Synthesis and preliminary evaluation of pro-RNA 2'-O-masked with biolabile pivaloyloxymethyl groups in an RNA interference assay

The cellular delivery of bioactive nucleic acid-based drugs such as small interfering RNA (siRNA) represents a major technical hurdle for their pharmaceutical application. Prodrug-like approaches provide an attractive concept to address the delivery problem. With the aim to prepare RNA-based prodrugs bearing biolabile protections which facilitate cellular uptake and are prone to be removed enzymatically inside cells in order to release functional RNA, we synthesized pro-RNA totally or partially masked in 2'-OH position with pivaloyloxymethyl (PivOM) groups. A suitable strategy has been developed to synthesize and to purify base-sensitive mixed 2'-OH/2'-O-PivOM oligoribonucleotides, and to include them in siRNA. In this strategy, the fluoride labile [(triisopropylsilyl)oxy]-benzyloxycarbonyl group (tboc) as nucleobase protection (for A and C), the TBS group as 2'-OH protection and the Q-linker to solid-support were compatible with the PivOM groups masking some 2'-OH. We have taken advantage of the specific stability of the PivOM group to apply selected acidic, basic, and fluoride ions treatment for the deprotection and release of pro-RNA. This kind of pro-siRNA was studied in a human cell culture-based RNAi assay and preliminary promising data are discussed.     

Delocalization due to correlations in two-dimensional disordered systems

We study the spectral statistics of interacting spin-less fermions in a two-dimensional disordered lattice. Within a full quantum treatment for small few-particle systems, we compute the low-energy many-body states numerically. While at weak disorder the interactions reduce spectral correlations and lead to localization, for the case of strong disorder we find that a moderate Coulomb interaction has a delocalizing effect. In addition, we observe a non-universal structure in the level-spacing distribution which we attribute to a mechanism reinforcing spectral correlations taking place in small systems at strong disorder.Received: 1 July 2004, Published online: 14 December 2004PACS: 71.27. + a Strongly correlated electron systems; heavy fermions - 73.20.Jc Delocalization processes - 72.15.Rn Localization effects (Anderson or weak localization)     

Analytical and numerical study of double diffusive convection in a vertical enclosure

This paper presents an analytical and numerical study of natural convection of a double-diffusive fluid contained in a rectangular slot subject to uniform heat and mass fluxes along the vertical sides. Governing parameters of the problem under study are the thermal Rayleigh number, Ra _T ; buoyancy ratio, N; Lewis number, Le; Prandtl number, Pr and aspect ratio of the cavity, A. In the first part of the analytical study a scale analysis is applied to the two extreme cases of heat-transfer and mass-transfer-driven flows. In the second part, an analytical solution, based on the parallel flow approximation, is reported for tall enclosures (A?1). Solutions for the flow fields, temperature and concentration distributions and Nusselt and Sherwood numbers are obtained in terms of the governing parameters of the problem. In the limits of heat-driven and solute-driven flows a good agreement is obtained between the prediction of the scale analysis and those of the analytical solution. The numerical solutions are based on the complete governing equations for two-dimensional flows, and cover the range 1≤Ra _T ≤10⁷, 0≤N≤10⁵, 10^-3≤Le≤10³, 1≤A≤20 and Pr=7. A good agreement is found between the analytical predictions and the numerical simulation.     

Buoyant plume above a line source of heat in an anisotropic porous medium

Buoyancy-induced convection arising from a horizontal line heat source embedded in an anisotropic porous medium is investigated analytically. The porous medium is anisotropic is permeability with its principal axes oriented in a direction that is oblique to the gravity vector. Assuming the boundary layer approximation, closed-form exact similarity solutions for both flow and temperature fields are presented and compared with those of isotropic case. Scale analysis is applied to predict the order of magnitudes involved in the boundary layer regime for which the conditions of validity are obtained. Effects of both anisotropic parameters (K* and %) and Rayleigh number Ra_L are observed to be strongly significant. It is demonstrated that a minimum (maximum) intensity of the thermal convective plume above the line source of heat can be obtained if the porous matrix is oriented with its principal axis with higher permeability parallel (perpendicular) to the vertical direction.     

Probability Density Function of the Output Current of Cascaded Multiplexer/Demultiplexers in Transparent Optical Networks

The influence of the concatenation of arbitrary optical multiplexers/demultiplexers (MUX/DEMUXs) on the probability density function (PDF) of the output current of a transparent optical network is assessed. All PDF results obtained analytically are compared with estimates from Monte Carlo simulation and an excellent agreement is achieved.

The non-Gaussian behavior of the PDFs, previously reported by other authors for square-law detectors, is significantly enhanced with the number of nodes increase due to the noise accumulation along the cascade of MUX/DEMUXs. The increase of the MUX/DEMUXs bandwidth and detuning also enhances the PDFs non-Gaussian behavior. The PDF shape variation with the detuning depends strongly on the number of nodes.

Explanations for the Gaussian approximation (GA) accuracy on the assessment of the performance of a concatenation of optical MUX/DEMUXs are also provided. For infinite extinction ratio and tuned MUX/DEMUXs, the GA error probabilities are, in general, pessimistic, due to the inaccurate estimation of the error probability for both bits. For low extinction ratio, the GA is very accurate due to a balance between the error probabilities estimated for the bits “1” and “0.” With the detuning increase, the GA estimates can become optimistic.     

On global motions of a compressible barotropic and selfgravitating gas with density-dependent viscosities

We consider the Cauchy problem for the equations of selfgravitating motions of a barotropic gas with density-dependent viscosities μ(ρ), and λ(ρ) satisfying the Bresch–Desjardins condition, when the pressure P(ρ) is not necessarily a monotone function of the density. We prove that this problem admits a global weak solution provided that the adiabatic exponent γ associated with P(ρ) satisfies ${gamma > frac{4}{3}}${gamma > frac{4}{3}}.