161 research outputs found

    Shuffle on array languages generated by array grammars

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    Motivated by the studies done by G. Siromoney et al. (1973) and Alexan- dru Mateescu et al. (1998) we examine the language theoretic results related to shuf- fle on trajectories by making use of Siromoney array grammars such as (R : R)AG, (R : C F )AG, (C F : R)AG, (C F : C F )AG, (C S : R)AG, (C S : C S)AG and (C F : C S)AG which are more powerful than the Siromoney matrix grammars (1972) and are used to make digital pictures

    SHUFFLE ON ARRAY LANGUAGES GENERATED BY ARRAY GRAMMARS

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    Abstract. Motivated by the studies done by G

    Monitoring of Multi-Aspect Drought Severity and Socio-Economic Status in the Semi-Arid Regions of Eastern Tamil Nadu, India

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    A framework was set up to monitor drought in the semi-arid regions of eastern Tamil Nadu, southern India, for the period of 2014–2018 CE with the application of the standardized precipitation index (SPI), the scaled drought-condition index (SDCI), and the standardized water-level index (SWI). The results emphasized that this region had a negative precipitation anomaly and vegetative stress, both of which triggered meteorological and agricultural droughts and caused significant losses in the farming sector. The distributions of extreme and high-level hydrological droughts were at their maximum in 2017 CE. The multi-drought severity index (MDSI), implemented to assess the combined impact and highlighting the gradient of affected areas, illustrated that the eastern region (i.e., Jayankondam block) was the most extremely affected, followed by the northern and southern regions (i.e., T.Palur and Andimadam), which were moderately affected by droughts. The extremely affected eastern region has less of an ability to overcome droughts due to its socio-economic vulnerability, with its greater population and household density leading to the over-exploitation of potential resources. Therefore, the focus of this study is on the monitoring of drought severity in micro-administrative units to suggest an appropriate management plan. Hence, the extreme-drought- prone block (Jayankondam) should be given high priority in monitoring and implementing long-term management practices for its conservation and resilience against the effects of severe droughts

    The role of acid-base imbalance in statin-induced myotoxicity

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    Disturbances in acid-base balance, such as acidosis and alkalosis, have potential to alter the pharmacological and toxicological outcomes of statin therapy. Statins are commonly prescribed for elderly patients who have multiple co-morbidities such as diabetes mellitus, cardiovascular and renal diseases. These patients are at risk of developing acid-base imbalance. In the present study, the effect of disturbances in acid-base balance on the inter-conversion of simvastatin and pravastatin between lactone and hydroxy acid forms have been investigated in physiological buffers, human plasma and cell culture medium over pH ranging from 6.8 to 7.8. The effects of such inter-conversion on cellular uptake and myotoxicity of statins were assessed in vitro using C2C12 skeletal muscle cells under conditions relevant to acidosis, alkalosis and physiological pH. Results indicate that the conversion of the lactone forms of simvastatin and pravastatin to the corresponding hydroxy acid is strongly pH-dependent. At physiological and alkaline pH, substantial proportions of simvastatin lactone (~ 87% and 99%, respectively) and pravastatin lactone (~ 98% and 99%, respectively) were converted to the active hydroxy acid forms after 24 hours of incubation at 37 °C. At acidic pH, conversion occurs to a lower extent, resulting in greater proportion of statin remaining in the more lipophilic lactone form. However, pH alteration did not influence the conversion of the hydroxy acid forms of simvastatin and pravastatin to the corresponding lactones. Furthermore, acidosis has been shown to hinder the metabolism of the lactone form of statins by inhibiting hepatic microsomal enzyme activities. Lipophilic simvastatin lactone was found to be more cytotoxic to undifferentiated and differentiated skeletal muscle cells compared to more hydrophilic simvastatin hydroxy acid, pravastatin lactone and pravastatin hydroxy acid. Enhanced cytotoxicity of statins was observed under acidic conditions and is attributed to increased cellular uptake of the more lipophilic lactone or unionized hydroxy acid form. Consequently, our results suggest that co-morbidities associated with acid-base imbalance can play a substantial role in the development and potentiation of statin-induced myotoxicity

    Over-expression of adenosine deaminase in mouse podocytes does not reverse puromycin aminonucleoside resistance

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    <p>Abstract</p> <p>Background</p> <p>Edema in nephrotic syndrome results from renal retention of sodium and alteration of the permeability properties of capillaries. Nephrotic syndrome induced by puromycin aminonucleoside (PAN) in rats reproduces the biological and clinical signs of the human disease, and has been widely used to identify the cellular mechanisms of sodium retention. Unfortunately, mice do not develop nephrotic syndrome in response to PAN, and we still lack a good mouse model of the disease in which the genetic tools necessary for further characterizing the pathophysiological pathway could be used. Mouse resistance to PAN has been attributed to a defect in glomerular adenosine deaminase (ADA), which metabolizes PAN. We therefore attempted to develop a mouse line sensitive to PAN through induction of normal adenosine metabolism in their podocytes.</p> <p>Methods</p> <p>A mouse line expressing functional ADA under the control of the podocyte-specific podocin promoter was generated by transgenesis. The effect of PAN on urinary excretion of sodium and proteins was compared in rats and in mice over-expressing ADA and in littermates.</p> <p>Results</p> <p>We confirmed that expression of ADA mRNAs was much lower in wild type mouse than in rat glomerulus. Transgenic mice expressed ADA specifically in the glomerulus, and their ADA activity was of the same order of magnitude as in rats. Nonetheless, ADA transgenic mice remained insensitive to PAN treatment in terms of both proteinuria and sodium retention.</p> <p>Conclusions</p> <p>Along with previous results, this study shows that adenosine deaminase is necessary but not sufficient to confer PAN sensitivity to podocytes. ADA transgenic mice could be used as a background strain for further transgenesis.</p

    Clathrin and LRP-1-Independent Constitutive Endocytosis and Recycling of uPAR

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    Background: The urokinase receptor (uPAR/CD87) is highly expressed in malignant tumours. uPAR, as a GPI anchored protein, is preferentially located at the cell surface, where it interacts with its ligands urokinase (uPA) and the extracellular matrix protein vitronectin, thus promoting plasmin generation, cell-matrix interactions and intracellular signalling events. Interaction with a complex formed by uPA and its inhibitor PAI-1 induces cell surface down regulation and recycling of the receptor via the clathrin-coated pathway, a process dependent on the association to LRP-1. Methodology/Principal Findings: In this study, we have found that along with the ligand-induced down-regulation, uPAR also internalizes and recycles constitutively through a second pathway that is independent of LRP-1 and clathrin but shares some properties with macropinocytosis. The ligand-independent route is amiloride-sensitive, does not require uPAR partitioning into lipid rafts, is independent of the activity of small GTPases RhoA, Rac1 and Cdc42, and does not require PI3K activity. Constitutively endocytosed uPAR is found in EEA1 positive early/recycling endosomes but does not reach lysosomes in the absence of ligands. Electron microscopy analysis reveals the presence of uPAR in ruffling domains at the cell surface, in macropinosome-like vesicles and in endosomal compartments. Conclusions/Significance: These results indicate that, in addition to the ligand-induced endocytosis of uPAR, efficient surface expression and membrane trafficking might also be driven by an uncommon macropinocytic mechanism couple

    Hepatitis C Virus Protects Human B Lymphocytes from Fas-Mediated Apoptosis via E2-CD81 Engagement

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    HCV infection is often associated with B-cell regulatory control disturbance and delayed appearance of neutralizing antibodies. CD81 is a cellular receptor for HCV and can bind to HCV envelope protein 2 (E2). CD81 also participates to form a B cell costimulatory complex. To investigate whether HCV influences B cell activation and immune function through E2 -CD81 engagement, here, human Burkitt's lymphoma cell line Raji cells and primary human B lymphocytes (PHB) were treated with HCV E2 protein and cell culture produced HCV particles (HCVcc), and then the related cell phenotypes were assayed. The results showed that both E2 and HCVcc triggered phosphorylation of IκBα, enhanced the expression of anti-apoptosis Bcl-2 family proteins, and protected Raji cells and PHB cells from Fas-mediated death. In addition, both E2 protein and HCVcc increased the expression of costimulatory molecules CD80, CD86 and CD81 itself, and decreased the expression of complement receptor CD21. The effects were dependent on E2-CD81 interaction on the cell surface, since CD81-silenced Raji cells did not respond to both treatments; and an E2 mutant that lose the CD81 binding activity, could not trigger the responses of both Raji cells and PHB cells. The effects were not associated with HCV replication in cells, for HCV pseudoparticle (HCVpp) and HCVcc failed to infect Raji cells. Hence, E2-CD81 engagement may contribute to HCV-associated B cell lymphoproliferative disorders and insufficient neutralizing antibody production

    Natural radionuclide of Po210 in the edible seafood affected by coal-fired power plant industry in Kapar coastal area of Malaysia

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    <p>Abstract</p> <p>Background</p> <p>Po<sup>210 </sup>can be accumulated in various environmental materials, including marine organisms, and contributes to the dose of natural radiation in seafood. The concentration of this radionuclide in the marine environment can be influenced by the operation of a coal burning power plant but existing studies regarding this issue are not well documented. Therefore, the aim of this study was to estimate the Po<sup>210 </sup>concentration level in marine organisms from the coastal area of Kapar, Malaysia which is very near to a coal burning power plant station and to assess its impact on seafood consumers.</p> <p>Methods</p> <p>Concentration of Po<sup>210 </sup>was determined in the edible muscle of seafood and water from the coastal area of Kapar, Malaysia using radiochemical separation and the Alpha Spectrometry technique.</p> <p>Results</p> <p>The activities of Po<sup>210 </sup>in the dissolved phase of water samples ranged between 0.51 ± 0.21 and 0.71 ± 0.24 mBql<sup>-1 </sup>whereas the particulate phase registered a range of 50.34 ± 11.40 to 72.07 ± 21.20 Bqkg<sup>-1</sup>. The ranges of Po<sup>210 </sup>activities in the organism samples were 4.4 ± 0.12 to 6.4 ± 0.95 Bqkg<sup>-1 </sup>dry wt in fish (<it>Arius maculatus</it>), 45.7 ± 0.86 to 54.4 ± 1.58 Bqkg<sup>-1 </sup>dry wt in shrimp (<it>Penaeus merguiensis</it>) and 104.3 ± 3.44 to 293.8 ± 10.04 Bqkg<sup>-1 </sup>dry wt in cockle (<it>Anadara granosa</it>). The variation of Po<sup>210 </sup>in organisms is dependent on the mode of their life style, ambient water concentration and seasonal changes. The concentration factors calculated for fish and molluscs were higher than the recommended values by the IAEA. An assessment of daily intake and received dose due to the consumption of seafood was also carried out and found to be 2083.85 mBqday<sup>-1</sup>person<sup>-1 </sup>and 249.30 μSvyr<sup>-1 </sup>respectively. These values are comparatively higher than reported values in other countries. Moreover, the transformation of Po<sup>210 </sup>in the human body was calculated and revealed that a considerable amount of Po<sup>210 </sup>can be absorbed in the internal organs. The calculated values of life time mortality and morbidity cancer risks were 24.8 × 10<sup>-4 </sup>and 34 × 10<sup>-4 </sup>respectively which also exceeded the recommended limits set by the ICRP.</p> <p>Conclusions</p> <p>The findings of this present study can be used to evaluate the safety dose uptake level of seafood as well as to monitor environmental health. However, as the calculated dose and cancer risks were found to cross the limit of safety, finding a realistic way to moderate the risk is imperative.</p
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