A molecular dynamics and knowledge-based computational strategy to predict native-like structures of polypeptides

One of the main research problems in structural bioinformatics is the prediction of three-dimensional structures (3-D) of polypeptides or proteins. The current rate at which amino acid sequences are identified increases much faster than the 3-D protein structure determination by experimental methods, such as X-ray diffraction and NMR techniques. The determination of protein structures is both experimentally expensive and time consuming. Predicting the correct 3-D structure of a protein molecule is an intricate and arduous task. The protein structure prediction (PSP) problem is, in computational complexity theory, an NP-complete problem. In order to reduce computing time, current efforts have targeted hybridizations between ab initio and knowledge-based methods aiming at efficient prediction of the correct structure of polypeptides. In this article we present a hybrid method for the 3-D protein structure prediction problem. An artificial neural network knowledge-based method that predicts approximated 3-D protein structures is combined with an ab initio strategy. Molecular dynamics (MD) simulation is used to the refinement of the approximated 3-D protein structures. In the refinement step, global interactions between each pair of atoms in the molecule (including non-bond interactions) are evaluated. The developed MD protocol enables us to correct polypeptide torsion angles deviation from the predicted structures and improve their stereo-chemical quality. The obtained results shows that the time to predict native-like 3-D structures is considerably reduced. We test our computational strategy with four mini proteins whose sizes vary from 19 to 34 amino acid residues. The structures obtained at the end of 32.0 nanoseconds (ns) of MD simulation were comparable topologically to their correspondent experimental structures.     

Simulation tool for prediction of cutting forces and surface quality of micro-milling processes

The improvement of micro-milling processes implies the application of advanced analysis and modeling techniques to derive a deeper process understanding. Because of micro-scale effects, monitoring, and measurement systems applied in conventional milling are in most cases not suitable for identifying optimal cutting conditions. Therefore, analytical and mechanical models have been developed in recent years to account for impact factors dominating the micro-milling errors. Within the research presented in this publication, geometric, kinematic, and dynamic models have been adjusted and dimensioned according to the dominating impact factors in micro-milling and have been consolidated to enable for a time-domain simulation. The effect of element size of discretized workpiece and tool as well as the time step size on cutting forces has been evaluated. The accuracy of predicting cutting forces has been investigated and a good agreement of measured and simulated cutting forces has been found. Finally, a mold for a micro-fluidic device has been machined virtually and experimentally to evaluate the accuracy of the integrated models in predicting the final quality of a micro-milled part in terms of surface quality parameters.     

Influence of environmental temperature on composition of lipids in edible flesh of rainbow trout (Oncorhynchus mykiss)

The adaptative changes in the fatty acid composition of the main lipid classes in rainbow trout (Oncorhynchus mykiss) edible flesh in response to environmental variation in water temperature were investigated. The research was carried out on intensively farmed trout sampled at different times of the year. Neutral lipids (NL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were separated using flash chromatography. Compared with summer acclimatisation, a decrease in neutral lipids of about 19% was observed in winter, accompanied by increases in phosphatidylethanolamine and phosphatidylcholine of about 41 and 29%, respectively. The metabolic adjustment in cold adaptation caused an increase in the levels of unsaturated fatty acids and monoenes of the oleic acid ω9 family and an increase in the levels of unsaturated fatty acids of the linoleic acid ω3 family. At the same time a reduction in the levels of saturated and monounsaturated fatty acids of the oleic acid ω9 family was observed. This pattern turned out to be particularly evident in phosphatidylcholine. The net result of these changes in composition was a significant increase in the polyunsaturated/saturated and polyunsaturated/monoenic fatty acid ratios in the edible flesh. Copyright © 2003 Society of Chemical Industry     

Knowledge networks and industrial structure for regional innovation: An analysis of patents collaborations in Italy

The aim of the research is to investigate whether the structure of knowledge networks and the variety of the local industrial structure are important for regional innovation and if the interplay between these two forces has an additional effect on local innovativeness. The research analyses co-patenting collaborations at firm level in the Italian provinces in three five-year intervals in the period 2001–2016. Results show that the structure of knowledge networks and agglomeration economies of inventors boost local inventive capacity. It also highlights how these forces have an increasing impact on innovation as the variety of the area increases.     

MAPKs and Signal Transduction in the Control of Gastrointestinal Epithelial Cell Proliferation and Differentiation

Mitogen-activated protein kinase (MAPK) pathways are activated by several stimuli and transduce the signal inside cells, generating diverse responses including cell proliferation, differentiation, migration and apoptosis. Each MAPK cascade comprises a series of molecules, and regulation takes place at different levels. They communicate with each other and with additional pathways, creating a signaling network that is important for cell fate determination. In this review, we focus on ERK, JNK, p38 and ERK5, the major MAPKs, and their interactions with PI3K-Akt, TGFβ/Smad and Wnt/β-catenin pathways. More importantly, we describe how MAPKs regulate cell proliferation and differentiation in the rapidly renewing epithelia that lines the gastrointestinal tract and, finally, we highlight the recent findings on nutritional aspects that affect MAPK transduction cascades.     

Influence of the arc length on metal transfer in the single potential double-wire MIG/MAG process

The search for competitiveness in the modern industries, represented by demands for higher productivity and cost reduction, leads to investment in new technologies. This is the context in which the double-wire MIG/MAG process was conceived; the idea was to design a process that combines the versatile features of the MIG/MAG process with the high productivity of the submerged arc process. The objective of this work was to evaluate the influence of different arc lengths, at the same current level, on the metal transfer modes and the bead geometry profiles. Using equipment consisting of two linked power sources and a torch with single electrical potential, the series of welds was carried out at three different arc length conditions.

A methodology to obtain different arc lengths at the same current and wire-feed speed levels was proposed and validated. The metal transfer was observed using the shadowgraph technique with a high-speed camera, while the geometry was evaluated from macrographies of weld bead transversal sections. A trend in transfer mode changes was observed from short circuit to spray for the highest arc lengths, and to a much higher attraction between the drops. This change in the transfer mode implies better beads finishing and higher thermal and deposition efficiencies.     

Influence of welding current in plasma–MIG weld process on the bead weld geometry and wire fusion rate

One of the versions of the plasma–metal inert gas (MIG) process is basically a combination of a plasma arc with a MIG/metal active gas (MAG) arc in a single torch. With this association, the advantages of each arc are combined. The main characteristic of this is the independence between the heat input by the process and the deposited material, resulting in greater facility to control bead weld geometry. In the current literature, there is a shortage of information related to the process, and most of this goes back to the 1970s and 1980s when the technology available was not able to make the process viable for industry. However, in recent years, the use of the diffusion of new electronic power sources used in welding has sparked up again the interest in plasma–MIG process. In this context, this paper aims to contribute to the studies related to the influence of the MIG and plasma current balance on the geometry of the bead weld and wire fusion rate. Bead-on-plate welds were carried out with plasma and MIG/MAG current combinations at three levels each, keeping, by welding speed corrections, the bead volume the same. It was observed that the introduction of the plasma current over the MIG/MAG current reduces penetration and dilution and leads to convex beads. On the other hand, the use of plasma current increases the MIG/MAG wire fusion rate. However, it seems that the intensity of the plasma current is not the governing parameter of those changes.     

A model-based deconvolution approach to solve fiber crossing in diffusion-weighted MR imaging

A deconvolution approach is presented to solve fiber crossing in diffusion magnetic resonance imaging. In order to provide a direct physical interpretation of the signal generation process, we started from the classical multicompartment model and rewrote this in terms of a convolution process, identifying a significant scalar parameter alpha to characterize the physical system response. Deconvolution is performed by a modified version of the Richardson-Lucy algorithm. Simulations show the ability of this method to correctly separate fiber crossing, even in the presence of noisy data, with lower signal-to-noise ratio, and imprecision in the impulse response function imposed during deconvolution. The in vivo data confirms the efficacy of this method to resolve fiber crossing in real complex brain structures. These results suggest the usefulness of our approach in fiber tracking or connectivity studies.     

Antifungal activity of 9-hydroxy-folianin and sucrose octaacetate from the seeds of Annona cornifolia A. St. -Hil. (Annonaceae)

In this study, 9-hydroxy-folianin and sucrose octaacetate were isolated from the seed ethanol extract of Annona cornifolia A. St. -Hil. (Annonaceae). We found that 9-hydroxy-folianin was able to inhibit several clinical strains of the pathogenic fungus Paracoccidioides brasiliensis. The minimal inhibitory concentrations of 9-hydroxy-folianin against twelve clinical strains of P. brasiliensis were found to be in the range between 3.4 and 27.7 ??g mL⁻¹ and were much more potent than the commercial antifungal trimethropin-sulfamethoxazole. P. brasiliensis isolates (Pb-18, Pb-11, Pb-01, Pb-B339, Pb-8 and Pb-18 virulent) were also susceptible to sucrose octaacetate. The growth of Candida albicans, C. tropicalis, C. parapsilosis and Cryptococcus gattii were not affected by these compounds. Sucrose octaacetate and 9-hydroxy-folianin showed no effects with amphotericin B and trimethropin-sulfamethoxazole, but they displayed a synergetic effect with itraconazole.