Characterization of microstructured optical fibers for wideband dispersion compensation

Microstructured optical fibers (MOFs) with small hole-to-hole spacing and large airholes are designed to compensate the anomalous dispersion and the dispersion slope of single-mode fibers. The geometrical parameters that characterize triangular MOFs are chosen to optimize the fiber length and the compensation over a wide wavelength range. A proper design of the photonic crystal fiber geometry allows us to achieve dispersion values of approximately -1700 ps nm(-1) km(-1) at 1550 nm and to compensate the dispersion of standard fibers within +/- 0.5 ps nm(-1) km(-1) over a 100-nm range. The MOF dispersion properties have been studied by means of a numerical simulator for modal analysis based on the finite-element method.     

Mono and Bifunctional Catalysts for Styrene Oxide Isomerization or Hydrogenation

Abstract  

Styrene oxide can be effectively isomerized to phenyl-acetaldehyde (98%) over amorphous silica alumina catalysts under very mild liquid phase conditions. On the other hand, a copper catalyst prepared using a silica zirconia support gave up to 80% yield in the hydrogenation of styrene oxide to 2-phenyl-ethanol.     

Room-Temperature Degradation of t-Zr(Pr)O2 in an Aqueous Suspension Revealed by Perturbed Angular Correlations

This paper deals with the phase stability of an aqueous suspension of tetragonal Zr_0.9Pr_0.1O₂ (20 wt%/vol%) at room temperature as a function of the aging time. The suspension is investigated in situ using the highly localized Perturbed Angular Correlations technique. The results indicate that an almost fully reversible degradation process toward monoclinic zirconia takes place through a first-order reaction of rate constant k =0.7 day⁻¹. Two successive diffusion mechanisms are observed that are interpreted as OH⁻ ions' migration in the grain surface and then, as proton defects' diffusion into the bulk.     

Understanding the Selectivity Mechanism of the Human Asialoglycoprotein Receptor (ASGP-R) toward Gal- and Man-type Ligands for Predicting Interactions with Exogenous Sugars

A practical approach for addressing the computer simulation of protein-carbohydrate interactions is described here. An articulated computational protocol was set up and validated by checking its ability to predict experimental data, available in the literature, and concerning the selectivity shown by the Carbohydrate Recognition Domain (CRD) of the human asialoglycoprotein receptor (ASGP-R) toward Gal-type ligands. Some required features responsible for the interactions were identified. Subsequently the same protocol was applied to monomer sugar molecules that constitute the building blocks for alginates and ulvans. Such sugar polymers may supply a low-cost source of rare sugars with a potential impact on several industrial applications, from pharmaceutical to fine chemical industry. An example of their applicative exploitation could be given by their use in developing biomaterial with adhesion properties toward hepatocytes, through interaction with the ASGP-R. Such a receptor has been already proposed as a target for exogenous molecules, specifically in the case of hepatocytes, for diagnostic and therapeutic purposes. The DOCK5.2 program was used to search optimal locations of the above ligands of interest into CRD binding site and to roughly estimate interaction energies. Finally, the binding ΔG of theoretical protein-ligand complexes was estimated by using the DelPhi program in which the solvation free energy is accounted for with a continuum solvent model, by solving the Poisson-Boltzmann equation. The structure analysis of the obtained complexes and their ΔG values suggest that one of the sugar monomers of interest shows the desired characteristics.     

Synthesis and Antiplasmodial Activity of Novel Chloroquine Analogues with Bulky Basic Side Chains

Chloroquine is commonly used in the treatment and prevention of malaria, but Plasmodium falciparum, the main species responsible for malaria‐related deaths, has developed resistance against this drug. Twenty‐seven novel chloroquine (CQ) analogues characterized by a side chain terminated with a bulky basic head group, i.e., octahydro‐2H‐quinolizine and 1,2,3,4,5,6‐hexahydro‐1,5‐methano‐8H‐pyrido[1,2‐a][1,5]diazocin‐8‐one, were synthesized and tested for activity against D‐10 (CQ‐susceptible) and W‐2 (CQ‐resistant) strains of P. falciparum. Most compounds were found to be active against both strains with nanomolar or sub‐micromolar IC₅₀ values. Eleven compounds were found to be 2.7‐ to 13.4‐fold more potent than CQ against the W‐2 strain; among them, four cytisine derivatives appear to be of particular interest, as they combine high potency with low cytotoxicity against two human cell lines (HMEC‐1 and HepG2) along with easier synthetic accessibility. Replacement of the 4‐NH group with a sulfur bridge maintained antiplasmodial activity at a lower level, but produced an improvement in the resistance factor. These compounds warrant further investigation as potential drugs for use in the fight against malaria.     

Next-Generation Sequencing Workflow for NSCLC Critical Samples Using a Targeted Sequencing Approach by Ion Torrent PGM? Platform

Next-generation sequencing (NGS) is a cost-effective technology capable of screening several genes simultaneously; however, its application in a clinical context requires an established workflow to acquire reliable sequencing results. Here, we report an optimized NGS workflow analyzing 22 lung cancer-related genes to sequence critical samples such as DNA from formalin-fixed paraffin-embedded (FFPE) blocks and circulating free DNA (cfDNA). Snap frozen and matched FFPE gDNA from 12 non-small cell lung cancer (NSCLC) patients, whose gDNA fragmentation status was previously evaluated using a multiplex PCR-based quality control, were successfully sequenced with Ion Torrent PGM™. The robust bioinformatic pipeline allowed us to correctly call both Single Nucleotide Variants (SNVs) and indels with a detection limit of 5%, achieving 100% specificity and 96% sensitivity. This workflow was also validated in 13 FFPE NSCLC biopsies. Furthermore, a specific protocol for low input gDNA capable of producing good sequencing data with high coverage, high uniformity, and a low error rate was also optimized. In conclusion, we demonstrate the feasibility of obtaining gDNA from FFPE samples suitable for NGS by performing appropriate quality controls. The optimized workflow, capable of screening low input gDNA, highlights NGS as a potential tool in the detection, disease monitoring, and treatment of NSCLC.     

Investigating the Role of Conformational Effects on Laccase Stability and Hyperactivation under Stress Conditions

Fungal laccase from Steccherinum ochraceum 1833 displays remarkable stability under different harsh conditions: organic/buffer mixtures, thermal treatment, and microwave radiation. The behavior is particularly significant in the light of the sharp inactivation observed for two different fungal laccases. Laccase from S. ochraceum 1833 also displays hyperactivation under mild thermal treatment (60 °C). Molecular dynamics simulations at 80 °C explained how this laccase retains the geometry of the electron transfer pathway, thereby assuring electron transfer through the copper ions and thus maintaining its catalytic activity at high temperature. Spectroscopic studies revealed that the thermal activation corresponds to specific conformational changes in the protein. The results indicate that this laccase is potentially applicable under denaturing conditions that might be beneficial for the biotransformation of recalcitrant substrates.     

Effective wind actions on ideal and real structures

Gust buffeting of structures is analyzed by Double Modal Transformation, a method consisting in the joint transformation into principal components of structural displacements (modal analysis) and of wind loading (proper orthogonal decomposition). It commonly occurs that modal truncation applies to both the series of structural and loading modes; besides, many loading modes are almost orthogonal respect the dominant structural modes, so they do not contribute to structural response. This set of conditions allows the introduction of an effective action, defined as the loading process reconstructed retaining only those loading modes that excite the structure. This paper discusses this method and the related concepts by analyzing a set of simple ideal structures in closed form; this approach allows the formulation of general criteria aimed at defining the effective wind action as a function of non-dimensional structural and wind parameters. The numerical analysis of a real structure confirms the tendencies pointed out by the analytical solutions.     

Improvement of Drug Therapy by Covalent PEG Conjugation: An Overview From a Research Laboratory

In the last two decades, efforts focused in the field of drug delivery have made it possible to reach important goals, especially with proteins and peptides. The story of the evolution of this matter is vast and it is difficult to summarize its various aspects in a single review. On the other hand, it could be really interesting to look at the inside story of a typical academic research lab that has dedicated almost all its resources to drug delivery. In our case, an initial interest in the issue of protein conformation stability soon paved the way for a new area of study: the modification of proteins with synthetic polymers. We have seen this technique transformed from a crude and inhomogeneous procedure into a well-recognized and successful approach. This great advance has been possible thanks to the development of dedicated chemical coupling methods and to the better understanding of the behavior of polymers in vivo. In particular, among the several polymers investigated, PEG has became the best polymer for protein modification. Exploiting the unique properties of this polymer, we have conducted several investigations in the field of protein PEGylation and then transferred the acquired know-how to the development of conjugates with low molecular weight drug. This last aspect still presents several unmet needs that are awaiting proper solutions.