Effect of the solvent on the conformational behavior of the alanine dipeptide deduced from MD simulations

In general, peptides do not exhibit a well-defined conformational profile in solution. However, despite the experimental blurred picture associated with their structure, compelling spectroscopic evidence shows that peptides exhibit local order. The conformational profile of a peptide is the result of a balance between intramolecular interactions between different atoms of the molecule and intermolecular interactions between atoms of the molecule and the solvent. Accordingly, the conformational profile of a peptide will change upon the properties of the solvent it is soaked. To get insight into the balance between intraand intermolecular interactions on the conformational preferences of the peptide backbone we have studied the conformational profile of the alanine dipeptide in diverse solvents using molecular dynamics as sampling technique. Solvents studied include chloroform, methanol, dimethyl sulfoxide, water and N-methylacetami de. Different treatments of the solvent have been studied in the present work including explicit solvent molecules, a generalized Born model and using the bulk dielectric constant of the solvent. The diverse calculations identify four major conformations with different populations in the diverse solvents: the C-7(eq) only sampled in chloroform; the C-5 or extended conformation; the polyproline (PII) conformation and the right-handed alpha-helix conformation (alpha(R)). The results of present calculations permit to analyze how the balance between intra- and intermolecular interactions explains the populations of the diverse conformations observed. (C) 2017 Elsevier Inc. All rights reserved

Conflict-free strides for vectors in matched memories

Address transformation schemes, such as skewing and linear transformations, have been proposed to achieve conflict-free access to one family of strides in vector processors with matched memories. The paper extends these schemes to achieve this conflict-free access for several families. The basic idea is to perform an out-of-order access to vectors of fixed length, equal to that of the vector registers of the processor. The hardware required is similar to that for the access in order.Peer ReviewedPostprint (author's final draft

Micropulse Transscleral Cyclophotocoagulation: A Hypothesis for the Ideal Parameters

MicroPulse transscleral cyclophotocoagulation (IRIDEX Corp., Mountain View, CA) is a novel technique that uses repetitive micropulses of active diode laser (On cycles) interspersed with resting intervals (Off cycles). It has been proposed that the OFF cycles allow thermal dissipation and, therefore, reduce collateral damage. The literature suggests that Micropulse has a better safety profile compared to traditional continuous-wave cyclophotocoagulation. However, because it is a relatively new technique, there are no clear guidelines stating the ideal laser parameters that would allow the best balance between high and sustained effectiveness with minimal side effects. This research reviewed the literature to approximate ideal parameters for single-session treatment. To simplify the comparison between studies, this study used Joules (J) as a way to standardize the energy levels employed. The reviewed clinical publications allowed reduction of these parameters to a range between 112 and 150 J of total energy, which allows a moderate IOP lowering effect of around 30% with few/no complications. An additional narrowing of the parameters was achieved after analyzing recently published experimental data. These data suggest a different mechanism of action for the Micropulse, similar to that of the pilocarpine. This effect was maximum at 150 J. Since clinical studies show few or no complications, even at those energy levels, it could be hypothesized that the ideal parameters can be located at a point closer to 150 J. This data also leads to the concept of dosimetry; the capacity to dose mTSCPC treatment based on desired IOP lowering effect and risk exposure. Further prospective studies are needed to test the proposed evidence-based hypothesis

Assessment of the Sampling Performance of Multiple-Copy Dynamics versus a Unique Trajectory

The goal of the present study was to ascertain the differential performance of a long molecular dynamics trajectory versus several shorter ones starting from different points in the phase space and covering the same sampling time. For this purpose, we selected the 16-mer peptide Bak(16)BH3 as a model for study and carried out several samplings in explicit solvent. These samplings included an 8 mu s trajectory (sampling Si); two 4 us trajectories (sampling S2); four 2 mu s trajectories (sampling S3); eight 1 mu s trajectories (sampling S4); 16 0.5 mu s trajectories (sampling S5), and 80 0.1 mu s trajectories (sampling S6). Moreover, the 8 mu s trajectory was further extended to 16 pis to have reference values of the diverse properties measured. The diverse samplings were compared qualitatively and quantitatively. Among the former, we carried out a comparison of the conformational profiles of the peptide using cluster analysis. Moreover, we also gained insight into the interchange among these structures along the sampling process. Among the latter, we computed the number of new conformational patterns sampled with time using strings defined from the conformations attained by each of the residues in the peptide. We also compared the locations and depths of the obtained minima on the free energy surface using principal component analysis. Finally, we also compared the helical profiles per residue at the end of the sampling process. The results suggest that a few short molecular dynamics trajectories may provide better sampling than one unique trajectory. Moreover, this procedure can also be advantageous to avoid getting trapped in a local minimum. However, caution should be exercised since short trajectories need to be long enough to overcome local barriers surrounding the starting point and the required sampling time depends on the number of degrees of freedom of the system under study. An effective way to gain insight into the minimum MD trajectory length is to monitor the convergence of different structural features, as shown in the present Wor

Viscoelastic behavior of a polyester resin concrete reinforced with nonmetallic bars under bending loads

This paper deals with the study of a highly durable polyester polymer concrete reinforced with glass fibre reinforced polymer rebars. The paper describes the properties of this specific concrete, which were tested using different experimental techniques such as porosimetry, scanning electron microscopy and petrography. Likewise, characterisation in a macro-scale was carried out to define the mechanical properties of the material (modulus of elasticity, stress-strain curve, ultimate strength and bond). Based on the latter properties, the paper presents a relatively simple method to estimate the ultimate bearing capacity of beams under bending load. The calculation method has been verified by testing beams and full-scale elements. At the end, and due to the viscoelastic nature of the polymer, several considerations will be made in order identify safety factors dependent on the loads nature: permanent loads (deferred deformations) and live loads.Peer ReviewedPostprint (author’s final draft

Micropulse Transscleral Cyclophotocoagulation: A Hypothesis for the Ideal Parameters

MicroPulse transscleral cyclophotocoagulation (IRIDEX Corp., Mountain View, CA) is a novel technique that uses repetitive micropulses of active diode laser (On cycles) interspersed with resting intervals (Off cycles). It has been proposed that the OFF cycles allow thermal dissipation and, therefore, reduce collateral damage. The literature suggests that Micropulse has a better safety profile compared to traditional continuous-wave cyclophotocoagulation. However, because it is a relatively new technique, there are no clear guidelines stating the ideal laser parameters that would allow the best balance between high and sustained effectiveness with minimal side effects. This research reviewed the literature to approximate ideal parameters for single-session treatment. To simplify the comparison between studies, this study used Joules (J) as a way to standardize the energy levels employed. The reviewed clinical publications allowed reduction of these parameters to a range between 112 and 150 J of total energy, which allows a moderate IOP lowering effect of around 30% with few/no complications. An additional narrowing of the parameters was achieved after analyzing recently published experimental data. These data suggest a different mechanism of action for the Micropulse, similar to that of the pilocarpine. This effect was maximum at 150 J. Since clinical studies show few or no complications, even at those energy levels, it could be hypothesized that the ideal parameters can be located at a point closer to 150 J. This data also leads to the concept of dosimetry; the capacity to dose mTSCPC treatment based on desired IOP lowering effect and risk exposure. Further prospective studies are needed to test the proposed evidence-based hypothesis

The molar extinction coefficient of bacteriochlorophyll e and the pigment stoichiometry in Chlorobium phaeobacteroides

We have determined the molar extinction coefficient of bacteriochlorophyll (BChl) e, the main light-harvesting pigment from brown-coloured photosynthetic sulfur bacteria. The extinction coefficient was determined using pure[Pr,E]BChl eF isolated by reversed-phase HPLC from crude pigment extracts of Chlorobium (Chl.) phaeobacteroides strain CL1401. The extinction coefficients at the Soret and Qy bands were determined in four organic solvents. The extinction coefficient of BChl e differs from those of other related Chlorobium chlorophylls (BChl c and BChl d) but is similar to that of chlorophyll b. The determined extinction coefficient was used to calculate the stoichiometric BChl e to BChl a and BChl e to carotenoids ratios in whole cells and isolated chlorosomes from Chl. phaeobacteroides strain CL1401 using the spectrum-reconstruction method (SRCM) described by Naqvi et al. (1997) (Spectrochim Acta A Mol Biomol Spectrosc 53: 2229–2234). In isolated chlorosomes, BChl a content was ca. 1% of the total BChl content and the stoichiometric ratio of BChl e to carotenoids was 6. In whole cells,however, BChl a content was 3–4%, owing to the presence of BChl a-containing elements, i.e. FMO protein and reaction centre. An average of 5 BChl e molecules per carotenoid was determined in whole cells.EU(Contract No FMRX–CT96–0081). Ministerio de Educación y Ciencia (Ref. BIO96–1229–002–01)Peer reviewe

Synchronization waves in geometric networks

We report synchronization of networked excitable nodes embedded in a metric space, where the connectivity properties are mostly determined by the distance between units. Such a high clustered structure, combined with the lack of long-range connections, prevents full synchronization and yields instead the emergence of synchronization waves. We show that this regime is optimal for information transmission through the system, as it enhances the options of reconstructing the topology from the dynamics. Measurements of topological and functional centralities reveal that the wave-synchronization state allows detection of the most structurally relevant nodes from a single observation of the dynamics, without any a priori information on the model equations ruling the evolution of the ensembl

Fragment Dissolved molecular dynamics: A systematic and efficient method to locate binding sites.

Fragment-based drug discovery (FBDD) has been popular in the last decade, but some drawbacks, such as protein denaturation or ligand aggregation, have not yet clearly overcome in the framework of biomolecular simulations. In this work a systematic and semi-automatic method is presented as a novel proposal, named fragment dissolved Molecular Dynamics (fdMD), to improve research in future FBDD projects. Our method employs simulation boxes of solvated small fragments, adding a repulsive Lennard-Jones potential term to avoid aggregation, which can be easily used to solvate the object of interest. This method has the advantage of solvating the target with a low number of ligands, thus preventing this way denaturation of the target, while simultaneously generating a database of ligand-solvated boxes that can be used with other targets. A number of scripts are made available to analyze the results and obtain the descriptors proposed as a means of trustfully discard spurious binding sites. To test our method, four sets of different complexity have been solvated with ligand boxes and four molecular dynamics runs of 200 ns length have been run for each system, which have been extended up to 1 μs when needed. The reported results point that the selected number of replicas are enough to identify the correct binding sites irrespective of the initial structure, even in the case of proteins having several close binding sites for the same ligand. Among the proposed descriptors, average MMGBSA and average KDEEP energies emerge as the most robust ones

Calculation methods of Radon-222 radiological activity for NORM plant with ventilation

A procedure is proposed to determine the radiological activity of air present in the working area of a NORM (Naturally-Occurring Radioactive Materials) plant. This NORM plant is located in the United Arab Emirates and is dedicated to the recycling of material and equipment used in oil extraction facilities. Substantial quantities of NORM waste will be present inside the enclosed plant facilities and will exhale significant amounts of Radon-222 into the working environment. The continued inhalation of this gas and its progeny has been shown to cause lung cancer. In order to reduce the concentration level of the aforementioned gas to an acceptable regulatory value, the best solution is by means of mechanical ventilation. The two calculation methods used to analysis the relationship between the ventilation rate and the degree of radioactive contamination are considered. The first being ventilation by perfect dilution, commonly employed in industrial environments with radiological contamination. The second method of analysis is by means of a CFD (Computational Fluid Dynamics) which permits a more precise calculation of the required fresh air quantity and spatial concentrations. Validation was carried out in a small experimental plant space, obtaining results reasonable approximate to those predicted by the computational analysis. The similarities and differences between the respective calculation methods and their respective fields of application are analyzed. It is concluded that for lower air change rates, less than five air changes per hour, the CFD analysis is the most appropriate method. By contrast, when using a higher rate of outside air changes in the plant, the perfect dilution method should be sufficient enough to control the presence of radon and its progeny. Both calculation methods consider the activity of radon and the activity of the most significant radioisotopes of its progeny