Aryl phosphate derivatives of bromo-methoxy-azidothymidine are dual-function spermicides with potent anti-human immunodeficiency virus

Detergent-based vaginal microbicides, in addition to their high contraceptive failure rates, cause mucosal erosion and local inflammation that might increase the risk of heterosexual human immunodeficiency virus (HIV) transmission. In a systematic effort to identify a microbicide contraceptive potentially capable of preventing the sexual transmission of HIV as well as providing fertility control, a series of novel aryl phosphate derivatives of 5-bromo-6-methoxy-3'-azido-3'-deoxythymidine (AZT; zidovudine) were synthesized and examined for dual anti-HIV and sperm-immobilizing activity (SIA). Whereas AZT displayed potent anti-HIV activity (IC50 = 0.006 microM) but lacked SIA (EC50 > 300 microM), two 5-bromo-6-methoxy-aryl phosphate derivatives of AZT, compounds WHI-05 and WHI-07, exhibited potent anti-HIV activity as well as SIA. The IC50 (HIV) and EC50 (SIA) values for WHI-07 were 439-fold and 13.5-fold lower, respectively, than those for the detergent-based virucidal spermicide, nonoxynol-9 (N-9). Sperm motion kinematics using computer-assisted sperm motion analysis combined with confocal laser scanning microscopy, high-resolution low-voltage scanning, and transmission electron microscopy demonstrated that both WHI-05 and WHI-07 cause a complete and irreversible loss of sperm motility in a concentration- and time-dependent fashion without concomitantly affecting the sperm acrosomal membrane integrity. In experiments designed to assess the fertilizing capacity of treated sperm, preincubation of sperm with either compound resulted in a concentration-dependent loss of the ability to adhere to and penetrate zona-free hamster eggs as well as inhibition of binding to human zona. WHI-07 applied intravaginally prior to artificial insemination of epididymal sperm drastically reduced fertility in hormonally primed CD-1 mice. Unlike the intravaginal application of N-9, repetitive intravaginal application of WHI-07 did not damage the vaginal epithelium or cause local inflammation. Structure-function relationship analyses showed that the addition of bromo-methoxy functional groups to AZT was essential for, and the aryl phosphate derivatization contributory to, the SIA of both compounds. Compounds WHI-05 and WHI-07 may be useful as dual-function vaginal contraceptives for women who are at high risk for acquiring HIV/acquired immunodeficiency virus syndrome by heterosexual vaginal transmission.     

Diskitis caused by Actinobacillus actinomycetemcomitans

A 32-year-old man with acquired immunodeficiency syndrome (AIDS) admitted to the hospital for treatment of visceral leishmaniasis was inadvertently given 10 times the prescribed first dose of sodium stibogluconate ([Sb] 6.5 g instead of 0.65 g). He experienced no immediate major toxicity during the first 48 hours, but a significant rise of pancreatic enzyme activities was observed (amylase at 10 times the upper limit of normal, lipase at 50 times the upper limit of normal) without clinical signs or indications on computed tomography (CT) of pancreatitis. The third day after the overdose, he developed appendicitis, which appeared coincidental; he recovered uneventfully from surgery. Most of the overdose of Sb was eliminated within the first few hours. Pharmacokinetics remained linear; the rapid, long elimination half-lives (2.7 hours and 54 hours, respectively) were similar to those in previously published results. The administration of a chelating agent, dimercaptosuccinic acid (DMSA), 72 hours after the Sb overdose did not modify the pharmacokinetics of the medication.     

Comparison of inter- and intra-chromosomal aberrations in blood samples exposed to different dose rates of gamma radiation

Peripheral blood samples obtained from a normal healthy volunteer were exposed in vitro to gamma radiation with various doses at different dose rates of 1.0, 0.1 and 0.0014 Gy min(-1). The exposed samples were analysed for different chromosomal aberrations such as dicentrics (DC), centric rings (CR) and double-minutes (DM). The ratio of DC chromosomes (inter) to the total number of centric rings (CR) and double-minutes (DM) (CR + DM = intra) were analysed for all the three dose rates. The study showed that the frequency of inter-arm chromosomal aberrations was more then three times higher than that observed with intra-arm chromosomal aberrations in samples exposed at a dose rate of 1.0 and 0.1 Gy min (-1). However, the frequency of inter- and intra-arm chromosomal aberrations were almost same (ratio 1:1) in samples exposed at a dose rate of 0.0014 Gy min(-1). This paper discusses the usefulness of the ratio of inter- and intra-arm chromosome aberration in finding out whether the sample was exposed to high or low dose rate radiation.     

In situ synthesised TiO2 ‐chitosan‐chondroitin 4–sulphate nanocomposites for bone implant applications

The artificial materials for bone implant applications are gaining more importance in the recent years. The series titania‐chitosan‐chondroitin 4–sulphate nanocomposites of three different concentrations (2:1:x, where x ‐ 0.125, 0.25, 0.5) have been synthesised by in situ sol–gel method and characterised by various techniques. The particle size of the nanocomposites ranges from 30–50 nm. The bioactivity, swelling nature, and the antimicrobial nature of the nanocomposites were investigated. The swelling ability and bioactivity of the composites is significantly greater and they possess high zone of inhibition against the microorganisms such as Staphylococcus aureus and Escherichia coli. The cell viability of the nanocomposites were evaluated by using MG‐63 and observed the composites possess high cell viability at low concentration. The excellent bioactivity and biocompatibility makes these nanocomposites a promising biomaterial for bone implant applications.Inspec keywords: titanium compounds, filled polymers, nanocomposites, bone, orthopaedics, biomedical materials, sol‐gel processing, nanofabrication, particle size, swelling, microorganisms, cellular biophysics, nanomedicine, prostheticsOther keywords: in situ synthesised TiO₂ ‐chitosan‐chondroitin 4‐sulphate nanocomposites, bone implant applications, artificial materials, in situ sol‐gel method, particle size, swelling nature, antimicrobial nature, microorganisms, Staphylococcus aureus, Escherichia coli, cell viability, MG‐63, biomaterial, size 30 nm to 50 nm, TiO₂      

Parameter Estimation in Water Distribution Networks

Estimation of pipe roughness coefficients is an important task to be carried out before any water distribution network model is used for online applications such as monitoring and control. In this study, a combined state and parameter estimation model for water distribution networks is presented. Typically, estimation of roughness coefficient for each individual pipe is not possible due to non-availability of sufficient number of measurements. In order to address this problem, a formal procedure based on K-means clustering algorithm is proposed for grouping the pipes which are likely to have the same roughness characteristics. Also, graph-theoretic concepts are used to reduce the dimensionality of the problem and thereby achieve significant computational efficiency. The performance of the proposed model is demonstrated on a realistic urban water distribution network.     

Modulation of (+/-)-anti-BPDE mediated p53 accumulation by inhibitors of protein kinase C and poly(ADP-ribose) polymerase

The rapid accumulation of the p53 gene product is considered to be an important component of the cellular response to a variety of genotoxins. In order to gain insights on the biochemical pathways leading to p53 stabilization, the effect of (+/-) 7,8-dihydroxy-anti-9, 10-epoxy-7,8,9,10-tetrahydrobenzo(a)-pyrene [(+/-)-anti-BPDE] induced DNA damage on p53 protein levels was investigated in various repair-proficient and repair-deficient human cells. Brief exposure of normal human fibroblasts to 0.05-1 microM (+/-)-anti-BPDE resulted in elevated p53 protein levels as compared to the constitutive levels of control cells. The rapid induction response, detectable within a few hours, was sustained up to a period of at least 24 h. Repair-proficient and repair-deficient (XPA) human lymphoblastoid cells showed a similar response. The poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide (3-AB), diminished the p53 induction response by concomitantly decreasing the extent of (+/-)-anti-BPDE induced DNA damage in cells pretreated with the inhibitor. However, the direct involvement of poly ADP-ribosylation was also apparent as 3-AB was able to attenuate (approximately 50%) the p53 response by post-damage inhibitor treatment of the cells. Inhibition of cellular DNA replication by hydroxyurea and AraC, in the presence or absence of DNA damage, also resulted in rapid p53 accumulation in repair-deficient cells. On the contrary, inhibition of protein kinase C (PKC) by calphostin-C led to an abrogation of (+/-)-anti-BPDE mediated p53 induction. Analysis of the downstream effects of carcinogen treatment showed that the lymphoblastoid cells undergo DNA fragmentation indicative of apoptosis while fibroblasts exhibit cell cycle arrest at the G1-S boundary.     

Mathematical modeling of thermoelectric generator driven by solar parabolic dish collector

This paper presents mathematical modeling of thermoelectric power generator driven by solar parabolic dish collector. The system is modeled by set of mathamatical equations from the first law of thermonadynamics for the subcompoents of solar parabolic dish collector and thermoelectric power generator. The model is solved analytically for the a set of operating and design parameters. Modeling results can be useful for further development of the system to study it economic viability.     

Technical note: Rotational transformation of remotely sensed data for land use classification

In this paper, the rotational transformation process is explained as a problem of rotation of remotely sensed data in the variance-covariance space. In particular, the rotation which maximizes the covariance-variance ratio is examined in detail for various land use and land cover classes in the Bombay suburban and Thana district area in India. A statistical approach to determine transformed components and other statistical variables on different band combinations is discussed. The results are analysed, and the best possible combinations selected for accurate classification are presented.     

Studies on the chlorination of zircon: Part I. Static bed investigations

Carbochlorination is an important unit operation in the processing of zirconium resources. In the article, the use of different reducing agents in zircon chlorination, to produce zirconium tetrachloride, has been examined on thermodynamic and other considerations. While numerous workers have investigated zircon chlorination, a literature survey shows that there is a wide variation in the reported effect of various process parameters on the chlorination rate and a wide scatter in the values for kinetic parameters such as order of reaction, activation energy, rate constant as also the rate law expression. This work is an extensive study on zircon chlorination and the article discusses the effect of process parameters such as charge particle size, gas and solid composition, gas flow rate, temperature, reaction duration, etc. on the chlorination rate, over a much wider range of the parameter values. During investigations in the static bed chlorinator, it was noticed that the initial rate and the total extent of chlorination are proportional to the exposed surface of the solid zircon-coke charge but independent of the depth or amount of the charge. Further, the stalled chlorination could be reactivated by remixing the solid charge. Also, while the reaction rate in general increased as the charge became finer, the effect of zircon particle size was much more predominant. The activation energy value for the chlorination showed a wide variation with other operating conditions. Likewise, the order of reaction with respect to chlorine decreased from two to zero as the chlorine concentration in the gaseous atmosphere increased. Interestingly, the chlorination rate initially increased with gas flow rate, then decreased, before finally becoming independent of the gas flow rate. Results also indicated that there is an optimum charge composition that yields the maximum chlorination rate and the article discusses the effect of the zircon to coke particle number ratio in the initial charge on the chlorination kinetics. With the help of these observations, it is possible to explain the wide variation in the reported effect of the various process parameters on zircon chlorination.     

ARTIFICIAL NEURAL NETWORKS: PRINCIPLE AND APPLICATION TO MODEL BASED CONTROL OF DRYING SYSTEMS - A REVIEW

Abstract

This paper reviews the developments in the model based control of drying systems using Artificial Neural Networks (ANNs). Survey of current research works reveals the growing interest in the application of ANN in modeling and control of non-linear, dynamic and time-variant systems. Over 115 articles published in this area are reviewed. All landmark papers are systematically classified in chronological order, in three distinct categories; namely, conventional feedback controllers, model based controllers using conventional methods and model based controllers using ANN for drying process. The principles of ANN are presented in detail. The problems and issues of the drying system and the features of various ANN models are dealt with upto-date. ANN based controllers lead to smoother controller outputs, which would increase actuator life. The paper concludes with suggestions for improving the existing modeling techniques as applied to predicting the performance characteristics of dryers. The hybridization techniques, namely, neural with fuzzy logic and genetic algorithms, presented, provide, directions for pursuing further research for the implementation of appropriate control strategies. The authors opine that the information presented here would be highly beneficial for pursuing research in modeling and control of drying process using ANN