2,630 research outputs found
A comparative QM/MM study of the reaction mechanism of the Hepatitis C virus NS3/NS4A protease with the three main natural substrates NS5A/5B, NS4B/5A and NS4A/4B
No full textThe reaction mechanism of the NS3/NS4A protease with the NS4B/5A and NS4A/4B natural substrates has been investigated using the QM/MM (quantum mechanics/molecular mechanics) approach, and some calculations have been performed on the reaction with the NS5A/5B natural substrate. This study widely extends a previous contribution of our group on the reaction mechanism with the NS5A/5B substrate, the main goal here being to understand the differences found between the reaction mechanism of each natural substrate and the role played by the enzymatic residues in the catalytic cycle. This knowledge will ultimately help in developing new NS3/NS4A protease inhibitors. The two first steps of the mechanism have been considered: Acylation and breaking of the peptide bond, with emphasis on the former one (rate limiting process). Energy and free energy profiles for both steps have been calculated at the AM1/MM level and corrected by means of MP2 ab initio calculations, being evident the importance of correlation energy. Acylation is the rate limiting step in all cases and occurs through a tetracoordinated intermediate, as previously suggested for other serine proteases. Specificities in the NS4B/5A mechanism can be attributed to the presence of a Proline residue in the substrate P2 position. The analysis of structures and energies confirm the importance of the oxyanion hole in the electrostatic stabilization of the tetracoordinated intermediate. Finally, the role of other residues, e.g., Arg-155 and Asp-79, has been explained, and the viability of Arg-155 mutants and its resistance to some protease inhibitors has been understood thanks to virtual mutation studies. © the Owner Societies
A quantum mechanics/molecular mechanics study of the reaction mechanism of the hepatitis C virus NS3 protease with the NS5A/5B substrate
No full textFormulas for Consumer Price Index at the elementary aggregate - A new proposal from the economic point of view
No full textThe price level in the aggregate economy and, more concretely, controlling its changes, has become one of the high-priority objectives within the framework of the regional macroeconomic analysis. Its different evolution could modify the interregional capital and commercial flows, being able to cause strong shocks, and of asymmetric nature, in each economy. The first step to reach this objective is obtaining a trustworthy and comparable measurement of the inflation in the different regions to be compared. The Index Number Theory is then used to calculate Consumer Price Indexes (CPI) the regional level. The calculation of CPI is made, at least, in two phases. In the first one, Elementary Price Index is considered (EPI). In the second and later phases, these EPI are combined, along with weighting information based on household’s expenditure, to obtain CPI for different aggregation levels to the country level. As previous step to the calculation of the IPE and CPI, the set of goods and services has to be defined based on households’ consumption behaviour. These sets are grouped in layers, named elementary aggregates, based on their homogeneity of satisfying consumer’s necessities. The COICOP (Classification Of Individual Consumption by Purpose) has important implications at the time of analyzing the behaviour of the consumer within each elementary aggregate, because of a high possibility of substitution between products. Nevertheless, this possibility diminishes and can get to be null when the goods and services satisfy necessities with very different nature. Whether what is wanted it is to calculate an EPI that correctly reflects the consumer behaviour, the described homogenous character cannot be forgotten, especially if, in addition, we take into account that National Statistics Agencies have no expenditure information available for weighting purposes, only data of prices to calculate EPI. This paper is focussed on analysis of the formula used to obtain the IPE, with the limitations of available information just commented. The election of the formula for the IPE has not been widely studied in the economic literature, being the proposal by Carli in 1764 and Dutot in 1738 [ extracted Reference of OIT (2003), chapter 20, pages 12-13 ] the most often used for practical purposes. Nevertheless, Fisher (1922) had already recommended not using the Carli’s formula because of the bias to the rise that it introduces [Fisher (1922), pages 29-30]. Throughout the 20th century different authors has continued looking for the ideal formula extending possible approaches to the subject: the approach of Divisia, the stochastic approach, the economic approach and the axiomatic approach. The final summary of these studies can be synthesized in "Toward to Dwells Accurate Measure of The Cost of Living” by the Advisory Commission To The Study The Consumer Price Index presented in 1996. This report, also known as Boskin’s Report, suggests the use of geometric mean price indices at the elementary aggregate for the EPI, this formula is attributed to Jevons in 1983 [OIT (2003), chapter 20, pages 12-13 ]. In the present paper, we demonstrate that all usually formulas for the calculation of the IPE are incoherent with the theory of consumer behaviour, in an aggregate characterized by the high level of substitution caused by homogeneity in the consumption purpose. In addition, the formula proposed by Rodriguez, González and Rodriguez (2004), is not only superior from the axiomatic point of view, but also from the economic approach, is the only one that is able to reflect the expected consumer behaviour.
Structure and electronic and charge-transfer properties of mercaptobenzoic acid and mercaptobenzoic acid-undecanethiol mixed monolayers on AU(111)
No full textThe surface structure, molecular conductance, and charge-transfer properties of pure mercaptobenzoic acid (MBA) and mixed MBA?undecanethiol (UDT) self-assembled monolayers (SAMs) on Au(111) are studied by scanning tunneling microscopy, scanning tunneling spectroscopy, electrochemical techniques, and density functional theory calculations. MBA forms ordered diluted lattices without evidence of Au adatom complexes at terraces (absence of vacancy islands) at low MBA concentrations, whereas disordered lattices with possible formation of these complexes are found at high concentrations (presence of vacancy islands). In addition, some other interesting facts have been established. The stability of the MBA SAMs is improved in mixed MBA-UDT SAMs, revealing aromatic-aliphatic attractive interactions. The mixed SAMs at equivalent amounts of thiols hinder the vacancy island formation typical of the pure UDT SAMs. The MBA SAMs exhibit good molecular conductance with filled states from S and aromatic ring contributions near the Fermi level. Finally, it has been proven that MBA molecules efficiently wire the electron transfer through UDT SAMs.Fil: Rodriguez Gonzalez, Miriam C.. Universidad de la Laguna; EspañaFil: Gonzalez Orive, Alejandro. Universidad de la Laguna; EspañaFil: Carro, Pilar. Universidad de la Laguna; EspañaFil: Salvarezza, Roberto Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Hernandez Creus, Alberto. Universidad de la Laguna; Españ
Geomorphological reconstruction and morphometric modelling applied to past volcanism
No full text16 páginas, 7 figuras, 10 tablas.Accurate and precise morphometric modelling can be extended to past eruptions after a careful palaeogeomorphological reconstruction of volcanic landforms in an oceanic island. This reconstruction was used to derive the pre-, post-eruption and present-day digital elevation models (DEM). The correct pixel size, interpolation method and quality of these DEMs are discussed. The process in a Geographical Information System framework of the geological information of cone, lava flow and tephra fall deposits together and the aforementioned DEMs allowed the determination of main morphological features of these volcanic landforms and their derivatives. The calibration and validation of morphometric modelling were performed on simulated volcanic landforms, and verified by a case study: a typical Holocene monogenetic basaltic eruption at Gran Canaria Island (Spain).The authors thank the University of Las Palmas
de Gran Canaria for their support through the pre-doctoral grant of
A. Rodriguez-Gonzalez. This work was partially funded by Project
PI2002/148 of the Canary Government and by Project GRANCA,
Spanish Commission CICYT, Ministry of Education and Science
(Ref. CGL2004-04039/BTE). The research was carried out in the
framework of the Research Consolidated Group SGR-2005-795
PEGEFA (Applied and Basic Petrology and Geochemistry), funded
by AGAUR-DURSI, Generalitat de Catalunya.Peer reviewe
Effects of progressive resistance exercise in akinetic-rigid Parkinson's disease patients: a randomized controlled trial
No full textSantos, Luis; Fernandez-Rio, Javier; Winge, Kristian; Barragan-Perez, Beatriz; Gonzalez-Gomez, Lucia; Rodriguez-Perez, Vicente; Gonzalez-Diez, Vicente; Lucia, Alejandro; Iglesias-Soler, Eliseo; Dopico-Calvo, Xurxo; Fernandez-del-Olmo, Miguel; del-Valle, Miguel; Blanco-Traba, Miguel; Suman, Oscar E.; Rodriguez-Gomez, Javie
Multivariate factorial analysis to design a robust batch leaching test to assess the volcanic ash geochemical hazard
No full textA method to obtain robust information on short term leaching behaviour of volcanic ashes has been developed independently on the sample age. A mixed factorial design (MFD) was employed as a multivariate strategy for the evaluation of the effects of selected control factors and their interactions (amount of sample (A), contact time (B), and liquid to solid ratio or L/S (C)) on the leaching process of selected metals (Na, K, Mg, Ca, Si, Al, V, Mn, Fe, and Co) and anions (Cl - and SO 4 2-). Box plots of the data acquired were used to evaluate the reproducibility achieved at different experimental conditions. Both the amount of sample (A) and leaching time (B) had a significant effect on the element stripping whereas the L/S ratio influenced only few elements. The lowest dispersion values have been observed when 1.0g was leached with an L/S ratio equal to 10, shaking during 4h. The entire method is completed within few hours, and it is simple, feasible and reliable in laboratory conditions.Fil: Ruggieri Flavia. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias de la Tierra Jaume Almera; EspañaFil: Gil, Raul Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Jose Luis Fernandez Turiel. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias de la Tierra Jaume Almera; EspañaFil: Julio Saavedra. Irnasa; EspañaFil: Domingo Gimeno. Facultad de Geologia; EspañaFil: Agustin Lobo. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias de la Tierra Jaume Almera; EspañaFil: Luis D. Martinez. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Alejandro Rodriguez Gonzalaez. Departamento de Fisica- Universidad de Las Palmas; Españ
Polyphenol oxidase expression in potato (Solanum tuberosum) tubers inhibited to sprouting by treatment with iodine atmosphere
No full textComparison of different quantum mechanical/molecular mechanics boundary treatments in the reaction of the hepatitis C virus NS3 protease with the NS5A/5B substrate
No full textWhich financial news to trust?:financial news article author assessment using sentiment analysis and named entity linking in a streaming environment
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