Charge propagation in "ion channel sensors" based on protein-modified electrodes and redox marker ions

The mechanism of charge propagation in "ion channel sensors" (ICSs) consisting of gold electrodes modified with a layer of charged proteins and highly charged redox-active marker ions in solution was investigated by electrochemical techniques, QCM and AFM. The study is based on seven proteins (concanavalin A, cytochrome c, glucose oxidase, lysozyme, thyroglobulin, catalase, aldolase, and EF1-ATPase) in combination with seven electroactive marker ions ([Fe(CN)6]3-, [Fe(CN)6]4-, [Ru(NH3)6]3+, mono-, di-, and trimeric viologens), as well as a series of suppressor and enhancer ions leading to the following general statements: (i) electrostatic binding of charged marker ions to the domains of the protein is a prerequisite for an electrochemical current and (ii) charge propagation through the layer consists of electron hopping along surface-confined marker ions into the pores between adsorbed proteins. It is further shown that (iii) marker ions and suppressor ions with identical charge compete for oppositely charged sites on the protein domain, (iv) electrostatically bound multilayers of marker or enhancer ions with alternating charge form on a charged protein domain, and (v) self-exchange and exergonic ET catalysis between adsorbed marker ions and marker ions in solution take place. In addition to fundamental insight into the mechanism of charge propagation, valuable information for the design, optimization, and tailoring of new biosensors based on the ICS concept is demonstrated by the current findings.     

An exact solution for a cavity model

Résumé On considère l'écoulement plan, permanent et irrotationnel d'un jet gazeux aux grandes vitesses subsoniques. En appliquant le procédé deFalkovich, concernant la méthode hodographique deChaplygin, on obtient la solution exacte pour le modèle de Roshko situé dans un canal aux parois parallèles (Figure). On détermine l'expression exacte du coefficient de résistance et on donne quelques relations entre les différents paramètres de la configuration.     

Raman and SERS study of metoclopramide at different pH values

Conjugate acid–base forms of the drug metoclopramide were investigated by Raman spectroscopy in aqueous solutions and by surface‐enhanced Raman scattering (SERS), when the molecules were adsorbed on colloidal silver surfaces. Raman spectra were recorded at pH values below 8, metoclopramide being poorly water soluble at higher pH values. The SERS spectra of metoclopramide were recorded in the 3–11 pH range, even in spite of its low solubility at basic pH values. The Raman and SERS spectra were assigned by means of density functional theory (DFT) calculations. By monitoring several SERS marker bands, the protonated, neutral or the coexistence of both molecular species adsorbed on the colloidal silver particles could be evidenced. The adsorbate orientation was deduced to be perpendicular to the metal surface for the protonated molecular species and tilted for the neutral metoclopramide molecular species. Copyright © 2009 John Wiley & Sons, Ltd.     

Perturbation Method for Particle-like Solutions of the Einstein–Dirac Equations

The aim of this work is to prove by a perturbation method the existence of solutions of the coupled Einstein–Dirac equations for a static, spherically symmetric system of two fermions in a singlet spinor state. We relate the solutions of our equations to those of the nonlinear Choquard equation and we show that the nondegenerate solution of Choquard’s equation generates solutions of the Einstein–Dirac equations.     

Synthesis and Biological Evaluation of Some New N1‐[4‐(4‐Chlorophenylsulfonyl)benzoyl]‐N 4‐(aryl)‐thiosemicarbazides and Products of Their Cyclization

In the present study, new 1,2,4‐triazoles, 1,3,4‐thiadiazoles, and acylthiosemicarbaz‐ides derived from 4‐(4‐chlorophenylsulfonyl)benzoic acid hydrazide were synthesized and screened for their antimicrobial and analgesic activities. Acylthiosemicarbazides 2–4 were synthesized by a reaction of 4‐(4‐chlorophenyl‐sulfonyl)benzoic acid hydrazide 1 with different arylisothiocyanates.4,5‐Disubstituted‐2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐thiones 5–7 and 2,5‐disubstituted‐1,3,4‐thiadiazoles 8–10 were obtained by dehydrative cyclization of corresponding acylthiosemicarbazide derivatives 2–4 in basic media (8% aqueous sodium hydroxide) and in acidic media (sulfuric acid or phosphorous oxychloride), respectively. The structures of the newly synthesized compounds have been confirmed on the basis of elemental analysis and spectral studies (IR, ¹H NMR, ¹³C NMR, MS). Their antimicrobial activities against some bacteria and yeasts were investigated. The analgesic activity of all compounds was performed with two pharmacological tests: the writhing test induced with acetic acid and hot‐plate test. The results showed that triazole 7 had the best antimicrobial activity against Bacillus cereus. In the chemical stimulus test, triazoles 6 and 7 were the most active compounds whereas in the hot‐plate test thiadiazoles 9 and 10 exhibited the highest analgesic activity.     

An inventory-transportation system with stochastic demand

We study a logistic system in which a supplier has to deliver a set of products to a set of retailers to face a stochastic demand over a given time horizon. The transportation from the supplier to each retailer can be performed either directly, by expensive and fast vehicles, or through an intermediate depot, by less expensive but slower vehicles. At most one time period is required in the former case, while two time periods are needed in the latter case. A variable transportation cost is charged in the former case, while a fixed transportation cost per journey is charged in the latter case. An inventory cost is charged at the intermediate depot. The problem is to determine, for each time period and for each product, the quantity to send from the supplier to the depot, from the depot to each retailer and from the supplier to each retailer, in order to minimize the total expected cost. We first show that the classical benchmark policy, in which the demand of each product at each retailer is set equal to the average demand, can give a solution which is infinitely worse with respect to the optimal solution. Then, we propose two classes of policies to solve this problem. The first class, referred to as Horizon Policies, is composed of policies which require the solution of the overall problem over the time horizon. The second class, referred to as Reoptimization Policies, is composed of a myopic policy and several rolling-horizon policies in which the problem is reoptimized at each time period, once the demand of the time period is revealed. We evaluate the performance of each policy dynamically, by using Monte Carlo Simulation.     

Continuous‐wave optical parametric oscillator based infrared spectroscopy for sensitive molecular gas sensing

Over the past 10 years, with the advent of new crystals designs and a new generation of pump lasers, continuous‐wave (cw) optical parametric oscillators (OPOs) have developed into mature monochromatic light sources. Nowadays, cw OPOs can fulfill a wide variety of criteria for sensitive molecular gas sensing. It can access the mid‐infrared wavelength region, where many molecules have their fundamental rotational‐vibrational transitions, with high power. This high power combined with wide wavelength tuning and narrow linewidth creates excellent conditions for sensitive, high‐resolution spectroscopy. OPOs combined with robust methods, such as photoacoustic spectroscopy and cavity‐enhanced spectroscopy, are well suited for field measurements and remote‐sensing applications. The wide tunability of cw OPOs allows detection of larger molecules with broad absorption band structures, and its fast scanning capabilities allow rapid detection of trace gases, the latter is a demand for life‐science applications. After a short introduction about the physical principle of cw OPOs, with its most recent physical developments, this review focuses on sensitive molecular gas sensing with a variety of spectroscopic applications in atmospheric and life sciences.     

Luciferase‐Induced Photouncaging: Bioluminolysis

Bioluminescence resonance energy transfer (BRET) has been widely used for studying dynamic processes in biological systems such as protein–protein interactions and other signaling events. Aside from acting as a reporter, BRET can also turn on functions in living systems. Herein, we report the application of BRET to performing a biorthogonal reaction in living cells; namely, releasing functional molecules through energy transfer to a coumarin molecule, a process termed bioluminolysis. An efficient BRET from Nanoluc‐Halotag chimera protein (H‐Luc) to a coumarin substrate yields the excited state of coumarin, which in turn triggers hydrolysis to uncage a target molecule. Compared to the conventional methods, this novel uncaging system requires no external light source and shows fast kinetics (t_1/2<2 min). We applied this BRET uncaging system to release a potent kinase inhibitor, ibrutinib, in living cells, highlighting its broad utility in controlling the supply of bioactive small molecules in vivo.