Interaction of Silver Nanoparticles with Serum Proteins Affects Their Antimicrobial Activity In Vivo

The emergence of multidrug-resistant bacteria is a global threat for human society. There exist recorded data that silver was used as an antimicrobial agent by the ancient Greeks and Romans during the 8th century. Silver nanoparticles (AgNPs) are of potential interest because of their effective antibacterial and antiviral activities, with minimal cytotoxic effects on the cells. However, very few reports have shown the usage of AgNPs for antibacterial therapy in vivo. In this study, we deciphered the importance of the chosen methods for synthesis and capping of AgNPs for their improved activity in vivo. The interaction of AgNPs with serum albumin has a significant effect on their antibacterial activity. It was observed that uncapped AgNPs exhibited no antibacterial activity in the presence of serum proteins, due to the interaction with bovine serum albumin (BSA), which was confirmed by UV-Vis spectroscopy. However, capped AgNPs with citrate or poly(vinylpyrrolidone)] exhibited antibacterial properties due to minimized interactions with serum proteins. The damage in the bacterial membrane was assessed by flow cytometry, which also showed that only capped AgNPs exhibited antibacterial properties, even in the presence of BSA. In order to understand the in vivo relevance of the antibacterial activities of different AgNPs, a murine salmonellosis model was used. It was conclusively proved that AgNPs capped with citrate or PVP exhibited significant antibacterial activities in vivo against Salmonella infection compared to uncapped AgNPs. These results clearly demonstrate the importance of capping agents and the synthesis method for AgNPs in their use as antimicrobial agents for therapeutic purposes.

System Reliability Analysis of Flexible Pavements

The uncertainty in material properties and traffic characterization in the design of flexible pavements has led to significant efforts in recent years to incorporate reliability methods and probabilistic design procedures for the design, rehabilitation, and maintenance of pavements. In the mechanistic-empirical (ME) design of pavements, despite the fact that there are multiple failure modes, the design criteria applied in the majority of analytical pavement design methods guard only against fatigue cracking and subgrade rutting, which are usually considered as independent failure events. This study carries out the reliability analysis for a flexible pavement section for these failure criteria based on the first-order reliability method (FORM) and the second-order reliability method (SORM) techniques and the crude Monte Carlo simulation. Through a sensitivity analysis, the most critical parameter affecting the design reliability for both fatigue and rutting failure criteria was identified as the surface layer thickness. However, reliability analysis in pavement design is most useful if it can be efficiently and accurately applied to components of pavement design and the combination of these components in an overall system analysis. The study shows that for the pavement section considered, there is a high degree of dependence between the two failure modes, and demonstrates that the probability of simultaneous occurrence of failures can be almost as high as the probability of component failures. Thus, the need to consider the system reliability in the pavement analysis is highlighted, and the study indicates that the improvement of pavement performance should be tackled in the light of reducing this undesirable event of simultaneous failure and not merely the consideration of the more critical failure mode. Furthermore, this probability of simultaneous occurrence of failures is seen to increase considerably with small increments in the mean traffic loads, which also results in wider system reliability bounds. The study also advocates the use of narrow bounds to the probability of failure, which provides a better estimate of the probability of failure, as validated from the results obtained from Monte Carlo simulation (MCS).

Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella

Objectives: The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella. Methods: The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model. Results: In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection, CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration. Conclusions: CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection, This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.

Post-absorptive glucose lowering in normal healthy individuals: An epidemiological observation

Post-absorptive glucose lowering (PALG) is observed in individuals with glucose intolerance and in healthy individuals. We report a prevalence of about 23% among healthy Asian Indians. Individuals with PALG are characterized by leaner phenotype, low body fat percentage, increased insulin sensitivity and higher fasting glucose levels. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

In vitro exposure of tobacco specific nitrosamines decreases the rat lung phospholipids by enhanced phospholipase A(2) activity

Tobacco-specific nitrosamines (TSNA) have implications in the pathogenesis of various lung diseases and conditions are prevalent even in non-smokers. N-nitrosonornicotine (NNN) and 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are potent pulmonary carcinogens present in tobacco product and are mainly responsible for lung cancer. TSNA reacts with pulmonary surfactants, and alters the surfactant phospholipid. The present study was undertaken to investigate the in vitro exposure of rat lung tissue slices to NNK or NNN and to monitor the phospholipid alteration by P-32]orthophosphate labeling. Phospholipid content decreased significantly in the presence of either NNK or NNN with concentration and time dependent manner. Phosphatidylcholine (PC) is the main phospholipid of lung and significant reduction was observed in PC similar to 61%, followed by phosphatidylglycerol (PG) with 100 mu M of NNK, whereas NNN treated tissues showed a reduction in phosphatidylserine (PS) similar to 60% and PC at 250 mu M concentration. The phospholipase A(2) assays and expression studies reveal that both compounds enhanced phospholipid hydrolysis, thereby reducing the phospholipid content. Collectively, our data demonstrated that both NNK and NNN significantly influenced the surfactant phospholipid level by enhanced phospholipase A(2) activity. (C) 2014 Elsevier Ltd. All rights reserved.

Shaking table tests to investigate the influence of various factors on the liquefaction resistance of sands

This paper presents the shaking table studies to investigate the factors that influence the liquefaction resistance of sand. A uniaxial shaking table with a perspex model container was used for the model tests, and saturated sand beds were prepared using wet pluviation method. The models were subjected to horizontal base shaking, and the variation of pore water pressure was measured. Three series of tests varying the acceleration and frequency of base shaking and density of the soil were carried out on sand beds simulating free field condition. Liquefaction was visualized in some model tests, which was also established through pore water pressure ratios. Effective stress was calculated at the point of pore water pressure measurement, and the number of cycles required to liquefy the sand bed were estimated and matched with visual observations. It was observed that there was a gradual variation in pore water pressure with change in base acceleration at a given frequency of shaking. The variation in pore water pressure is not significant for the range of frequency used in the tests. The frequency of base shaking at which the sand starts to liquefy when the sand bed is subjected to any specific base acceleration depends on the density of sand, and it was observed that the sand does not liquefy at any other frequency less than this. A substantial improvement in liquefaction resistance of the sand was observed with the increase in soil density, inferring that soil densification is a simple technique that can be applied to increase the liquefaction resistance.

Influence of Spatial Variability on Pavement Responses Using Latin Hypercube Sampling on Two-Dimensional Random Fields

Although uncertainties in material properties have been addressed in the design of flexible pavements, most current modeling techniques assume that pavement layers are homogeneous. The paper addresses the influence of the spatial variability of the resilient moduli of pavement layers by evaluating the effect of the variance and correlation length on the pavement responses to loading. The integration of the spatially varying log-normal random field with the finite-difference method has been achieved through an exponential autocorrelation function. The variation in the correlation length was found to have a marginal effect on the mean values of the critical strains and a noticeable effect on the standard deviation which decreases with decreases in correlation length. This reduction in the variance arises because of the spatial averaging phenomenon over the softer and stiffer zones generated because of spatial variability. The increase in the mean value of critical strains with decreasing correlation length, although minor, illustrates that pavement performance is adversely affected by the presence of spatially varying layers. The study also confirmed that the higher the variability in the pavement layer moduli, introduced through a higher value of coefficient of variation (COV), the higher the variability in the pavement response. The study concludes that ignoring spatial variability by modeling the pavement layers as homogeneous that have very short correlation lengths can result in the underestimation of the critical strains and thus an inaccurate assessment of the pavement performance. (C) 2014 American Society of Civil Engineers.

Nanorod to quantum dot conversion in ZnO dispersions with co-surfactants

A chemically-induced nanorod to quantum dot transition is reported in ZnO. This transition is achieved using co-surfactants in a marginally polar solvent in chimie douce (soft chemical) conditions. This is different from the physical instability driven transitions reported so far in metal nanowires and polymers. We propose a suitable mechanism for the observed phenomenon.

Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella

Objectives: The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella. Methods: The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model. Results: In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection, CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration. Conclusions: CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection, This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.

Influence of Anisotropy on Pavement Responses Using Adaptive Sparse Polynomial Chaos Expansion

Modeling the spatial variability that exists in pavement systems can be conveniently represented by means of random fields; in this study, a probabilistic analysis that considers the spatial variability, including the anisotropic nature of the pavement layer properties, is presented. The integration of the spatially varying log-normal random fields into a linear-elastic finite difference analysis has been achieved through the expansion optimal linear estimation method. For the estimation of the critical pavement responses, metamodels based on polynomial chaos expansion (PCE) are developed to replace the computationally expensive finite-difference model. The sparse polynomial chaos expansion based on an adaptive regression-based algorithm, and enhanced by the combined use of the global sensitivity analysis (GSA) is used, with significant savings in computational effort. The effect of anisotropy in each layer on the pavement responses was studied separately, and an effort is made to identify the pavement layer wherein the introduction of anisotropic characteristics results in the most significant impact on the critical strains. It is observed that the anisotropy in the base layer has a significant but diverse effect on both critical strains. While the compressive strain tends to be considerably higher than that observed for the isotropic section, the tensile strains show a decrease in the mean value with the introduction of base-layer anisotropy. Furthermore, asphalt-layer anisotropy also tends to decrease the critical tensile strain while having little effect on the critical compressive strain. (C) 2015 American Society of Civil Engineers.

Las tensiones de la idea de la justicia de Amartya Sen

Resumen: En este artículo, se ensaya un análisis crítico del libro de Amartya Sen La idea de la justicia. En primer lugar, se analizan los contrastes entre pragmatismo y objetividad en la idea de justicia propuesta por Sen. Luego se desarrolla el concepto de ‘capacidad’ propuesto por este economista, y se presentan las objeciones de Martha Nussbaum a este planteo. A continuación, el artículo señala los vínculos entre la idea de justicia y las concepciones económicas de Amartya Sen y analiza el debate acerca del esquema de maximización protagonizado por este pensador y Elizabeth Anderson. Finalmente, se realiza una valoración de la obra como totalidad, destacando la importancia de la razón práctica en el análisis de la justicia.

O novo pacto federativo: porque a apresentação de uma emenda possibilitou uma discussão na redefinição da Federação Brasileira

Estudo de caso que analisa a aprovação da emenda de plenário nº 387 de 2010, chamada de emenda Ibsen Pinheiro/Humberto Souto, que pretendeu redistribuir as riquezas advindas dos royalties do petróleo, a partir do estabelecimento de critérios de maior equalização como o da distribuição via Fundo de Participação de Estados e Municípios (FPE/FPM). A partir do entendimento segundo o qual tal aprovação se deu por causa da fragmentação (derrocada) do pacto federativo, dado a centralização histórica do processo de arrecadação tributária nas mãos da União, posição alcançada e motivada, diga-se de passagem, pela abdicação de Estados e Municípios do papel de principal arrecadador, se tornando atores secundários. O estudo argumenta que a principal dificuldade enfrentada pelos entes subnacionais é de ordem econômica e os desenhos constitucionais desde a promulgação da Constituição republicana de 1891, não foi capaz de dirimir tal situação. E mesmo com a promulgação da Constituição de 1988, chamada de a mais descentralizadora, uma melhor distribuição de recursos falhou em suas tentativas.

A cicatriz do Tatarana: o sagrado feminino em Grande sertão: veredas

O trabalho analisa, na obra Grande Sertão: Veredas de João Guimarães Rosa (1956), elementos discursivos indicadores de um modo de narrar que ficcionaliza, tanto na forma quanto no teor de sua mensagem, manifestações do sagrado originárias da Antiguidade grega e da tradição judaico-cristã. A partir da analogia entre a obra de Guimarães Rosa e a Odisseia de Homero, tornam-se evidentes vestígios do épico e de modelos clássicos de narrativa que, revestidos do peculiar trabalho da linguagem rosiana, adensam a complexidade do romance. O paralelismo com as Sagradas Escrituras, mais difuso, projeta as ações num patamar dramático, em que se decidem o destino das personagens e a solenidade do discurso memorável. A fundamentação teórica articula o pensamento de Erich Auerbach, André Jolles, Rudolf Otto e também de estudiosos que se dedicaram à obra do autor mineiro, como Kathrin Rosenfield. Esse recorte mostrou a presença do sagrado em microcélulas entretecidas ao emaranhado de histórias e causos que costuram a obra prima de Rosa. A cicatriz da Tatarana alude à cicatriz de Ulisses, sinal revelador da identidade do herói grego e que, no caso do jagunço Riobaldo, desoculta um amor negado por meio da purgação do passado, elaborada numa conversa "unilateral com um suposto interlocutor. Em linguagem mítica e mágica, a figura nebulosa de Diadorim funciona como índice de ambiguidade e, ao mesmo tempo, da revelação alcançada através da morte. A pesquisa, por seu turno, segue as veredas abertas pelo estudo de Tereza Virgínia Ribeiro Barbosa a respeito das mulheres vestidas de sol, metáfora relacionada a Medeia, mas que se projeta na Virgem Maria e numa linhagem de figuras femininas da América Latina ligadas ao sagrado. Verificamos, na perspectiva das transferências culturais do tipo passado místico-mistérico/posteridade fabular, que o discurso de Riobaldo é atravessado por micronarrativas de longa tradição que sincretizam diferentes símbolos exotéricos. O trabalho encerra sua investigação desvendando a dualidade do sertão rosiano, onde impera o embate entre fé e ceticismo, a dúvida e a razão, o amor e o ódio, o masculino e o feminino, que resulta no inacabado, na travessia, a vida como metáfora, no campo das infinitas possibilidades do homem humano

As representações da mulher nas letras luso-brasileiras do século XVII

O propósito desta dissertação é estudar as representações femininas nas letras luso-brasileiras do século XVII, sempre levando em conta os pressupostos teóricos formulados pela crítica brasileira atual. Pretende-se examinar as práticas letradas seiscentistas pelo prisma dos critérios retórico-poéticos vigentes na época, em que se destacam a importância dos elementos visuais. O estudo tem como base o contraponto das figuras de Eva e Maria, formando o grande paradigma da dualidade feminina nas letras coloniais; tal construção da imagem da mulher como tentadora e salvadora foi um longo processo desde as letras dos tempos antigos, se intensificando no período medieval até chegar no século XVII. Desse modo, focalizamos as poesias de Gregório de Matos e alguns sermões do padre Antonio Vieira, dialogando com questões históricas, sociais e artísticas no momento de produção das obras para tentar reduzir os riscos de anacronismo, sempre presentes quando abordamos períodos tão distanciados no tempo. Analisamos variadas configurações femininas nas poesias líricas e satíricas de Gregório de Matos; já nos sermões de Vieira, percebemos que o contraponto entre as concepções mariana e eviana fica mais evidente. Mostramos como as figuras femininas examinadas se aproximavam de Eva ou de Maria, levando em conta o contexto sócio-econômico das mesmas. Notamos que o modelo ideal de mulher encarnando na figura de Maria, difundido pela Igreja com o objetivo de alcançar todas as mulheres, não correspondia à realidade das mesmas no sistema colonial e não se adequava as suas necessidades. Examinamos igualmente como tal construção feminina perfeita e submissa circulava nos manuais de boa conduta em que a família patriarcal se encaixava, atendendo às exigências dos modelos propagados pela Igreja Católica na época. Apesar de todos os esforços da Igreja Católica e do homem para domesticar a mulher, tão temida e admirada pelos mesmos, muitas mulheres fugiram aos padrões sociais e foram estigmatizadas, rotuladas, discriminadas, mas acima de tudo foram mulheres que ficaram registradas nas páginas da Inquisição, na história e principalmente, nas letras luso-brasileiras do século XVII, escritas por homens, como o poeta Gregório de Matos e o padre Antonio Vieira