The preparation, characterization, and pharmacokinetic studies of chitosan nanoparticles loaded with paclitaxel/dimethyl-β-cyclodextrin inclusion complexes.

A novel biocompatible and biodegradable drug-delivery nanoparticle (NP) has been developed to minimize the severe side effects of the poorly water-soluble anticancer drug paclitaxel (PTX) for clinical use. PTX was loaded into the hydrophobic cavity of a hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), using an aqueous solution-stirring method followed by lyophilization. The resulting PTX/DM-β-CD inclusion complex dramatically enhanced the solubility of PTX in water and was directly incorporated into chitosan (CS) to form NPs (with a size of 323.9–407.8 nm in diameter) using an ionic gelation method. The formed NPs had a zeta potential of +15.9–23.3 mV and showed high colloidal stability. With the same weight ratio of PTX to CS of 0.7, the loading efficiency of the PTX/DM-β-CD inclusion complex-loaded CS NPs was 30.3-fold higher than that of the PTX-loaded CS NPs. Moreover, it is notable that PTX was released from the DM-β-CD/CS NPs in a sustained-release manner. The pharmacokinetic studies revealed that, compared with reference formulation (Taxol(®)), the PTX/DM-β-CD inclusion complex-loaded CS NPs exhibited a significant increase in AUC(0→24h) (the area under the plasma drug concentration–time curve over the period of 24 hours) and mean residence time by 2.7-fold and 1.4-fold, respectively. Therefore, the novel drug/DM-β-CD inclusion complex-loaded CS NPs have promising applications for the significantly improved delivery and controlled release of the poorly water-soluble drug PTX or its derivatives, thus possibly leading to enhanced therapeutic efficacy and less severe side effects

The effectiveness of the biannual application of silver nitrate solution followed by sodium fluoride varnish in arresting early childhood caries in preschool children: study protocol for a randomised controlled trial

published_or_final_versio

Liquid Metal Bandwidth-Reconfigurable Antenna

This letter shows how slugs of liquid metal can be used to connect/disconnect large areas of metalization and achieve a radiation performance not possible by using conventional switches. The proposed antenna can switch its operating bandwidth between ultrawideband and narrowband by connecting/disconnecting the ground plane for the feedline from that of the radiator. This could be achieved by using conventional semiconductor switches. However, such switches provide point-like contacts. Consequently, there are gaps in electrical contact between the switches. Surface currents, flowing around these gaps, lead to significant back radiation. In this letter, the slugs of a liquid metal are used to completely fill the gaps. This significantly reduces the back radiation, increases the bore-sight gain, and produces a pattern identical to that of a conventional microstrip patch antenna. Specifically, the realized gain and total efficiency are increased by 2 dBi and 24%, respectively. The antenna has potential applications in wireless systems employing cognitive radio (CR) and spectrum aggregation

The MDM2–p53–pyruvate carboxylase signalling axis couples mitochondrial metabolism to glucose-stimulated insulin secretion in pancreatic β-cells

published_or_final_versio

BOB-RED queue management for IEEE 802.15.4 wireless sensor networks

This study is aimed at exploring why many economists propose a transfer scheme and debt mutualisation for the Eurozone. This would equip the Eurozone with better tools to deal with an economic shock, like the 2010-2012 sovereign debt crisis, thus making it more financially stable. After the theoretical presentation, the study presents a unique institutional design with an EU Treasury that manages debt mutualisation and a transfer scheme as well as other competences that address other present economic challenges. Crucial to the study are the issues of moral hazard and adverse selection that arise when thinking of European economic integration.L’objectiu del treball és explorar la raó per la qual molts economistes proposen un sistema de transferències fiscals i la mutualització del deute a l’Eurozona. Així se la dotaria amb eines més efectives per pal·liar un xoc econòmic, com la crisi del deute sobirà del 2010-2012. A continuació, es presenta un disseny institucional únic d’un Tresor de l’Euro que gestionaria les competències esmentades (i d’altres) per combatre alguns dels reptes econòmics actuals. El risc moral i de selecció adversa, qüestions que sorgeixen en pensar la drecera que ha de prendre la integració econòmica Europea, són cabdals per aquest estudi

A Replicating Modified Vaccinia Tiantan Strain Expressing an Avian-Derived Influenza H5N1 Hemagglutinin Induce Broadly Neutralizing Antibodies and Cross-Clade Protective Immunity in Mice

published_or_final_versio

Meta-analysis of binary outcomes via generalized linear mixed models: a simulation study

Background: Systematic reviews and meta-analyses of binary outcomes are widespread in all areas of application. The odds ratio, in particular, is by far the most popular effect measure. However, the standard meta-analysis of odds ratios using a random-effects model has a number of potential problems. An attractive alternative approach for the meta-analysis of binary outcomes uses a class of generalized linear mixed models (GLMMs). GLMMs are believed to overcome the problems of the standard random-effects model because they use a correct binomial-normal likelihood. However, this belief is based on theoretical considerations, and no sufficient simulations have assessed the performance of GLMMs in meta-analysis. This gap may be due to the computational complexity of these models and the resulting considerable time requirements. Methods: The present study is the first to provide extensive simulations on the performance of four GLMM methods (models with fixed and random study effects and two conditional methods) for meta-analysis of odds ratios in comparison to the standard random effects model. Results: In our simulations, the hypergeometric-normal model provided less biased estimation of the heterogeneity variance than the standard random-effects meta-analysis using the restricted maximum likelihood (REML) estimation when the data were sparse, but the REML method performed similarly for the point estimation of the odds ratio, and better for the interval estimation. Conclusions: It is difficult to recommend the use of GLMMs in the practice of meta-analysis. The problem of finding uniformly good methods of the meta-analysis for binary outcomes is still open

The outer-membrane export signal of Porphyromonas gingivalis type IX secretion system (T9SS) is a conserved C-terminal \beta-sandwich domain

In the recently characterized Type IX Secretion System (T9SS), the conserved C-terminal domain (CTD) in secreted proteins functions as an outer membrane translocation signal for export of virulence factors to the cell surface in the Gram-negative Bacteroidetes phylum. In the periodontal pathogen Porphyromonas gingivalis, the CTD is cleaved off by PorU sortase in a sequence-independent manner, and anionic lipopolysaccharide (A-LPS) is attached to many translocated proteins, thus anchoring them to the bacterial surface. Here, we solved the atomic structure of the CTD of gingipain B (RgpB) from P. gingivalis, alone and together with a preceding immunoglobulin-superfamily domain (IgSF). The CTD was found to possess a typical Ig-like fold encompassing seven antiparallel β-strands organized in two β-sheets, packed into a β-sandwich structure that can spontaneously dimerise through C-terminal strand swapping. Small angle X-ray scattering (SAXS) revealed no fixed orientation of the CTD with respect to the IgSF. By introducing insertion or substitution of residues within the inter-domain linker in the native protein, we were able to show that despite the region being unstructured, it nevertheless is resistant to general proteolysis. These data suggest structural motifs located in the two adjacent Ig-like domains dictate the processing of CTDs by the T9SS secretion pathway

Interplay between SIRT1 and hepatitis B virus X protein in the activation of viral transcription

postprin

Higher-order multipole amplitudes in charmonium radiative transitions

Using 24 million $\psi' \equiv \psi(2S)$ decays in CLEO-c, we have searched for higher multipole admixtures in electric-dipole-dominated radiative transitions in charmonia. We find good agreement between our data and theoretical predictions for magnetic quadrupole (M2) amplitudes in the transitions $\psi' \to \gamma \chi_{c1,2}$ and $\chi_{c1,2} \to \gamma J/\psi$, in striking contrast to some previous measurements. Let $b_2^J$ and $a_2^J$ denote the normalized M2 amplitudes in the respective aforementioned decays, where the superscript $J$ refers to the angular momentum of the $\chi_{cJ}$. By performing unbinned maximum likelihood fits to full five-parameter angular distributions, we determine the ratios $a_2^{J=1}/a_2^{J=2} = 0.67^{+0.19}_{-0.13}$ and $a_2^{J=1}/b_2^{J=1} = -2.27^{+0.57}_{-0.99}$, where the theoretical predictions are independent of the charmed quark magnetic moment and are $a_2^{J=1}/a_2^{J=2} = 0.676 \pm 0.071$ and $a_2^{J=1}/b_2^{J=1} = -2.27 \pm 0.16$.Comment: 32 pages, 7 figures, acceptance updat