E-pharmacophore based screening to identify potential HIV-1 gp120 and CD4 interaction blockers for wild and mutant types.

HIV-1 gp120 provides a multistage viral entry process through the conserved CD4 binding site. Hunting of potential blockers can diminish the interaction of gp120 with the CD4 host receptor leading to the suppression of HIV-1 infection. Structure-based pharmacophore virtual screening followed by binding free energy calculation, molecular dynamics (MD) simulation and density functional theory (DFT) calculation is applied to discriminate the potential blockers from six small molecule databases. Five compounds from six databases exhibited vital interactions with key residues ASP368, GLU370, ASN425, MET426, TRP427 and GLY473 of gp120, involved in the binding with CD4, host receptor. Most importantly, compound NCI-254200 displayed strong communication with key residues of wild type and drug resistance single mutant gp120 (M426L and W427V) even in the dynamic condition, evidenced from MD simulation. This investigation provided a potential compound NCI-254200 which may show inhibitory activity against HIV-1 gp120 variant interactions with CD4 host cell receptors.

DRD4 and DAT1 VNTR Genotyping in Children with Attention Deficit Hyperactivity Disorder.

The dopamine receptor-D4 and the dopamine transporter have been investigated for their role in attention deficit hyperactivity disorder (ADHD) in children. Reports of their genetic association with ADHD have shown mixed results. The aim of the study was to evaluate the association of variable number tandem repeats (VNTRs) of the DRD4 and DAT1 genes with ADHD in children. A pilot 1:1 case control study, with 44 clinically confirmed ADHD cases and 44 age/gender matched healthy controls, was conducted at a tertiary care centre in Mumbai. Variable number tandem repeats of DRD4 exon 3, DAT1 intron 8 and 3'UTR were genotyped by PCR-AGE. Several allele repeats of the genes were observed in the screened subjects. Statistical significance was observed for the 10R/10R genotype of the DAT1 3'UTR VNTR between cases and controls.

Note: A vortex cross-correlation flowmeter with enhanced turndown ratio.

In the present study, a novel dual sensor vortex cross correlation technique is suggested and implemented to extend the lower operating range of the flowmeter. The first sensor located at an optimum streamwise location of 0.85 times the width of the bluff body is employed to compute the vortex shedding frequency under high Reynolds number conditions. Under low Reynolds number conditions, when the strength of the vortex signal is poor, the outputs from the two piezoelectric sensors are correlated to compute the vortex convection velocity. This vortex convection velocity is used to compute the volume flow rate. This novel dual flow rate estimation technique has demonstrated its robustness under low Reynolds number flow conditions with a remarkable turndown ratio of 1:66 as compared to 1:20 for conventional vortex flowmeters.

Thermocouple error correction for measuring the flame temperature with determination of emissivity and heat transfer coefficient.

Temperature measurement by thermocouples is prone to errors due to conduction and radiation losses and therefore has to be corrected for precise measurement. The temperature dependent emissivity of the thermocouple wires is measured by the use of thermal infrared camera. The measured emissivities are found to be 20%-40% lower than the theoretical values predicted from theory of electromagnetism. A transient technique is employed for finding the heat transfer coefficients for the lead wire and the bead of the thermocouple. This method does not require the data of thermal properties and velocity of the burnt gases. The heat transfer coefficients obtained from the present method have an average deviation of 20% from the available heat transfer correlations in literature for non-reacting convective flow over cylinders and spheres. The parametric study of thermocouple error using the numerical code confirmed the existence of a minimum wire length beyond which the conduction loss is a constant minimal. Temperature of premixed methane-air flames stabilised on 16 mm diameter tube burner is measured by three B-type thermocouples of wire diameters: 0.15 mm, 0.30 mm, and 0.60 mm. The measurements are made at three distances from the burner tip (thermocouple tip to burner tip/burner diameter = 2, 4, and 6) at an equivalence ratio of 1 for the tube Reynolds number varying from 1000 to 2200. These measured flame temperatures are corrected by the present numerical procedure, the multi-element method, and the extrapolation method. The flame temperatures estimated by the two-element method and extrapolation method deviate from numerical results within 2.5% and 4%, respectively.

Measurement of surface temperature and emissivity of different materials by two-colour pyrometry.

An experimental investigation is performed to substantiate the capability of a charge coupled device camera to measure local temperature and emissivity of different materials heated to temperatures above 500 °C by two-colour pyrometric technique using colorimetric method. Materials investigated are Inconel 718 with pyromark (high temperature paint), Inconel 718, stainless steel SS 304 and SS 316. Centerline temperature and emissivity distribution is obtained for target plates maintained at constant temperature by AC heating while complete temperature and emissivity distribution is provided for plates heated by flame impingement. The obtained results are compared with a calibrated infrared camera and thermocouples and the temperature distribution is found to be in close agreement. These results pertain to partially oxidized metal alloys covered in this study. Deviation in the measurement of emissivity can be attributed to its dependence on wavelength range, oxidation, and sensitivity of the image detector.

Experimental determination of heat transfer coefficient in the slip regime and its anomalously low value.

In this paper, the measurement of the heat transfer coefficient in rarefied gases is presented; these are among the first heat transfer measurements in the slip flow regime. The experimental setup is validated by comparing friction factor in the slip regime and heat transfer coefficient in the continuum regime. Experimental results suggest that the Nusselt number is a function of Reynolds and Knudsen numbers in the slip flow regime. The measured values for Nusselt numbers are smaller than that predicted by theoretical or simulation results, and can become a few orders of magnitude smaller than the theoretical values in the continuum regime. The results are repeatable and expected to be useful for further experimentation and modeling of flow in the slip and transition regimes.

Macrophage activation syndrome: experience from a tertiary referral centre.

Over a period of 3 years, 13 patients with Macrophage Activation Syndrome were seen. Most had underlying connective tissue disease or malignancy. High-grade fever, cytopenia and elevated transaminases were the common presenting manifestations. Elevated LDH and ferritin were characteristic. Due to low index of suspicion the diagnosis was delayed in majority of cases. Five of the 13 expired. Macrophage Activation Syndrome is associated with a high mortality and should be considered in the differential diagnosis of unexplained pancytopenia in-patients with connective tissue disease and malignancy.

Isolation and identification of impurities in L-696, 229 drug substance.

Two low level impurities in 3-[2-(2-benzoxazolyl)ethyl]-5-ethyl-6-methyl-2(1H)-pyridinone drug substance (L-696,229) have been isolated by a combination of preparative HPLC, solid-phase extraction and liquid-liquid extraction. They were identified as 3-[2-(2-benzoxazolyl)ethyl]-5-ethyl-6-(2-phenylethyl)-2(1H)-pyridinone (I) and 6,6'-(2-phenyl-1,3-propanediyl)bis[3-[2-(2-benzoxazolyl)ethyl]-5-ethyl-2(1H)-pyridinone] (II) by mass spectrometry and by their (13)C and (1)H-NMR spectra.

Child labor in Bombay.

Of the world's largest child labor force in India, Bombay has over 30,000 working children, most of them migrants. In a prospective study of 73 working children from a part of Dharavi, the biggest slum in Asia, 68% were working as hotel boys; 22% had started working before their 10th birthday, a large number doing so to increase the family income, but earning less than Rs. 100 ($11) per month. Forty percent worked more than 12 hours a day and only 16% continued schooling. Two-thirds depended entirely on their employers for food which was adequate and no child in the study was malnourished. Overall incidence of anemia and vitamin deficiency was 10% each. Only 7% had ailments related to their occupation. Because this was a cross-sectional study no conclusions can be drawn regarding long term and residual effects. Preventing children from working is likely to make worse their own as well as their families' problems unless substitute sources of income or welfare are available. Legal protection and other services near their working places are essential for those who have to work.