In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization

Context and objective: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery.

Materials and methods: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings.

Results and discussion: There was a big deviation between the T_g of the polymeric caplet from the T_g's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012–0.332?mg/mL and 0.009–0.256?mg/mL for AZT and PSS over 1–28 d.

Conclusion: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.     

On the network effect in Web 2.0 applications

In recent years, the proliferation of the world wide web has lead to an increase in a number of applications such as search, social networks and auctions, whose success depends critically upon the number of users of that service. Two examples of such applications are internet auctions and social networks. One of the characteristics of online auctions is that a successful implementation requires a high volume of buyers and sellers at its website. Consequently, auction sites which have a high volume of traffic have an advantage over those in which the volume is limited. This results in even greater polarization of buyers and sellers towards a particular site. The same is true for social networks in which greater use of a given social network increases the use from other participants on the network. This is often referred to as the “network effect” in a variety of interaction-centric applications in networks. While this effect has qualitatively been known to increase the value of the overall network, its effect has never been modeled or studied rigorously. In this paper, we construct a Markov model to analyze the network effect in the case of two important classes of web applications. These correspond to auctions and social networks. We show that the network effect is very powerful and can result in a situation in which an auction or a social networking site can quickly overwhelm its competing sites. Thus, the results of this paper show the tremendous power of the network effect for Web 2.0 applications.     

CONTOUR: an efficient algorithm for discovering discriminating subsequences

In recent years we have witnessed several applications of frequent sequence mining, such as feature selection for protein sequence classification and mining block correlations in storage systems. In typical applications such as clustering, it is not the complete set but only a subset of discriminating frequent subsequences which is of interest. One approach to discovering the subset of useful frequent subsequences is to apply any existing frequent sequence mining algorithm to find the complete set of frequent subsequences. Then, a subset of interesting subsequences can be further identified. Unfortunately, it is very time consuming to mine the complete set of frequent subsequences for large sequence databases. In this paper, we propose a new algorithm, CONTOUR, which efficiently mines a subset of high-quality subsequences directly in order to cluster the input sequences. We mainly focus on how to design some effective search space pruning methods to accelerate the mining process and discuss how to construct an accurate clustering algorithm based on the result of CONTOUR. We conducted an extensive performance study to evaluate the efficiency and scalability of CONTOUR, and the accuracy of the frequent subsequence-based clustering algorithm.     

Use of distributed data sources in facility location

Facility location decisions are usually determined by cost and coverage related factors although empirical studies show that such factors as infrastructure, labor conditions and competition also play an important role in practice. The objective of this paper is to develop a multi-objective facility location model accounting for a wide range of factors affecting decision-making. The proposed model selects potential facilities from a set of pre-defined alternative locations according to the number of customers, the number of competitors and real-estate cost criteria. However, that requires large amount of both spatial and non-spatial input data, which could be acquired from distributed data sources over the Internet. Therefore, a computational approach for processing input data and representation of modeling results is elaborated. It is capable of accessing and processing data from heterogeneous spatial and non-spatial data sources. Application of the elaborated data gathering approach and facility location model is demonstrated using an example of fast food restaurants location problem.     

Exploring context and content links in social media: a latent space method

Social media networks contain both content and context-specific information. Most existing methods work with either of the two for the purpose of multimedia mining and retrieval. In reality, both content and context information are rich sources of information for mining, and the full power of mining and processing algorithms can be realized only with the use of a combination of the two. This paper proposes a new algorithm which mines both context and content links in social media networks to discover the underlying latent semantic space. This mapping of the multimedia objects into latent feature vectors enables the use of any off-the-shelf multimedia retrieval algorithms. Compared to the state-of-the-art latent methods in multimedia analysis, this algorithm effectively solves the problem of sparse context links by mining the geometric structure underlying the content links between multimedia objects. Specifically for multimedia annotation, we show that an effective algorithm can be developed to directly construct annotation models by simultaneously leveraging both context and content information based on latent structure between correlated semantic concepts. We conduct experiments on the Flickr data set, which contains user tags linked with images. We illustrate the advantages of our approach over the state-of-the-art multimedia retrieval techniques.     

Differences in prevalence of tobacco use among Indian urban youth: the role of socioeconomic status

This study examined whether the distribution of tobacco use and related psychosocial risk factors among youth in urban India vary by socioeconomic status (SES). Data were derived from a cross-sectional survey of students enrolled in the 6th and 8th grades in 32 schools in Delhi and Chennai (N = 11,642). The survey was conducted in 2004, before the implementation of a program designed to prevent and reduce tobacco use (MYTRI). Mixed-effect regression models were used (a) to determine the prevalence of tobacco use among private (higher SES) and government (lower SES) school students, (b) to investigate whether certain psychosocial factors were associated with increased tobacco use, and (c) to determine how these factors varied by school type. Ever-use of multiple forms of tobacco (e.g., gutkha, bidis, and cigarettes) was more prevalent among government school students than private school students. After adjusting for city, gender, grade, and age, we found the prevalence rate for ever-use of any tobacco product to be 18.9% for government school students, compared with 12.2% for private school students (p<.01). Students in government schools scored lower than private school students on most psychosocial risk factors for tobacco use studied here, indicating higher risk. Government school students scored the lowest for refusal skills, self-efficacy, and reasons not to use tobacco. Social susceptibility to chewing tobacco and social susceptibility to smoking were strong correlates of current tobacco use among government school students. Exposure to tobacco advertising was also a strong correlate of current tobacco use for government school students but not private school students. In two large cities of India, students attending government schools are using many forms of tobacco at higher rates than private school students. The psychosocial risk profile of government school students suggests they are more vulnerable to initiation and use and to outside influences that encourage use.     

Characterization of Thermal-Sprayed HAP and HAP/TiO<Subscript>2</Subscript> Coatings for Biomedical Applications

In the present study, hydroxyapatite (HAP) coating along with HAP/TiO₂ coating has been deposited by high-velocity flame spray (HVFS) technique onto 316LSS. Titania was used as a bond coat and HAP as top coat in HAP/TiO₂ coating. The main aim of the study is to investigate the corrosion behavior of thermal spray coating of HAP and HAP/TiO₂ on steel. Electrochemical corrosion testing was carried out using potentiodynamic polarization test. The corrosion behavior of bare and as-sprayed specimens was analyzed in simulated body fluid known as Hank’s solution. As-sprayed specimens along with corroded specimens were further characterized by XRD, SEM/EDS, and x-ray mapping analysis. It was observed that the HAP/TiO₂ coating possessed higher microhardness (280 Hv) as compared to HAP coating (254 Hv). Surface roughness also got enhanced in case of HAP/TiO₂ coating (9.35 μm) as compared to pure HAP coating (7.37 μm). The porosity of the HAP coating was found to be higher than the bond coating. It was observed that the Ca/P ratio almost resembled that of the natural bone composition. The corrosion resistance of steel increased after the deposition of HAP and HAP/TiO₂ coatings. The maximum corrosion resistance was exhibited by HAP/TiO₂ coating.     

Assessment of integrated binary process by coupling photocatalysis and photo-Fenton for the removal of cephalexin from aqueous solution

A novel concept of integrated process by coupling photocatalysis and photo-Fenton especially in fixed mode has been presented in the current study for the removal of recalcitrant pharmaceuticals like cephalexin (CEX) from aqueous solution in reduced treatment time. Waste materials like foundry sand (FS) was used as a substitute for iron along with TiO₂. The parametric optimization was carried out in slurry mode using Box–Behnken design model (BBD) and response surface methodology. For fixed-bed studies, support materials of varying shapes (hollow circular disk, rectangular slabs, spherical beads) were prepared using clay in conjunction with FS for TiO₂ immobilization. Different supports were compared on the basis of degradation efficiency, exposed surface area of catalyst as well as their recyclability capacity for the degradation of CEX. Iron was leaching by default from the supports during the degradation process which contributed simultaneously to photo-Fenton process along with photocatalysis. Spherical beads with 0.0265 m² exposed surface area of catalyst and better recyclability efficiency (10 cycles) yielded best degradation efficiency (80%) of CEX after 240 min of treatment time. The presence of iron along with TiO₂ on the surface of beads was confirmed through TGA, SEM/EDS, XRD, DRS and FTIR. The mineralization of CEX was validated through quantification of nitrite, nitrate and sulfate ions along with reduction in COD. A tentative pathway for the degradation of CEX was also proposed based on the identification of intermediates through GC–MS analysis.