Drug and ion releasing tetracalcium phosphate based dual action cement for regenerative treatment of infected bone defects

Calcium phosphate cements (CPCs) are ideally suited for the local delivery of antibiotics in infected bone defects as they have multiple binding sites for loading various drugs. CPCs can also be substituted with ions such as Ag⁺, Zn²⁺, Mg²⁺, Sr²⁺, etc., to exhibit extended broad-spectrum antimicrobial activity. Strontium (Sr) in particular is known to enhance the new bone formation and decrease bone resorption. The current work aims to develop a dual action tetracalcium phosphate (TTCP) based cement which releases both the Sr²⁺ ion and ornidazole antibiotic drug for the treatment of bone infections. The TTCP with Sr²⁺ ion substitution was prepared by the solid state reaction method and it was used to form ornidazole loaded CPC. The ornidazole loaded cement prepared using 8?at% Sr substituted TTCP (8SCPC-O) showed complete hydroxyapatite (HA) formation in phosphate buffered solution at the end of 1 week. Fine needle-shaped HA crystals were observed in 8SCPC-O cement. In vitro drug release studies showed an accelerated ornidazole release from the 8SCPC-O sample when compared to samples without Sr substitution. Ornidazole releasing cements were found to be biocompatible with skeletal myoblast (L6) cells. Antibacterial activity of ornidazole releasing cement was evident from day 1 onwards against E. coli. The above results suggest 8SCPC-O as a good candidate for treating local bone infections.     

S-Ribosylhomocysteine analogues modified at the ribosyl C-4 position

4-C-Alkyl/aryl-S-ribosylhomocysteine (SRH) analogues were prepared by coupling of homocysteine with 4-substituted ribofuranose derivatives. The diastereoselective incorporation of the methyl substituent into the 4 position of the ribose ring was accomplished by the addition of methylmagnesium bromide to the protected ribitol-4-ulose yielding the 4-C-methylribitol in 85% yield as single 4R diastereomer. The 4-C hexyl, octyl, vinyl, and aryl ribitols were prepared analogously. Chelation controlled addition of a carbanion to ketones from the Si-face was responsible for the observed stereochemical outcome. Oxidation of the primary alcohol of the 4-C ribitols with catalytic amounts of tetrapropylammonium perruthenate in the presence of N-methylmorpholine N-oxide produced 4-C-alkylribono-1,4-lactones in high yields. Mesylation of the latter compounds at the 5-hydroxyl position and treatment with a protected homocysteine thiolate afforded protected 4-C-alkyl/aryl-SRH analogues as the lactones. Reduction with lithium triethylborohydride and successive global deprotections with TFA afforded 4-C-alkyl/aryl SRH analogues. These analogues might impede the S-ribosylhomocysteinase(LuxS)-catalyzed reaction by preventing β-elimination of a homocysteine molecule, and thus depleting the production of quorum sensing signaling molecule AI-2.     

Experimental calibration of density-dependent modified Drucker-Prager/Cap model using an instrumented cubic die for powder compact

Theory and experimental calibration of density dependent modified Drucker-Prager/Cap (DPC) model are presented by using a novel instrumented cubic die in powder compaction tests. The cubic die is designed for directly determining the loading and unloading forces and displacements of powder compact inside the die in compaction and transverse directions without any additional calibration. The cap surface parameters and elastic properties are characterized by fitting stress and strain curves recorded during loading and unloading at different green density values and the plastic material parameters for failure surface are obtained by additional radial and axial compressive tests. The experimental data is subsequently used in the simulation of cubic die compaction to verify the results from the density dependent modified DPC model.     

High order parameter-robust numerical method for time dependent singularly perturbed reaction–diffusion problems

We introduce a high order parameter-robust numerical method to solve a Dirichlet problem for one-dimensional time dependent singularly perturbed reaction-diffusion equation. A small parameter ε is multiplied with the second order spatial derivative in the equation. The parabolic boundary layers appear in the solution of the problem as the perturbation parameter ε tends to zero. To obtain the approximate solution of the problem we construct a numerical method by combining the Crank–Nicolson method on an uniform mesh in time direction, together with a hybrid scheme which is a suitable combination of a fourth order compact difference scheme and the standard central difference scheme on a generalized Shishkin mesh in spatial direction. We prove that the resulting method is parameter-robust or ε-uniform in the sense that its numerical solution converges to the exact solution uniformly well with respect to the singular perturbation parameter ε. More specifically, we prove that the numerical method is uniformly convergent of second order in time and almost fourth order in spatial variable, if the discretization parameters satisfy a non-restrictive relation. Numerical experiments are presented to validate the theoretical results and also indicate that the relation between the discretization parameters is not necessary in practice.     

An Efficient and Scalable Quasi-Aggregate Signature Scheme Based on LFSR Sequences

Aggregate signatures can be a crucial building block for providing scalable authentication of a large number of users in several applications like building efficient certificate chains, authenticating distributed content management systems, and securing path vector routing protocols. Aggregate signatures aim to prevent resources (signature and storage elements, and computation) from growing linearly in the number of signers participating in a network protocol. In this paper, we present an efficient and scalable quasi-aggregate signature scheme, {rm CLFSR}- {rm QA}, based on third-order linear feedback shift register (cubic LFSR) sequences that can be instantiated using both XTR and GH public key cryptosystems. In the proposed {rm CLFSR}-{rm QA} construction, signers sign messages sequentially; however, the verfier need not know the order in which messages were signed. The proposed scheme offers constant length signatures, fast signing, aggregation, and verification operations at each node, and requires the least storage elements (public keys needed to verify the signature), compared to any other aggregate signature scheme. To the best of our knowledge, {rm CLFSR}- {rm QA} is the first aggregate signature scheme to be constructed using LFSR sequences. We believe that the {rm CLFSR}- {rm QA} signature scheme can be catalytic in improving the processing latency as well as reducing space requirements in building secure, large-scale distributed network protocols. We perform extensive theoretical analysis including correctness and security of {rm CLFSR}- {rm QA} and also present a performance (computation and communication costs, storage overhead) comparison of the proposed scheme with well-known traditional constructions.     

Effect of doping on TSD relaxation in cellulose acetate films

Thermally stimulated depolarization current (TSDC) studies have been performed on solution grown cellulose acetate films doped with different concentrations of acrylic acid (AA) prepared at the poling temperatures (40–75°C) with poling fields (10–50 kV/cm). The TSDC spectra of pure and AA doped CA films reveal two relaxation peaks at 80°C and 180 ±2°C, having activation energies centred around 0.25 and 0.55 eV. The phenomena of the existence of these current maxima have been analyzed and discussed in terms of the molecular motion of the polar side groups and release of the remaining part of the frozen dipoles by their cooperative motion with adjoining segments of the main polymer chain. The peak currents, released charge and activation energies associated with the peaks are affected by AA doping. The effect of doping with acrylic acid on the discharge current indicates the formation of molecular aggregates     

Uncoupled non-linear equations method for determining kinetic parameters in case of hydrogen evolution reaction following Volmer–Heyrovsky–Tafel mechanism and Volmer–Heyrovsky mechanism

Hydrogen evolution reaction following Volmer–Heyrovsky–Tafel mechanism and not under diffusion control can be characterized using Tafel polarization and alternating current admittance data at various frequencies and at various overpotentials. Such reaction has four independent kinetic parameters. One empirical constant related to charge required for complete surface coverage is also involved.

In case of systems where only one time constant (related to charging/discharging of electrical double layer) is discerned, Volmer–Heyrovsky mechanism is assumed. Such systems have three independent kinetic parameters. Experimental data may provide maximum two independent conditions at a less cathodic overpotential and maximum one independent condition at a more cathodic overpotential.

A new approach to determine kinetic parameters utilizing these data and neglecting Heyrovsky and Tafel backward reaction rates has been proposed. The conditions involved are coupled non-linear equations. Uncoupled non-linear equations have been derived and iterated using Newton–Raphson method. The approach has been validated using literature data. The graphical relationships between experimental parameters and kinetic parameters have also been shown.     

A 243-GHz F/sub t/ and 208-GHz F/sub max/, 90-nm SOI CMOS SoC technology with low-power mm-wave digital and RF circuit capability

A 90-nm silicon-on-insulator (SOI) CMOS system on-chip integrates high-performance FETs with 243-GHz F/sub t/, 208-GHz F/sub max/, 1.45-mS//spl mu/m gm, and sub 1.1-dB NFmin up to 26 GHz. Inductor Q of 20, VNCAP of 1.8-fF//spl mu/m/sup 2/, varactor with a tuning range as high as 25:1, and a low-loss microstrip. Transmission lines were successfully integrated without extra masks and processing steps. SOI and its low parasitic junction capacitance enables this high level of performance and will expand the use of CMOS for millimeter-wave applications.