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Published: 4 June 2021
Last updated: 20 February 2023

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1

Rangel, Rafael E., M. Judith Percino, and Edwin A. Murillo. "Resinas alquídicas altamente ramificadas obtenidas sin compuestos orgánicos volátiles." Respuestas 23, no. 1 (April 14, 2018): 19. http://dx.doi.org/10.22463/0122820x.1325.

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Antecedentes: Las resinas alquídicas altamente ramificadas,usualmente han sido obtenidas a partir de poliésteres polioles altamente ramificados (HBP) de segunda, tercera y cuarta generación. Objetivo: En este estudio se evaluó la influencia de la proporción de TOFA en las propiedades estructurales, térmicas, reológicas y de película de unas resinas alquídicas altamente ramificadas (NRA). Metodología: Para obtener las NRA, las respectivas cantidades de un HBP de primera generación (HBP1G), ácidos grasos de tall oil (TOFA) y de ácido p-toluensulfónico (0.1 %), fueron llevadas al reactor. La temperatura fue mantenida a 200°C. El sistema se mantuvo bajo agitación mecánica (200 rpm) y la conversión de la reacción fue evaluada por mediciones de valor ácido (VA). Las relaciones molares de HBP1G: TOFA, fueron las siguientes: 1:3 (NRA1), 1:4 (NRA2), 1:5 (NRA3) y 1:6 (NRA4). Resultados: El VA de las NRA fue inferior al de TOFA, el valor hidroxilo (VOH) fue inferior al del HBP1G. Esto indica que se llevó a cabo la reacción de esterificación entre TOFA y el HBP1G. La conversión de la reacción para obtener las NRA fue superior al 90 %. Por análisis de resonancia magnética nuclear (RMN) fue evidenciada la señal de los protones metilenos unidos a grupos OH del HBP1G y disminuyó su intensidad en la NRA1, debido a la reacción entre el HBP1G y TOFA. Las dimensiones hidrodinámicas de las NRA1, NRA2 y NRA3 fueron nanométricas. Las propiedades de película fueron buenas. Conclusión: Las NRA presentaron baja viscosidad. Además, todas exhibieron grupos OH y dobles enlaces, los cuales permite que estos materiales sean empleados para obtener materiales híbridos y como agentes entrecruzantes. Las NRA presentaron buenas propiedades de película.Palabras clave: Ácidos grasos de tall oil, poliéster poliol altamente ramificado, propiedades, resinas alquídicas. AbstractBackground: Hyperbranched alkyd resins have usually been obtained from hyperbranched polyester polyols (HBP) of second, third and fourth generations. Objectives: In this work the influence of the proportion of TOFA on the structural, thermal, and rheological and films properties of hyperbranched alkyd resins (NRA) were evaluated. Methodology: In order to obtain the NRA, the respective amount of HBP of fifth generation (HBP1G), tall oil fatty acids (TOFA) and p-toluenesulphonic acid (0.1wt%), were taken to the reactor. The temperature was kept at 200 °C. The system was kept under mechanical stirring (200 rpm) and the conversion of the reaction was evaluated by measurement of acid value (VA). The molar ratios of HBP:TOFA were as follows; 1:3 (NRA1), 1:4 (NRA2), 1:5 (NRA3) y 1:6 (NRA4). Results: VA of the NRA was lower than that of TOFA, the hydroxyl value (VOH) was minor compared to that of HBP1G. This is an indication that the esterification reaction between TOFA and HBP1G was carried out. The reaction conversion for obtaining the conversion to NRA was higher than 90 %. By nuclear magnetic resonance (NMR) analysis, the signals of the methylene protons joined to OH groups of the HBP1G were evidenced and decreased in their intensity in the NRA1, due to the reaction between HBP1G and TOFA. The hydrodynamic dimensions of the NRA1, NRA2 and NRA3 were nanometrics. Conclusions: The NRA presented the lowest viscosity. Furthermore all NRA, exhibited OH groups and double bonds, which allow that these materials be employed for obtaining hybrid materials and also as crosslinking agents. The NRA showed good film properties.Keywords: tall oil fatty acids, hyperbranched polyester polyol, properties, alkyd resins. ResumoAntecedentes: (foram obtidas) As resinas alquídicas altamente ramificadas foram usualmente obtidas (construção inglesa) de poliésteres poliol altamente ramificados (HBP) de segunda, terceira e quarta geração. Objetivo: Neste estudo foi avaliada a influência da proporção de TOFA nas propriedades estruturais, térmicas, reológicas e de filmes de resinas alquídicas altamente ramificadas (ARN). Metodologia: Para obter a ARN, as quantidades respectivas de uma primeira gera�o de HBP (HBP1G), �idos gordos de tall oil (TOFA) e �ido p-toluenossulf�ico (0,1%) foram levadas para o reactor. A temperatura foi mantida a 200 ° C. O sistema foi mantido sob agitação mecânica (200 rpm) e a conversão da reação foi avaliada por medidas do valor ácido (VA). As proporções molares de HBP1G: TOFA foram as seguintes: 1: 3 (NRA1), 1: 4 (NRA2), 1: 5 (NRA3) e 1: 6 (NRA4). Resultados: VA ARN TOFA foi menor do que o valor de hidroxilo (OHV) foi menor do que HBP1G.Esto indica que realizada a reaco de esterificao entre o TOFA e HBP1G. A conversão da reação para obter a ARN foi maior que 90%. Por análise de ressonância magnética nuclear (RMN), evidenciou-se o sinal dos prótons de metileno ligados aos grupos OH de HBP1Gy e sua intensidade diminuiu em NRA1, devido à reação entre HBP1G e TOFA. As dimensões hidrodinâmicas do NRA1, NRA2 e NRA3 foram nanométricas. As propriedades do filme eram boas. Conclusão: A NRA apresentou baixa viscosidade. Além disso, todos exibiram grupos OH e ligações duplas, o que permite que estes materiais sejam utilizados para obter materiais híbridos e como agentes de reticulação. As NRAs mostraram boas propriedades de filme.Palavras-chave: Ácidos grasos de tall oil, poliéster poliol altamente ramificado, propiedades, resinas alquídicas.
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2

Bochicchio, Francesco, David Fenton, Heloísa Fonseca, Marta García-Talavera, Pierrick Jaunet, Stephanie Long, Bård Olsen, Jelena Mrdakovic Popic, and Wolfgang Ringer. "National Radon Action Plans in Europe and Need of Effectiveness Indicators: An Overview of HERCA Activities." International Journal of Environmental Research and Public Health 19, no. 7 (March 30, 2022): 4114. http://dx.doi.org/10.3390/ijerph19074114.

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Protection of the population and of workers from exposure to radon is a unique challenge in radiation protection. Many coordinated actions and a variety of expertise are needed. Initially, a National Radon Action Plan (NRAP) has been developed and implemented by some countries, while it is currently recommended by international organizations (e.g., World Health Organization) and required by international regulations, such as the European Council Directive 2013/59/Euratom and the International Basic Safety Standards on Radiation Protection and Safety of Radiation Sources, cosponsored by eight international organizations. Within this framework, the Heads of the European Radiological Protection Competent Authorities (HERCA) have organized activities aimed at sharing experiences to contribute toward the development and implementation of effective NRAPs. Two workshops were held in 2014 and 2015, the latter on radon in workplaces. As a follow-up to these, an online event took place in March 2021, and a second specific workshop on NRAP is planned for June 2022. These workshops were attended by experts from the competent authorities of European countries, relevant national and international organizations. The experience of several countries and the outcomes from these workshops have highlighted the need for adequate indicators of the effectiveness and progress of the actions of NRAPs, which could also be useful to implement the principle of optimization and the graded approach in NRAPs. In this paper, the activities of HERCA to support the development and implementation of effective NRAPs are described and some examples of effectiveness indicators are reported, including those already included in the NRAP of some European countries.
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3

Koskenvuo, Juha W., Inka Saarinen, Saija Ahonen, Johanna Tommiska, Sini Weckström, Eija H. Seppälä, Sari Tuupanen, et al. "Biallelic loss-of-function in NRAP is a cause of recessive dilated cardiomyopathy." PLOS ONE 16, no. 2 (February 3, 2021): e0245681. http://dx.doi.org/10.1371/journal.pone.0245681.

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Background Familial dilated cardiomyopathy (DCM) is typically a monogenic disorder with dominant inheritance. Although over 40 genes have been linked to DCM, more than half of the patients undergoing comprehensive genetic testing are left without molecular diagnosis. Recently, biallelic protein-truncating variants (PTVs) in the nebulin-related anchoring protein gene (NRAP) were identified in a few patients with sporadic DCM. Methods and results We determined the frequency of rare NRAP variants in a cohort of DCM patients and control patients to further evaluate role of this gene in cardiomyopathies. A retrospective analysis of our internal variant database consisting of 31,639 individuals who underwent genetic testing (either panel or direct exome sequencing) was performed. The DCM group included 577 patients with either a confirmed or suspected DCM diagnosis. A control cohort of 31,062 individuals, including 25,912 individuals with non-cardiac (control group) and 5,150 with non-DCM cardiac indications (Non-DCM cardiac group). Biallelic (n = 6) or two (n = 5) NRAP variants (two PTVs or PTV+missense) were identified in 11 unrelated probands with DCM (1.9%) but none of the controls. None of the 11 probands had an alternative molecular diagnosis. Family member testing supports co-segregation. Biallelic or potentially biallelic NRAP variants were enriched in DCM vs. controls (OR 1052, p<0.0001). Based on the frequency of NRAP PTVs in the gnomAD reference population, and predicting full penetrance, biallelic NRAP variants could explain 0.25%-2.46% of all DCM cases. Conclusion Loss-of-function in NRAP is a cause for autosomal recessive dilated cardiomyopathy, supporting its inclusion in comprehensive genetic testing.
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4

Jirka, Caroline, Jasmine H. Pak, Claire A. Grosgogeat, Michael Mario Marchetii, and Vandana A. Gupta. "Dysregulation of NRAP degradation by KLHL41 contributes to pathophysiology in nemaline myopathy." Human Molecular Genetics 28, no. 15 (April 15, 2019): 2549–60. http://dx.doi.org/10.1093/hmg/ddz078.

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Abstract Nemaline myopathy (NM) is the most common form of congenital myopathy that results in hypotonia and muscle weakness. This disease is clinically and genetically heterogeneous, but three recently discovered genes in NM encode for members of the Kelch family of proteins. Kelch proteins act as substrate-specific adaptors for Cullin 3 (CUL3) E3 ubiquitin ligase to regulate protein turnover through the ubiquitin-proteasome machinery. Defects in thin filament formation and/or stability are key molecular processes that underlie the disease pathology in NM; however, the role of Kelch proteins in these processes in normal and diseases conditions remains elusive. Here, we describe a role of NM causing Kelch protein, KLHL41, in premyofibil-myofibil transition during skeletal muscle development through a regulation of the thin filament chaperone, nebulin-related anchoring protein (NRAP). KLHL41 binds to the thin filament chaperone NRAP and promotes ubiquitination and subsequent degradation of NRAP, a process that is critical for the formation of mature myofibrils. KLHL41 deficiency results in abnormal accumulation of NRAP in muscle cells. NRAP overexpression in transgenic zebrafish resulted in a severe myopathic phenotype and absence of mature myofibrils demonstrating a role in disease pathology. Reducing Nrap levels in KLHL41 deficient zebrafish rescues the structural and function defects associated with disease pathology. We conclude that defects in KLHL41-mediated ubiquitination of sarcomeric proteins contribute to structural and functional deficits in skeletal muscle. These findings further our understanding of how the sarcomere assembly is regulated by disease-causing factors in vivo, which will be imperative for developing mechanism-based specific therapeutic interventions.
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5

Coe, William H., Jason Feinberg, Robert Grunier, Brenda Eskenazi, and Heather Volk. "2110 Prenatal near roadway air pollution exposure and early neurodevelopment in young Mexican-American children: Findings from the CHAMACOS prospective birth cohort study." Journal of Clinical and Translational Science 2, S1 (June 2018): 86. http://dx.doi.org/10.1017/cts.2018.300.

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OBJECTIVES/SPECIFIC AIMS: Previous studies suggest that prenatal exposure to environmental pollutants can have an adverse effect on brain development. We examine the association between prenatal near roadway air pollution (NRAP) exposure and early neurodevelopment. METHODS/STUDY POPULATION: The Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study is a prospective birth cohort that began in 1999 with 605 mother-child pairs of primarily Mexican-American descent. Maternal residence during pregnancy was geocoded using ArcGIS and prenatal NRAP exposure was assigned using the CALINE4 line source dispersion model. We used composite Bayley Scale scores for cognitive and motor development, and created separate linear regression models at 6, 12, and 24 months of age. RESULTS/ANTICIPATED RESULTS: After adjusting for relevant maternal and child characteristics, preliminary estimates suggest that prenatal NRAP exposure is associated with a nonsignificant increase in Bayley Scale scores at 6 and 24 months (cognitive: β=0.13, p-value=0.20 and motor: β=0.08, p-value=0.58 at 6 months; cognitive: β=0.16, p-value=0.42 and motor: β=0.20, p-value=0.25 at 24 months) and a nonsignificant decrease at 12 months (cognitive: β=−0.07, p-value=0.64 and motor: β=−0.12, p-value=0.56). DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary findings do not suggest that prenatal NRAP exposure is associated with early cognitive development. Additional exploration of co-exposures known to effect neurodevelopment should be examined in this rural population.
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6

Gall, Kim, Juha Koskenvuo, Inka Saarinen, Johanna Tommiska, Sini Weckstrom, Eija Seppala, Sari Tuupanen, et al. "Biallelic NRAP variants are a significant cause of dilated cardiomyopathy." Molecular Genetics and Metabolism 132 (April 2021): S220. http://dx.doi.org/10.1016/s1096-7192(21)00425-x.

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7

Lu, Shajia, Garland L. Crawford, Justin Dore, Stasia A. Anderson, Daryl DesPres, and Robert Horowits. "Cardiac-specific NRAP overexpression causes right ventricular dysfunction in mice." Experimental Cell Research 317, no. 8 (May 2011): 1226–37. http://dx.doi.org/10.1016/j.yexcr.2011.01.020.

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8

Maurer, Constance, Olga Boleti, Paria Najarzadeh Torbati, Farzaneh Norouzi, Anna Nicole Rebekah Fowler, Shima Minaee, Khalid Hama Salih, et al. "Genetic Insights from Consanguineous Cardiomyopathy Families." Genes 14, no. 1 (January 10, 2023): 182. http://dx.doi.org/10.3390/genes14010182.

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Inherited cardiomyopathies are a prevalent cause of heart failure and sudden cardiac death. Both hypertrophic (HCM) and dilated cardiomyopathy (DCM) are genetically heterogeneous and typically present with an autosomal dominant mode of transmission. Whole exome sequencing and autozygosity mapping was carried out in eight un-related probands from consanguineous Middle Eastern families presenting with HCM/DCM followed by bioinformatic and co-segregation analysis to predict the potential pathogenicity of candidate variants. We identified homozygous missense variants in TNNI3K, DSP, and RBCK1 linked with a dilated phenotype, in NRAP linked with a mixed phenotype of dilated/hypertrophic, and in KLHL24 linked with a mixed phenotype of dilated/hypertrophic and non-compaction features. Co-segregation analysis in family members confirmed autosomal recessive inheritance presenting in early childhood/early adulthood. Our findings add to the mutational spectrum of recessive cardiomyopathies, supporting inclusion of KLHL24, NRAP and RBCK1 as disease-causing genes. We also provide evidence for novel (recessive) modes of inheritance of a well-established gene TNNI3K and expand our knowledge of the clinical heterogeneity of cardiomyopathies. A greater understanding of the genetic causes of recessive cardiomyopathies has major implications for diagnosis and screening, particularly in underrepresented populations, such as those of the Middle East.
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Lei, Ning, Jerry E. Mellem, Penelope J. Brockie, David M. Madsen, and Andres V. Maricq. "NRAP-1 Is a Presynaptically Released NMDA Receptor Auxiliary Protein that Modifies Synaptic Strength." Neuron 96, no. 6 (December 2017): 1303–16. http://dx.doi.org/10.1016/j.neuron.2017.11.019.

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10

Luo, Gang, Elisabeth Leroy, Christine A. Kozak, Mihael H. Polymeropoulos, and Robert Horowits. "Mapping of the Gene (NRAP) Encoding N-RAP in the Mouse and Human Genomes." Genomics 45, no. 1 (October 1997): 229–32. http://dx.doi.org/10.1006/geno.1997.4917.

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11

Utama, Budi, Derek Kennedy, Kelin Ru, and John S. Mattick. "Isolation and characterization of a new nucleolar protein, Nrap, that is conserved from yeast to humans." Genes to Cells 7, no. 2 (February 2002): 115–32. http://dx.doi.org/10.1046/j.1356-9597.2001.00507.x.

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12

Vasylkivska, Veronika, Robert Dilmore, Greg Lackey, Yingqi Zhang, Seth King, Diana Bacon, Bailian Chen, Kayyum Mansoor, and Dylan Harp. "NRAP-open-IAM: A flexible open-source integrated-assessment-model for geologic carbon storage risk assessment and management." Environmental Modelling & Software 143 (September 2021): 105114. http://dx.doi.org/10.1016/j.envsoft.2021.105114.

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Pawar, Rajesh, Grant Bromhal, Robert Dilmore, Bill Foxall, Edwin Jones, Curtis Oldenburg, Philip Stauffer, Stephen Unwin, and George Guthrie. "Quantification of Risk Profiles and Impacts of Uncertainties as part of US DOE's National Risk Assessment Partnership (NRAP)." Energy Procedia 37 (2013): 4765–73. http://dx.doi.org/10.1016/j.egypro.2013.06.386.

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14

Saïdou, Shinji Tokonami, Masahiro Hosoda, Augustin Simo, Joseph Victor Hell, Olga German, and Esmel Gislere Oscar Meless. "From Radon and Thoron Measurements, Inhalation Dose Assessment to National Regulation and Radon Action Plan in Cameroon." Journal of Radiation Protection and Research 47, no. 4 (December 30, 2022): 237–45. http://dx.doi.org/10.14407/jrpr.2021.00213.

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Background: The current study reports measurements of activity concentrations of radon (<sup>222</sup>Rn) and thoron (<sup>220</sup>Rn) in dwellings, followed by inhalation dose assessment of the public, and then by the development of regulation and the national radon action plan (NRAP) in Cameroon.Materials and Methods: Radon, thoron, and thoron progeny measurements were carried out from 2014 to 2017 using radon-thoron discriminative detectors (commercially RADUET) in 450 dwellings and thoron progeny monitors in 350 dwellings. From 2019 to 2020, radon track detectors (commercially RADTRAK) were deployed in 1,400 dwellings. It was found that activity concentrations of radon range in 1,850 houses from 10 to 2,620 Bq/m<sup>3</sup> with a geometric mean of 76 Bq/m<sup>3</sup>.Results and Discussion: Activity concentrations of thoron range from 20 to 700 Bq/m<sup>3</sup> with a geometric mean of 107 Bq/m<sup>3</sup>. Thoron equilibrium factor ranges from 0.01 to 0.6, with an arithmetic mean of 0.09 that is higher than the default value of 0.02 given by UNSCEAR. On average, 49%, 9%, and 2% of all surveyed houses have radon concentrations above 100, 200, and 300 Bq/m<sup>3</sup>, respectively. The average contribution of thoron to the inhalation dose due to radon and thoron exposure is about 40%. Thus, thoron cannot be neglected in dose assessment to avoid biased results in radio-epidemiological studies. Only radon was considered in the drafted regulation and in the NRAP adopted in October 2020. Reference levels of 300 Bq/m<sup>3</sup> and 1,000 Bq/m<sup>3</sup> were recommended for dwellings and workplaces.Conclusion: Priority actions for the coming years include the following: radon risk mapping, promotion of a protection policy against radon in buildings, integration of the radon prevention and mitigation into the training of construction specialists, mitigation of dwellings and workplaces with high radon levels, increased public awareness of the health risks associated with radon, and development of programs on the scientific and technical aspects.
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15

Buggiotti, Laura, Andrey A. Yurchenko, Nikolay S. Yudin, Christy J. Vander Jagt, Nadezhda V. Vorobieva, Mariya A. Kusliy, Sergei K. Vasiliev, et al. "Demographic History, Adaptation, and NRAP Convergent Evolution at Amino Acid Residue 100 in the World Northernmost Cattle from Siberia." Molecular Biology and Evolution 38, no. 8 (March 30, 2021): 3093–110. http://dx.doi.org/10.1093/molbev/msab078.

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Abstract Native cattle breeds represent an important cultural heritage. They are a reservoir of genetic variation useful for properly responding to agriculture needs in the light of ongoing climate changes. Evolutionary processes that occur in response to extreme environmental conditions could also be better understood using adapted local populations. Herein, different evolutionary histories of the world northernmost native cattle breeds from Russia were investigated. They highlighted Kholmogory as a typical taurine cattle, whereas Yakut cattle separated from European taurines approximately 5,000 years ago and contain numerous ancestral and some novel genetic variants allowing their adaptation to harsh conditions of living above the Polar Circle. Scans for selection signatures pointed to several common gene pathways related to adaptation to harsh climates in both breeds. But genes affected by selection from these pathways were mostly different. A Yakut cattle breed-specific missense mutation in a highly conserved NRAP gene represents a unique example of a young amino acid residue convergent change shared with at least 16 species of hibernating/cold-adapted mammals from six distinct phylogenetic orders. This suggests a convergent evolution event along the mammalian phylogenetic tree and fast fixation in a single isolated cattle population exposed to a harsh climate.
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Pawar, Rajesh, Robert Dilmore, Shaoping Chu, Yingqi Zhang, Curtis Oldenburg, Philip Stauffer, George Guthrie, and Grant Bromhal. "Informing Geologic CO2 Storage Site Management Decisions under Uncertainty: Demonstration of NRAP's Integrated Assessment Model (NRAP-IAM-CS) Application." Energy Procedia 114 (July 2017): 4330–37. http://dx.doi.org/10.1016/j.egypro.2017.03.1582.

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17

Pawar, Rajesh, Grant Bromhal, Susan Carroll, Shaoping Chu, Robert Dilmore, Jason Gastelum, Curt Oldenburg, Philip Stauffer, Yingqi Zhang, and George Guthrie. "Quantification of Key Long-term Risks at CO2 Sequestration Sites: Latest Results from US DOE's National Risk Assessment Partnership (NRAP) Project." Energy Procedia 63 (2014): 4816–23. http://dx.doi.org/10.1016/j.egypro.2014.11.512.

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18

Kissinger, Gabrielle. "Policy Responses to Direct and Underlying Drivers of Deforestation: Examining Rubber and Coffee in the Central Highlands of Vietnam." Forests 11, no. 7 (July 6, 2020): 733. http://dx.doi.org/10.3390/f11070733.

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Viet Nam’s Central Highlands are a priority region for its National REDD+ Action Plan (NRAP) to reduce emissions from deforestation and forest degradation but are under strong pressures from rubber and coffee production and expansion into forests, and future climate stress. This research explores to what extent REDD+ and sectoral policy interventions have addressed both the direct and underlying drivers of deforestation and forest degradation in this region, with particular focus on the actors and scales that policy interventions must reach to affect driver pressure. National-level policy responses to driver pressures are assessed, with the results indicating poor correlations between the direct drivers and related underlying drivers. The research proposes a framework to guide the policy design and evaluation of response options to enable identification of the causal connections between direct and underlying drivers, and consider future pressures, which actors to target (or not miss) and which scales are best suited for interventions (from international to national, sub-national and local). This is highly relevant for countries pursuing forest and land use sector solutions through Nationally Determined Contributions to the Paris Agreement and REDD+.
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Ohtsuka, Toshihisa, Yutaka Hata, Nobuyuki Ide, Takeo Yasuda, Eiji Inoue, Takahiro Inoue, Akira Mizoguchi, and Yoshimi Takai. "nRap GEP: A Novel Neural GDP/GTP Exchange Protein for Rap1 Small G Protein That Interacts with Synaptic Scaffolding Molecule (S-SCAM)." Biochemical and Biophysical Research Communications 265, no. 1 (November 1999): 38–44. http://dx.doi.org/10.1006/bbrc.1999.1619.

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D’Avila, Francesca, Mirella Meregalli, Sara Lupoli, Matteo Barcella, Alessandro Orro, Francesca De Santis, Clementina Sitzia, et al. "Exome sequencing identifies variants in two genes encoding the LIM-proteins NRAP and FHL1 in an Italian patient with BAG3 myofibrillar myopathy." Journal of Muscle Research and Cell Motility 37, no. 3 (June 2016): 101–15. http://dx.doi.org/10.1007/s10974-016-9451-7.

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Lee, Si-Yong, Ken Hnottavange-Telleen, Wei Jia, Ting Xiao, Hari Viswanathan, Shaoping Chu, Zhenxue Dai, Feng Pan, Brian McPherson, and Robert Balch. "Risk Assessment and Management Workflow—An Example of the Southwest Regional Partnership." Energies 14, no. 7 (March 30, 2021): 1908. http://dx.doi.org/10.3390/en14071908.

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This paper summarizes the risk assessment and management workflow developed and applied to the Southwest Regional Partnership on Carbon Sequestration (SWP) Phase III Demonstration Project. The risk assessment and management workflow consists of six primary tasks, including management planning, identification, qualitative analysis, quantitative analysis, response planning, and monitoring. Within the workflow, the SWP assembled and iteratively updated a risk registry that identifies risks for all major activities of the project. Risk elements were ranked with respect to the potential impact to the project and the likelihood of occurrence. Both qualitative and quantitative risk analyses were performed. To graphically depict the interactions among risk elements and help building risk scenarios, process influence diagrams were used to represent the interactions. The SWP employed quantitative methods of risk analysis including Response Surface Method (RSM), Polynomial Chaos Expansion (PCE), and the National Risk Assessment Partnership (NRAP) toolset. The SWP also developed risk response planning and performed risk control and monitoring to prevent the risks from affecting the project and ensure the effectiveness of risk management. As part of risk control and monitoring, existing and new risks have been tracked and the response plan was subsequently evaluated. Findings and lessons learned from the SWP’s risk assessment and management efforts will provide valuable information for other commercial geological CO2 storage projects.
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Eswara, Manoja B. K., Ashley Clayton, and Dev Mangroo. "Utp22p acts in concert with Utp8p to channel aminoacyl-tRNA from the nucleolus to the nuclear tRNA export receptor Los1p but not Msn5p." Biochemistry and Cell Biology 90, no. 6 (December 2012): 731–49. http://dx.doi.org/10.1139/o2012-034.

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Utp8p is an essential nucleolar protein that channels aminoacyl-tRNAs from aminoacyl-tRNA synthetases in the nucleolus to the nuclear tRNA export receptors located in the nucleoplasm and nuclear pore complex in Saccharomyces cerevisiae . Utp8p is also part of the U3 snoRNA-associated protein complex involved in 18S rRNA biogenesis in the nucleolus. We report that Utp22p, which is another member of the U3 snoRNA-associated protein complex, is also an intranuclear component of the nuclear tRNA export machinery. Depletion of Utp22p results in nuclear retention of mature tRNAs derived from intron-containing and intronless precursors. Moreover, Utp22p copurifies with the nuclear tRNA export receptor Los1p, the aminoacyl-tRNA synthetase Tys1p and Utp8p, but not with the RanGTPase Gsp1p and the nuclear tRNA export receptor Msn5p. Utp22p interacts directly with Utp8p and Los1p in a tRNA-independent manner in vitro. Utp22p also interacts directly with Tys1p, but this binding is stimulated when Tys1p is bound to tRNA. However, Utp22p, unlike Utp8p, does not bind tRNA saturably. These data suggest that Utp22p recruits Utp8p to aminoacyl-tRNA synthetases in the nucleolus to collect aminoacyl-tRNA and then accompanies the Utp8p–tRNA complex to deliver the aminoacyl-tRNAs to Los1p but not Msn5p. It is possible that Nrap/Nol6, the mammalian orthologue of Utp22p, plays a role in channelling aminoacyl-tRNA to the nuclear tRNA export receptor exportin-t.
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Bacon, Diana H., Catherine M. R. Yonkofski, Christopher F. Brown, Deniz I. Demirkanli, and Jonathan M. Whiting. "Risk-based post injection site care and monitoring for commercial-scale carbon storage: Reevaluation of the FutureGen 2.0 site using NRAP-Open-IAM and DREAM." International Journal of Greenhouse Gas Control 90 (November 2019): 102784. http://dx.doi.org/10.1016/j.ijggc.2019.102784.

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Eisenhut, Sian E., Ida Holásková, and Kirsten Stephan. "Role of Tree Species, the Herb Layer and Watershed Characteristics in Nitrate Assimilation in a Central Appalachian Hardwood Forest." Nitrogen 3, no. 2 (June 3, 2022): 333–52. http://dx.doi.org/10.3390/nitrogen3020022.

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Forest plants that can assimilate nitrate may act as nitrate sink and, consequently, reduce nitrate losses from watershed ecosystems through leaching. This study, conducted at the Fernow Experimental Forest in West Virginia, quantified via nitrogen reductase activity (NRA) the nitrate assimilation of two tree species, red maple and sugar maple, and surrounding common herb-layer species at the tissue (foliage, roots) and plot level. NRA measurements were conducted in summer and spring. Furthermore, NRA was quantified under varying levels of soil nitrate availability due to fertilization, different stages in secondary forest succession, and watershed aspect. This study confirmed that NRA of mature maples does not respond to varying levels of soil nitrate availability. However, some herb-layer species’ NRA did increase with nitrogen fertilization, and it may be greater in spring than in summer. Combined with biomass, the herb layer’s NRA at the plot-level (NRAA) comprised 9 to 41% of the total (tree + herb-layer) foliar NRAA during the growing season. This demonstrates that the herb layer contributes to nitrate assimilation disproportionally to its small biomass in the forest and may provide a vernal dam to nitrate loss not only by its early presence but also by increased spring NRA relative to summer.
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Baylor, Norman W. "Role of the national regulatory authority for vaccines." International Journal of Health Governance 22, no. 3 (September 4, 2017): 128–37. http://dx.doi.org/10.1108/ijhg-04-2017-0017.

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Purpose Before vaccines are marketed and used, they must be evaluated and approved by a national regulatory authority (NRA). The Food and Drug Administration (FDA) is the NRA in the USA responsible for overseeing and regulating the manufacturing, marketing, and distribution of vaccines. The paper aims to discuss this issue. Design/methodology/approach Expert review. Findings Developed countries have established governmental regulatory agencies to review and determine the safety and effectiveness of vaccines to ensure that the manufacture, sale, and use of vaccines are adequately regulated. However, even today, many developing countries do not have established NRAs. Furthermore, despite similarities, there are still substantial differences in how regulatory authorities in different countries perform minimum functions required for effective regulation of pharmaceutical products, including vaccines. The World Health Organization (WHO), although not a governmental NRA, uses a consultative approach involving its Expert Committee on Biological Standardization and Biologicals Unit to develop regulatory criteria and identify and consolidate current consensus opinions on key regulatory issues. It is through this approach that WHO informs NRAs on the necessary scientific background required to assess and advise on optimal regulatory approaches and methodologies. This paper will focus on the evolution of the US FDA and its role in regulation of vaccines to illustrate the function of a vaccine NRA. Originality/value Vaccines are an important resource for protecting people and communities from the mortality and morbidity associated with many infectious diseases. The assessment, licensure, control and surveillance of vaccines are the responsibilities of government regulatory authorities.
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Silva, Rodrigo de Souza, Elisa Ferreira Moura, João Tomé de Farias Neto, and José Edson Sampaio. "Genetic parameters and agronomic evaluation of cassava genotypes." Pesquisa Agropecuária Brasileira 51, no. 7 (July 2016): 834–41. http://dx.doi.org/10.1590/s0100-204x2016000700006.

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Abstract: The objective of this work was to estimate genetic parameters and predict genetic values for the selection of cassava (Manihot esculenta) genotypes in the state of Pará, Brazil. The trial was performed with 56 genotypes in two growing seasons (2012/2013 and 2013/2014), in the municipality of Igarapé-Açu, in the state of Pará, using the augmented blocks design with two control treatments. The evaluated traits were: plant shoot weight (PSW), number of roots per plant (NRP), number of rotten roots per plant (NRRP), fresh root yield (FRY), harvest index (HI), and starch content in the roots (SCR). The restricted maximum likelihood (REML) and best linear unbiased prediction (BLUP) methods were used. There was genetic variability among genotypes for PSW, NRP, HI, and SCR. Broad-sense heritability estimates were low for PSW and SCR, but were moderate for NRP and HI. However, the heritabilities of the average of genotypes were higher for PSW and SCR. The genetic gains of the five best genotypes varied from 6.0 to 11.08% (PSW), 15.81 to 27.10% (NRP), 9.82 to 12.14% (HI), and 1.90 to 2.20% (SCR). There is genetic variability among cassava genotypes, and the possibility of genetic gains based on selection is moderate for this region in the state of Pará.
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AL-Zahrani, Asla A., Zulkarnain Zainal, Zainal Abidin Talib, Hong Ngee Lim, Laimy Mohd Fudzi, Araa Mebdir Holi, and Mahanim Sarif @ Mohd Ali. "Synthesis of Binary Bi2S3/ZnO Nanorod Array Heterostructure and Their Photoelectrochemical Performance." Journal of Nanomaterials 2019 (August 8, 2019): 1–10. http://dx.doi.org/10.1155/2019/5212938.

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One of the most effective strategies to improve the photoconversion efficiency in the photoelectrochemical cell is by using an assembly of heterostructures. To do so, a simple and inexpensive method, that is successive ionic layer adsorption and reaction (SILAR), is used to deposit the narrow band gap energy semiconductor Bi2S3 on ZnO nanorod arrays (NRAs) at different SILAR cycles. The obtained binary heterostructure thin films were characterized by using X-ray diffraction (XRD), UV-Vis Spectroscopy, field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray analysis (EDX), Raman spectroscopy, high-resolution transmission electron microscopy (HRTEM), and linear sweep voltammogram (LSV) to prove the crystal structure, optical properties, band gap energy, morphological structure, composition of elements, and electrical properties. The XRD revealed that ZnO NRAs possessed a single wurtzite crystal structure while Bi2S3 possessed an orthorhombic crystal structure. The as-fabricated Bi2S3/ZnO heterostructure exhibited enhanced visible light absorption and charge separation efficiency of photoinduced electron-hole pairs. The band gap energy of binary heterostructure Bi2S3/ZnO NRAs is 3.11, 3.00, 2.33, 1.96, and 1.89 eV at 3, 5, 7, 9, and 11 SILAR cycles, respectively, confirming the substantial improvement of ZnO NRA optical properties. The highest photocurrent density has been achieved by 1.92 mA/cm2 of Bi2S3/ZnO NRAs fabricated at 7 cycles, exhibiting sixfold enhancement compared to that of intrinsic ZnO NRAs (0.336 mA/cm2). This impressive enhancement was ascribed to the significant improvement in morphological structure, crystallinity, and optical properties of heterostructure photoanodes. Significant improvement was achieved in the photoelectrochemical cell (PEC) performance attributed to the fast separation, low recombination rate, and low impedance of the photoinduced electron-hole pairs as shown throughout the electrochemical impedance spectra.
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Ha, Wi-Ho, Jaeryong Yoo, Seokwon Yoon, Seung-Sook Lee, and Jong Kyoung Kim. "Performance test of urine bioassay through participation in the NRIP." Journal of Radiation Protection and Research 39, no. 2 (June 30, 2014): 96–102. http://dx.doi.org/10.14407/jrp.2014.39.2.096.

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Hamilton, Julia, and Turgut Var. "NRPA conference." Annals of Tourism Research 17, no. 3 (January 1990): 475–77. http://dx.doi.org/10.1016/0160-7383(90)90013-h.

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Grill, Christine, and Lionel Larue. "NRAS, NRAS, Which Mutation Is Fairest of Them All?" Journal of Investigative Dermatology 136, no. 10 (October 2016): 1936–38. http://dx.doi.org/10.1016/j.jid.2016.06.011.

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Mustafa, Usman, and M. Afzal Mir. "Sustaining Economic Development by Reforming Basic Institutions through Community Participation." Pakistan Development Review 38, no. 4II (December 1, 1999): 1233–46. http://dx.doi.org/10.30541/v38i4iipp.1233-1246.

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It is universally accepted and advocated that without community involvement and participation, development initiatives either in the economic or social sector, have little chances of success/sustainability, especially at the grassroots level, where the majority of the country’s population lives [AKRSP (1984, 1999); FAO (1989); Khan et al. (1984) and Mustafa (1998)]. In this connection the concept and approaches of community development have been tested in Northern Areas of Pakistan and the principles and experiences have been replicated in some other parts of the country by Non Government Organisations (NGOs), different national and international government projects and programmes [Mustafa and Grunewald (1996); NRMP (1993) and NRSP (1995)]. The need for conceptualising a realistic framework for collaboration between government/other development agencies and community organisations engaged in pursuit of both social and economic goals is imperative for an equitable and sustainable development because when it comes to community involvement, the two sectors cannot be divorced from each other [Khan (1999) and Reid and Khan (1996)].
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Wang, Jinyong, Yangang Liu, Zeyang Li, Zhongde Wang, Li Xuan Tan, Myung-Jeom Ryu, Benjamin Meline, et al. "Endogenous oncogenic Nras mutation initiates hematopoietic malignancies in a dose- and cell type-dependent manner." Blood 118, no. 2 (July 14, 2011): 368–79. http://dx.doi.org/10.1182/blood-2010-12-326058.

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Abstract Both monoallelic and biallelic oncogenic NRAS mutations are identified in human leukemias, suggesting a dose-dependent role of oncogenic NRAS in leukemogenesis. Here, we use a hypomorphic oncogenic Nras allele and a normal oncogenic Nras allele (Nras G12Dhypo and Nras G12D, respectively) to create a gene dose gradient ranging from 25% to 200% of endogenous Nras G12D/+. Mice expressing Nras G12Dhypo/G12Dhypo develop normally and are tumor-free, whereas early embryonic expression of Nras G12D/+ is lethal. Somatic expression of Nras G12D/G12D but not Nras G12D/+ leads to hyperactivation of ERK, excessive proliferation of myeloid progenitors, and consequently an acute myeloproliferative disease. Using a bone marrow transplant model, we previously showed that ∼ 95% of animals receiving Nras G12D/+ bone marrow cells develop chronic myelomonocytic leukemia (CMML), while ∼ 8% of recipients develop acute T-cell lymphoblastic leukemia/lymphoma [TALL] (TALL-het). Here we demonstrate that 100% of recipients transplanted with Nras G12D/G12D bone marrow cells develop TALL (TALL-homo). Although both TALL-het and -homo tumors acquire Notch1 mutations and are sensitive to a γ-secretase inhibitor, endogenous Nras G12D/+ signaling promotes TALL through distinct genetic mechanism(s) from Nras G12D/G12D. Our data indicate that the tumor transformation potential of endogenous oncogenic Nras is both dose- and cell type-dependent.
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Posch, Christian, and Susana Ortiz-Urda. "NRAS mutant melanoma - undrugable?" Oncotarget 4, no. 4 (April 13, 2013): 494–95. http://dx.doi.org/10.18632/oncotarget.970.

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34

Feder, Toni. "Lo to Lead NRAO." Physics Today 55, no. 8 (August 2002): 28. http://dx.doi.org/10.1063/1.1510277.

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Williams, K. J. "Improving the NRMP board." Academic Medicine 73, no. 6 (June 1998): 623–4. http://dx.doi.org/10.1097/00001888-199806000-00002.

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36

Kelleher, Fergal C., and Grant A. McArthur. "Targeting NRAS in Melanoma." Cancer Journal 18, no. 2 (2012): 132–36. http://dx.doi.org/10.1097/ppo.0b013e31824ba4df.

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Posch, Christian, Martina Sanlorenzo, Igor Vujic, Juan A. Oses-Prieto, Brian D. Cholewa, Sarasa T. Kim, Jeffrey Ma, et al. "Phosphoproteomic Analyses of NRAS(G12) and NRAS(Q61) Mutant Melanocytes Reveal Increased CK2α Kinase Levels in NRAS(Q61) Mutant Cells." Journal of Investigative Dermatology 136, no. 10 (October 2016): 2041–48. http://dx.doi.org/10.1016/j.jid.2016.05.098.

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38

Wang, Jinyong, Yangang Liu, Juan Du, Myung-Jeom Ryu, Erik A. Ranheim, and Jing Zhang. "Endogenous Oncogenic Nras Signaling Promotes Proliferative Exhaustion of Hematopoietic Stem Cells Through a Dose-Dependent Hyperactivation of ERK,." Blood 118, no. 21 (November 18, 2011): 3997. http://dx.doi.org/10.1182/blood.v118.21.3997.3997.

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Abstract Abstract 3997 Both monoallelic and biallelic oncogenic NRAS mutations are identified in human leukemias, suggesting a dose-dependent role of oncogenic NRAS in leukemogenesis. We recently characterized conditional mouse models that express one or two copies of constitutively active Nras G12D in the hematopoietic compartment (Nras G12D/+ and Nras G12D/G12D). Nras G12D/G12D results in stronger downstream signaling than Nras G12D/+ and consequently distinct hematopoietic phenotypes. In particular, we found that somatic expression of Nras G12D/G12D but not Nras G12D/+ leads to an acute myeloproliferative neoplasm (MPN). The development of acute MPN is associated with cytokine-evoked hyperactivation of ERK but not Stat5 and Akt in hematopoietic stem/progenitor cells (HSPCs). Interestingly, genetically altered HSCs appear to be required for initiation and maintenance of chronic and acute MPD phenotypes mediated by Nras G12D/+ and Nras G12D/G12D, respectively. Furthermore, Nras G12D/G12D-mediated signaling promotes excessive HSC proliferation and leading to HSC exhaustion. Exhaustion of HSCs is tightly associated with diminished MPN phenotypes in non-engineered recipient mice into which Nras G12D/G12D HSCs are transferred by bone marrow transplantation. To investigate the molecular mechanisms underlying the exhaustion of Nras G12D/G12D HSCs, we performed a microarray analysis using highly purified control, Nras G12D/+, and Nras G12D/G12D HSCs. To our surprise, neither p16INK4a and p15INK4b, critical cell senescence genes, or other genes or pathways known to involve in HSC self-renewal were differentially expressed in Nras G12D/G12D HSCs. In contrast, gene ontology analysis revealed significant differential expression of genes in the MEK/ERK pathway in Nras G12D/G12D HSCs. This result is consistent with our phospho-flow study showing that Nras G12D/G12D selectively hyperactivates ERK in HSPCs. It has been documented that prolonged ERK signaling is a potent inducer of differentiation in cultured PC12 cells and inhibition of normal ERK signaling by a chemical inhibitor increases self-renewal in mouse embryonic stem cells. Thus, we are currently testing whether hyperactivation of ERK promotes depletion of Nras G12D/G12D HSCs through promoting HSC differentiation and whether blocking hyperactivation of ERK restores the normal HSC function and prevents MPN development. Disclosures: No relevant conflicts of interest to declare.
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Ardiyana, M., C. Sumantri, S. Murtini, and T. Sartika. "Keragaman Gen NRAMP-1 dan INOS pada Ayam Sentul Seleksi." Jurnal Ilmu Produksi dan Teknologi Hasil Peternakan 6, no. 2 (June 29, 2018): 48–52. http://dx.doi.org/10.29244/jipthp.6.2.48-52.

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40

James, J. A., and J. B. Harley. "Human lupus anti-spliceosome A protein autoantibodies bind contiguous surface structures and segregate into two sequential epitope binding patterns." Journal of Immunology 156, no. 10 (May 15, 1996): 4018–26. http://dx.doi.org/10.4049/jimmunol.156.10.4018.

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Abstract High levels of anti-spliceosomal autoantibodies are commonly found in systemic lupus erythematosus (lupus) sera. We have evaluated the binding of lupus autoantibodies to octapeptides of nuclear ribonucleoprotein (nRNP) A, identified patterns of binding that vary between sera, quantified the proportion of anti-nRNP that binds individual peptides, and related these data to the partial tertiary structure of nRNP A. Anti-nRNP A-positive lupus sera share binding to eight antigenic groups of octapeptides from nRNP A. The four shared antigenic sites in the known nRNP A tertiary structure are contiguous on its surface and include surface loops between beta sheets and/or alpha helices. Anti-peptide Abs account for a significant portion of the human autoimmune response to nRNP A. Lupus sera are also obviously divisible into two subsets by their binding to nRNP A-derived peptides. Eight of the thirteen anti-nRNP A sera tested bind most of the eight common antigenic regions of nRNP A. All five sera in the other subset bind to two and only two groups of nRNP A octapeptides. Of this subset, absorption experiments show that as much as 75% of the anti-nRNP found in a patient serum is bound to these two octapeptides from nRNP A. The 70K spliceosome protein contains similar peptides that are also bound by these sera (OR=13.5, p&lt;0.001). Lupus autoantibodies bind to peptides of nRNP A in discernibly consistent patterns that identify serologic subsets and in a manner that provides useful insights into the autoimmunity and antigenic structure of the nRNP A spliceosomal protein.
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41

Jobe, Alan H. "Teaching NRP." Journal of Pediatrics 154, no. 4 (April 2009): A1. http://dx.doi.org/10.1016/j.jpeds.2009.02.013.

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42

Madhusudanannair, Vinu, Filip Janku, Gerald Steven Falchook, David S. Hong, Jennifer J. Wheler, Aung Naing, Siqing Fu, et al. "NRAS mutations in patients with advanced cancers treated with target-based therapies in early-phase clinical trials." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 3106. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.3106.

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3106 Background: NRAS mutations in cancers increase MAPK signaling. It is plausible that NRAS mutations may be associated with sensitivity to drugs targeting the MAPK pathway. Methods: Tumors from 689 patients with advanced cancers referred to the Clinical Center for Targeted Therapy (phase I program) were screened in a CLIA-certified laboratory for NRAS mutations and if feasible, for PIK3CA, KRAS, BRAF mutations and PTEN aberrations. Whenever possible, patients with NRAS mutations were treated with agents targeting the RAF-MEK pathway. Results: Of the 689 patients, 58 (8%) had NRAS mutations. NRAS mutations were most prevalent in melanoma (26/170, 25%), thyroid (5/26, 19%), endometrial (2/27, 7%), non-small cell lung (1/31, 3%), ovarian (1/60, 2%) and colorectal cancers (1/74, 1%). NRAS mutations were not seen in any of the tested head and neck squamous cell cancers (n = 44); sarcomas (n = 41) and breast cancers (n = 25). None (0/62, 0%) of the patients tested for KRAS had simultaneous NRAS and KRAS mutations, and only 2/42 (5%) tested for BRAF had simultaneous NRAS and BRAF mutations. Of 58 patients with NRAS mutations, 14 (24%) were enrolled in trials that included MEK axis inhibitors. Of these 14 patients, 13 had melanoma and 1 had ovarian cancer and 4/14 (29%) demonstrated tumor shrinkage >10% from baseline. In comparison, only 22/187 (12%) patients with wild-type/unknown NRAS, KRAS and BRAF treated on the same trials demonstrated tumor shrinkage >10% (p=0.086). Conclusions: NRAS mutations are diagnosed in variety of advanced cancers. Patients with NRAS mutations demonstrated a trend to better antitumor activity with MEK axis inhibitors compared to patients without NRAS, KRAS or BRAF mutations. Further studies are warranted to delineate the role of NRAS mutations in patients treated with MEK axis inhibitors.
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Sun, Guangli, Gang Su, Fang Liu, and Wenjie Han. "NRAS Contributes to Retinoblastoma Progression Through SNHG16/miR-183-5p/NRAS Regulatory Network." OncoTargets and Therapy Volume 12 (December 2019): 10703–15. http://dx.doi.org/10.2147/ott.s232470.

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44

Parikh, Chaitali, Ramesh Subrahmanyam, and Ruibao Ren. "Oncogenic NRAS rapidly and efficiently induces CMML- and AML-like diseases in mice." Blood 108, no. 7 (October 1, 2006): 2349–57. http://dx.doi.org/10.1182/blood-2004-08-009498.

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Abstract Activating mutations in RAS, predominantly NRAS, are common in myeloid malignancies. Previous studies in animal models have shown that oncogenic NRAS is unable to induce myeloid malignancies effectively, and it was suggested that oncogenic NRAS might only act as a secondary mutation in leukemogenesis. In this study, we examined the leukemogenicity of NRAS using an improved mouse bone marrow transduction and transplantation model. We found that oncogenic NRAS rapidly and efficiently induced chronic myelomonocytic leukemia (CMML)– or acute myeloid leukemia (AML)– like disease in mice, indicating that mutated NRAS can function as an initiating oncogene in the induction of myeloid malignancies. In addition to CMML and AML, we found that NRAS induced mastocytosis in mice. This result indicates that activation of the RAS pathway also plays an important role in the pathogenesis of mastocytosis. The mouse model for NRAS leukemogenesis established here provides a system for further studying the molecular mechanisms in the pathogenesis of myeloid malignancies and for testing relevant therapies.
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Patterson, Scott D., Marc Peeters, Salvatore Siena, Eric Van Cutsem, Yves Humblet, Jean-Luc Van Laethem, Thierry Andre, Ying Tian, Roger Sidhu, and Kelly S. Oliner. "Comprehensive analysis of KRAS and NRAS mutations as predictive biomarkers for single agent panitumumab (pmab) response in a randomized, phase III metastatic colorectal cancer (mCRC) study (20020408)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 3617. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.3617.

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3617 Background: An exploratory biomarker analysis of the randomized, phase 3 monotherapy 20020408 study of pmab vs best supportive care (BSC) demonstrated that mutations in KRAS exon 3 and NRAS exons 2 and 3 appeared to be predictive of pmab response (Peeters et al, 2013). We expanded these results to determine whether mutations in exon 4 of the KRAS and NRAS genes are predictive for pmab treatment and to determine the treatment effect in the overall wild-type (WT) KRAS and NRAS population. Methods: Using a combination of Next Generation Sequencing, Sanger Sequencing, and WAVE-based SURVEYOR Scan Kits from Transgenomic, archival patient tumors were examined for mutations in KRAS and NRAS exon 4. These data were combined with previously presented data from KRAS and NRAS exon 2 and 3 analyses for evaluation of the comprehensive WT KRAS and NRAS subgroup. Results: 9/243 (3.7%) and 2/243 (0.8%) patient tumors with WT KRAS exon 2 status harbored a mutation in KRAS or NRAS exon 4, respectively. One tumor had mutations in both KRAS and NRAS exon 4. In the pmab arm, patients with WT KRAS and WT NRAS tumor status had an objective response rate (ORR) of 15% (11/72) whereas patients with mutant (MT) KRAS or MT NRAS tumor status had an ORR of 1% (1/95; 1 patient with MT KRAS exon 4 had a partial response). There were no responses in the BSC arm regardless of the tumor status. In this analysis set, the treatment hazard ratio (HR; pmab:BSC) for progression-free survival (PFS) in the WT KRAS and WT NRAS subgroup was 0.38 (95% CI: 0.27 - 0.56), and in the MT KRAS or MT NRAS subgroup was 0.98 (95% CI: 0.73 - 1.31). The original WT KRAS exon 2 subgroup PFS HR was 0.45 (95% CI: 0.34 - 0.59) (Amado et al, 2007). Conclusions: This exploratory analysis suggests that mutations in KRAS and NRAS exon 4 occur in a small, but meaningful percentage of patients with mCRC. Extending previous findings from this study in patients with MT KRAS and/or MT NRAS exon 2 and/or 3 tumors, patients with MT KRAS and/or MT NRAS exon 4 tumors do not appear to benefit from pmab therapy. Clinical trial information: NCT00113763.
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Kim, Won-Il, Ilze Matise, Miechaleen Diers, and David Largaespada. "Continued Expression of the NRAS(G12V) Oncogene Is Required for the Maintenance of Acute Myeloid Leukemia Induced in Cooperation with MLL-AF9." Blood 110, no. 11 (November 16, 2007): 1615. http://dx.doi.org/10.1182/blood.v110.11.1615.1615.

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Abstract To study the role of the NRAS(G12V) oncogene in the context of acute myeloid leukemia (AML) cells developing with in cooperation with MLL fusion oncogene (MLL-AF9), we used a Vav promoter-Tet transactivator (Vav-tTA)-driven repressible system of NRAS(G12V) expression in Mll-AF9 mice. Vav-tTA; TRE-NRAS(G12V); Mll-AF9 triply-transgenic mice were generated by crossing the Vav-tTA; TRE-NRAS(G12V) doubly-transgenic FVB/n and Mll-AF9 knock-in BL6 mice. The triply-transgenic FVB/n × BL6 F1 mice expressing both the NRAS(G12V) and Mll-AF9 transgenes developed AML, which showed a trend of decreased latency compared with those carrying only the Mll-AF9 knock-in transgene. Mast cell disease also occurred accordingly in the Vav-tTA; TRE-NRAS(G12V) co-transgenic mice. Since the mastocytosis disease is not transplantable, we transplanted bone marrow cells from four independent AML mice into recipient SCID mice to determine whether NRAS(G12V) expression is necessary to maintain AML in the recipient mice without mastocytosis. Continuously treating the transplanted SCID mice with doxycycline (Dox) in drinking water, we found the expression of NRAS(G12V) oncogene was required for AML persistence in three out of the four independent primary AML cells. Furthermore, we transplanted the AML bone marrow cells previously xenografted in the recipient SCID mice into other SCID mice to conditionally repress NRAS(G12V) expression only after the transplanted AML was fully established. We found the number of WBC cells was greatly decreased 4–6 days after the Dox treatment and this was correlated with the significant increase of apoptotic cells in bone marrow and peripheral bloods. The transplanted AML blast cells underwent apoptosis and were mostly removed from the circulating blood, bone marrow, and spleen after 8 days post Dox treatment. In 2–3 weeks after beginning Dox treatment and observing AML remission, Dox-resistant leukemia relapse was observed in recipient SCID mice. The relapsed leukemia failed to express NRAS(G12V) and showed significantly reduced aggressiveness along with less myelosuppression and more differentiated myeloid lineage cells than AML prior to repression of NRAS(G12V) expression. The NRAS(G12V)-independent relapsed disease histopathologically resembles an aggressive myeloproliferative disease (MPD) rather than AML, because the proportion of AML blast cells was less than 20% of myeloid lineage cells. The NRAS(G12V)-independent MPD could be transplanted into recipient SCID mice, but the subsequent anemia was greatly attenuated compared to transplant of the same AML clone expressing NRAS(G12V). We conclude that NRAS(G12V) can be a good molecular target to treat AML, because NRAS(G12V) expression is required for persistence and specific malignant features in AML induced in cooperation with MLL-AF9. Targeting NRAS(G12V) can strongly disturb the maintenance of AML blast cells and myelosuppression, although leukemia cells can relapse without NRAS(G12V) expression.
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&NA;. "7th Edition NRP Brings Big Changes for NRP Instructors." Advances in Neonatal Care 15, no. 3 (June 2015): 225–27. http://dx.doi.org/10.1097/anc.0000000000000194.

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48

Condon, J. J., W. D. Cotton, E. W. Greisen, Q. F. Yin, R. A. Perley, G. B. Taylor, and J. J. Broderick. "The NRAO VLA Sky Survey." Astronomical Journal 115, no. 5 (May 1998): 1693–716. http://dx.doi.org/10.1086/300337.

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49

Peranson, E., and R. R. Randlett. "The NRMP matching algorithm revisited." Academic Medicine 70, no. 6 (June 1995): 477–84. http://dx.doi.org/10.1097/00001888-199506000-00008.

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50

Castilla, Lucio H. "NRAS palmitoylation and oncogenic fitness." Blood 135, no. 20 (May 14, 2020): 1725–26. http://dx.doi.org/10.1182/blood.2020005720.

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