Synthesis of 4-hetaryl-substituted 5-amino- and 5-sulfanyl-1,3-oxazole derivatives

Previously unknown 5-amino- and 5-sulfanyl-1,3-oxazole derivatives containing a 1,3,4-oxadiazole, 1,3,4-thiadiazole, or 1,2,4-triazole fragment at C⁴ were synthesized from accessible 1,3-oxazole-4-carboxylic acid hydrazides.     

Simvastatin inhibits osteoclast differentiation by scavenging reactive oxygen species

Osteoclasts, together with osteoblasts, control the amount of bone tissue and regulate bone remodeling. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. Reactive oxygen species (ROS) acts as a signal mediator in osteoclast differentiation. Simvastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A, is a hypolipidemic drug which is known to affect bone metabolism and suppresses osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In this study, we analyzed whether simvastatin can inhibit RANKL-induced osteoclastogenesis through suppression of the subsequently formed ROS and investigated whether simvastatin can inhibit H2O2-induced signaling pathways in osteoclast differentiation. We found that simvastatin decreased expression of tartrate-resistant acid phosphatase (TRAP), a genetic marker of osteoclast differentiation, and inhibited intracellular ROS generation in RAW 264.7 cell lines. ROS generation activated NF-κB, protein kinases B (AKT), mitogen-activated protein kinases signaling pathways such as c-JUN N-terminal kinases, p38 MAP kinases as well as extracellular signal- regulated kinase. Simvastatin was found to suppress these H2O2-induced signaling pathways in osteoclastogenesis. Together, these results indicate that simvastatin acts as an osteoclastogenesis inhibitor through suppression of ROS-mediated signaling pathways. This indicates that simvastatin has potential usefulness for osteoporosis and pathological bone resorption.     

Expression of Codon-Optmized Phosphoenolpyruvate Carboxylase Gene from Glaciecola sp. HTCC2999 in Escherichia coli and its Application for C4 Chemical Production

We examined the expression of the phosphoenolpyruvate carboxylase (PEPC) gene from marine bacteria in Escherichia coli using codon optimization. The codon-optimized PEPC gene was expressed in the E. coli K-12 strain W3110. SDS-PAGE analysis revealed that the codon-optimized PEPC gene was only expressed in E. coli, and measurement of enzyme activity indicated the highest PEPC activity in the E. coli SGJS112 strain that contained the codon-optimized PEPC gene. In fermentation assays, the E. coli SGJS112 produced the highest yield of oxaloacetate using glucose as the source and produced a 20-times increase in the yield of malate compared to the control. We concluded that the codon optimization enabled E. coli to express the PEPC gene derived from the Glaciecola sp. HTCC2999. Also, the expressed protein exhibited an enzymatic activity similar to that of E. coli PEPC and increased the yield of oxaloacetate and malate in an E. coli system.     

Diffusion coefficient distribution from NMR-DOSY experiments using Hopfield neural network

Diffusion ordered spectroscopy (DOSY) is a powerful two-dimensional NMR method to study molecular translation in various systems. The diffusion coefficients are usually retrieved, at each frequency, from a fit procedure on the experimental data, considering a unique coefficient for each molecule or mixture. However, the fit can be improved if one regards the decaying curve as a multiexponential function and the diffusion coefficient as a distribution. This work presents a computer code based on the Hopfield neural network to invert the data. One small-molecule binary mixture with close diffusion coefficients is treated with this approach, demonstrating the effectiveness of the method.     

3D Numerical Analysis of Concrete Degradation at Macrostructure Level

This work was intended as an attempt to assess the degradation of compressed concrete sample with regard to heterogeneity. The aim of this paper is to estimate of microdamages in heterogeneous materials as such as concrete. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Time-delayed phase-control for suppression of the flow-induced noise from an open cavity

A flow over an open cavity causes a cavity resonance, which is a feedback mechanism between the acoustic waves and the pressure fluctuation of the cavity flow. Previous research on the reduction of the cavity resonance has focused on suppressing the flow disturbance. This paper presents a time-delayed phase-control method to reduce the global noise of the cavity. Acoustic feedback of the cavity noise, which amplifies the flow disturbance, can be generally reduced by this control method, regardless of the flow physics. The positions of the sensors and the actuator are determined to increase the control efficiency. Experiments show that this control method reduces the peak of the flow oscillation by suppressing the acoustic feedback.     

Accessible Mannitol‐Based Amphiphiles (MNAs) for Membrane Protein Solubilisation and Stabilisation

Integral membrane proteins are amphipathic molecules crucial for all cellular life. The structural study of these macromolecules starts with protein extraction from the native membranes, followed by purification and crystallisation. Detergents are essential tools for these processes, but detergent‐solubilised membrane proteins often denature and aggregate, resulting in loss of both structure and function. In this study, a novel class of agents, designated mannitol‐based amphiphiles (MNAs), were prepared and characterised for their ability to solubilise and stabilise membrane proteins. Some of MNAs conferred enhanced stability to four membrane proteins including a G protein‐coupled receptor (GPCR), the β₂ adrenergic receptor (β₂AR), compared to both n‐dodecyl‐d ‐maltoside (DDM) and the other MNAs. These agents were also better than DDM for electron microscopy analysis of the β₂AR. The ease of preparation together with the enhanced membrane protein stabilisation efficacy demonstrates the value of these agents for future membrane protein research.     

Mesitylene‐Cored Glucoside Amphiphiles (MGAs) for Membrane Protein Studies: Importance of Alkyl Chain Density in Detergent Efficacy

Detergents serve as useful tools for membrane protein structural and functional studies. Their amphipathic nature allows detergents to associate with the hydrophobic regions of membrane proteins whilst maintaining the proteins in aqueous solution. However, widely used conventional detergents are limited in their ability to maintain the structural integrity of membrane proteins and thus there are major efforts underway to develop novel agents with improved properties. We prepared mesitylene‐cored glucoside amphiphiles (MGAs) with three alkyl chains and compared these agents with previously developed xylene‐linked maltoside agents (XMAs) with two alkyl chains and a conventional detergent (DDM). When these agents were evaluated for four membrane proteins including a G protein‐coupled receptor (GPCR), some agents such as MGA‐C13 and MGA‐C14 resulted in markedly enhanced stability of membrane proteins compared to both DDM and the XMAs. This favourable behaviour is due likely to the increased hydrophobic density provided by the extra alkyl chain. Thus, this study not only describes new glucoside agents with potential for membrane protein research, but also introduces a new detergent design principle for future development.     

Complex density of a suspension in an oscillatiory wave process

The effective viscous inertia properties exhibited by suspensions in the presence of oscillatory wave processes are considered. A cell model of a concentrated suspension is used to derive the dependence for the complex density, whose real and imaginary parts characterize the effective inertia and the bulk viscous resistance to oscillatory motion, respectively. From hydrodynamic models of low-frequency and high-frequency translatory oscillations of spherical inclusions in the host liquid, estimates are obtained for the internal dynamic parameters of the suspension, namely, the apparent mass factor and the inclusion relaxation time, which specify the general formulas for the complex density.     

Organoamido- and aryloxo-lanthanoids. XIII [1]. Organometallic compounds of the lanthanoids. CV [2]. New Lanthanoid(III) Complexes with Pyrazolate Ligands

The complexes Er(Me₂pz)₃(thf) and Ln(Ph₂pz)₃(thf)_n (Ln = Sc, Y, Gd, Er, n = 2; Ln = Lu, n = 3) (Me₂pz^? = 3,5-dimethylpyrazolate, thf = tetrahydrofuran, Ph₂pz^? = 3,5-diphenylpyrazolate) have been prepared by reaction of the lanthanoid metal with bis(pentafluorophenyl)mercury and the pyrazole in thf. The Ln(Ph₂pz)₃(thf)₂ complexes are considered to be eight coordinate with three η²-Ph₂pz ligands. Other lanthanoid pyrazolate complexes, Y(pz)₃(thf)₂, La(Me₂pz)₃(thf), Cp₂Ln(Me₂pz)(thf)_n (Ln = Y, Lu, n = 0; Ln = Lu, n = 1), (C₅Me₅)₂Y(pz)(thf), (C₅Me₅)₂Y(Mepz)(thf), (C₅Me₅)₂Y(Me₂pz)(thf)₂ (pz^? = pyrazolate, Mepz^? = 3-methylpyrazolate, Cp = cyclopentadienyl) have been synthesized by reaction of LnCl₃, Cp₂LnCl, or (C₅Me₅)₂LnCl with the appropriate sodium pyrazolate in thf. The structure of Ln(Me₂pz)₃(thf) (Ln = La or Er) is considered to be a symmetrical dimer with four chelating and two bridging Me₂pz groups, and two bridging thf ligands, whereas the cyclopentadienyl complexes are most likely dimers with bridging pyrazolate groups, and lattice thf of solvation.