Molecular modelling studies of binding of DACD derivatives into G-Quadruplex DNA: comparison of force field and quantum polarized ligand docking methods

The DNA G-qadruplexes are one of the targets being actively explored for anti-cancer therapy by inhibiting them through small molecules. This computational study was conducted to predict the binding strengths and orientations of a set of novel dimethyl-amino-ethyl-acridine (DACA) analogues that are designed and synthesized in our laboratory, but did not diffract in Synchrotron light.Thecrystal structure of DNA G-Quadruplex(TGGGGT)4(PDB: 1O0K) was used as target for their binding properties in our studies.We used both the force field (FF) and QM/MM derived atomic charge schemes simultaneously for comparing the predictions of drug binding modes and their energetics. This study evaluates the comparative performance of fixed point charge based Glide XP docking and the quantum polarized ligand docking schemes. These results will provide insights on the effects of including or ignoring the drug-receptor interfacial polarization events in molecular docking simulations, which in turn, will aid the rational selection of computational methods at different levels of theory in future drug design programs. Plenty of molecular modelling tools and methods currently exist for modelling drug-receptor or protein-protein, or DNA-protein interactionssat different levels of complexities.Yet, the capasity of such tools to describevarious physico-chemical propertiesmore accuratelyis the next step ahead in currentresearch.Especially, the usage of most accurate methods in quantum mechanics(QM) is severely restricted by theirtedious nature. Though the usage of massively parallel super computing environments resulted in a tremendous improvement in molecular mechanics (MM) calculations like molecular dynamics,they are still capable of dealing with only a couple of tens to hundreds of atoms for QM methods. One such efficient strategy that utilizes thepowers of both MM and QM are the QM/MM hybrid methods. Lately, attempts have been directed towards the goal of deploying several different QM methods for betterment of force field based simulations, but with practical restrictions in place. One of such methods utilizes the inclusion of charge polarization events at the drug-receptor interface, that is not explicitly present in the MM FF.

Iterative Methods for Equality-Constrained Least Squares Problems

We consider the linear equality-constrained least squares problem (LSE) of minimizing ${\|c - Gx\|}_2 $, subject to the constraint $Ex = p$. A preconditioned conjugate gradient method is applied to the Kuhn–Tucker equations associated with the LSE problem. We show that our method is well suited for structural optimization problems in reliability analysis and optimal design. Numerical tests are performed on an Alliant FX/8 multiprocessor and a Cray-X-MP using some practical structural analysis data.

The Impact of office productivity cloud computing on energy consumption and greenhouse gas emissions

Cloud computing is usually regarded as being energy efficient and thus emitting less greenhouse gases (GHG) than traditional forms of computing. When the energy consumption of Microsoft’s cloud computing Office 365 (O365) and traditional Office 2010 (O2010) software suites were tested and modeled, some cloud services were found to consume more energy than the traditional form. The developed model in this research took into consideration the energy consumption at the three main stages of data transmission; data center, network, and end user device. Comparable products from each suite were selected and activities were defined for each product to represent a different computing type. Microsoft provided highly confidential data for the data center stage, while the networking and user device stages were measured directly. A new measurement and software apportionment approach was defined and utilized allowing the power consumption of cloud services to be directly measured for the user device stage. Results indicated that cloud computing is more energy efficient for Excel and Outlook which consumed less energy and emitted less GHG than the standalone counterpart. The power consumption of the cloud based Outlook (8%) and Excel (17%) was lower than their traditional counterparts. However, the power consumption of the cloud version of Word was 17% higher than its traditional equivalent. A third mixed access method was also measured for Word which emitted 5% more GHG than the traditional version. It is evident that cloud computing may not provide a unified way forward to reduce energy consumption and GHG. Direct conversion from the standalone package into the cloud provision platform can now consider energy and GHG emissions at the software development and cloud service design stage using the methods described in this research.

Computing Fresnel integrals via modified trapezium rules

In this paper we propose methods for computing Fresnel integrals based on truncated trapezium rule approximations to integrals on the real line, these trapezium rules modified to take into account poles of the integrand near the real axis. Our starting point is a method for computation of the error function of complex argument due to Matta and Reichel (J Math Phys 34:298–307, 1956) and Hunter and Regan (Math Comp 26:539–541, 1972). We construct approximations which we prove are exponentially convergent as a function of N , the number of quadrature points, obtaining explicit error bounds which show that accuracies of 10−15 uniformly on the real line are achieved with N=12 , this confirmed by computations. The approximations we obtain are attractive, additionally, in that they maintain small relative errors for small and large argument, are analytic on the real axis (echoing the analyticity of the Fresnel integrals), and are straightforward to implement.

Advanced feature selection methods in multinominal dementia classification from structural MRI data

Recent studies showed that features extracted from brain MRIs can well discriminate Alzheimer’s disease from Mild Cognitive Impairment. This study provides an algorithm that sequentially applies advanced feature selection methods for findings the best subset of features in terms of binary classification accuracy. The classifiers that provided the highest accuracies, have been then used for solving a multi-class problem by the one-versus-one strategy. Although several approaches based on Regions of Interest (ROIs) extraction exist, the prediction power of features has not yet investigated by comparing filter and wrapper techniques. The findings of this work suggest that (i) the IntraCranial Volume (ICV) normalization can lead to overfitting and worst the accuracy prediction of test set and (ii) the combined use of a Random Forest-based filter with a Support Vector Machines-based wrapper, improves accuracy of binary classification.

Plane wave discontinuous Galerkin methods: exponential convergence of the hp-version

We consider the two-dimensional Helmholtz equation with constant coefficients on a domain with piecewise analytic boundary, modelling the scattering of acoustic waves at a sound-soft obstacle. Our discretisation relies on the Trefftz-discontinuous Galerkin approach with plane wave basis functions on meshes with very general element shapes, geometrically graded towards domain corners. We prove exponential convergence of the discrete solution in terms of number of unknowns.

Colonisation of soft lining materials by micro-organisms

Objective:This study evaluated the in vitro adherence of pathogenic micro-organisms, Candida albicans, Staphylococcus aureus and Pseudomonas aeruginosa, to soft lining materials and their inhibitory effect on these micro-organisms.Materials and Methods:To measure adherence, specimens of Molloplast B and Ufi Gel P were inoculated [107 colony-forming units per millimetre (cfu/ml)] with TSB media containing the micro-organisms. To determine the number of micro-organisms in the 10-2-10-5 dilutions, 25 mu l of the suspension were transferred to plates of selective media. Colony counts of each specimen were quantified (cfu/ml). The surface roughness was measured with a perfilometer to assess the relationship between the adherence of micro-organisms and surface roughness of each material. For the inhibition test, specimens of materials were placed in agar plates inoculated individually with the micro-organisms. After 48 h, the inhibition zones around the specimens were measured.Results:None of the materials exhibited inhibition zones. The number of cfu/ml of S. aureus and P. aeruginosa were significantly greater than C. albicans for both materials. The Ufi Gel P exhibited greater adherence of C. albicans than Molloplast B. No correlation was observed between the adherence of micro-organisms and surface roughness.Conclusion:The surface roughness of the materials is not the only factor governing micro-organism adherence.

Effect of thermocycling on hardness, absorption, solubility and colour change of soft liners

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

MATHEMATICA notebook for computing tetrahedral finite element shape functions and matrices for the Helmholtz equation

A MATHEMATICA notebook to compute the elements of the matrices which arise in the solution of the Helmholtz equation by the finite element method (nodal approximation) for tetrahedral elements of any approximation order is presented. The results of the notebook enable a fast computational implementation of finite element codes for high order simplex 3D elements reducing the overheads due to implementation and test of the complex mathematical expressions obtained from the analytical integrations. These matrices can be used in a large number of applications related to physical phenomena described by the Poisson, Laplace and Schrodinger equations with anisotropic physical properties.

Effect of an experimental 4% titanium tetrafluoride varnish on dental erosion by a soft drink

Objectives: This in vitro study assessed the effect of an experimental 4%TiF4 varnish on enamel erosion.Methods: Sixty bovine enamel blocks were randomly allocated to each type of varnish:Duraphat((R)) -D (NaF, 2.26%F), Duofluorid((R))-F(NaF, 2.71% F), TiF4-T(2.45%F) and no-fluoride-P. After application of the varnishes, the blocks were subjected to six sequential pH cycles (cola drink for 10 min and artificial saliva for 50 min, each) per day, during 4 days. After the pH cycles, the blocks were maintained in artificial saliva for 18 h. Enamel alterations were determined in the 2nd and 4th days, using profilometry (wear) and microhardness (%SMHC) tests. Data were tested using ANOVA and Tukey's tests (p < 0.05).Results: the mean %SMHC (+/- S.D.) at the 2nd and 4th day was, respectively, D (-77.26 +/- 5.04(a) and -88.59 +/- 5.11(A)), F (-76.79 +/- 7.82(a) and -88.78 +/- 6.10(A)), T(-88.28 +/- 3.19(b) and -92.04 +/- 2.54(A,B)) and P (-87.96 +/- 2.23(b) and -94.15 +/- 1.14(B)). The mean wear (mu m +/- S.D.) at the 2nd and 4th day was, respectively, D (3.16 +/- 0.32(a) and 7.56 +/- 0.90(A)), F(3.35 +/- 0.78(a,b) and 7.92 +/- 0.98(A)), T (3.81 +/- 0.43(b) and 7.69 +/- 0.76(A)) and P (3.43 +/- 1.13(a,b) and 7.31 +/- 0.53(A)).Conclusions: the NaF varnishes reduced the softening, but had no effect on the reduction of the wear. The TiF4 varnish was not able to reduce the softening and wear. (C) 2007 Elsevier Ltd. All rights reserved.

Effect of thermocycling on bond strength and elasticity of 4 long-term soft denture liners

Statement of problem. Two problems found in prostheses with soft liners are bond failure to the acrylic resin base and loss of elasticity due to material aging.Purpose. This in vitro study evaluated the effect of thermocycling on the bond strength and elasticity of 4 long-term soft denture liners to acrylic resin bases.Material and methods. Four soft lining materials (Molloplast-B, Flexor, Permasoft, and Pro Tech) and 2 acrylic resins (Classico, and Lucitone 199) were processed for testing according to manufacturers' instructions. Twenty rectangular specimens (10 X 10-mm(2) cross-sectional area) and twenty cylinder specimens (12.7-mm diameter X 19.0-mm height) for each liner/resin combination were used for the tensile and deformation tests, respectively. Specimen shape and liner thickness were standardized. Samples were divided into a test group that was thermocycled 3000 times and a control group that was stored for 24 hours in water at 37degreesC. Mean bond strength, expressed in megapascals (Wa), was determined in the tensile test with the use of a universal testing machine at a crosshead speed of 5 mm/min. Elasticity, expressed as percent of permanent deformation, was calculated with an instrument for measuring permanent deformation described in ADA/ANSI specification 18. Data from both tests were examined with 1-way analysis of variance and a Tukey test, with calculation of a Scheffe interval at a 95% confidence level.Results. In the tensile test under control conditions, Molloplast-B (1.51 +/- 0.28 MPa [mean SD]) and Pro Tech (1.44 +/- 0.27 MPa) liners had higher bond strength values than the others (P < .05). With regard to the permanent deformation test, the lowest values were observed for Molloplast-B (0.48% +/- 0.19%) and Flexor (0.44% +/- 0.14%) (P < .05). Under thermocycling conditions, the highest bond strength occurred with Molloplast-B (1.37 +/- 0.24 MPa) (P < .05) With regard to the deformation test, Flexor (0.46% +/- 0.13%) and Molloplast-B (0.44% +/- 0.17%) liners had lower deformation values than the others (P < .05).Conclusion. The results of this in vitro study indicated that bond strength and permanent deformity values of the 4 soft denture liners tested varied according to their chemical composition. These tests are not completely valid for application to dental restorations because the forces they encounter are more closely related to shear and tear. However, the above protocol serves as a good method of investigation to evaluate differences between thermocycled and control groups.

On the dissimilarity between the algorithms for computing the symmetric energy-momentum tensor in ordinary field theory and general relativity

The recipe used to compute the symmetric energy-momentum tensor in the framework of ordinary field theory bears little resemblance to that used in the context of general relativity, if any. We show that if one stal ts fi om the field equations instead of the Lagrangian density, one obtains a unified algorithm for computing the symmetric energy-momentum tensor in the sense that it can be used for both usual field theory and general relativity.

Development of metal oxide nanoparticles by soft chemical method

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of implants with different sizes and configurations installed immediately into extraction sockets on peri-implant hard and soft tissues: an experimental study in dogs

Aim: To study the influence on the healing of soft and hard peri-implant tissues when implants of different sizes and configurations were installed into sockets immediately after tooth extraction.Material and methods: Transmucosal cylindrical implants, 3.3 mm in diameter in the control sites, and conical 5 mm in diameter in the test sites, were installed into the distal socket of the fourth mandibular premolars in dogs immediately after tooth extraction. After 4 months, the hard and soft tissue healing was evaluated histologically. Results: All implants were integrated in mineralized mature bone. Both at the test and control sites, the alveolar crest underwent resorption. The buccal bony surface at the implant test sites (conical; 3.8 mm) was more resorbed compared with the control sites (cylindrical; 1.6 mm). The soft tissue dimensions were similar in both groups. However, in relation to the implant shoulder, the peri-implant mucosa was located more apically at the test compared with the control sites.Conclusion: The present study confirmed that the distance between the implant surface and the outer contour of the buccal alveolar bony crest influenced the degree of resorption of the buccal bone plate. Consequently, in relation to the implant shoulder, the peri-implant mucosa will be established at a more apical level, if the distance between the implant surface and the outer contour of the alveolar crest is small.