395 resultados para NAC
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Este trabajo focaliza su mirada en la crisis de la Universidad Argentina en el marco del proceso de transformación que fue imponiendo la economía capitalista, a partir de las últimas décadas del siglo XX, hasta nuestros días. La "modernización" impuesta a la Universidad desde los parámetros de la eficiencia, provocaron actos de resistencia por parte de la comunidad educativa. A través de la selección de tres "acontecimientos" institucionales considerados relevantes se pretende reconstruir un fragmento de la memoria colectiva de la Facultad de Humanidades y Artes de la U.N.R. (Univ. Nac. de Rosario). Estos "actos del recuerdo" provocan una dinámica al servicio de las acciones presentes, para no renunciar a un deseo emancipatorio. Desde ese lugar se consideran valiosas las ponencias de los distintos docentes, que junto con los autores seleccionados pretenden generar un debate para dar respuestas a la crisis socio-económica e institucional de estos "nuevos tiempos". Ante la nueva ideología que impone un "lenguaje unidimensional" se pone en escena la dimensión histórica del significado/s de los actores en este proceso que permanentemente sostiene la relación dialéctica entre educación-sociedad. Las demandas "pragmáticas" de adaptación al mundo laboral requieren que la Universidad tenga una mirada crítica cuando se propongan cambios curriculares
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Thesis (Master's)--University of Washington, 2016-06
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Clark 1 (diphenylarsine chloride) and Clark 2 ( diphenylarsine cyanide) were used as chemical weapon agents (CWA), and the soil contamination by these CWA and their degraded products, diphenyl and phenyl arsenicals, has been one of the most serious environmental issues. In a series of comparisons in toxicity between trivalent and pentavalent arsenicals we investigated differences in the accumulation and toxicity of phenylarsine oxide (PAO(3+)) and phenylarsonic acid (PAA(5+)) in rat heart microvascular endothelial cells. Both the cellular association and toxicity of PAO(3+) were much higher than those of PAA(5+), and LC50 values of PAO(3+) and PAA(5+) were calculated to be 0.295 muM and 1.93 mM, respectively. Buthionine sulfoximine, a glutathione depleter, enhanced the cytotoxicity of both PAO(3+) and PAA(5+). N-Acetyl-L-cysteine (NAC) reduced the cytotoxicity and induction of heme oxygenase-1 (HO-1) mRNA in PAO(3+)-exposed cells, while NAC affected neither the cytotoxicity nor the HO-1 mRNA level in PAA(5+)-exposed cells. The effect of NAC may be due to a strong affinity of PAO(3+) to thiol groups because both NAC and GSH inhibited the cellular accumulation of PAO(3+), but PAA(3+) increased tyrosine phosphorylation levels of cellular proteins. These results indicate that the inhibition of protein phosphatases as well as the high affinity to cellular components may confer PAO(3+) the high toxicity.
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1. The mechanism of action by which methotrexate (MTX) exerts its anti-inflammatory and immunosuppressive effects remains unclear. The aim of this study is to investigate the hypothesis that MTX exerts these effects via the production of reactive oxygen species (ROS). 2. Addition of MTX (100 nM-10 μM) to U937 monocytes induced a time and dose dependent increase in cytosolic peroxide [peroxide] cyt from 6-16 h. MTX also caused corresponding monocyte growth arrest, which was inhibited (P<0.05) by pre-treatment with N-acetylcysteine (NAC; 10 mM) or glutathione (GSH; 10 mM). In contrast, MTX induction of [peroxide] cyt in Jurkat T cells was more rapid (4 h; P<0.05), but was associated with significant apoptosis at 16 h at all doses tested (P<0.05) and was significantly inhibited by NAC or GSH (P<0.05). 3. MTX treatment of monocytes (10 nM-10 μM) for 16 h significantly reduced total GSH levels (P<0.05) independently of dose (P>0.05). However in T-cells, GSH levels were significantly elevated following 30 nM MTX treatment (P<0.05) but reduced by doses exceeding 1 μM compared to controls (P<0.05). 4. MTX treatment significantly reduced monocyte adhesion to 5 h and 24 h LPS (1 μg ml -1) activated human umbilical vein endothelial cells (HUVEC; P<0.05) but not to resting HUVEC. Pre-treatment with GSH prevented MTX-induced reduction in adhesion. 5. In conclusion, ROS generation by MTX is important for cytostasis in monocytes and cytotoxicity T-cells. Furthermore, MTX caused a reduction in monocyte adhesion to endothelial cells, where the mechanism of MTX action requires the production of ROS. Therefore its clinical efficacy can be attributed to multiple targets.
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The effect of sodium cholate (NaC; concentration 1-16 mM), a biological surfactant, on the aggregation behavior of 1% (w/v, 2.2 × 10(-3) M) poly(N-isopropylacrylamide) (PNIPAM) aqueous solutions was studied as a function of temperature. From turbidity, dynamic light scattering, viscosity, and fluorescence measurements, it was observed that (i) there is NaC-induced nanoscale aggregation of PNIPAM in its sol state and (ii) the lower critical solution temperature corresponding to sol-gel transition shifts to a lower temperature by about 2 °C.
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A series of antioxidants was used to explore the cytotoxicity of one particularly toxic antimycobacterial 2-pyridylcarboxamidrazone anti-tuberculosis agent against human mononuclear leucocytes (MNL), in comparison with isoniazid (INH) to aid future compound design. INH caused a significant reduction of nearly 40% in cell recovery compared with control (P < 0.0001), although the co-incubation with either glutathione (GSH, 1 mM) or (NAC, 1 mM) showed abolition of INH toxicity. In contrast, the addition of GSH or NAC 1 h after INH failed to protect the cells from INH toxicity (P < 0.0001). The 2-pyridyl-carboxamidrazone 'Compound 1' caused a 50% reduction in cell recovery compared with control (P < 0.001), although this was abolished by the presence of either GSH or NAC. A 1 h post incubation with either NAC or GSH after Compound 1 addition failed to protect the cells from toxicity (P < 0.001). Co-administration of lipoic acid (LA) abolished Compound 1-mediated toxicity, although again, this effect did not occur after LA addition 1 h post incubation with Compound 1 (P < 0.001). However, co-administration of dihydrolipoic acid (DHLA) prevented Compound 1-mediated cell death when incubated with the compound and also after 1 h of Compound 1 alone. Pre-treatment with GSH, then removal of the antioxidant resulted in abolition of Compound 1 toxicity (vehicle control, 63.6 ± 16.7 versus Compound 1 alone 26.1 ± 13.6% versus GSH pre-treatment, 65.7 ± 7.3%). In a cell-free incubation, NMR analysis revealed that GSH does not react with Compound 1, indicating that this agent is not likely to directly deplete membrane thiols. Compound 1's MNL toxicity is more likely to be linked with changes in cell membrane conformation, which may induce consequent thiol depletion that is reversible by exogenous thiols. © 2004 Elsevier B.V. All rights reserved.
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Gamma-hydroxybutyric acid (GHB) is an endogenous brain substance that has diverse neuropharmacological actions, including rewarding properties in different animal species and in humans. As other drugs of abuse, GHB affects the firing of ventral tegmental neurons (VTA) in anaesthetized animals and hyperpolarizes dopaminergic neurons in VTA slices. However, no direct behavioural data on the effects of GHB applied in the VTA or in the target regions of its dopaminergic neurons, e.g. the nucleus accumbens (NAc), are available. Here, we investigated the effects of various doses of intravenous GHB in maintaining self-administration (from 0.001 to 10 mg/kg per infusion), and its ability to induce conditioned place preference (CPP) in rats when given orally (175-350 mg/kg) or injected directly either in the VTA or NAc (from 10 to 300 microg/0.5 microl per side). Our results indicate that while only 0.01 mg/kg per infusion GHB maintained self-administration, although not on every test day, 350 mg/kg GHB given orally induced CPP. CPP was also observed when GHB was injected in the VTA (30-100 microg/0.5 microl per side) but not in the NAc. Together with recent in-vitro findings, these results suggest that the rewarding properties of GHB mainly occur via disinhibition of VTA dopaminergic neurons.
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Aims: Pulmonary arterial hypertension [1] is a proliferative disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMCs). Reactive oxygen species (ROS) is implicated in the development of PAH and regulates the vascular tone and functions. However, which cellular signaling mechanisms are triggered by ROS in PAH is still unknown. Hence, here we wished to characterize the signaling mechanisms triggered by ROS. Methods and Results: By Western blots, we showed that increased intracellular ROS caused inhibition of the glycolytic pyruvate kinase M2 (PKM2) activity through promoting the phosphorylation of PKM2. Monocrotaline (MCT)-induced rats developed severe PAH and right ventricular hypertrophy, with a significant increase in the P-PKM2 and decrease in pyruvate kinase activity which could be attenuated with the treatments of PKM2 activators, FBP and l-serine. The antioxidant NAC, apocynin and MnTBAP had the similar protective effects in the development of PAH. In vitro assays confirmed that inhibition of PKM2 activity could modulate the flux of glycolytic intermediates in support of cell proliferation through the increased pentose phosphate pathway (PPP). Increased ROS and decreased PKM2 activity also promoted the Cav1.2 expression and intracellular calcium. Conclusion: Our data provide new evidence that PKM2 makes a critical regulatory contribution to the PAHs for the first time. Decreased pyruvate kinase M2 activity confers additional advantages to rat PASMCs by allowing them to sustain anti-oxidant responses and thereby support cell survival in PAH. It may become a novel treatment strategy in PAH by using of PKM2 activators.
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A series of N1-benzylidene pyridine-2-carboxamidrazone anti-tuberculosis compounds has been evaluated for their cytotoxicity using human mononuclear leucocytes (MNL) as target cells. All eight compounds were significantly more toxic than dimethyl sulphoxide control and isoniazid (INH) with the exception of a 4-methoxy-3-(2-phenylethyloxy) derivative, which was not significantly different in toxicity compared with INH. The most toxic agent was an ethoxy derivative, followed by 3-nitro, 4-methoxy, dimethylpropyl, 4-methylbenzyloxy, 3-methoxy-4-(-2-phenylethyloxy) and 4-benzyloxy in rank order. In comparison with the effect of selected carboxamidrazone agents on cells alone, the presence of either N-acetyl cysteine (NAC) or glutathione caused a significant reduction in the toxicity of INH, as well as on the 4-benzyloxy derivative, although both increased the toxicity of a 4-N,N-dimethylamino-1-naphthylidene and a 2-t-butylthio derivative. The derivatives from this and three previous studies were subjected to computational analysis in order to derive equations designed to establish quantitative structure activity relationships for these agents. Twenty-five compounds were thus resolved into two groups (1 and 2), which on analysis yielded equations with r2 values in the range 0.65-0.92. Group 1 shares a common mode of toxicity related to hydrophobicity, where cytotoxicity peaked at logP of 3.2, while Group 2 toxicity was strongly related to ionisation potential. The presence of thiols such as NAC and GSH both promoted and attenuated toxicity in selected compounds from Group 1, suggesting that secondary mechanisms of toxicity were operating. These studies will facilitate the design of future low toxicity high activity anti-tubercular carboxamidrazone agents. © 2003 Elsevier Science B.V. All rights reserved.
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Loss aversion (LA), the idea that negative valuations have a higher psychological impact than positive ones, is considered an important variable in consumer research. The literature on aging and behavior suggests older individuals may show more LA, although it is not clear if this is an effect of aging in general (as in the continuum from age 20 and 50 years), or of the state of older age (e.g., past age 65 years). We also have not yet identified the potential biological effects of aging on the neural processing of LA. In the current study we used a cohort of subjects with a 30 year range of ages, and performed whole brain functional MRI (fMRI) to examine the ventral striatum/nucleus accumbens (VS/NAc) response during a passive viewing of affective faces with model-based fMRI analysis incorporating behavioral data from a validated approach/avoidance task with the same stimuli. Our a priori focus on the VS/NAc was based on (1) the VS/NAc being a central region for reward/aversion processing; (2) its activation to both positive and negative stimuli; (3) its reported involvement with tracking LA. LA from approach/avoidance to affective faces showed excellent fidelity to published measures of LA. Imaging results were then compared to the behavioral measure of LA using the same affective faces. Although there was no relationship between age and LA, we observed increasing neural differential sensitivity (NDS) of the VS/NAc to avoidance responses (negative valuations) relative to approach responses (positive valuations) with increasing age. These findings suggest that a central region for reward/aversion processing changes with age, and may require more activation to produce the same LA behavior as in younger individuals, consistent with the idea of neural efficiency observed with high IQ individuals showing less brain activation to complete the same task.
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The School of Hospitality Management at Florida International University recently offered a new course, recreational food service management, in an effort to address the specialized needs of that segment of the industry. The author discusses the size and scope of this area, its history and presentations, its specialized operational nature, its menu structure and style of service, and the unique management requirements for success.
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In the western North Atlantic, warm and saline water is brought by the North Atlantic Current (NAC) from the subtropics into the subpolar gyre. Four inverted echo sounders with high precision pressure sensors (PIES) were moored between 47°40' N and 52°30' N to study the main pathways of the NAC from the western into the eastern basin. The array configuration that forms three segments (northern, central, and southern) allows partitioning of the NAC and some assessment of NAC flow paths through the different Mid-Atlantic Ridge fracture zones. We exploit the correlation between the NAC transport measured between 2006 and 2010 and the geostrophic velocity from altimeter data to extend the time series of NAC transports to the period from 1992 to 2013. The mean NAC transport over the entire 21 years is 27 ± 5 Sv, consisting of 60% warm water of subtropical origin and 40% subpolar water. We did not find a significant trend in the total transport time series, but individual segments had opposing trends, leading to a more focused NAC in the central subsection and decreasing transports in the southern and northern segments. The spectral analysis exhibits several significant peaks. The two most prominent are around 120 days, identified as the time scale of meanders and eddies, and at 4-9 years, most likely related to the NAO. Transport composites for the years of highest and lowest NAO indices showed a significantly higher transport (+2.9 Sv) during strong NAO years, mainly in the southern segment.
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The southwestern part of the subpolar North Atlantic east of the Grand Banks of Newfoundland and Flemish Cap is a crucial area for the Atlantic Meridional Overturning Circulation. Here the exchange between subpolar and subtropical gyre takes place, southward flowing cold and fresh water is replaced by northward flowing warm and salty water within the North Atlantic Current (NAC). As part of a long-term experiment, the circulation east of Flemish Cap has been studied by seven repeat hydrographic sections along inline image (2003-2011), a 2 year time series of current velocities at the continental slope (2009-2011), 19 years of sea surface height, and 47 years of output from an eddy resolving ocean circulation model. The structure of the flow field in the measurements and the model shows a deep reaching NAC with adjacent recirculation and two distinct cores of southward flow in the Deep Western Boundary Current (DWBC): one core above the continental slope with maximum velocities at mid-depth and the second farther east with bottom-intensified velocities. The western core of the DWBC is rather stable, while the offshore core shows high temporal variability that in the model is correlated with the NAC strength. About 30 Sv of deep water flow southward below a density of sigma-theta = 27.68 kg/m**3 in the DWBC. The NAC transports about 110 Sv northward, approximately 15 Sv originating from the DWBC, and 75 Sv recirculating locally east of the NAC, leaving 20 Sv to be supplied by the NAC from the south.
GESTÃO DA CULTURA NA UNIVERSIDADE: O NÚCLEO DE ARTE E CULTURA DA UNIVERSIDADE METODISTA DE SÃO PAULO
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Essa dissertação resulta de um processo de reflexão autobiográfica, com base no resgate de memórias e vivências do percurso de vida-trabalho da pesquisadora, a partir da experiência na gestão do Núcleo de Arte e Cultura (NAC) da Universidade Metodista de São Paulo (UMESP), desde a sua criação, em 2005. Compreender o processo de criação, constituição e inserção do NAC na UMESP, como também o exercício da gestão cultural nesse espaço universitário, foram objetivos dessa pesquisa, que destaca o diálogo entre Educação e Cultura, mediado pela Arte, a partir da inserção de ações artístico-culturais focadas no respeito às diferenças e na valorização da diversidade humana e cultural. Qual o papel da ação cultural dentro de uma universidade? Como essas ações podem somar com o processo de formação educacional? Que desafios envolveram a construção e constituição do Núcleo de Arte e Cultura da UMESP? Essas são questões geradoras do desenvolvimento desse trabalho, no qual é utilizada a abordagem (auto)biográfica como metodologia de pesquisa. Na narrativa propiciada por essa abordagem, a pesquisadora procurou revisitar e ressignificar, numa perspectiva de produção de conhecimento, memórias e histórias que contribuíram para a construção da sua própria identidade e que alavancaram sua inserção na gestão da Cultura na UMESP, legitimando e firmando a atuação do Núcleo de Arte e Cultura, ao longo dos seus 10 anos de existência. Ao refletir sobre essa práxis, evidenciou-se que trabalhar com as subjetividades é o grande desafio da gestão da Cultura, como também a construção de processos colaborativos, na perspectiva do “fazer com” e não do “fazer para” é o caminho para o fortalecimento e enraizamento das ações.
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The position of the North Atlantic Current (NAC) during the intensification of Northern Hemisphere glaciation (iNHG) has been evaluated using dinoflagellate cyst assemblages and foraminiferal geochemistry from a ~260 kyr interval straddling the base of the Quaternary System from two sites: eastern North Atlantic Deep Sea Drilling Project Site 610 in the path of the present NAC and central North Atlantic Integrated Ocean Drilling Program Site U1313 in the subtropical gyre. Stable isotope and foraminiferal Mg/Ca analyses confirm cooling near the marine isotope stage (MIS) G7-G6 transition (2.74 Ma). However, a continued dominance of the dinoflagellate cyst Operculodinium centrocarpum sensu Wall and Dale (1966) indicates an active NAC in the eastern North Atlantic for a further 140 kyr. At MIS 104 (~2.60 Ma), a profound dinoflagellate cyst assemblage turnover indicates NAC shutdown in the eastern North Atlantic, implying elevated atmospheric pressure over the Arctic and a resulting shift in the westerlies that would have driven the NAC. These findings challenge recent suggestions that there was no significant southward shift of the NAC or the Arctic Front during iNHG, and reveal a fundamental climatic reorganization near the base of the Quaternary.