98 research outputs found
Importance of Architecture and Planning of Kanchipuram and the Dynamics of Implementing Architectural Restoration
The importance of traditional architecture and planning of Kanchipuram is expressed through a set of objective and subjective map based indicators. The analysis is done at the block level. The results brings out values expressing the epitome of the traditional architecture and planning. The paper presents the map based analysis of the traditional core. The map based analysis perceives changes in the tissues of the study area. The paper emphasizes the importance of social activities as a key to good urban life. The importance of social activities in par with physical component holding it is also presented. A subjective note on climatic considerations at the block level is given based on observations. To compliment conservation measures, a feasibility study to revamp vernacular elements in the modern facades of the city is probed. Stated preference survey method was adopted for the feasibility study. Emphasis is given to public participation and professional involvement in the process of planning and implementing conservation measures. The measures shall realize economic development and life processes. Further certain morale ethics involved in the process methods of planning is discussed. Though the changes are high; the city upholds bright quos towards conservation pertaining to acceptance of traditional aspects and the urge for socialization
A Review on Security Attacks in Vehicular Ad hoc Network
Whenever a communication takes place between two or more vehicles there has been a need for protection. The attacker can gain access to the network by compromising either the vehicle or road side unit or the communication medium that transfers the messages between vehicles. Vehicular Ad hoc Network (VANET) have motivated the interest towards the passenger comfort and secure driving environment. However, the open-wide communication becomes a tedious challenge for VANET organization. Because of the wireless self-structured background, VANET are prone to many attackers. In this paper, we are focusing on security issues like DoS, Sybil, DDoS, jamming and flooding attacks as well as techniques like TESLA which causes harm to VANET and also security countermeasures like digital signature which are used to prevent the mentioned security issues that alleviate VANET
Monitoring of Noctiluca Bloom in Mandapam and Keelakarai Coastal Waters; Southeast Coast of India
Monitoring the Harmful Algal Blooms was carried out during July to December 2008 in Mandapam and Keelakarai coastal waters of Tamil Nadu, Southeast coast of India. In the month of October several fishes and shellfishes were died due to Noctiluca blooms along these two areas. The present investigation the following species of phyto and zooplankton were found to be common; phytoplankton such as Coscinodiscus sp., Skeletonema costatum, Bacillaria paradoxa, Thallassiothrix frauenfeldii, T. longisima, Leptocylindrus sp., and zooplankton such as Paracalanus parvus, Acrocalanus gracilis, Pseudodiaptomus serricautatus, Rhincalanus cornutus, R. nasutus, Euterpina acutifrons, Nannocalanus minor, Eucalanus attenuates, E. crassus, Fish larvae, Fish eggs, Barnacle nauplii, Bivalve larvae, Gastropod larvae, Copepod nauplii and Mysis larvae. The hydrobiological parameters also analysed during bloom and after blooms; the dissolved oxygen (2.6 – 4.9µM L-1) nutrients varied between nitrate (0.66 – 1.01µM L-1) nitrite (0.11 – 0.21µM L-1) phosphate (0.51 – 0.86µM L-1) and silicate (0.81 – 4.2µM L-1)
High occurrence of Jellyfish (Catostylus perezi, Ranson 1945) in proximity to industrial development, Gulf of Kutch/ Kachchh, India
Here, the mass occurrence of Jellyfish, Catostylus perezi, Ranson 1945 is reported from the coastal waters of Gulf of Kutch/ Kachchh, Gujarat, India. Although high productivity is a possible reason the presence of man-made infrastructures like thermal power plants and ports are further highlighted. A further assessment of the effects of these structures on marine life is suggested in this article
Why Are Saccharides Dehydrated in the Presence of Electrolytes? Insights from Molecular Modeling and Thermodynamic Measurements
The mechanisms governing the interactions of neutral polar solutes with ions in aqueous solutions are still poorly understood, despite the importance of this phenomenon in many fields (chemistry, physicochemistry, biology, food industries). In order to go further through the understanding of the molecular mechanisms governing the ions’ specific effects, this paper presents a generic method dealing with the characterization and understanding of interactions between saccharides and ions in aqueous systems. For that, an original approach combining a computational technique and experimental measurements (thermodynamic properties) is proposed to explain and rationalize the relationship between the solute hydration and the physical chemistry of the ions in solution (cation/anion, charge, size, and hydration). These relationships make it possible to evaluate the hydration state of a saccharide, a polar neutral molecule, according to the ionic composition, from the knowledge of the ions’ hydration properties. This work proposes new insight into molecular mechanisms governing the polar neutral solute/ion interactions and a new understanding of the hydration phenomenon in electrolytic solutions
Metabolism of Low-Dose Inorganic Arsenic in a Central European Population: Influence of Sex and Genetic Polymorphisms
BACKGROUND: There is a wide variation in susceptibility to health effects of arsenic, which, in part, may be due to differences in arsenic metabolism. Arsenic is metabolized by reduction and methylation reactions, catalyzed by reductases and methyltransferases. OBJECTIVES: Our goal in this study was to elucidate the influence of various demographic and genetic factors on the metabolism of arsenic. METHODS: We studied 415 individuals from Hungary, Romania, and Slovakia by measuring arsenic metabolites in urine using liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). We performed genotyping of arsenic (+III) methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), and methylene-tetrahydrofolate reductase (MTHFR). RESULTS: The results show that the M287T (T-->C) polymorphism in the AS3MT gene, the A222V (C-->T) polymorphism in the MTHFR gene, body mass index, and sex are major factors that influence arsenic metabolism in this population, with a median of 8.0 microg/L arsenic in urine. Females C) polymorphism in the AS3MT gene on the methylation capacity was much more pronounced in men than in women. CONCLUSIONS: The factors investigated explained almost 20% of the variation seen in the metabolism of arsenic among men and only around 4% of the variation among women. The rest of the variation is probably explained by other methyltransferases backing up the methylation of arsenic
The Influence of Sex, Ethnicity, and CYP2B6 Genotype on Bupropion Metabolism as an Index of Hepatic CYP2B6 Activity in Humans
The effects of sex, ethnicity, and genetic polymorphism on hepatic CYP2B6 (cytochrome P450 2B6) expression and activity were previously demonstrated in vitro. Race/ethnic differences in CYP2B6 genotype and phenotype were observed only in women. To identify important covariates associated with interindividual variation in CYP2B6 activity in vivo, we evaluated these effects in healthy volunteers using bupropion (Wellbutrin SR GlaxoSmithKline, Research Triangle Park, NC) as a CYP2B6 probe substrate. A fixed 150-mg oral sustained-release dose of bupropion was administered to 100 healthy volunteers comprising four sex/ethnicity cohorts (n = 25 each): Caucasian men and Caucasian, African American, and Hispanic women. Blood samples were obtained at 0 and 6 hours postdose for the measurement of serum bupropion (BU) and hydroxybupropion (HB) concentrations. Whole blood was obtained at baseline for CYP2B6 genotyping. To characterize the relationship between CYP2B6 activity and ethnicity, sex, and genotype when accounting for serum BU concentrations (dose-adjusted log10-transformed), analysis of covariance model was fitted in which the dependent variable was CYP2B6 activity represented as the log10-transformed, metabolic ratio of HB to BU concentrations. Several CYP2B6 polymorphisms were associated with CYP2B6 activity. Evidence of dependence of CYP2B6 activity on ethnicity or genotype-by-ethnicity interactions was not detected in women. These results suggest that CYP2B6 genotype is the most important patient variable for predicting the level of CYP2B6 activity in women, when measured by the metabolism of bupropion. The bupropion metabolic ratio appears to detect known differences in CYP2B6 activity associated with genetic polymorphism, across different ethnic groups. Prospective studies will be needed to validate the use of bupropion as a probe substrate for clinical use
B-RAF and N-RAS Mutations Are Preserved during Short Time In Vitro Propagation and Differentially Impact Prognosis
In melanoma, the RAS/RAF/MEK/ERK signalling pathway is an area of great interest, because it regulates tumor cell proliferation and survival. A varying mutation rate has been reported for B-RAF and N-RAS, which has been largely attributed to the differential source of tumor DNA analyzed, e.g., fixed tumor tissues or in vitro propagated melanoma cells. Notably, this variation also interfered with interpreting the impact of these mutations on the clinical course of the disease. Consequently, we investigated the mutational profile of B-RAF and N-RAS in biopsies and corresponding cell lines from metastatic tumor lesions of 109 melanoma patients (AJCC stage III/IV), and its respective impact on survival. 97 tissue biopsies and 105 biopsy-derived cell lines were screened for B-RAF and N-RAS mutations by PCR single strand conformation polymorphism and DNA sequencing. Mutations were correlated with patient survival data obtained within a median follow-up time of 31 months. B-RAF mutations were detected in 55% tissues and 51% cell lines, N-RAS mutations in 23% tissues and 25% cell lines, respectively. There was strong concordance between the mutational status of tissues and corresponding cell lines, showing a differing status for B-RAF in only 5% and N-RAS in only 6%, respectively. Patients with tumors carrying mutated B-RAF showed an impaired median survival (8.0 versus 11.8 months, p = 0.055, tissues; 7.1 versus 9.3 months, p = 0.068, cell lines), whereas patients with N-RAS-mutated tumors presented with a favorable prognosis (median survival 12.5 versus 7.9 months, p = 0.084, tissues; 15.4 versus 6.8 months, p = 0.0008, cell lines), each in comparison with wildtype gene status. Multivariate analysis qualified N-RAS (p = 0.006) but not B-RAF mutation status as an independent prognostic factor of overall survival. Our findings demonstrate that B-RAF and N-RAS mutations are well preserved during short term in vitro propagation and, most importantly, differentially impact the outcome of melanoma patients
Adherent Human Alveolar Macrophages Exhibit a Transient Pro-Inflammatory Profile That Confounds Responses to Innate Immune Stimulation
Alveolar macrophages (AM) are thought to have a key role in the immunopathogenesis of respiratory diseases. We sought to test the hypothesis that human AM exhibit an anti-inflammatory bias by making genome-wide comparisons with monocyte derived macrophages (MDM). Adherent AM obtained by bronchoalveolar lavage of patients under investigation for haemoptysis, but found to have no respiratory pathology, were compared to MDM from healthy volunteers by whole genome transcriptional profiling before and after innate immune stimulation. We found that freshly isolated AM exhibited a marked pro-inflammatory transcriptional signature. High levels of basal pro-inflammatory gene expression gave the impression of attenuated responses to lipopolysaccharide (LPS) and the RNA analogue, poly IC, but in rested cells pro-inflammatory gene expression declined and transcriptional responsiveness to these stimuli was restored. In comparison to MDM, both freshly isolated and rested AM showed upregulation of MHC class II molecules. In most experimental paradigms ex vivo adherent AM are used immediately after isolation. Therefore, the confounding effects of their pro-inflammatory profile at baseline need careful consideration. Moreover, despite the prevailing view that AM have an anti-inflammatory bias, our data clearly show that they can adopt a striking pro-inflammatory phenotype, and may have greater capacity for presentation of exogenous antigens than MDM
X-Linked thrombocytopenia causing mutations in WASP (L46P and A47D) impair T cell chemotaxis
BACKGROUND: Mutation in the Wiskott-Aldrich syndrome Protein (WASP) causes Wiskott-Aldrich syndrome (WAS), X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN). The majority of missense mutations causing WAS and XLT are found in the WH1 (WASP Homology) domain of WASP, known to mediate interaction with WIP (WASP Interacting Protein) and CIB1 (Calcium and Integrin Binding). RESULTS: We analyzed two WASP missense mutants (L46P and A47D) causing XLT for their effects on T cell chemotaxis. Both mutants, WASP(R)(L46P) and WASP(R)(A47D) (S1-WASP shRNA resistant) expressed well in Jurkat(WASP-KD) T cells (WASP knockdown), however expression of these two mutants did not rescue the chemotaxis defect of Jurkat(WASP-KD) T cells towards SDF-1α. In addition Jurkat(WASP-KD) T cells expressing these two WASP mutants were found to be defective in T cell polarization when stimulated with SDF-1α. WASP exists in a closed conformation in the presence of WIP, however both the mutants (WASP(R)(L46P) and WASP(R)(A47D)) were found to be in an open conformation as determined in the bi-molecular complementation assay. WASP protein undergoes proteolysis upon phosphorylation and this turnover of WASP is critical for T cell migration. Both the WASP mutants were found to be stable and have reduced tyrosine phosphorylation after stimulation with SDF-1α. CONCLUSION: Thus our data suggest that missense mutations WASP(R)(L46P) or WASP(R)(A47D) affect the activity of WASP in T cell chemotaxis probably by affecting the turnover of the protein. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-014-0091-1) contains supplementary material, which is available to authorized users
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