Structural and Functional Characterization of the ABCC6 Transporter in Hepatic Cells: Role on PXE,Cancer Therapy and Drug Resistance

Pseudoxanthoma elasticum (PXE) is a complex autosomal recessive disease caused by mutations of ABCC6 transporter and characterized by ectopic mineralization of soft connective tissues. Compared to the other ABC transporters, very few studies are available to explain the structural components and working of a full ABCC6 transporter, which may provide some idea about its physiological role in humans. Some studies suggest that mutations of ABCC6 in the liver lead to a decrease in some circulating factor and indicate that PXE is a metabolic disease. It has been reported that ABCC6 mediates the efflux of ATP, which is hydrolyzed in PPi and AMP; in the extracellular milieu, PPi gives potent anti-mineralization effect, whereas AMP is hydrolyzed to Pi and adenosine which affects some cellular properties by modulating the purinergic pathway. Structural and functional studies have demonstrated that silencing or inhibition of ABCC6 with probenecid changed the expression of several genes and proteins such as NT5E and TNAP, as well as Lamin, and CDK1, which are involved in cell motility and cell cycle. Furthermore, a change in cytoskeleton rearrangement and decreased motility of HepG2 cells makes ABCC6 a potential target for anti-cancer therapy. Collectively, these findings suggested that ABCC6 transporter performs functions that modify both the external and internal compartments of the cells.     

Annealing temperature-dependent structural and electrical properties of (Ta2O5)1-x - (TiO2)x thin films,x ≤ 0.11

(Ta₂O₅)_1-x- (TiO₂)_x (TTO_x) thin films, with x = 0, 0.03, 0.06, 0.08, and 0.11, were deposited using magnetron direct current (DC) sputtering method onto the P/boron-silicon (1 0 0) substrates by varying areas of Tantalum and Titanium metallic targets, in oxygen environment at ambient temperature. The as-deposited thin films were annealed at temperatures ranging from 500 to 800 °C. Generally, the formation of the Ta₂O₅ structure was observed from the X-ray diffraction measurements of the annealed films. The capacitance of prepared metal– oxide– semiconductor (MOS) structures of Ag/TTO_x/p-Si was measured at 1 MHz. The dielectric constant of the deposited films was observed altering with varying composition and annealing temperature, showing the highest value 71, at 1 MHz, for the TTO_x films, x = 0.06, annealed at 700 °C. With increasing annealing temperature, from 700 to 800 °C, the leakage current density was observed, generally decreasing, from 10^?5 to 10^?8 A cm^?2, for the prepared compositions. Among the prepared compositions, films with x = 0.06, annealed at 800 °C, having the observed value of dielectric constant 48, at 1 MHz; and the leakage current density 2.7 × 10^?8 A cm^?2, at the electric field of 3.5 × 10⁵ V cm^?1, show preferred potential as a dielectric for high-density silicon memory devices.     

Pr（Ⅲ） and Nd（Ⅲ） Absorption Spectroscopic Probe to Investigate Interaction with Lysozyme （HEW）

Pr（ Ⅲ ） and Nd（ Ⅲ ） can be utilized as absorption spectroscopic probes to investigate the interaction of biomolecules like Lysozyme （HEW） with Ca（ Ⅱ ） in-vitro ; the most abundant metal ion in the human body system. The spectroscopic techniques involving comparative absorption, absorption difference, and quantitative intensity analysis using 4f-4f transitions are utilized for changes in the inner sphere coordination pattern of Pr（ Ⅲ ） and Nd（Ⅲ ） in solution as well as in solid state. The present study deals with an important biomolecule in human metabolism, that is, Lysozyme （HEW）. The absorption er-Condon the probab spectral parameters such as the oscillator strength （P）, the Judd-Ofelt （Tλ） intensity parameters, and the Slatinter electronic parameters are calculated using chi square methods. The obtained results are used to determine le geometry of the complex in the solution, the nature of the bond between Pr（Ⅲ）/Nd（Ⅲ） with lysozyme, and the inner sphere coordination environment of f-f transitions. The results obtained from various experimental conditions are utilized to investigate the coordination changes in the Pr（Ⅲ）/Nd（Ⅲ） complexes caused by different coordinating sites of lysozyme, normalized bite, denticity, the solvent nature, the coordination number, the nature of bond and other parameters to mimic the interaction of the Ca（ Ⅱ ） ion with such biomolecule.     

Effect of Microfabric on Mechanical Behavior of Kaolin Clay Using Cubical True Triaxial Testing

Various aspects of the mechanical behavior of kaolin clay are discussed in light of experimental observations from a series of strain controlled true triaxial undrained tests performed on cubical kaolin clay specimens with flocculated and dispersed microfabric, using a fully automated flexible boundary experimental setup with real-time feedback control system. The laboratory procedures used to prepare flocculated and dispersed microfabric specimens are presented. Mercury intrusion porosimetry is used to evaluate the pore structure of these specimens. The influence of microfabric on the consolidation behavior of kaolin clay is evaluated based on the data obtained from K0 consolidation during constant rate of strain tests and the isotropic consolidation during true triaxial tests. Undrained tests on kaolin clay show that the following vary with microfabric of specimen: The shear stiffness, excess pore pressure generated during shear, and strength and strain to failure. For both microfabrics, the observed strength behavior using cubical triaxial testing shows a similar pattern of variation with applied stress anisotropy; hence, only a marginal influence of fabric-induced anisotropy.     

Thermal impact of an active 3-D microelectrode array implanted in the brain.

A chronically implantable, wireless neural interface device will require integrating electronic circuitry with the interfacing microelectrodes in order to eliminate wired connections. Since the integrated circuit (IC) dissipates a certain amount of power, it will raise the temperature in surrounding tissues where it is implanted. In this paper, the thermal influence of the integrated 3-D Utah electrode array (UEA) device implanted in the brain was investigated by numerical simulation using finite element analysis (FEA) and by experimental measurement in vitro as well as in vivo. The numerically calculated and experimentally measured temperature increases due to the UEA implantation were in good agreement. The experimentally validated numerical model predicted that the temperature increases linearly with power dissipation through the UEA, with a slope of 0.029 degree C/mW over the power dissipation levels expected to be used. The influences of blood perfusion, brain metabolism, and UEA geometry on tissue heating were also investigated using the numerical model.     

Adaptive value function approximation for continuous-state stochastic dynamic programming

Approximate dynamic programming (ADP) commonly employs value function approximation to numerically solve complex dynamic programming problems. A statistical perspective of value function approximation employs a design and analysis of computer experiments (DACE) approach, where the “computer experiment” yields points on the value function curve. The DACE approach has been used to numerically solve high-dimensional, continuous-state stochastic dynamic programming, and performs two tasks primarily: (1) design of experiments and (2) statistical modeling. The use of design of experiments enables more efficient discretization. However, identifying the appropriate sample size is not straightforward. Furthermore, identifying the appropriate model structure is a well-known problem in the field of statistics. In this paper, we present a sequential method that can adaptively determine both sample size and model structure. Number-theoretic methods (NTM) are used to sequentially grow the experimental design because of their ability to fill the design space. Feed-forward neural networks (NNs) are used for statistical modeling because of their adjustability in structure-complexity . This adaptive value function approximation (AVFA) method must be automated to enable efficient implementation within ADP. An AVFA algorithm is introduced, that increments the size of the state space training data in each sequential step, and for each sample size a successive model search process is performed to find an optimal NN model. The new algorithm is tested on a nine-dimensional inventory forecasting problem.     

Healing substrates with mobile, particle-filled microcapsules: designing a 'repair and go' system.

We model the rolling motion of a fluid-driven, particle-filled microcapsule along a heterogeneous, adhesive substrate to determine how the release of the encapsulated nanoparticles can be harnessed to repair damage on the underlying surface. We integrate the lattice Boltzmann model for hydrodynamics and the lattice spring model for the micromechanics of elastic solids to capture the interactions between the elastic shell of the microcapsule and the surrounding fluids. A Brownian dynamics model is used to simulate the release of nanoparticles from the capsule and their diffusion into the surrounding solution. We focus on a substrate that contains a damaged region (e.g. a crack or eroded surface coating), which prevents the otherwise mobile capsule from rolling along the surface. We isolate conditions where nanoparticles released from the arrested capsule can repair the damage and thereby enable the capsules to again move along the substrate. Through these studies, we establish guidelines for designing particle-filled microcapsules that perform a 'repair and go' function and thus, can be utilized to repair damage in microchannels and microfluidic devices.     

Synthesis of Bisindolylmethanes and Their Cytotoxicity Properties

Polymer supported dichlorophosphate (PEG-OPOCl₂) is an efficient green catalyst for the electrophilic substitution reaction of indole with aromatic aldehydes, in neat condition, to afford an excellent yield of bis(indolyl) methanes with short reaction time, at room temperature. The synthesized compounds and their anti-cancer activity are evaluated.     

Synthesis of novel sulfonium salts and cationic polymerization of epoxides and vinyl ether

Novel 1‐methoxycarbonylethylmethylphenylsulfonium salts with nonnucleophilic anions, namely, hexafluorophosphate, hexafluoroantimonate, and tetrafluoroborate, were synthesized by the reaction of 1‐methoxycarbonylethylphenylsulfide and dimethyl sulfate followed by anion exchange with potassium hexafluorophosphate, sodium hexafluoroantimonate, and sodium tetrafluoroborate, respectively. The cationic polymerization (photopolymerization and thermal polymerization) of epoxy and vinyl ether monomers was carried out to demonstrate the applicability of the newly synthesized sulfonium salts. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3157–3163, 2007