Rationally designed inhibitors as tools for comparing the mechanism of squalene-hopene cyclase with oxidosqualene cyclase

The inhibition of squalene-hopene cyclase (SHC) (E.C. 5.4.99.-), an enzyme of bacterial membranes catalyzing the formation of pentacyclic sterol-like triterpenes, was studied by using different classes of compounds originally developed as inhibitors of oxidosqualene cyclase (OCS) (E.C. 5.4.99.7), the enzyme of eukaryotes responsible for the formation of tetracyclic precursors of sterols. The mechanism of cyclization of squalene by SHC, beginning with a protonation of the 2,3 double bond by an acidic residue of the enzyme, followed by a series of electrophilic additions of the carbocationic intermediates to the double bonds, is similar to the mechanism of cyclization of 2,3-oxidosqualene by OSC. The inhibitors studied included: (i) analogs of the carbocationic intermediates formed during cyclization, such as aza-analogs of squalene and 2,3-oxidosqualene; (ii) affinity-labeling inhibitors bearing a methylidene reactive group; and (iii) vinyldioxidosqualenes and vinylsulfide derivatives of the substrates. Comparison of the results obtained with the two enzymes, SHC and OSC, showed that many of the most effective inhibitors of OSC were also able to inhibit SHC, while some derivatives acted as specific inhibitors. Differences could be easily explained on the basis of the different substrate specificity of the two enzymes.     

Fluoroelastomers-dependence of relaxation phenomena on composition

The dynamic-mechanical properties of some fluoroelastomers were determined as a function of composition at low frequency (≈ 1 Hz), by means of a free oscillation torsion pendulum, between −180°C and the softening point. Vinylidenefluoride (VDF)-hexafluoropropene (HFP) copolymers of molar composition 0–39% HFP and terpolymers of VDF and HFP with up to 30mol% tetrafluoroethylene (TFE) and a constant VDF to HFP molar ratio of 3.4 were considered. Two relaxation processes typical of the amorphous phase were found. The first, located at about −87°C, is related to local motions and the transition temperature was found to be independent of composition for copolymers, while it depends on TFE molar content for terpolymers. The second is related to the glass transition and the transition temperature depends on the composition. However, for semicrystalline copolymers the double glass transition phenomenon was observed. When crystallinity goes to zero at about 20 mol% HFP, only one transition is observed. It was also found that ordered structures can take place for terpolymers when TFE molar concentration exceeds 20%. The crystal disorder transition of pure PVDF (75°C) is observed also for low HFP concentrations but the transition temperature is strongly reduced. Analogies between the VDF-HFP and E-P systems are also discussed.     

Statics Aware Grid Shells

We introduce a framework for the generation of polygonal gridshell architectural structures, whose topology is designed in order to excel in static performances. We start from the analysis of stress on the input surface and we use the resulting tensor field to induce an anisotropic nonEuclidean metric over it. This metric is derived by studying the relation between the stress tensor over a continuous shell and the optimal shape of polygons in a corresponding gridshell. Polygonal meshes with uniform density and isotropic cells under this metric exhibit variable density and anisotropy in Euclidean space, thus achieving a better distribution of the strain energy over their elements. Meshes are further optimized taking into account symmetry and regularity of cells to improve aesthetics. We experiment with quad meshes and hexdominant meshes, demonstrating that our gridshells achieve better static performances than stateoftheart gridshells.     

Portfolio approaches for constraint optimization problems

Within the Constraint Satisfaction Problems (CSP) context, a methodology that has proven to be particularly performant consists of using a portfolio of different constraint solvers. Nevertheless, comparatively few studies and investigations have been done in the world of Constraint Optimization Problems (COP). In this work, we provide a generalization to COP as well as an empirical evaluation of different state of the art existing CSP portfolio approaches properly adapted to deal with COP. The results obtained by measuring several evaluation metrics confirm the effectiveness of portfolios even in the optimization field, and could give rise to some interesting future research.     

Topological and Variational Properties of a Model for the Reconstruction of Three-Dimensional Transparent Images with Self-Occlusions

We introduce and study a two-dimensional variational model for the reconstruction of a smooth generic solid shape E, which may handle the self-occlusions and that can be considered as an improvement of the 2.1D sketch of Nitzberg and Mumford (Proceedings of the Third International Conference on Computer Vision, Osaka, 1990). We characterize from the topological viewpoint the apparent contour of E, namely, we characterize those planar graphs that are apparent contours of some shape E. This is the classical problem of recovering a three-dimensional layered shape from its apparent contour, which is of interest in theoretical computer vision. We make use of the so-called Huffman labeling (Machine Intelligence, vol. 6, Am. Elsevier, New York, 1971), see also the papers of Williams (Ph.D. Dissertation, 1994 and Int. J. Comput. Vis. 23:93–108, 1997) and the paper of Karpenko and Hughes (Preprint, 2006) for related results. Moreover, we show that if E and F are two shapes having the same apparent contour, then E and F differ by a global homeomorphism which is strictly increasing on each fiber along the direction of the eye of the observer. These two topological theorems allow to find the domain of the functional ℱ describing the model. Compactness, semicontinuity and relaxation properties of ℱ are then studied, as well as connections of our model with the problem of completion of hidden contours.

Driving business performance: innovation complementarities and persistence patterns

Complementarities between technological and non-technological innovation are crucial determinants of firm performance. Although innovation complementarity has been extensively tested in the empirical literature, it has not been analysed in conjunction with innovation persistence. This fact is mainly due to the lack of data sets able to provide adequate longitudinal information. The capacities to develop market-oriented behaviour and introduce new organisational innovations, together with technological innovation, are the drivers of a firm’s productivity and profitability. We find that these activities complement technological innovation and that their impact is greater when they persist over time, thus introducing a more general concept of innovation persistence. We present an empirical model based on a large new panel of Italian manufacturing firms covering the period 2000–2012 which enables us to determine the precise impacts of a firm’s innovative attitude, in a broad definition that incorporates non-technological innovation and persistence, on its productivity and profitability.     

Performance evaluation of efficient multi-objective evolutionary algorithms for design space exploration of embedded computer systems

Multi-objective evolutionary algorithms (MOEAs) have received increasing interest in industry because they have proved to be powerful optimizers. Despite the great success achieved, however, MOEAs have also encountered many challenges in real-world applications. One of the main difficulties in applying MOEAs is the large number of fitness evaluations (objective calculations) that are often needed before an acceptable solution can be found. There are, in fact, several industrial situations in which fitness evaluations are computationally expensive and the time available is very short. In these applications efficient strategies to approximate the fitness function have to be adopted, looking for a trade-off between optimization performance and efficiency. This is the case in designing a complex embedded system, where it is necessary to define an optimal architecture in relation to certain performance indexes while respecting strict time-to-market constraints. This activity, known as design space exploration (DSE), is still a great challenge for the EDA (electronic design automation) community. One of the most important bottlenecks in the overall design flow of an embedded system is due to simulation. Simulation occurs at every phase of the design flow and is used to evaluate a system which is a candidate for implementation. In this paper we focus on system level design, proposing an extensive comparison of the state-of-the-art of MOEA approaches with an approach based on fuzzy approximation to speed up the evaluation of a candidate system configuration. The comparison is performed in a real case study: optimization of the performance and power dissipation of embedded architectures based on a Very Long Instruction Word (VLIW) microprocessor in a mobile multimedia application domain. The results of the comparison demonstrate that the fuzzy approach outperforms in terms of both performance and efficiency the state of the art in MOEA strategies applied to DSE of a parameterized embedded system.     

Product interface design: A participatory approach based on virtual reality

The usability of the user interface is a key aspect for the success of several industrial products. This assumption has led to the introduction of numerous design methodologies addressed to evaluate the user-friendliness of industrial products. Most of these methodologies follow the participatory design approach to involve the user in the design process. Virtual Reality is a valid tool to support Participatory Design, because it facilitates the collaboration among designers and users.The present study aims to evaluate the feasibility and the efficacy of an innovative Participatory Design approach where Virtual Reality plays a ‘double role’: a tool to evaluate the usability of the virtual product interface, and a communication channel that allows users to be directly involved in the design process as co-designers.In order to achieve these goals, we conducted three experiments: the purpose of the first experiment is to determine the influence of the virtual interface on the usability evaluation by comparing “user–real product” interaction and “user–virtual product” interaction. Subsequently, we tested the effectiveness of our approach with two experiments involving users (directly or through their participation in a focus group) in the redesign of a product user interface. The experiments were conducted with two typologies of consumer appliances: a microwave oven and a washing machine.     

Large area forest stem volume mapping in the boreal zone using synergy of ERS-1/2 tandem coherence and MODIS vegetation continuous fields

ERS-1/2 tandem coherence was reported to have high potential for the mapping of boreal forest stem volume (e.g. Santoro et al., 2002, 2007a; Wagner et al., 2003; Askne & Santoro, 2005). Large-scale application of the data for forest stem volume mapping, however, is hindered by the variability of coherence with meteorological and environmental acquisition conditions. The traditional way of stem volume retrieval is based on the training of models, relating coherence to stem volume, with the aid of forest inventory data which is generally available for a few small test sites but not for large areas. In this paper a new approach is presented that allows model training using the MODIS Vegetation Continuous Fields canopy cover product (Hansen et al., 2003) without further need for ground data. A comparison of the new approach with the traditional regression-based and ground-data dependent model training is presented in this paper for a multi-seasonal ERS-1/2 tandem dataset covering several well known Central Siberian forest sites. As a test scenario for large-area application, the approach was applied to a multi-seasonal ERS-1/2 tandem dataset of 223 ERS-1 and ERS-2 image pairs covering Northeast China (~ 1.5 million km²) to map four stem volume classes (0-20, 20-50, 50-80, and > 80 m³/ha).