Influence of pH and sequence in peptide aggregation via molecular simulation

We employ a recently developed coarse-grained model for peptides and proteins where the effect of pH is automatically included. We explore the effect of pH in the aggregation process of the amyloidogenic peptide KTVIIE and two related sequences, using three different pH environments. Simulations using large systems (24 peptides chains per box) allow us to correctly account for the formation of realistic peptide aggregates. We evaluate the thermodynamic and kinetic implications of changes in sequence and pH upon peptide aggregation, and we discuss how a minimalistic coarse-grained model can account for these details.Comment: 21 pages, 4 figure

pH-dependent coarse-grained model of peptides

We propose the first, to our knowledge, coarse-grained modeling strategy for peptides where the effect of changes of the pH can be efficiently described. The idea is based on modeling the effects of the pH value on the main driving interactions. We use reference data from atomistic simulations and experimental databases and transfer its main physical features to the coarse-grained resolution according the principle of "consistency across the scales". The coarse-grained model is refined by finding a set of parameters that, when applied to peptides with different sequences and experimental properties, reproduces the experimental and atomistic data of reference. We use the such parameterized model for performing several numerical tests to check its transferability to other systems and to prove the universality of the related modeling strategy. We have tried systems with rather different response to pH variations, showing a highly satisfactory performance of the model.Comment: accepted for publication in Soft Matte

Finite-discrete element modelling of masonry infill walls subjected to out-of-plane loads

In this paper, the out-of-plane response of infill walls is investigated by means of non-linear monotonic (push-over) analyses through a combined finite and discrete modelling approach. The model accounts for material deformability, crack formation, sliding, separa-tion and formation of new contacts. Masonry units are modelled as finite elements, and differ-ent material models are assumed for the masonry. Contact between masonry units, and between masonry and frame elements is modelled by means of interfaces, which permit tan-gential motion with frictional sliding. Frame elements are modelled by means of a linear-elastic material. The results of the numerical analyses are compared with those of experimen-tal tests available in the literature. The advantages and disadvantages of the adopted model-ling strategy are investigated

The Determinants of Suppliers’ Performance in E-Procurement: Evidence from the Italian Government’s E-Procurement Platform

Participation of small businesses in the market for public contracts is widely recognized as a key policy issue. It is also commonly held that the adoption of e-procurement solutions can be effective in pursuing such an objective. To this end, we analyze the transactions completed in the period 2004-2007 through the Italian Government’s e-procurement platform, that is, the marketplace managed by the Italian Public Procurement Agency (Consip S.p.A.). Although descriptive statistics indicate that micro suppliers are the most represented group of firms in the marketplace, our econometric treatment provides some evidence that the former are less successful than all other suppliers in getting public contracts. Degree of loyalty with buyers, location and the use of other MEPA negotiation tools, also emerge as relevant factors of success in the e-procurement market.E-Procurement, Small Suppliers, Request For Quotations, Performance, Public Contracts, Count Data

New N,N-dimethylcarbamate inhibitors of acetylcholinesterase: design synthesis and biological evaluation

A series of N,N-dimethylcarbamates containing a N,N-dibenzylamino moiety was synthesized and tested to evaluate their ability to inhibit Acetylcholinesterase (AChE). The most active compounds 4 and 8, showed 85 and 69% of inhibition at 50 mM, respectively. Furthermore, some basic SAR rules were outlined: an alkyl linker of six methylene units is the best spacer between the carbamoyl and dibenzylamino moieties; electron-withdrawal substituents on aromatics rings of the dibenzylamino group reduce the inhibitory power. Compound 4 produces a slow onset inhibition of AChE and this is not due to the carbamoylation of the enzyme, as demonstrated by the time-dependent inhibition assay of AChE with compound 4 and by MALDI-TOF MS analysis of trypsinized AChE inhibited by compound 4. Instead, compound 4 could act as a slow-binding inhibitor of AChE, probably because of its high conformational freedom due to the linear alkyl chain

Explicit recognition of emotional facial expressions is shaped by expertise: evidence from professional actors

Can reading others' emotional states be shaped by expertise? We assessed processing of emotional facial expressions in professional actors trained either to voluntary activate mimicry to reproduce character's emotions (as foreseen by the “Mimic Method”), or to infer others' inner states from reading the emotional context (as foreseen by “Stanislavski Method”). In explicit recognition of facial expressions (Experiment 1), the two experimental groups differed from each other and from a control group with no acting experience: the Mimic group was more accurate, whereas the Stanislavski group was slower. Neither acting experience, instead, influenced implicit processing of emotional faces (Experiment 2). We argue that expertise can selectively influence explicit recognition of others' facial expressions, depending on the kind of “emotional expertise”

Space-based and object-centered gaze cuing of attention in right hemisphere-damaged patients

Gaze cuing of attention is a well established phenomenon consisting of the tendency to shift attention to the location signaled by the averted gaze of other individuals. Evidence suggests that such phenomenon might follow intrinsic object-centered features of the head containing the gaze cue. In the present exploratory study, we aimed to investigate whether such object-centered component is present in neuropsychological patients with a lesion involving the right hemisphere, which is known to play a critical role both in orienting of attention and in face processing. To this purpose, we used a modified gaze-cuing paradigm in which a centrally placed head with averted gaze was presented either in the standard upright position or rotated 90° clockwise or anti-clockwise. Afterward, a to-be-detected target was presented either in the right or in the left hemifield. The results showed that gaze cuing of attention was present only when the target appeared in the left visual hemifield and was not modulated by head orientation. This suggests that gaze cuing of attention in right hemisphere-damaged patients can operate within different frames of reference

pH-dependent Response of Coiled Coils: A Coarse-Grained Molecular Simulation Study

In a recent work we proposed a coarse-grained methodology for studying the response of peptides when simulated at different values of pH; in this work we extend the methodology to analyze the pH-dependent behavior of coiled coils. This protein structure presents a remarkable chain stiffness andis formed by two or more long helical peptides that are interacting like the strands of a rope. Chain length and rigidity are the key aspects needed to extend previous peptide interaction potentials to this particular case; however the original model is naturally recovered when the length or the ridigity of the simulated chain are reduced. We apply the model and discuss results for two cases: (a) the folding/unfolding transition of a generic coiled coil as a function of pH; (b) behavior of a specific sequence as a function of the acidity conditions. In this latter case results are compared with experimental data from the literature in order to comment about the consistency of our approach

Hacia un diseño eficiente de sistemas de transporte público en áreas urbanas

Trabajo presentado en:III Congreso de Ingeniería Civil, Territorio Y Medio Ambiente “Agua, Biodiversidad e Ingeniería”, Zaragoza, 25-27 de octubre de 2006Hoy día, la generación de un sistema de transporte eficiente es un problema de gran relevancia en el desarrollo urbano. La importancia del tema se basa en que distintos modos de transporte conllevan diferentes resultados en cuanto a nivel de servicio percibido por los usuarios, así como del coste de funcionamiento del sistema. De esta manera, estas diversidades conducen a diversos niveles de bienestar social. Por ello, el desarrollo de metodologías que permitan obtener y adaptar dinámicamente el sistema de transporte público de acuerdo a los cambios que experimenta una urbe es un problema primario para los planificadores del transporte. El objetivo de este artículo es analizar las variables que influyen en el problema de diseño de redes eficientes de transporte público urbano y estudiar las relaciones que existen entre la oferta de transporte público y la demanda de viaje, y resaltar la importancia del transporte público como instrumento para un desarrollo sostenible. Las conclusiones que se sacan son que un diseño eficiente de las redes hace que el transporte público sea más atractivo, y se pueden obtener beneficios económicos y sociales relevantes a un coste admisible, optimizando unas variables de diseño de las redes de transporte público urbano

Ensemble harbour forecast performance

Deliverable D3.3 del Proyecto MyWave: A pan-European concerted and integrated approach to operational wave modelling and forecasting – a complement to GMES MyOcean services. Work programme topic: SPA.2011.1.5.03 – R&D to enhance future GMES applications in the Marine and Atmosphere areas.Funded under: FP7-SPACE-2011-284455