Formulation and Development of Dendrimer-Based Transdermal Patches of Meloxicam for the Management of Arthritis

Purpose: To develop transdermal patches of meloxicam (MLX) using chitosan and hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) as hydrophilic polymers, polyamido amine (PAMAM) dendrimer as a permeation enhancer, and dibutyl pthalate as a plasticizerMethods: The patches were prepared by solvent casting evaporation technique using 3-factor, 3-level Box-Behnken design. The patches were evaluated for physical appearance, thickness, weight variation, folding endurance, drug content uniformity, tensile strength, moisture absorption and moisture loss, in vitro drug release, as well as by field-emission scanning electron microscopy (FESEM) and x-ray diffraction (XRD). A specially designed glass diffusion cell was used for the in vitro drug release study. The effect of concentrations of dependent variables (PAMAM G3, chitosan and dibutyl pthalate) on drug release was investigated.Results: The patches demonstrated satisfactory characteristics. PAMAM dendrimer significantly enhanced (p < 0.5) the permeation of MLX. A maximum of 85.7 % drug release was achieved in 24 h.Conclusion: Dendrimer increased the release of MLX by increasing its solubility and permeation through the membrane. Thus, dendrimer patches are a potentially suitable transdermal drug delivery system for the management of some diseased conditions.Keywords: Dendrimers, Transdermal patches, Skin permeation, Permeation enhancer, Chitosan, Hydroxypropyl methyl cellulose, Meloxicam, Plasticize

Ternary hypervalent silicon hydrides via lithium at high pressure

Hydrogen is rarely observed as ligand in hypervalent species, however, we find that high-pressure hydrogenation may stabilise hypervalent hydrogen-rich materials. Focussing on ternary silicon hydrides via lithium doping, we find anions composed of hypervalent silicon with H ligands formed under high pressure. Our results reveal two new hypervalent anions: layered-SiH−5 and tricapped triangular prismatic SiH2−. These differ from octahedral SiH2− described in earlier studies. In addition, there are further hydrogen-rich structures, Li3SiH10 and Li2SiH6+δ, which may be stabilised at high pressure. Our work provides pointers to future investigations on hydrogen rich materials

Long-distance quantum communication with atomic ensembles and linear optics

Quantum communication holds a promise for absolutely secure transmission of secret messages and faithful transfer of unknown quantum states. Photonic channels appear to be very attractive for physical implementation of quantum communication. However, due to losses and decoherence in the channel, the communication fidelity decreases exponentially with the channel length. We describe a scheme that allows to implement robust quantum communication over long lossy channels. The scheme involves laser manipulation of atomic ensembles, beam splitters, and single-photon detectors with moderate efficiencies, and therefore well fits the status of the current experimental technology. We show that the communication efficiency scale polynomially with the channel length thereby facilitating scalability to very long distances.Comment: 2 tex files (Main text + Supplement), 4 figure

Molecular Dissection of Neuroligin 2 and Slitrk3 Reveals an Essential Framework for GABAergic Synapse Development

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record In the brain, many types of interneurons make functionally diverse inhibitory synapses onto principal neurons. Although numerous molecules have been identified to function in inhibitory synapse development, it remains unknown whether there is a unifying mechanism for development of diverse inhibitory synapses. Here we report a general molecular mechanism underlying hippocampal inhibitory synapse development. In developing neurons, the establishment of GABAergic transmission depends on Neuroligin 2 (NL2), a synaptic cell adhesion molecule (CAM). During maturation, inhibitory synapse development requires both NL2 and Slitrk3 (ST3), another CAM. Importantly, NL2 and ST3 interact with nanomolar affinity through their extracellular domains to synergistically promote synapse development. Selective perturbation of the NL2-ST3 interaction impairs inhibitory synapse development with consequent disruptions in hippocampal network activity and increased seizure susceptibility. Our findings reveal how unique postsynaptic CAMs work in concert to control synaptogenesis and establish a general framework for GABAergic synapse development. Li et al. report a hierarchical process mediated by Neuroligin 2 and Slitrk3 for GABAergic synapse development. Neuroligin 2 also interacts with Slitrk3 to regulate GABAergic synaptogenesis. Selective perturbation of this interaction decreases GABAergic synaptic transmission and impairs hippocampal network activities.NIH/NINDS Intramural Research ProgramNIH/NICHD Intramural Research ProgramNIH/NEI Intramural Research Progra

Pioglitazone Prevents Capillary Rarefaction in Streptozotocin-Diabetic Rats Independently of Glucose Control and Vascular Endothelial Growth Factor Expression

Background/Aims: Reduction of capillary network density occurs early in the development of metabolic syndrome and may be relevant for the precipitation of diabetes. Agonists of the peroxisome proliferator-activated receptor (PPAR)-gamma transcription factor are vasculoprotective, but their capacity for structural preservation of the microcirculation is unclear. Methods: Male Wistar rats were rendered diabetic by streptozotocin and treated with pioglitazone in chow for up to 12 weeks. Capillary density was determined in heart and skeletal muscle after platelet endothelial cell adhesion molecule-1 (PECAM-1) immunostaining. Hallmarks of apoptosis and angiogenesis were determined. Results: Capillary density deteriorated progressively in the presence of hyperglycemia (from 971/mm(2) to 475/mm(2) in quadriceps muscle during 13 weeks). Pioglitazone did not influence plasma glucose, left ventricular weight, or body weight but nearly doubled absolute and relative capillary densities compared to untreated controls (1.2 vs. 0.6 capillaries/myocyte in heart and 1.5 vs. 0.9 capillaries/myocyte in quadriceps muscle) after 13 weeks of diabetes. No antiapoptotic or angiogenic influence of pioglitazone was detected while a reduced expression of hypoxia-inducible factor-3 alpha and PPAR coactivator-1 alpha (PGC-1 alpha) mRNA as well as vascular endothelial growth factor (VEGF) protein possibly occurred as a consequence of improved vascularization. Conclusion: Pioglitazone preserves microvascular structure in diabetes independently of improvements in glycemic control and by a mechanism unrelated to VEGF-mediated angiogenesis. Copyright (C) 2012 S. Karger AG, Base

Carrier-mediated magnetoelectricity in complex oxide heterostructures

While tremendous success has been achieved to date in creating both single phase and composite magnetoelectric materials, the quintessential electric-field control of magnetism remains elusive. In this work, we demonstrate a linear magnetoelectric effect which arises from a novel carrier-mediated mechanism, and is a universal feature of the interface between a dielectric and a spin-polarized metal. Using first-principles density functional calculations, we illustrate this effect at the SrRuO$_3$/SrTiO$_3$ interface and describe its origin. To formally quantify the magnetic response of such an interface to an applied electric field, we introduce and define the concept of spin capacitance. In addition to its magnetoelectric and spin capacitive behavior, the interface displays a spatial coexistence of magnetism and dielectric polarization suggesting a route to a new type of interfacial multiferroic

Photonic quantum state transfer between a cold atomic gas and a crystal

Interfacing fundamentally different quantum systems is key to build future hybrid quantum networks. Such heterogeneous networks offer superior capabilities compared to their homogeneous counterparts as they merge individual advantages of disparate quantum nodes in a single network architecture. However, only very few investigations on optical hybrid-interconnections have been carried out due to the high fundamental and technological challenges, which involve e.g. wavelength and bandwidth matching of the interfacing photons. Here we report the first optical quantum interconnection between two disparate matter quantum systems with photon storage capabilities. We show that a quantum state can be faithfully transferred between a cold atomic ensemble and a rare-earth doped crystal via a single photon at telecommunication wavelength, using cascaded quantum frequency conversion. We first demonstrate that quantum correlations between a photon and a single collective spin excitation in the cold atomic ensemble can be transferred onto the solid-state system. We also show that single-photon time-bin qubits generated in the cold atomic ensemble can be converted, stored and retrieved from the crystal with a conditional qubit fidelity of more than $85\%$. Our results open prospects to optically connect quantum nodes with different capabilities and represent an important step towards the realization of large-scale hybrid quantum networks

Application of Bayesian network structure learning to identify causal variant SNPs from resequencing data

Using single-nucleotide polymorphism (SNP) genotypes from the 1000 Genomes Project pilot3 data provided for Genetic Analysis Workshop 17 (GAW17), we applied Bayesian network structure learning (BNSL) to identify potential causal SNPs associated with the Affected phenotype. We focus on the setting in which target genes that harbor causal variants have already been chosen for resequencing; the goal was to detect true causal SNPs from among the measured variants in these genes. Examining all available SNPs in the known causal genes, BNSL produced a Bayesian network from which subsets of SNPs connected to the Affected outcome were identified and measured for statistical significance using the hypergeometric distribution. The exploratory phase of analysis for pooled replicates sometimes identified a set of involved SNPs that contained more true causal SNPs than expected by chance in the Asian population. Analyses of single replicates gave inconsistent results. No nominally significant results were found in analyses of African or European populations. Overall, the method was not able to identify sets of involved SNPs that included a higher proportion of true causal SNPs than expected by chance alone. We conclude that this method, as currently applied, is not effective for identifying causal SNPs that follow the simulation model for the GAW17 data set, which includes many rare causal SNPs

Synthesis of Tapered CdS Nanobelts and CdSe Nanowires with Good Optical Property by Hydrogen-Assisted Thermal Evaporation

The tapered CdS nanobelts and CdSe nanowires were prepared by hydrogen-assisted thermal evaporation method. Different supersaturation leads to two different kinds of 1D nanostructures. The PL measurements recorded from the as-prepared tapered CdS nanobelts and CdSe nanowires show only a bandgap emission with relatively narrow full-width half maximum, which means that they possess good optical property. The as-synthesized high-quality tapered CdS nanobelts and CdSe nanowires may be excellent building blocks for photonic devices

Laboratory toxicity studies demonstrate no adverse effects of Cry1Ab and Cry3Bb1 to larvae of Adalia bipunctata (Coleoptera: Coccinellidae): the importance of study design

Scientific studies are frequently used to support policy decisions related to transgenic crops. Schmidt et al., Arch Environ Contam Toxicol 56:221–228 (2009) recently reported that Cry1Ab and Cry3Bb were toxic to larvae of Adalia bipunctata in direct feeding studies. This study was quoted, among others, to justify the ban of Bt maize (MON 810) in Germany. The study has subsequently been criticized because of methodological shortcomings that make it questionable whether the observed effects were due to direct toxicity of the two Cry proteins. We therefore conducted tritrophic studies assessing whether an effect of the two proteins on A. bipunctata could be detected under more realistic routes of exposure. Spider mites that had fed on Bt maize (events MON810 and MON88017) were used as carriers to expose young A. bipunctata larvae to high doses of biologically active Cry1Ab and Cry3Bb1. Ingestion of the two Cry proteins by A. bipunctata did not affect larval mortality, weight, or development time. These results were confirmed in a subsequent experiment in which A. bipunctata were directly fed with a sucrose solution containing dissolved purified proteins at concentrations approximately 10 times higher than measured in Bt maize-fed spider mites. Hence, our study does not provide any evidence that larvae of A. bipunctata are sensitive to Cry1Ab and Cry3Bb1 or that Bt maize expressing these proteins would adversely affect this predator. The results suggest that the apparent harmful effects of Cry1Ab and Cry3Bb1 reported by Schmidt et al., Arch Environ Contam Toxicol 56:221–228 (2009) were artifacts of poor study design and procedures. It is thus important that decision-makers evaluate the quality of individual scientific studies and do not view all as equally rigorous and relevant