Characterization of an Evolutionarily Conserved Metallophosphoesterase That Is Expressed in the Fetal Brain and Associated with the WAGR Syndrome

Among the human diseases that result from chromosomal aberrations, a de novo deletion in chromosome 11p13 is clinically associated with a syndrome characterized by Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR). Not all genes in the deleted region have been characterized biochemically or functionally. We have recently identified the first Class III cyclic nucleotide phosphodiesterase, Rv0805, from Mycobacterium tuberculosis, which biochemically and structurally belongs to the superfamily of metallophosphoesterases. We performed a large scale bioinformatic analysis to identify orthologs of the Rv0805 protein and identified many eukaryotic genes that included the human 239FB gene present in the region deleted in the WAGR syndrome. We report here the first detailed biochemical characterization of the rat 239FB protein and show that it possesses metallophosphodiesterase activity. Extensive mutational analysis identified residues that are involved in metal interaction at the binuclear metal center. Generation of a rat 239FB protein with a mutation corresponding to a single nucleotide polymorphism seen in human 239FB led to complete inactivation of the protein. A close ortholog of 239FB is found in adult tissues, and biochemical characterization of the 239AB protein demonstrated significant hydrolytic activity against 2',3'-cAMP, thus representing the first evidence for a Class III cyclic nucleotide phosphodiesterase in mammals. Highly conserved orthologs of the 239FB protein are found in Caenorhabditis elegans and Drosophila and, coupled with available evidence suggesting that 239FB is a tumor suppressor, indicate the important role this protein must play in diverse cellular events.

Design of an optimal auction for sponsored search auctions

In this paper we first describe a framework to model the sponsored search auction on the web as a mechanism design problem. Using this framework, we design a novel auction which we call the OPT (optimal) auction. The OPT mechanism maximizes the search engine's expected revenue while achieving Bayesian incentive compatibility and individual rationality of the advertisers. We show that the OPT mechanism is superior to two of the most commonly used mechanisms for sponsored search namely (1) GSP (Generalized Second Price) and (2) VCG (Vickrey-Clarke-Groves). We then show an important revenue equivalence result that the expected revenue earned by the search engine is the same for all the three mechanisms provided the advertisers are symmetric and the number of sponsored slots is strictly less than the number of advertisers.

Microscopic theory of solvation of an ion in a binary dipolar liquid

A microscopic theory of the statics and the dynamics of solvation of an ion in a binary dipolar liquid is presented. The theory properly includes the different intermolecular correlations that are present in a binary mixture. As a result, the theory can explain several important aspects of both the statics and the dynamics of solvation that are observed in experiments. It provides a microscopic explanation of the preferential solvation of the more polar species by the solute ion. The dynamics of solvation is predicted to be highly non-exponential, in general. The average relaxation time is found to change nonlinearly with the composition of the mixture. These predictions are in qualitative agreement with the experimental results.

Optimization of hot workability of an Al-Mg-Si alloy using processing maps

The hot workability of an Al-Mg-Si alloy has been studied by conducting constant strain-rate compression tests. The temperature range and strain-rate regime selected for the present study were 300-550 degrees C and 0.001-1 s(-1), respectively. On the basis of true stress data, the strain-rate sensitivity values were calculated and used for establishing processing maps following the dynamic materials model. These maps delineate characteristic domains of different dissipative mechanisms. Two domains of dynamic recrystallization (DRX) have been identified which are associated with the peak efficiency of power dissipation (34%) and complete reconstitution of as-cast microstructure. As a result, optimum hot ductility is achieved in the DRX domains. The strain rates at which DRX domains occur are determined by the second-phase particles such as Mg2Si precipitates and intermetallic compounds. The alloy also exhibits microstructural instability in the form of localized plastic deformation in the temperature range 300-350 degrees C and at strain rate 1 s(-1).

Improved utilisation of an HF transformer in DC–AC application

Power conversion using high frequency (HF) link converters is popular because of compact size and light weight of highfrequency transformer. This study focuses on improved utilisation of HF transformer in DC–AC applications. In practical application, the operating condition of the power converter deviates significantly from the designed considerations. These deviating factors are commutation requirements (dead-time, overlap), mismatch in device drops and presence of the fundamental frequency in load current. As a result, the HF transformer handles some amount of low-frequency components (including DC) other than desired HF components. This causes the operating point in B-H curve to shift away from its normal or idealised position and hence results poor utilisation of the HF transformer and unwanted losses. This study investigates the nature of the problem with experimental determination of approximate lumped parameter modelling and saturation behaviour (B-H curve) of the HF transformer. A simple closed-loop control algorithm with online tuning of the controller parameters is proposed to improve the utilisation of the isolation transformer. The simulation and experimental results are presented.

Segregation into Chiral Enantiomeric Conformations of an Achiral Molecule by Concomitant Polymorphism

An analogue of the green fluorescent protein (GFP) luminophore crystallizes from a methanol solution impregnated with dichloromethane, into a pair of chiral crystals. Thermal analysis, fluorescence emission studies, and crystal packing analysis show that the two crystals are different materials. The two polymorphs arise from the rotation of a monosubstituted benzene ring about a C-N bond which results in the formation of two strong bifurcated C-H center dot center dot center dot O intermolecular bonds to oxygen O(6). The color difference has been ascribed to a difference in the packing of the two crystal forms. Theoretical studies supported by low temperature NMR show low kinetic energy barriers (similar to 10 kJ mol(-1)) separating the asymmetric units of the two crystal structures, suggesting that the driving force for the polymorphism could be the result of packing of two different asymmetric units.

The force distribution function of an oscillator model of polymer stretching at constant velocity

Recent simulations of the stretching of tethered biopolymers at a constant speed v (Ponmurugan and Vemparala, 2011 Phys. Rev. E 84 060101(R)) have suggested that for any time t, the distribution of the fluctuating forces f responsible for chain deformation is governed by a relation of the form P(+ f)/ P(- f) = expgamma f], gamma being a coefficient that is solely a function of v and the temperature T. This result, which is reminiscent of the fluctuation theorems applicable to stochastic trajectories involving thermodynamic variables, is derived in this paper from an analytical calculation based on a generalization of Mazonka and Jarzynski's classic model of dragged particle dynamics Mazonka and Jarzynski, 1999 arXiv:cond-\textbackslashmat/9912121v1]. However, the analytical calculations suggest that the result holds only if t >> 1 and the force fluctuations are driven by white rather than colored noise; they further suggest that the coefficient gamma in the purported theorem varies not as v(0.15)T-(0.7), as indicated by the simulations, but as vT(-1).

Rapid synthesis and characterization of an oxygen-deficient defect perovskite La4BaCu5O13+d phase

Oxygen-deficient defect perovskite La4BaCu5O13+d phase has been synthesized by the nitrate-citrate gel combustion method at 950 C for 2 h. Structural parameters were refined by the Rietveld refinement method using room-temperature powder XRD data. The La4BaCu5O13+d crystallizes in the tetragonal structure with space group P4/m (no. 83) and having the lattice parameters a=8.6508 c=3.8606 (1) Å and (2) Å, respectively. Oxygen content was determined by the iodometric titration. Low-temperature resistivity result reveals that La4BaCu5O13+d compound exhibit metallic behavior up to 15 K.

Switching and release dynamics of an electrostatically actuated MEMS switch under the influence of squeeze-film damping

This paper reports analytical modeling, simulation and experimental validation for switching and release times of an electrostatically actuated micromachined switch. Presented work is an extension of our earlier work [1] that analytically argued, and numerically and experimentally demonstrated, why pull-in time is larger that pull-up time when the actuation voltage is less than twice of the pull-in voltage. In this paper, switching dynamics is investigated under the influence of squeeze-film damping. Tests were performed on SOI (silicon-on-insulator) based parallel beams structures.Typical voltage requirement for actuation is in the range of 10-30 V. All the experiments were performed in normal atmospheric pressure. Measurement results confirm that the quality factor Q has appreciable effect on the release time compared to the switching time. The quality factor Q is extracted from the response measurement and compared with the ANSYS simulation result. In addition, the dynamic pull-in effect has also been studied and reported in this paper. A contribution of this work includes the effect of various phenomena such as squeeze-film damping, dynamic pull-in, and frequency pull-in effects on the switching dynamics of a MEMS switch.

Evaluation of the accuracy of an impact load cell using lumped parameter modeling and analysis

The objective of the current study is to evaluate the fidelity of load cell reading during impact testing in a drop-weight impactor using lumped parameter modeling. For the most common configuration of a moving impactor-load cell system in which dynamic load is transferred from the impactor head to the load cell, a quantitative assessment is made of the possible discrepancy that can result in load cell response. A 3-DOF (degrees-of-freedom) LPM (lumped parameter model) is considered to represent a given impact testing set-up. In this model, a test specimen in the form of a steel hat section similar to front rails of cars is represented by a nonlinear spring while the load cell is assumed to behave in a linear manner due to its high stiffness. Assuming a given load-displacement response obtained in an actual test as the true behavior of the specimen, the numerical solution of the governing differential equations following an implicit time integration scheme is shown to yield an excellent reproduction of the mechanical behavior of the specimen thereby confirming the accuracy of the numerical approach. The spring representing the load cell, however,predicts a response that qualitatively matches the assumed load-displacement response of the test specimen with a perceptibly lower magnitude of load.

Two-point correlation function of an exclusion process with hole-dependent rates

We consider an exclusion process on a ring in which a particle hops to an empty neighboring site with a rate that depends on the number of vacancies n in front of it. In the steady state, using the well-known mapping of this model to the zero-range process, we write down an exact formula for the partition function and the particle-particle correlation function in the canonical ensemble. In the thermodynamic limit, we find a simple analytical expression for the generating function of the correlation function. This result is applied to the hop rate u(n) = 1 + (b/n) for which a phase transition between high-density laminar phase and low-density jammed phase occurs for b > 2. For these rates, we find that at the critical density, the correlation function decays algebraically with a continuously varying exponent b - 2. We also calculate the two-point correlation function above the critical density and find that the correlation length diverges with a critical exponent nu = 1/(b - 2) for b < 3 and 1 for b > 3. These results are compared with those obtained using an exact series expansion for finite systems.

Significant photocytotoxic effect of an iron(III) complex of a Schiff base ligand derived from vitamin B-6 and thiosemicarbazide in visible light

Iron(III)-Schiff base complexes, namely, Fe(tsc-py)(2)](NO3) (1), Fe(tsc-acpy)(2)](NO3) (2) and Fe(tsc-VB6)(2)](NO3) (3), where tsc-py, tsc-acpy and tsc-VB6 are the respective Schiff bases derived from thiosemicarbazide (tsc) and pyridine-2-aldehyde (tsc-py), 2-acetyl pyridine (tsc-acpy) and vitamin B-6 (pyridoxal, tsc-VB6), have been prepared, structurally characterized and their photocytotoxicity studied in cancer HeLa cells. The single crystal X-ray structures of the complexes 1 and 2 show a distorted octahedral geometry formed by the FeN4S2 core. The low-spin and 1 : 1 electrolytic complexes display a broad absorption band in the visible region. Complexes 1 and 2, without any VB6 moiety are not cytotoxic under light or dark conditions. Complex 3 is significantly photocytotoxic under visible light of 400-700 nm giving an IC50 value of 22.5 mu M in HeLa cells with no dark toxicity (IC50 > 100 mu M). The photo-induced cell death is attributable to apoptotic pathways involving photo-assisted generation of intracellular ROS. The observed photocytotoxicity of complex 3 could be the result of its better photosensitizing property combined with its enhanced uptake into cancer cells via a VB6 transporting membrane carrier (VTC) mediated diffusion pathway due to the presence of the VB6 moiety compared to the two non-vitamin B-6 analogues, complexes 1 and 2.

Unsteady Compressible Boundary-Layer Flow On The Stagnation Line Of An Infinite Swept Cylinder

Numerical solutions of flow and heat transfer process on the unsteady flow of a compressible viscous fluid with variable gas properties in the vicinity of the stagnation line of an infinite swept cylinder are presented. Results are given for the case where the unsteady temperature field is produced by (i) a sudden change in the wall temperature (enthalpy) as the impulsive motion is started and (ii) a sudden change in the free-stream velocity. Solutions for the simultaneous development of the thermal and momentum boundary layers are obtained by using quasilinearization technique with an implicit finite difference scheme. Attention is given to the transient phenomenon from the initial flow to the final steady-state distribution. Results are presented for the skin friction and heat transfer coefficients as well as for the velocity and enthalpy profiles. The effects of wail enthalpy parameter, sweep parameter, fluid properties and transpiration cooling on the heat transfer and skin friction are considered.