniques. This method does not require gradients, is found to compute the NNMs accurately up to moderate response amplitudes, and could be readily extended to experimentally characterize nonlinear structures. The method is demonstrated on a nonlinear mass-spring-damper system, computing its NNMs up to a 35% shift in frequency. The results are compared with those from a gradient based algorithm and the relative merits of each method are discussed.
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Yu, Xiang, Shi-Jian Zhu, and Shu-Yong Liu. "Nonlinear Normal Modes for Multi-Degree-of-Freedom Nonlinear Vibration Isolation System." In ASME 2006 International Mechanical Engineering Congress and Exposition. ASMEDC, 2006. http://dx.doi.org/10.1115/imece2006-13661.

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Nonlinear vibration isolation system (VIS) plays an important role for improving the capability of hydroacoustic stealth of naval vessels. In engineering, Nonlinear VIS is generally a multi-degree-of-freedom system and its mathematical model is a set of coupled differential equations. Nonlinear normal mode (NNM) is an effective tool for decoupling and analyzing the dynamics of this coupled system. In this paper, taking the flexibility of the base into consideration, the equations of motion of an on-board VIS with quadric and cubic nonlinearities is formulated. The NNMs of this multi-degree-of-freedom nonlinear VIS are constructed by using the invariant manifold approach. The invariant surfaces of the NNMs and the decoupled oscillators are presented.
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9

Latini, F. "Identification of normal modes of a set of strongly nonlinear springs." In AIMETA 2022. Materials Research Forum LLC, 2023. http://dx.doi.org/10.21741/9781644902431-72.

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Abstract. The dynamics of connecting elements should be identified to evaluate their effects on the assemblies where they are employed. In general, a linear analysis is sufficient to determine their dynamics. However, in some cases, their responses depend on the amplitude and frequency of the excitation, thus nonlinear analyses must be carried out. Following a modal approach, Nonlinear Normal Modes (NNMs) can be used. The aim of this work is to identify the NNMs of a set of nonlinear connecting elements properly designed to be considered as strongly nonlinear springs. These elements have been manufactured and tested to measure some of their NNMs. The time series of the oscillation on some points is recorded using a laser vibrometer for different amplitude and frequencies of excitation. Then, the Virtual Point Transformation (VPT) is used to reduce the obtained data on the two physical points through which the spring is connected to other subsystems. The procedure is repeated for each NNM and the modal basis of each element is expressed as function of the level of excitation.
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10

Gavassoni, Elvidio, Paulo Batista Gonçalves, and Deane M. Roehl. "Nonlinear Dynamics of a Spar Platform." In ASME 2012 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/detc2012-70384.

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Spar floating platforms have been largely used for deep water drilling, oil and natural gas production and storage of these fluids. In extreme weather conditions such structures may exhibit a highly nonlinear dynamic behavior. In this paper a 2-DOF model is used to study the heave and pitch coupled response in free and forced vibration. Special attention is given to the determination of the nonlinear vibration modes (NNMs). Non-similar and similar NNMs are obtained analytically by direct application of asymptotic methods and the results show important NNM features such as instability and multiplicity of modes. The NNMs are used to generate reduced order models that consist of 1-DOF nonlinear oscillators. It facilitates the parametric analysis and the derivation of important features of the system such as the frequency-amplitude relation associated to each nonlinear mode and resonance curves. The stability is analyzed by the Floquet theory. Bifurcation diagrams and Mathieu charts are used to identify the unstable regions in the force parameter space. The analytical results show good agreement with the numerical solution obtained by direct integration of the equation of motion.
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Reports on the topic "NNMT"

1

Hanawalt, Margaret, and Karissa Kilgore. NNMC–DP Continuing Education Summary. Office of Scientific and Technical Information (OSTI), February 2022. http://dx.doi.org/10.2172/1846892.

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2

Ramirez, R. Building 151 NNMA Clean Laboratory ProjectSoil Sampling and Analysis Plan. Office of Scientific and Technical Information (OSTI), January 2023. http://dx.doi.org/10.2172/1975607.

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