Three-dimensional structure of heat shock protein 90 from Plasmodium falciparum: molecular modelling approach to rational drug design against malaria

We have recently implicated heat shock protein 90 from Plasmodium falciparum (PfHsp90) as a potential drug target against malaria. Using inhibitors specific to the nucleotide binding domain of Hsp90, we have shown potent growth inhibitory effects on development of malarial parasite in human erythrocytes. To gain better understanding of the vital role played by PfHsp90 in parasite growth, we have modeled its three dimensional structure using recently described full length structure of yeast Hsp90. Sequence similarity found between PfHsp90 and yeast Hsp90 allowed us to model the core structure with high confidence. The superimposition of the predicted structure with that of the template yeast Hsp90 structure reveals an RMSD of 3.31 angstrom. The N-terminal and middle domains showed the least RMSD (1.76 angstrom) while the more divergent C-terminus showed a greater RMSD (2.84 angstrom) with respect to the template. The structure shows overall conservation of domains involved in nucleotide binding, ATPase activity, co-chaperone binding as well as inter-subunit interactions. Important co-chaperones known to modulate Hsp90 function in other eukaryotes are conserved in malarial parasite as well. An acidic stretch of amino acids found in the linker region, which is uniquely extended in PfHsp90 could not be modeled in this structure suggesting a flexible conformation. Our results provide a basis to compare the overall structure and functional pathways dependent on PfHsp90 in malarial parasite. Further analysis of differences found between human and parasite Hsp90 may make it possible to design inhibitors targeted specifically against malaria.

Heat-shock protein 70-2 (HSP70-2) expression in bladder urothelial carcinoma is associated with tumour progression and promotes migration and invasion

Purpose: Testis specific heat-shock protein 70-2 (HSP70-2), a member of HSP70 chaperone family, is essential for the growth of spermatocytes and cancer cells. We investigated the association of HSP70-2 expression with clinical behaviour and progression of urothelial carcinoma of bladder. Experimental design: We assessed the HSP70-2 expression by RT-PCR and HSP70-2 protein expression by immunofluorescence, flow cytometry, immunohistochemistry and Western blotting in urothelial carcinoma patient specimens and HTB-1, UMUC-3, HTB-9, HTB-2 and normal human urothelial cell lines. Further, to investigate the role of HSP70-2 in bladder tumour development, HSP70-2 was silenced in the high-grade invasive HTB-1 and UMUC-3 cells. The malignant properties of urothelial carcinoma cells were examined using colony formation, migration assay, invasion assay in vitro and tumour growth in vivo. Results: Our RT-PCR analysis and immunohistochemistry analysis revealed that HSP70-2 was expressed in both moderate to well-differentiated and high-grade invasive urothelial carcinoma cell lines studied and not in normal human urothelial cells. In consistence with these results, HSP70-2 expression was also observed in superficially invasive (70%) and muscle-invasive (90%) patient's tumours. Furthermore, HSP70-2 knockdown significantly suppressed cellular motility and invasion ability. An in vivo xenograft study showed that inhibition of HSP70-2 significantly suppressed tumour growth. Conclusions: In conclusion, our data suggest that the HSP70-2 expression is associated with early spread and progression of urothelial carcinoma of bladder cancer and that HSP70-2 can be the potential therapeutic target for bladder urothelial carcinoma. (C) 2009 Elsevier Ltd. All rights reserved.

Heat transfer in plane Couette flow of a rarefied gas using Bhatnagar-Gross-Krook model

Using the linearized BGK model and the method of moments of half-range distribution functions the temperature jumps at two plates are determined, and it is found that the results are in fair agreement with those of Gross and Ziering, and Ziering.

Free convection heat transfer from vertical cylinders and wires

Free convection heat transfer from vertical long cylinders and wires were investigated experimentally. The experiments were designed to check the analytical results and the radius of curvature criteria formulated by the same authors. The results for water, the fluid medium used in the present set of experiments, are in excellent agreement with the theory. The results of Hama, Recesso and Christiaens, Kyte, Madden and Piret, in air are also shown to be in close agreement with proposed correlations.

On latent heat of vaporization, surface tension, and temperature

A semitheoretical equation for latent heat of vaporization has been derived and tested. The average error in predicting the value at the normal boiling point in the case of about 90 compounds, which includes polar and nonpolar liquids, is about 1.8%. A relation between latent heat of vaporization and surface tension is also derived and is shown to lead to Watson's empirical relation which gives the change of latent heat of vaporization with temperature. This gives a physico-chemical justification for Watson's empirical relation and provides a rapid method of determining latent heats by measuring surface tension.

Heat transfer to newtonian fluids in coiled pipes in laminar flow

Data on pressure drop and heat transfer to aqueous solutions of glycerol flowing in different types of coiled pipes are presented for laminar flow in the range of NRe from 80 to 6000. An empirical correlation is set up which can account the present data as well as the data available in literature within ±10 per cent deviation. Conventional momentum and heat transfer analogy equation is used to analyse the present data.

Intraseasonal response of mixed layer temperature and salinity in the Bay of Bengal to heat and freshwater flux

Buoy and satellite data show pronounced subseasonal oscillations of sea surface temperature (SST) in the summertime Bay of Bengal. The SST oscillations are forced mainly by surface heat flux associated with the active break cycle of the south Asian summer monsoon. The input of freshwater (FW) from summer rain and rivers to the bay is large, but not much is known about subseasonal salinity variability. We use 2002-2007 observations from three Argo floats with 5 day repeat cycle to study the subseasonal response of temperature and salinity to surface heat and freshwater flux in the central Bay of Bengal. About 95% of Argo profiles show a shallow halocline, with substantial variability of mixed layer salinity. Estimates of surface heat and freshwater flux are based on daily satellite data sampled along the float trajectory. We find that intraseasonal variability of mixed layer temperature is mainly a response to net surface heat flux minus penetrative radiation during the summer monsoon season. In winter and spring, however, temperature variability appears to be mainly due to lateral advection rather than local heat flux. Variability of mixed layer freshwater content is generally independent of local surface flux (precipitation minus evaporation) in all seasons. There are occasions when intense monsoon rainfall leads to local freshening, but these are rare. Large fluctuations in FW appear to be due to advection, suggesting that freshwater from rivers and rain moves in eddies or filaments.

The buoyant plume above a heat source

The boundary-layer type conservation equations of mass, momentum and energy for the steady free turbulent flow in gravitational convection over heat sources are set up for both two-dimensional and axisymmetric cases. These are reduced to ordinary differential equations in a similarity parameter by suitable transformations. The three classical hypotheses of turbulent diffusion-the Constant Exchange Coefficient hypothesis, Prandtl's Momentum Transfer theory and Taylor's Vorticity Transfer theory-are then incorporated into these equations in succession. The resulting equations are solved numerically and the results compared with some experimental results on gravitational convection over heat sources reported by Rouse et al.

Effect of impulsive change of wall velocity and wall temperature in viscous heat-conducting gas

A study of compression waves produced in a viscous heat-conducting gas by the impulsive start of a one-dimensional piston and by the inpulsive change of piston wall temperature is made using Laplace Transform Technique for Prandt1 number unity. Expressions for velocity, temperature and density have also been obtained using small-time expansion procedure in this case. For arbitrary Prandt1 number solutions have been developed using large-time expansion procedure. A number of graphs exhibiting the distribution of the fluid velocity, temperature and density have been drawn.

Numerical procedure for second order non-linear ordinary differential equations and application to heat transfer problem

In this paper, we have first given a numerical procedure for the solution of second order non-linear ordinary differential equations of the type y″ = f (x;y, y′) with given initial conditions. The method is based on geometrical interpretation of the equation, which suggests a simple geometrical construction of the integral curve. We then translate this geometrical method to the numerical procedure adaptable to desk calculators and digital computers. We have studied the efficacy of this method with the help of an illustrative example with known exact solution. We have also compared it with Runge-Kutta method. We have then applied this method to a physical problem, namely, the study of the temperature distribution in a semi-infinite solid homogeneous medium for temperature-dependent conductivity coefficient.

Free convection heat transfer in vertical annuli

Free convection heat transfer in vertical concentric, cylindrical annuli is investigated analytically and experimentally. The approximate double boundary layer model used by Emery and Chu for the case of vertical parallel plates is extended to the present case in obtaining heat transfer correlations in laminar free convection. Different correlations for the inner cylinder depending on the radius to the length ratio of the inner cylinder and the Rayleigh number, were used in the derivation of correlations for the annuli. The results for the case of short cylinders inside tubes are in agreement (within about 10 per cent) with the existing correlations. For other cases, namely long cylinders in annuli and wires in annuli, experiments conducted show the agreement of the analysis with experiments.