Electro-initiated cationic polymerizations-VI: Anodic electrochemical behaviour and direct electropolymerization of anethole in 1,2-dichloroethane

A study has been made of the cationic electropolymerization of trans-anethole initiated by a direct electron transfer mechanism at a Pt anode in 1,2-dichloroethane solution with tetrabutylammonium perchlorate as supporting electrolyte. The electrochemical behaviour of the system has been preliminarily investigated by voltammetry at rotating and stationary Pt electrode and also by chronoamperometry. The results are consistent with an ECE oxidation process of anethole with formation first of a radical cation and finally of a dication. Polymerization experiments by electrolysis at the oxidation potential of the monomer have been also carried out both under continuous electrolysis and with short initial pulses of current. The results have been analysed and some kinetic parameters of the system have been evaluated.     

Assessment of pharmacokinetic interaction between piracetam and l‐carnitine in healthy subjects

A rapid, sensitive and specific method for quantifying piracetam in human plasma using Piracetam d‐8 as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by one‐step precipitation of protein using an acetonitrile (100%). The extracts were analyzed by high‐performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC‐MS/MS). The method had a chromatographic run time of 3.8 min and a linear calibration curve over the range 0.5–50 µg/mL (r > 0.99). This LC‐MS‐MS procedure was used to assess the bioavailability of two piracetam formulations: piracetam + l‐carnitine (Piracar®; 270/330 mg tablet) and piracetam (Nootropil®; 800 mg tablet) in healthy volunteers of both sexes. The geometric means with corresponding 90% confidence interval (CI) for test/reference percentage ratios were 88.49% (90% CI = 81.19 – 96.46) for peak concentration/dose and 102.55% (90% CI = 100.62 – 104.51) for AUC_inf/dose. The limit of quantitation of 0.5 µg/mL is well suited for pharmacokinetic studies in healthy volunteers. It was concluded that piracetam (Piracar®; 270/330 mg tablet) has a bioavailability equivalent to the piracetam (Nootropil®; 800 mg tablet) formulation with regard to both the rate and the extent of absorption. Copyright © 2015 John Wiley & Sons, Ltd.     

Optimization of Biocompatibility for a Hydrophilic Biological Molecule Encapsulation System

Despite considerable advances in recent years, challenges in delivery and storage of biological drugs persist and may delay or prohibit their clinical application. Though nanoparticle-based approaches for small molecule drug encapsulation are mature, encapsulation of proteins remains problematic due to destabilization of the protein. Reverse micelles composed of decylmonoacyl glycerol (10MAG) and lauryldimethylamino-N-oxide (LDAO) in low-viscosity alkanes have been shown to preserve the structure and stability of a wide range of biological macromolecules. Here, we present a first step on developing this system as a future platform for storage and delivery of biological drugs by replacing the non-biocompatible alkane solvent with solvents currently used in small molecule delivery systems. Using a novel screening approach, we performed a comprehensive evaluation of the 10MAG/LDAO system using two preparation methods across seven biocompatible solvents with analysis of toxicity and encapsulation efficiency for each solvent. By using an inexpensive hydrophilic small molecule to test a wide range of conditions, we identify optimal solvent properties for further development. We validate the predictions from this screen with preliminary protein encapsulation tests. The insight provided lays the foundation for further development of this system toward long-term room-temperature storage of biologics or toward water-in-oil-in-water biologic delivery systems.     

IGP Link Weight Assignment for Operational Tier-1 Backbones

Intradomain routing protocols, such as IS-IS or OSPF, associate a weight (or cost) with each link to compute traffic routes. Proposed methods for selecting link weights largely ignore two practical issues, that of service-level agreement (SLA) requirements and of failures. Optimizing the routing configuration, without bounding the SLA, could severely violate this requirement, which is one of the most important vehicles used by carriers to attract new customers. Since most failures are short-lived, it is much more practical not to have to change weight settings during these episodes. In this paper we propose a tabu-search heuristic for choosing link weights that takes into account both SLA requirements and link failures. Our algorithm selects link weights that still perform well, without having to be changed, even under failure events. To validate the heuristic, we develop a lower bound based on a formal integer linear program (ILP) model, and show that our heuristic solution is within 10% of the optimal ILP lower bound. We study the performance of the heuristic using two operational Tier-1 backbones. Our results illustrate two tradeoffs, between link utilization and the SLA provided, and between performances under failures versus performance without failures. We find that performance under transient failures can be dramatically improved at the expense of a small degradation during normal network operation (i.e., no failures), while simultaneously satisfying SLA requirements. We use our algorithm inside a prototype tool to conduct a case study and illustrate how systematic link weight selection can facilitate topology planning.     

Mapping the hydration dynamics of ubiquitin

The nature of water's interaction with biomolecules such as proteins has been difficult to examine in detail at atomic resolution. Solution NMR spectroscopy is potentially a powerful method for characterizing both the structural and temporal aspects of protein hydration but has been plagued by artifacts. Encapsulation of the protein of interest within the aqueous core of a reverse micelle particle results in a general slowing of water dynamics, significant reduction in hydrogen exchange chemistry and elimination of contributions from bulk water thereby enabling the use of nuclear Overhauser effects to quantify interactions between the protein surface and hydration water. Here we extend this approach to allow use of dipolar interactions between hydration water and hydrogens bonded to protein carbon atoms. By manipulating the molecular reorientation time of the reverse micelle particle through use of low viscosity liquid propane, the T(1ρ) relaxation time constants of (1)H bonded to (13)C were sufficiently lengthened to allow high quality rotating frame nuclear Overhauser effects to be obtained. These data supplement previous results obtained from dipolar interactions between the protein and hydrogens bonded to nitrogen and in aggregate cover the majority of the molecular surface of the protein. A wide range of hydration dynamics is observed. Clustering of hydration dynamics on the molecular surface is also seen. Regions of long-lived hydration water correspond with regions of the protein that participate in molecular recognition of binding partners suggesting that the contribution of the solvent entropy to the entropy of binding has been maximized through evolution.     

Lightning induced disturbances in buried cables - part II: experiment and model validation

This paper presents experimental results obtained at the International Center for Lightning Research and Testing (ICLRT) at Camp Blanding, Florida during the summers of 2002 and 2003. Currents induced by triggered and natural lightning events were measured at the terminations of a buried power cable, in the cable shield, and in the inner cable conductor. Measurements of the horizontal component of the magnetic field above the ground surface for both natural and triggered lightning are also presented. For distant natural lightning events, locations of ground strike points were determined using the U.S. National Lightning Detection Network (NLDN). Based on the theoretical developments presented in Part I of this paper , the field-to-buried cable coupling equations are solved in both the time domain and in the frequency domain. The obtained experimental results are then used to validate the numerical simulations provided by the relevant developed codes.     

Ubiquitous symmetries

We review some of our recent work devoted to the problem of quantization with preservation of Noether symmetries, finding hidden linearity in superintegrable systems, and showing that nonlocal symmetries are in fact local. In particular, we derive the Schrödinger equation for the isochronous Calogero goldfish model using its relation to Darwin equation. We prove the linearity of a classical superintegrable system on a plane of nonconstant curvature. We find the Lie point symmetries that correspond to the nonlocal symmetries (also reinterpreted as λ-symmetries) of the Riccati chain.     

Phosphate Assisted Proton Transfer in Water and Sugar Glasses: A Study Using Fluorescence of Pyrene-1-carboxylate and IR Spectroscopy

The role of water’s H-bond percolation network in acid-assisted proton transfer was studied in water and glycerol solutions and in sugar glasses. Proton transfer rates were determined by the fluorescence of pyrene-1-carboxylate, a compound with a higher pK in its excited state relative to the ground state. Excitation of pyrene-1-COO⁻ produces fluorescence from pyrene-1-COOH when a proton is accepted during the excited singlet state lifetime of pyrene-1-COO⁻. The presence of glycerol as an aqueous cosolvent decreases proton transfer rates from phosphoric and acetic acid in a manner that does not follow the Stokes relationship on viscosity. In sugar glass composed of trehalose and sucrose, proton transfer occurs when phosphate is incorporated in the glass. Sugar glass containing phosphate retains water and it is suggested that proton transfer requires this water. The infrared (IR) frequency of water bending mode in sugar glass and in aqueous solution is affected by the presence of phosphate and the IR spectral bands of all phosphate species in water are temperature dependent; both results are consistent with H-bonding between water and phosphate. The fluorescence results, which studied the effect of cosolvent, highlight the role of water in assisting proton transfer in reactions involving biological acids, and the IR results, which give spectroscopic evidence for H-bonding between water and phosphate, are consistent with a mechanism of proton transfer involving H-bonding. The possibility that the phosphate-rich surface of membranes assists in proton equilibration in cells is discussed.