The progressive scaling of CMOS technology towards nanometre sizes has made the implementation of highly integrated systems for the wireless communication systems possible. Additionally, higher speed, lower power consumption and area reduction has been reached. Due to the high-density integration needs, as well as to low cost fabrication, RF applications, such as the LC-voltage controlled oscillator (LC-VCO), are usually implemented in CMOS technology. The complexity of designing LC-VCOs has lead to the development of several design methodologies. This chapter introduces an optimization based methodology for the design of LC-VCOs, where its efficiency is granted by the use of analytical models to characterize the active and passive elements’ behaviour.

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.

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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.

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The preferential binding of anions and cations in aqueous solutions of the ionic liquids (ILs) 1-butyl- 3-methylimidazolium ([C₄mim]⁺) and 1-ethyl-3-methylimidazolium ([C₂mim]⁺) chloride and dicyanamide (dca^-) with the small alpha-helical protein Im7 was investigated using a combination of differential scanning calorimetry, NMR spectroscopy and molecular dynamics (MD) simulations. Our results show that direct ion interactions are crucial to understand the effects of ILs on the stability of proteins and that an anion effect is dominant. We show that the binding of weakly hydrated anions to positively charged or polar residues leads to the partial dehydration of the backbone groups, and is critical to control stability, explaining why dca^- is more denaturing than Cl^-. Direct cation–protein interactions also mediate stability; cation size and hydrophobicity are relevant to account for destabilisation as shown by the effect of [C₄mim]⁺ compared to [C₂mim]⁺. The specificity in the interaction of IL ions with protein residues established by weak favourable interactions is confirmed by NMR chemical shift perturbation, amide hydrogen exchange data and MD simulations. Differences in specificity are due to the balance of interaction established between ion pairs and ion-solvent that determine the type of residues affected. When the interaction of both cation and anion with the protein is strong the net result is similar to a non-specific interaction, leading ultimately to unfolding. Since the nature of the ions is a determinant of the level of interaction with the protein towards denaturation or stabilisation, ILs offer a unique possibility to modulate protein stabilisation or even folding events.

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Spreadsheets are being used with many different purposes that range from toy applications to complete information systems. In any of these cases, they are often used as data repositories that can grow significantly. As the amount of data grows, it also becomes more difficult to extract concrete information out of them. This paper focuses on the problem of spreadsheet querying. In particular, we propose an expressive and composable technique where intuitive queries can be defined. Our approach builds on a model-driven spreadsheet development environment, and queries are expressed referencing entities in the model of a spreadsheet instead of in its actual data. Finally, the system that we have implemented relies on Google's query function for spreadsheets.

This paper presents a tool, named QUERYSHEET, to query spreadsheets. We defined a language to write the queries, which resembles SQL, the language to query databases. This allows to write queries which are more related to the spreadsheet content than with current approaches.

We introduce a class of finite semigroups obtained by considering Rees
quotients of numerical semigroups.
Several natural questions concerning this class, as well as particular
subclasses obtained by considering some special ideals, are answered while
others remain open. We exhibit nice presentations for these semigroups and
prove that the Rees quotients by ideals of N, the positive integers under
addition, constitute a set of generators for the pseudovariety of commutative
and nilpotent semigroups.