Heat Shock Protein 90 as a Drug Target against Protozoan Infections Biochemical characterization of HSP90 From plasmodium falciparum and trypanosoma evansi and evaluation of its inhibitor as a candidate drug

Using a pharmacological inhibitor of Hsp90 in cultured malarial parasite, we have previously implicated Plasmodium falciparum Hsp90 (PfHsp90) as a drug target against malaria. In this study, we have biochemically characterized PfHsp90 in terms of its ATPase activity and interaction with its inhibitor geldanamycin (GA) and evaluated its potential as a drug target in a preclinical mouse model of malaria. In addition, we have explored the potential of Hsp90 inhibitors as drugs for the treatment of Trypanosoma infection in animals. Our studies with full-length PfHsp90 showed it to have the highest ATPase activity of all known Hsp90s; its ATPase activity was 6 times higher than that of human Hsp90. Also, GA brought about more robust inhibition of PfHsp90 ATPase activity as compared with human Hsp90. Mass spectrometric analysis of PfHsp90 expressed in P. falciparum identified a site of acetylation that overlapped with Aha1 and p23 binding domain, suggesting its role in modulating Hsp90 multichaperone complex assembly. Indeed, treatment of P. falciparum cultures with a histone deacetylase inhibitor resulted in a partial dissociation of PfHsp90 complex. Furthermore, we found a well known, semisynthetic Hsp90 inhibitor, namely 17-(allylamino)-17-demethoxygeldanamycin, to be effective in attenuating parasite growth and prolonging survival in a mouse model of malaria. We also characterized GA binding to Hsp90 from another protozoan parasite, namely Trypanosoma evansi. We found 17-(allylamino)-17-demethoxygeldanamycin to potently inhibit T. evansi growth in a mouse model of trypanosomiasis. In all, our biochemical characterization, drug interaction, and animal studies supported Hsp90 as a drug target and its inhibitor as a potential drug against protozoan diseases.

Thermal expansion of doped lanthanum gallates

Thermal expansion of several compositions of Sr and Mg-doped LaGaO3 including an A-site deficient composition (La0.9Sr0.1)(0.98)(Ga0.8Mg0.2)O-2.821 were measured in the temperature range from 298 to 1273 K. The effect of doping on thermal expansion was studied by varying the composition at one site of the perovskite structure (either A or B), while keeping the composition at the other site invariant. Thermal expansion varied nonlinearly with temperature and exhibited an inflexion between 550 and 620 K, probably related to the change in crystal structure from orthorhombic to rhombohedral. The dependence of average thermal expansion coefficient (alpha (av)) on the dopant concentration on either A or B site of the perovskite structure was found to be linear, when the composition at the other site was kept constant. Mg doping on the B-site had a greater effect on the average thermal expansion coefficient than Sr doping on the A-site. Cation deficiency at the A-site decreases thermal expansion when compositions at both sites are held constant.

Effect of wall thickness on the end corrections of the extended inlet and outlet of a double-tuned expansion chamber

Simple expansion chambers, the simplest of the muffler configurations, have very limited practical application due to the presence of periodic troughs in the transmission loss spectrum which drastically lower the overall transmission loss of the muffler. Tuned extended inlet and outlet can be designed to nullify three-fourths of these troughs, making use of the plane wave theory. These cancellations would not occur unless one altered the geometric lengths for the extended tube in order to incorporate the effect of evanescent higher-order modes (multidimensional effect) through end corrections or lumped inertance approximation at the area discontinuities or junctions. End corrections of the extended inlet and outlet have been studied by several researchers. However the effect of wall thickness of the inlet/outlet duct on end correction has not been studied explicitly. This has significant effect on the tuning of an extended inlet/outlet expansion chamber. It is investigated here experimentally as well as numerically (through use of 3-D FEM software) for stationary medium. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.

A Heat and Light Mediated Synthetic Sequence Serendipitous Synthesis of Methyl Ester of Tris-Norpterosin-E

Synthesis of methyl ester of 3-oxo-indan-5-acetic acid (3), an analogue of the natura1 product pterosin-E (4), starting from cyclopentadiene (1) and p-benzoquinone (2) using a sequence of six ground and excited state reactions, is described.

A High Pressure Study of the Phase Diagram and the Critical Exponent β of Binary Liquid Systems

The pressure dependence of critical parameters xc, Tc, and β have been analysed in four systems namely cyclohexane + acetic anhydride, n-heptane + acetic anhydride, methanol + n-heptane, and carbon disulphide + acetonitrile. The separation temperature was found to increase linearly with pressure the value of dTc/dP being 28 mK, 11 mK, 22 mK, and 25 mK respectively. These are in fair agreement with earlier measurements available for two systems. For the methanol + n-heptane system dTc/dP is apparently not consistent with the value predicted from the specific heat and thermal expansion data.Die Druckabhängigkeit der kritischen Parameter xc, Tc und β ist in den vier Systemen Cyclohexan + Essigsäureanhydrid, n-Heptan + Essigsäureanhydrid, Methanol + n-Heptan und Schwefelkohlenstoff + Acetonitril analysiert worden. Es wurde gefunden, daß die kritische Temperatur linear mit dem Druck ansteigt. Die Werte für dTc/dP betragen 28 mK, 11 mK, 22 mK und 25 mK. Sie sind in guter überein-stimmung mit früheren Messungen an zweien dieser Systeme. Für Methanol + n-Heptan stimmt der Wert für dT/dP offensichtlich nicht mit Werten, die mit Hilfe von Daten für die spezifische Wärme und die thermische Ausdehnung vorhergesagt wurden, überein.

Non-Newtonian boundary layers on a moving cylinder

The analysis of steady laminar forced convection boundary layer of power-law non-Newtonian fluids on a continuously moving cylinder with the surface maintained at a uniform temperature or uniform heat flux is presented. Of interest were the effects of power-law viscosity index, transverse curvature, generalized Prandtl number and streamwise coordinate on the local Nusselt number as well as on the velocity and temperature profiles. The two thermal boundary conditions yield quite similar results. Comparison of the calculated results with available series expansion solutions for a Newtonian fluid shows a very good performance of the present numerical procedure.

Analytical and numerical solutions of inward spherical solidification of a superheated melt with radiative-convective heat transfer and density jump at freezing front

Analytical and numerical solutions of a general problem related to the radially symmetric inward spherical solidification of a superheated melt have been studied in this paper. In the radiation-convection type boundary conditions, the heat transfer coefficient has been taken as time dependent which could be infinite, at time,t=0. This is necessary, for the initiation of instantaneous solidification of superheated melt, over its surface. The analytical solution consists of employing suitable fictitious initial temperatures and fictitious extensions of the original region occupied by the melt. The numerical solution consists of finite difference scheme in which the grid points move with the freezing front. The numerical scheme can handle with ease the density changes in the solid and liquid states and the shrinkage or expansions of volumes due to density changes. In the numerical results, obtained for the moving boundary and temperatures, the effects of several parameters such as latent heat, Boltzmann constant, density ratios, heat transfer coefficients, etc. have been shown. The correctness of numerical results has also been checked by satisfying the integral heat balance at every timestep.

Analysis of heat and mass transfer during bulk hydraircooling of spherical food products

Hydraircooling is a technique used for precooling food products. In this technique chilled water is sprayed over the food products while cold unsaturated air is blown over them. Hydraircooling combines the advantages of both air- and hydrocooling. The present study is concerned with the analysis of bulk hydraircooling as it occurs in a package filled with several layers of spherical food products with chilled water sprayed from the top and cold unsaturated air blown from the bottom. A mathematical model is developed to describe the hydrodynamics and simultaneous heat and mass transfer occurring inside the package. The non-dimensional governing equations are solved using the finite difference numerical methods. The results are presented in the form of time-temperature charts. A correlation is obtained to calculate the process time in terms of the process parameters.

Trafficking in human beings and Foucauldian biopower : A case study in the expansion of the human rights phenomenon

Trafficking in human beings has become one of the most talked about criminal concerns of the 21st century. But this is not all that it has become. Trafficking has also been declared as one of the most pressing human rights issues of our time. In this sense, it has become a part of the expansion of the human rights phenomenon. Although it is easy to see that the crime of trafficking violates several of the human rights of its victims, it is still, in its essence, a fairly conventional although particularly heinous and often transnational crime, consisting of acts between private actors, and lacking, therefore, the vertical effect associated traditionally with human rights violations. This thesis asks, then, why, and how, has the anti-trafficking campaign been translated in human rights language. And even more fundamentally: in light of the critical, theoretical studies surrounding the expansion of the human rights phenomenon, especially that of Costas Douzinas, who has declared that we have come to the end of human rights as a consequence of the expansion and bureaucratization of the phenomenon, can human rights actually bring salvation to the victims of trafficking? The thesis demonstrates that the translation process of the anti-trafficking campaign into human rights language has been a complicated process involving various actors, including scholars, feminist NGOs, local activists and global human rights NGOs. It has also been driven by a complicated web of interests, the most prevalent one the sincere will to help the victims having become entangled with other aims, such as political, economical, and structural goals. As a consequence of its fragmented background, the human rights approach to trafficking seeks still its final form, consisting of several different claims. After an assessment of these claims from a legal perspective, this thesis concludes that the approach is most relevant regarding the mistreatment of victims of trafficking in the hands of state authorities. It seems to be quite common that authorities have trouble identifying the victims of trafficking, which means that the rights granted to themin international and national documents are not realized in practice, but victims of trafficking are systematically deported as illegal immigrants. It is argued that in order to understand the measures of the authorities, and to assess the usefulness of human rights, it is necessary to adopt a Foucauldian perspective and to observe the measures as biopolitical defence mechanisms. From a biopolitical perspective, the victims of trafficking can be seen as a threat to the population a threat that must be eliminated either by assimilating them to the main population with the help of disciplinary techniques, or by excluding them completely from the society. This biopolitical aim is accomplished through an impenetrable net of seemingly insignificant practices and discourses that not even the participants are aware of. As a result of these practices and discourses, trafficking victims only very few of fit the myth of the perfect victim, produced by biopolitical discourses become invisible and therefore subject to deportation as (risky) illegal immigrants, turning them into bare life in the Agambenian sense, represented by the homo sacer, who cannot be sacrificed, yet does not enjoy the protection of the society and its laws. It is argued, following Jacques Rancière and Slavoj i ek, that human rights can, through their universality and formal equality, provide bare life the tools to formulate political claims and therefore utilize their politicization through their exclusion to return to the sphere of power and politics. Even though human rights have inevitably become entangled with biopolitical practices, they are still perhaps the most efficient way to challenge biopower. Human rights have not, therefore, become useless for the victims of trafficking, but they must be conceived as a universal tool to formulate political claims and challenge power .In the case of trafficking this means that human rights must be utilized to constantly renegotiate the borders of the problematic concept of victim of trafficking created by international instruments, policies and discourses, including those that are sincerely aimed to provide help for the victims.

Casting and heat treatment variables of Al–7Si–Mg alloy

A review of the research work that has been carried out thus far relating the casting and heat treatment variables to the structure and mechanical properties of Al–7Si–Mg (wt-%) is presented here. Although specifications recommend a wide range of magnesium contents and a fairly high content of iron, a narrow range of magnesium contents, closer to either the upper or lower specified limits depending on the properties desired, and a low iron content will have to be maintained to obtain optimum and consistent mechanical properties. A few studies have revealed that the modification of eutectic silicon slightly increases ductility and fracture toughness and also that the effect of modification is predominant at low iron content. Generally, higher solidification rates give superior mechanical properties. Delayed aging (the time elapsed between quenching and artificial aging during precipitation hardening) severely affects the strength of the alloy. The mechanism of delayed aging can be explained on the basis of Pashley's kinetic model. It has been reported that certain trace additions (cadmium, indium, tin, etc.) neutralise the detrimental effect of delayed aging. In particular, it should be noted that delayed aging is not mentioned in any of the specifications. With reference to the mechanism by which trace additions neutralise the detrimental effect of delayed aging, various hypotheses have been postulated, of which impurity–vacancy interaction appears to be the most widely accepted.

Effect of Substitution of Ca on Thermal Expansion of Cordierite (Mg2Al4Si5O18)

The effect of substitution of calcium on the anisotropic axial thermal expansion of cordierite was investigated by using a high-temperature X-ray diffraction technique. The compositions were prepared by the sol–gel route. In the Mg2-xCax-Al4Si5O18 system, single-phase cordierite can be prepared for x up to 0.5. Thermal expansion anisotropy (αa–αc) of cordierites reduces progressively by the substitution of increasing amounts of Ca for Mg.

Reynolds stress and heat flux in spherical shell convection

Context. Turbulent fluxes of angular momentum and heat due to rotationally affected convection play a key role in determining differential rotation of stars. Aims. We compute turbulent angular momentum and heat transport as functions of the rotation rate from stratified convection. We compare results from spherical and Cartesian models in the same parameter regime in order to study whether restricted geometry introduces artefacts into the results. Methods. We employ direct numerical simulations of turbulent convection in spherical and Cartesian geometries. In order to alleviate the computational cost in the spherical runs and to reach as high spatial resolution as possible, we model only parts of the latitude and longitude. The rotational influence, measured by the Coriolis number or inverse Rossby number, is varied from zero to roughly seven, which is the regime that is likely to be realised in the solar convection zone. Cartesian simulations are performed in overlapping parameter regimes. Results. For slow rotation we find that the radial and latitudinal turbulent angular momentum fluxes are directed inward and equatorward, respectively. In the rapid rotation regime the radial flux changes sign in accordance with earlier numerical results, but in contradiction with theory. The latitudinal flux remains mostly equatorward and develops a maximum close to the equator. In Cartesian simulations this peak can be explained by the strong 'banana cells'. Their effect in the spherical case does not appear to be as large. The latitudinal heat flux is mostly equatorward for slow rotation but changes sign for rapid rotation. Longitudinal heat flux is always in the retrograde direction. The rotation profiles vary from anti-solar (slow equator) for slow and intermediate rotation to solar-like (fast equator) for rapid rotation. The solar-like profiles are dominated by the Taylor-Proudman balance.

Heat capacity measurements on Ge20Se80−xBix glasses

The specific heat Cp of glassy Ge20Se80−xBix (0 ≤ × ≤ 12) samples is investigated. The Cp at 323K and the ΔCp at glass transition temperature Tg1 show anomalous features around x = 8 at.%, where p−n conduction type inversion also take place. These features are discussed in the light of Phillips model of phase separation in these glasses at the microscopic level.

Simultaneous heat and mass transfer under unsteady mixed convection along a vertical slender cylinder embedded in a porous medium

Unsteady laminar mixed convection flow (combined free and forced convection flow) along a vertical slender cylinder embedded in a porous medium under the combined buoyancy effect of thermal and species diffusion has been studied. The effect of the permeability of the medium as well as the magnetic field has been included in the analysis. The partial differential equations with three independent variables governing the flow have been solved numerically using a implicit finite difference scheme in combination with the quasilinearization technique. Computations have been carried out for accelerating, decelerating and oscillatory free stream velocity distributions. The effects of the permeability of the medium, buoyancy forces, transverse curvature and magnetic field on skin friction, heat transfer and mass transfer have been studied. It is found that the effect of free stream velocity distribution is more pronounced on the skin friction than on the heat and mass transfer. The permeability and magnetic parameters increase the skin friction, but reduce the heat and mass transfer. The skin friction, heat transfer and mass transfer are enhanced due to the buoyancy forces and curvature parameter. The heat transfer is strongly dependent on the viscous dissipation parameter and the Prandtl number, and the mass transfer on the Schmidt number. Untersucht wurde die instationäre laminare Mischkonvektion längs eines vertikalen, in einem porösen Medium eingebetteten Zylinders unter kombinierten Auftriebseffekten von thermischer und spezieller Diffusion. Der Einfluß der Permeabilität des Mediums sowie des magnetischen Feldes wurden in die Betrachtung einbezogen. Die partiellen Differentialgleichungen mit drei unabhängigen Variablen, welche die Strömung beschreiben, wurde numerisch anhand des Schemas der endlichen Differenzen in Verbindung mit der Technik der Quasilinearisation gelöst. Berechnungen für die beschleunigte, verzögerte und oszillierende Geschwindigkeitsverteilung der freien Strömung sind durchgeführt worden. Untersucht wurden ebenfalls die Effekte der Permeabilität des Mediums, der Auftriebskräfte, der transversalen Krümmung, des magnetischen Feldes auf die Oberflächenreibung sowie die Wärmeund Stoffübertragung. Es wurde festgestellt, daß die Geschwindigkeit mehr Einfluß auf die Oberflächenreibung als auf die Wärmeund Stoffübertragung hat. Die Oberflächenreibung sowie die Wärme- und Stoffübertragung werden durch die Auftriebskräfte und die Krümmungsparameter verbessert. Die Wärmeübertragung ist stark abhängig von den Parametern der viskosen Dissipation und der Prandtl-Zahl; die Stoffübertragung von der Schmidt-Zahl.