Second generation of fucose-based DC-SIGN ligands: affinity improvement and specificity versus Langerin

DC-SIGN and Langerin are two C-type lectins involved in the initial steps of HIV infections: the former acts as a viral attachment factor and facilitates viral invasion of the immune system, the latter has a protective effect. Potential antiviral compounds targeted against DC-SIGN were synthesized using a common fucosylamide anchor. Their DC-SIGN affinity was tested by SPR and found to be similar to that of the natural ligand Lewis-X (Le(X)). The compounds were also found to be selective for DC-SIGN and to interact only weakly with Langerin. These molecules are potentially useful therapeutic tools against sexually transmitted HIV infection.     

Analytical characterization of chitosan nanoparticles for peptide drug delivery applications

Chitosan-cyclodextrin hybrid nanoparticles (NPs) were obtained by the ionic gelation process in the presence of glutathione (GSH), chosen as a model drug. NPs were characterized by means of transmission electron microscopy and zeta-potential measurements. Furthermore, a detailed X-ray photoelectron spectroscopy study was carried out in both conventional and depth-profile modes. The combination of controlled ion-erosion experiments and a scrupulous curve-fitting approach allowed for the first time the quantitative study of the GSH in-depth distribution in the NPs. NPs were proven to efficiently encapsulate GSH in their inner cores, thus showing promising perspectives as drug carriers.     

Correlated motion and mechanical gearing in amphidynamic crystalline molecular machines

In this review we highlight the recent efforts towards the development of molecular gears with an emphasis on building molecular gears in the solid state and the role that molecular gearing and correlated motions may play in the function of crystalline molecular machines. We discuss current molecular and crystal engineering strategies, challenges associated with engineering correlated motion in crystals, and outline experimental and theoretical tools to explore gearing dynamics while highlighting key advances made to date.

Here we highlight recent efforts towards the development of molecular gears in the solid state and the role that molecular gearing and correlated motions may play in the function of crystalline molecular machines.     

Scalable Synthesis of Multi-Metal Electrocatalyst Powders and Electrodes and their Application for Oxygen Evolution and Water Splitting

Multi-metal electrocatalysts provide nearly unlimited catalytic possibilities arising from synergistic element interactions. We propose a polymer/metal precursor spraying technique that can easily be adapted to produce a large variety of compositional different multi-metal catalyst materials. To demonstrate this, 11 catalysts were synthesized, characterized, and investigated for the oxygen evolution reaction (OER). Further investigation of the most active OER catalyst, namely CoNiFeMoCr, revealed a polycrystalline structure, and operando Raman measurements indicate that multiple active sites are participating in the reaction. Moreover, Ni foam-supported CoNiFeMoCr electrodes were developed and applied for water splitting in flow-through electrolysis cells with electrolyte gaps and in zero-gap membrane electrode assembly (MEA) configurations. The proposed alkaline MEA-type electrolyzers reached up to 3 A cm⁻², and 24 h measurements demonstrated no loss of current density of 1 A cm⁻².     

A semiparametric Bayesian joint model for multiple mixed-type outcomes: an application to acute myocardial infarction

We propose a Bayesian semiparametric regression model to represent mixed-type multiple outcomes concerning patients affected by Acute Myocardial Infarction. Our approach is motivated by data coming from the ST-Elevation Myocardial Infarction (STEMI) Archive, a multi-center observational prospective clinical study planned as part of the Strategic Program of Lombardy, Italy. We specifically consider a joint model for a variable measuring treatment time and in-hospital and 60-day survival indicators. One of our main motivations is to understand how the various hospitals differ in terms of the variety of information collected as part of the study. To do so we postulate a semiparametric random effects model that incorporates dependence on a location indicator that is used to explicitly differentiate among hospitals in or outside the city of Milano. The model is based on the two parameter Poisson-Dirichlet prior, also known as the Pitman-Yor process prior. We discuss the resulting posterior inference, including sensitivity analysis, and a comparison with the particular sub-model arising when a Dirichlet process prior is assumed.     

Determination of trimethylamine‐N‐oxide in combination with l‐carnitine and γ‐butyrobetaine in human plasma by UPLC/MS/MS

An ultra‐high‐performance liquid chromatography–mass spectrometry (UPLC/MS/MS) method was developed and validated for the quantification of trimethylamine‐N‐oxide (TMAO) simultaneously with TMAO‐related molecules l ‐carnitine and γ‐butyrobetaine (GBB) in human blood plasma. The separation of analytes was achieved using a Hydrophilic interaction liquid chromatography (HILIC)‐type column with ammonium acetate–acetonitrile as the mobile phase. TMAO determination was validated according to valid US Food and Drug Administration guidelines. The developed method was successfully applied to plasma samples from healthy volunteers. Copyright © 2015 John Wiley & Sons, Ltd.     

Divergent Pathways and Competitive Mechanisms of Metathesis Reactions between 3‐Arylprop‐2‐ynyl Esters and Aldehydes: An Experimental and Theoretical Study

Mechanistic studies of the reaction between 3‐arylprop‐2‐ynyl esters and aldehydes catalyzed by BF₃ ? Et₂O were performed by isotopic labeling experiments and quantum chemical calculations. The reactions are shown to proceed by either a classical alkyne–carbonyl metathesis route or an unprecedented addition–rearrangement cascade. Depending on the structure of the starting materials and the reaction conditions, the products of these reactions can be Morita–Baylis–Hillman (MBH) adducts that are unavailable by traditional MBH reactions or E‐ and Z‐α,β‐unsaturated ketones. ¹⁸O‐Labeling studies suggested the existence of two different reaction pathways to the products. These pathways were further examined by quantum chemical calculations that employed the DFT(wB97XD)/6‐311+G(2d,p) method, together with the conductor‐like screening model for realistic solvation (COSMO‐RS). By using the wB97XD functional, the accuracy of the computed data is estimated to be 1–2 kcal mol^?1, shown by the careful benchmarking of various DFT functionals against coupled cluster calculations at the CCSD(T)/aug‐cc‐pVTZ level of theory. Indeed, most of the experimental data were reproduced and explained by theory and it was convincingly shown that the branching point between the two distinct mechanisms is the formation of the first intermediate on the reaction pathway: either the four‐membered oxete or the six‐membered zwitterion. The deep mechanistic understanding of these reactions opens new synthetic avenues to chemically and biologically important α,β‐unsaturated ketones.     

Nonlinear nonparametric mixed-effects models for unsupervised classification

In this work we propose a novel EM method for the estimation of nonlinear nonparametric mixed-effects models, aimed at unsupervised classification. We perform simulation studies in order to evaluate the algorithm performance and we apply this new procedure to a real dataset.