n/a

Acetylcholinesterase (AChE) inhibition is one of the most currently available therapies for the management of Alzheimer’s disease (AD) symptoms. In this context, NMR spectroscopy binding studies were accomplished to explain the inhibition of AChE activity by Salvia sclareoides extracts. HPLC-MS analyses of the acetone, butanol and water extracts eluted with methanol and acidified water showed that rosmarinic acid is present in all the studied samples and is a major constituent of butanol and water extracts. Moreover, luteolin 4′-O-glucoside, luteolin 3′,7-di-O-glucoside and luteolin 7-O-(6′′-O-acetylglucoside) were identified by MS2 and MS3 data acquired during the LC-MSn runs. Quantification of rosmarinic acid by HPLC with diode-array detection (DAD) showed that the butanol extract is the richest one in this component (134 μg mg−1 extract). Saturation transfer difference (STD) NMR spectroscopy binding experiments of S. sclareoides crude extracts in the presence of AChE in buffer solution determined rosmarinic acid as the only explicit binder for AChE. Furthermore, the binding epitope and the AChE-bound conformation of rosmarinic acid were further elucidated by STD and transferred NOE effect (trNOESY) experiments. As a control, NMR spectroscopy binding experiments were also carried out with pure rosmarinic acid, thus confirming the specific interaction and inhibition of this compound against AChE. The binding site of AChE for rosmarinic acid was also investigated by STD-based competition binding experiments using Donepezil, a drug currently used to treat AD, as a reference. These competition experiments demonstrated that rosmarinic acid does not compete with Donepezil for the same binding site. A 3D model of the molecular complex has been proposed. Therefore, the combination of the NMR spectroscopy based data with molecular modelling has permitted us to detect a new binding site in AChE, which could be used for future drug development.

The continuing size reduction of electronic devices imposes design challenges to optimize the performances of modern electronic systems, such as: wireless services, telecom and mobile computing. Fortunately, those design challenges can be overcome thanks to the development of Electronic Design Automation (EDA) tools. In the analog, mixed signal and radio-frequency (AMS/RF) domains, circuit optimization tools have demonstrated their usefulness in addressing design problems taking into account downscaling technological aspects. Recent advances in EDA have shown that the simulation-based sizing technique is a very interesting solution to the ‘complex’ modelling task in the circuit design optimization problem. In this paper we propose a multi-objective simulation-based optimization tool. A CMOS LC-VCO circuit is presented to show the viability of this tool. The tool is used to generate the Pareto front linking two conflicting objectives, namely the VCO Phase Noise and Power Consumption. The accuracy of the results is checked against HSPICE/RF simulations.

n/a

Prion protein (PrPC) biosynthesis involves a multi-step process that includes translation and post-translational modifications. While PrP has been widely investigated, for the homolog Doppel (Dpl), limited knowledge is available. In this study, we focused on a vital step of eukaryotic protein biosynthesis: targeting by the signal recognition particle (SRP). Taking the ovine Dpl (OvDpl(1-30)) peptide as a template, we studied its behavior in two different hydrophobic environments using CD and NMR spectroscopy. In both trifluoroethanol (TFE) and dihexanoyl-sn-glycero-3-phosphatidylcholine (DHPC), the OvDpl(1-30) peptide revealed to fold in an alpha-helical conformation with a well-defined central region extending from residue Cys8 until Ser22. The NMR structure was subsequently included in a computational docking complex with the conserved M-domain of SRP54 protein (SRP54M), and further compared with the N-terminal structures of mouse Dpl and bovine PrPC proteins. This allowed the determination of (i) common predicted N-terminal/SRP54M polar contacts (Asp331, Gln335, Glu365 and Lys432) and (ii) different N–C orientations between prion and Dpl peptides at the SRP54M hydrophobic groove, that are in agreement with each peptide electrostatic potential. Together, these findings provide new insights into the biosynthesis of prion-like proteins. Besides they also show the role of protein conformational switches in signalization toward the endoplasmic membrane, a key event of major significance in the cell cycle. They are thus of general applicability to the study of the biological function of prion-like as well as other proteins.

The paper analyses numerical solutions for the process leading to debonding failure of fiber reinforced polymers (FRP)-to-concrete interfaces in shear tests with the FRP plate subjected to a tensile load at one end. Any realistic local nonlinear bond-slip law can be used in the numerical analysis proposed in the present study. However, only a Popovics’ type expression is employed in the numerical process due to its use in different studies found in the literature. Effective bond length (Leff) is discussed and an expression depending on the Popovics’ constant (nP) is proposed to calculate it. Assuming a fracture in pure Mode II, the debonding process is analyzed in detail and distributions of bond stresses and strains in the FRP plate along the interface are presented. The load-displacement behaviour is also presented and the influence of the local bond-slip law on the debonding process is discussed.

n/a

n/a

This paper is discussing the intuitive interaction with robotic systems and the conceptualisation connected with known organisational problems. In particular, the focus will be on the manufacturing industry with respect to its social dimension. One of the aims is to identify relevant research questions about the possibility of development of safer robot systems in closer human-machine intuitive interaction systems at the manufacturing shop-floor level. We try to contribute to minimize the cognitive and perceptual workload for robot operators in complex working systems. In particular that will be highly relevant when more different robots with different roles and produced by different companies or designers are to be used in the manufacturing industry to a larger extent. The social sciences approach to such technology assessment is of high relevance to understand the dimensions of the intuitive interaction concept.