An ensemble evolutionary constraint-based approach to understand the emergence of metabolic phenotypes

Constraint-based modeling is largely used in computational studies of metabolism. We propose here a novel approach that aims to identify ensembles of flux distributions that comply with one or more target phenotype(s). The methodology has been tested on a small-scale model of yeast energy metabolism. The target phenotypes describe the differential pattern of ethanol production and O₂ consumption observed in “Crabtree-positive” and “Crabtree-negative” yeasts in changing environment (i.e., when the upper limit of glucose uptake is varied). The ensembles were obtained either by selection among sampled flux distributions or by means of a search heuristic (genetic algorithm). The former approach provided indication about the probability to observe a given phenotype, but the resulting ensembles could not be unambiguously partitioned into “Crabtree-positive” and “Crabtree-negative” clusters. On the contrary well-separated clusters were obtained with the latter method. The cluster analysis further allowed identification of distinct groups within each target phenotype. The method may thus prove useful in characterizing the design principles underlying metabolic plasticity arising from evolving physio-pathological or developmental constraints.     

Alder ene functionalization of polyisobutene oligomer and styrene-butadiene-styrene triblock copolymer

The Alder ene functionalization reaction of double bonds containing macromolecules such as polyisobutene oligomer (PIB) and a styrene-butadiene-styrene triblock copolymer (SBS) samples with maleic anhydride (MAH) or diethyl maleate (DEM) as enophiles is described. The analysis of the products by means of different techniques assesses the addition of the polar molecules to the reactive vinylidene units of the polymer with functional degrees (FD) depending on the type of enophile and polymer reactivity. The role of the reaction conditions and the use as Lewis acids as catalysts are discussed in terms of their influence on the addition reaction extent and on the polymer molecular weight.     

Sequence analysis and fiber properties of a blend of poly(ethylene terephthalate) and poly(ethylene terephthalate‐co‐4,4′‐bibenzoate)

Blends of poly(ethylene terephthalate) (PET) and poly(ethylene terephthalate‐co‐4,4′‐ bibenzoate) (PETBB) are prepared by coextrusion. Analysis by ¹³C‐NMR spectroscopy shows that little transesterification occurs during the blending process. Additional heat treatment of the blend leads to more transesterification and a corresponding increase in the degree of randomness, R. Analysis by differential scanning calorimetry shows that the as‐extruded blend is semicrystalline, unlike PETBB15, a random copolymer with the same composition as the non‐ random blend. Additional heat treatment of the blend leads to a decrease in the melting point, T_m, and an increase in glass transition temperature, T_g. The T_m and T_g of the blend reach minimum and maximum values, respectively, after 15 min at 270°C, at which point the blend has not been fully randomized. The blend has a lower crystallization rate than PET and PETBB55 (a copolymer containing 55 mol % bibenzoate). The PET/PETBB55 (70/30 w/w) blend shows a secondary endothermic peak at 15°C above an isothermal crystallization temperature. The secondary peak was confirmed to be the melting of small and/or imperfect crystals resulting from secondary crystallization. The blend exhibits the crystal structure of PET. Tensile properties of the fibers prepared from the blend are comparable to those of PET fiber, whereas PETBB55 fibers display higher performance. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1793–1803, 2004     

A bio-inspired predictive sensory-motor coordination scheme for robot reaching and preshaping

This paper presents a sensory-motor coordination scheme for a robot hand-arm-head system that provides the robot with the capability to reach an object while pre-shaping the fingers to the required grasp configuration and while predicting the tactile image that will be perceived after grasping. A model for sensory-motor coordination derived from studies in humans inspired the development of this scheme. A peculiar feature of this model is the prediction of the tactile image. The implementation of the proposed scheme is based on a neuro-fuzzy module that, after a learning phase, starting from visual data, calculates the position and orientation of the hand for reaching, selects the best-suited hand configuration, and predicts the tactile feedback. The implementation of the scheme on a humanoid robot allowed experimental validation of its effectiveness in robotics and provided perspectives on applications of sensory predictions in robot motor control.     

Fibroblast protein profile analysis highlights the role of oxidative stress and vitamin K recycling in the pathogenesis of pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is a genetic disorder associated to mutations in the ABCC6 gene; however, the pathogenetic mechanisms leading to elastic fibre calcifications and to clinical manifestations are still unknown. Dermal fibroblasts, directly involved in the production of the extracellular milieu, have been isolated from healthy subjects and from patients affected by PXE, cultured in vitro and characterized for their ability to produce reactive oxygen species, for structural and functional properties of their cell membranes, for changes in their protein profile. Data demonstrate that oxidative stress has profound and endurable consequences on PXE fibroblast phenotype being responsible for: reduced levels of global DNA methylation, increased amount of carbonylated proteins and of lipid peroxidation products, altered structural properties of cell membranes, modified protein expression. Data shed new light on the pathogenetic pathways in PXE, by identifying a network of proteins affecting elastic fibre calcification through inefficient vitamin K recycling, and highlight the role of differentially expressed proteins as targets for validating the efficacy of future therapeutic strategies aiming to delay and/or revert the pathologic phenotype of PXE fibroblasts. Moreover, data open new perspectives for investigating PXE-like phenotypes in the absence of ABCC6 mutations.     

Secondary bioreceptivity of granite: effect of salt weathering on subaerial biofilm growth

Salt crystallisation is a very common and powerful weathering agent that can modify the petrophysical properties of building stone such as granite. In addition, the weathering can affect the susceptibility of the stone to biological colonisation. The aims of the present study were to examine the properties of a granite weathered by sodium chloride crystallisation and to evaluate the effects of the weathering on the secondary bioreceptivity of the stone to subaerial phototrophic biofilms. For this purpose, granite samples were subjected to a laboratory-based accelerated salt weathering test, and changes in weight, open porosity, bulk density, capillary water content, abrasion pH and surface roughness of the samples were determined. Samples of both weathered and non-weathered granite were then inoculated with a multi-species phototrophic culture derived from a natural subaerial biofilm and incubated under standardised laboratory conditions for 3 months. The weight loss produced by the weathering process was consistent with significant changes in abrasion pH and surface roughness. The bioreceptivity of the stone was also altered. According to the bioreceptivity index, the granite under study was characterised by ‘mild primary bioreceptivity’, but ‘high secondary bioreceptivity’ after the salt weathering process. Study of the secondary bioreceptivity of stone materials can provide very useful information about response to weathering effects, and the findings can be used to improve the selection of materials for building purposes.     

A model checking-based approach for security policy verification of mobile systems

This article describes an approach for the automated verification of mobile systems. Mobile systems are characterized by the explicit notion of location (e.g., sites where they run) and the ability to execute at different locations, yielding a number of security issues. To this aim, we formalize mobile systems as Labeled Kripke Structures, encapsulating the notion of location net that describes the hierarchical nesting of the threads constituting the system. Then, we formalize a generic security-policy specification language that includes rules for expressing and manipulating the code location. In contrast to many other approaches, our technique supports both access control and information flow specification. We developed a prototype framework for model checking of mobile systems. It works directly on the program code (in contrast to most traditional process-algebraic approaches that can model only limited details of mobile systems) and uses abstraction-refinement techniques, based also on location abstractions, to manage the program state space. We experimented with a number of mobile code benchmarks by verifying various security policies. The experimental results demonstrate the validity of the proposed mobile system modeling and policy specification formalisms and highlight the advantages of the model checking-based approach, which combines the validation of security properties with other checks, such as the validation of buffer overflows.     

Semantics-driven annotation of patient-specific 3D data: a step to assist diagnosis and treatment of rheumatoid arthritis

In the digital era, patient-specific 3D models (3D-PSMs) are becoming increasingly relevant in computer-assisted diagnosis, surgery training on digital models, or implant design. While advanced imaging and reconstruction techniques can create accurate and detailed 3D models of patients’ anatomy, software tools that are able to fully exploit the potential of 3D-PSMs are still far from being satisfactory. In particular, there is still a lack of integrated approaches for extracting, coding, sharing and retrieving medically relevant information from 3D-PSMs and use it concretely as a support to diagnosis and treatment. In this article, we propose the SemAnatomy3D framework, which demonstrates how the ontology-driven annotation of 3D-PSMs and of their anatomically relevant features (parts of relevance) can assist clinicians to document more effectively pathologies and their evolution. We exemplify the idea in the context of the diagnosis of rheumatoid arthritis of the hand district, and show how feature extraction tools and semantic 3D annotation can provide a rich characterization of anatomical landmarks (e.g., articular facets, prominent features, ligament attachments) and pathological markers (erosions, bone loss). The core contributions are an ontology-driven part-based annotation method for the 3D-PSMs and a novel automatic localization of erosion and quantification of the OMERACT RAMRIS erosion score. Finally, our results have been compared against a medical ground truth.     

Firms’ involvement in Open Source projects: A trade-off between software structural quality and popularity

Open Source (OS) was born as a pragmatic alternative to the ideology of Free Software and it is now increasingly seen by companies as a new approach to developing and making business upon software. Whereas the role of firms is clear for commercial OS projects, it still needs investigation for projects based on communities. This paper analyses the impact of firms’ participation on popularity and internal software design quality for 643 SourceForge.net projects. Results show that firms’ involvement improves the ranking of OS projects, but, on the other hand, puts corporate constraints to OS developing practices, thus leading to lower structural software design quality.