Hygrothermal effects on painted carbon fibre composite surfaces

In this article, the effect of hygrothermal aging on the painted surface finish of unidirectional and fabric carbon fibre composite laminates, with and without surfacing film was investigated. The results highlighted the importance of ensuring that the composite surface directly beneath the paint layer is made from a uniform material with a consistent thickness in order to minimise surface defects from occurring during aging. The surfacing film was found to minimise the print through development on the painted unidirectional and twill composite surfaces. However, the surfacing film layer was found to intermingle with the carbon fibre plies during cure, which resulted in an uneven film thickness that caused increased levels of orange peel. The twill laminate painted surface produced high levels of print through and surface waviness that was caused by the large resin rich regions located within the tow intersections at the surface which enlarged due to thermal expansion and swelling of the matrix with hygrothermal aging. It was also noted that the small resin rich regions between the individual carbon fibres on the unidirectional composite surface were sufficiently large to print through the painted surface

Evaluation of decellularization of porcine pericardium: Decellularization of porcine pericardium

The porcine pericardium has been used for its great potential as a biological scaffold, produced from the extracellular matrix (ECM) and used mainly in surgeries reconstructive, tissue repair and surgical procedures for corneal reconstruction. The adequate preservation and biocompatibility of the pericardial ECM structure during the decellularization process is fundamental, the biggest challenge being the total removal of cellular material without damage to the structure. All agents used in decellularization change the composition and cause some damage to the ultrastructure. Sodium Dodecil Sulfate (SDS) is the most effective for removing cell residue from tissue compared to other detergents, which is also the most used for the decellularization process. This work aimed to test 3 different concentrations of SDS, in order to assess the concentration (0.1, 0.5 and 1%) that best preserves the structure of the ECM pericardial. In addition, we listed the type of daily wash to make the process more effective (only distilled water or PBS 1x), in order to assess the concentration capable of decellularizing the tissue and better preserving the pericardial ECM. The concentration of SDS at 1%, when compared to the lowest concentrations of 0.1 and 0.5%, was more effective in the decellularization process, however it did not obtain good results in the preservation of the ECM. Regarding daily washing, there was no difference in the frequency assessed in the experimental groups

Influence of slow sand filter cleaning process type on filter media biomass: backwashing versus scraping

Biomass was assessed as a new approach for evaluating backwashed slow sand filters (BSF). Slow sand filtration (SSF) is a simple technology for water treatment, where biological mechanisms play a key role in filtration efficiency. Backwashed slow sand filters were previously recommended for small-scale filters (~1 m² of filtration area) as an alternative to conventional filters that are usually cleaned by scraping (ScSF). Biomass was never evaluated in BSF, which is a gap in the knowledge of this technology, considering the importance of its biological mechanisms. Therefore, for the first time, two filters operating under the same conditions were used to compare the influence of backwashing on biomass; one filter was cleaned by backwashing and the other by scraping. Biomass along the filter media depth (40 cm) was assessed by different techniques and compared in terms of cellular biomass (by chloroform fumigation), volatile solids, bacterial community (by 16S rRNA gene sequencing), and observations by scanning electron and fluorescence microscopy. Filters were also monitored and compared regarding filtered water quality and headloss; their differences were related to the different cleaning processes. Overall, filtered water quality was acceptable for slow sand filter standards (turbidity 1 log). However, headloss developed faster on scraped filters, and biomass was different between the two filters. Backwashing did not significantly disturb biomass while scraping changed its surface sand layers. Cell biomass was more abundant and spread across the filtration depth, related to lower headloss, turbidity, and cyanobacterial breakthrough. These results agreed with the water quality and microscopy observations. The bacterial community was also less stratified in the backwashed filter media. These results expand the knowledge of backwashing use in slow sand filters, demonstrating that this process preserves more biomass than scraping. In addition, biomass preservation can lead to bacterial selectivity and faster filter ripening. Considering the importance of biomass preservation on slow sand filtration and its biological filtration mechanisms, the results presented in this paper are promising. The novel insight that BSF can preserve biomass after backwashing may contribute to increasing its application in small communities

Effect of the explicit flexibility of the InhA enzyme from Mycobacterium tuberculosis in molecular docking simulations

Background: Protein/receptor explicit flexibility has recently become an important feature of molecular docking simulations. Taking the flexibility into account brings the docking simulation closer to the receptors’ real behaviour in its natural environment. Several approaches have been developed to address this problem. Among them, modelling the full flexibility as an ensemble of snapshots derived from a molecular dynamics simulation (MD) of the receptor has proved very promising. Despite its potential, however, only a few studies have employed this method to probe its effect in molecular docking simulations. We hereby use ensembles of snapshots obtained from three different MD simulations of the InhA enzyme from M. tuberculosis (Mtb), the wild-type (InhA_wt), InhA_I16T, and InhA_I21V mutants to model their explicit flexibility, and to systematically explore their effect in docking simulations with three different InhA inhibitors, namely, ethionamide (ETH), triclosan (TCL), and pentacyano (isoniazid)ferrate(II) (PIF). Results: The use of fully-flexible receptor (FFR) models of InhA_wt, InhA_I16T, and InhA_I21V mutants in docking simulation with the inhibitors ETH, TCL, and PIF revealed significant differences in the way they interact as compared to the rigid, InhA crystal structure (PDB ID: 1ENY). In the latter, only up to five receptor residues interact with the three different ligands. Conversely, in the FFR models this number grows up to an astonishing 80 different residues. The comparison between the rigid crystal structure and the FFR models showed that the inclusion of explicit flexibility, despite the limitations of the FFR models employed in this study, accounts in a substantial manner to the induced fit expected when a protein/receptor and ligand approach each other to interact in the most favourable manner. Conclusions: Protein/receptor explicit flexibility, or FFR models, represented as an ensemble of MD simulation snapshots, can lead to a more realistic representation of the induced fit effect expected in the encounter and proper docking of receptors to ligands. The FFR models of InhA explicitly characterizes the overall movements of the amino acid residues in helices, strands, loops, and turns, allowing the ligand to properly accommodate itself in the receptor’s binding site. Utilization of the intrinsic flexibility of Mtb’s InhA enzyme and its mutants in virtual screening via molecular docking simulation may provide a novel platform to guide the rational or dynamicalstructure-based drug design of novel inhibitors for Mtb’s InhA. We have produced a short video sequence of each ligand (ETH, TCL and PIF) docked to the FFR models of InhA_wt. These videos are available at http://www.inf.pucrs. br/~osmarns/LABIO/Videos_Cohen_et_al_19_07_2011.htm

A novel mechanism for bubble formation in fluidized systems: The effects of granular temperature on the stability in fluidization

This work contains a novel approach for the study of stability in fluidized systems. It includes the influence of solid particle kinetic energy variations, which are known as granular temperature. The stability is verified by the temporal evolution of bed fluid-dynamics properties (solid volumetric fraction, fluid velocity, solid particles velocity) after small perturbations. The bed is stable when the amplitudes of perturbations decrease with time. The work departs from the mass and momentum continuity equations for the solid and fluid phase, as proposed by Anderson and Jackson (1968). Those are complemented by an equation describing the energy balance from the point of view of granular temperature. Then, a linear approximation for the equations after the introduction of small magnitude perturbations is obtained. The application of harmonic solutions allows arriving to the temporal description of the perturbations. Results show the occurrence of instabilities on the direction transverse to gravity. This cannot be observed by previous approaches (Anderson and Jackson, 1968, 1969; Homsy et al., 1980; Liu, 1982). The present work also suggests a new mechanism for the formation of bubbles in fluidized systems. The parametric influence of the model on the stability of fluidized systems is also verified.21347948

FReDoWS: a method to automate molecular docking simulations with explicit receptor flexibility and snapshots selection

<p>Abstract</p> <p>Background</p> <p><it>In silico</it> molecular docking is an essential step in modern drug discovery when driven by a well defined macromolecular target. Hence, the process is called structure-based or rational drug design (RDD). In the docking step of RDD the macromolecule or receptor is usually considered a rigid body. However, we know from biology that macromolecules such as enzymes and membrane receptors are inherently flexible. Accounting for this flexibility in molecular docking experiments is not trivial. One possibility, which we call a fully-flexible receptor model, is to use a molecular dynamics simulation trajectory of the receptor to simulate its explicit flexibility. To benefit from this concept, which has been known since 2000, it is essential to develop and improve new tools that enable molecular docking simulations of fully-flexible receptor models.</p> <p>Results</p> <p>We have developed a Flexible-Receptor Docking Workflow System (FReDoWS) to automate molecular docking simulations using a fully-flexible receptor model. In addition, it includes a snapshot selection feature to facilitate acceleration the virtual screening of ligands for well defined disease targets. FReDoWS usefulness is demonstrated by investigating the docking of four different ligands to flexible models of <it>Mycobacterium tuberculosis’</it> wild type InhA enzyme and mutants I21V and I16T. We find that all four ligands bind effectively to this receptor as expected from the literature on similar, but wet experiments.</p> <p>Conclusions</p> <p>A work that would usually need the manual execution of many computer programs, and the manipulation of thousands of files, was efficiently and automatically performed by FReDoWS. Its friendly interface allows the user to change the docking and execution parameters. Besides, the snapshot selection feature allowed the acceleration of docking simulations. We expect FReDoWS to help us explore more of the role flexibility plays in receptor-ligand interactions. FReDoWS can be made available upon request to the authors.</p

Antiplasmodial activity of chloroquine analogs against chloroquine-resistant parasites, docking studies and mechanisms of drug action

Submitted by Nuzia Santos ([email protected]) on 2015-03-02T17:19:49Z No. of bitstreams: 1 2014_121.pdf: 1273925 bytes, checksum: 09c618c236f85c7e45f2ad6a53efc484 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-03-02T17:19:57Z (GMT) No. of bitstreams: 1 2014_121.pdf: 1273925 bytes, checksum: 09c618c236f85c7e45f2ad6a53efc484 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-03-02T17:23:45Z (GMT) No. of bitstreams: 1 2014_121.pdf: 1273925 bytes, checksum: 09c618c236f85c7e45f2ad6a53efc484 (MD5)Made available in DSpace on 2015-03-02T17:23:45Z (GMT). No. of bitstreams: 1 2014_121.pdf: 1273925 bytes, checksum: 09c618c236f85c7e45f2ad6a53efc484 (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Malária. Belo Horizonte, MG, BrazilUniversidade Federal de Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, BrazilUniversidade Federal de Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, BrazilInstituto Militar de Engenharia. Laboratório de Modelagem Molecular Aplicada à Defesa Química e Biológica. Rio de Janeiro, RJ, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Malária. Belo Horizonte, MG, BrazilBackground: Given the threat of resistance of human malaria parasites, including to artemisinin derivatives, new agents are needed. Chloroquine (CQ) has been the most widely used anti-malarial, and new analogs (CQAns) presenting alkynes and side chain variations with high antiplasmodial activity were evaluated. Methods: Six diaminealkyne and diaminedialkyne CQAns were evaluated against CQ-resistant (CQ-R) (W2) and CQ-sensitive (CQ-S) (3D7) Plasmodium falciparum parasites in culture. Drug cytotoxicity to a human hepatoma cell line (HepG2) evaluated, allowed to calculate the drug selectivity index (SI), a ratio of drug toxicity to activity in vitro. The CQAns were re-evaluated against CQ-resistant and -sensitive P. berghei parasites in mice using the suppressive test. Docking studies with the CQAns and the human (HssLDH) or plasmodial lactate dehydrogenase (PfLDH) enzymes, and, a β-haematin formation assay were performed using a lipid as a catalyst to promote crystallization in vitro. Results: All tested CQAns were highly active against CQ-R P. falciparum parasites, exhibiting half-maximal inhibitory concentration (IC50) values below 1 μΜ. CQAn33 and CQAn37 had the highest SIs. Docking studies revealed the best conformation of CQAn33 inside the binding pocket of PfLDH; specificity between the residues involved in H-bonds of the PfLDH with CQAn37. CQAn33 and CQAn37 were also shown to be weak inhibitors of PfLDH. CQAn33 and CQAn37 inhibited β-haematin formation with either a similar or a 2-fold higher IC50 value, respectively, compared with CQ. CQAn37 was active in mice with P. berghei, reducing parasitaemia by 100%. CQAn33, -39 and -45 also inhibited CQ-resistant P. berghei parasites in mice, whereas high doses of CQ were inactive. Conclusions: The presence of an alkyne group and the size of the side chain affected anti-P. falciparum activityin vitro. Docking studies suggested a mechanism of action other than PfLDH inhibition. The β-haematin assay suggested the presence of an additional mechanism of action of CQAn33 and CQAn37. Tests with CQAn34, CQAn37, CQAn39 and CQAn45 confirmed previous results against P. berghei malaria in mice, and CQAn33, 39 and 45 were active against CQ-resistant parasites, but CQAn28 and CQAn34 were not. The result likely reflects structure-activity relationships related to the resistant phenotype

The pain experiences of powered wheelchair users

Copyright © 2012 Informa UK, Ltd. This is the author's accepted manuscript. The final published article is available from the link below.Purpose: To explore the experience of pain and discomfort in users of electric-powered indoor/outdoor wheelchairs (EPIOCs) provided by a National Health Service. Methods: EPIOC users receiving their chair between February and November 2002 (N=74) were invited to participate in a telephone questionnaire/interview and 64 (aged 1081 years) agreed. Both specific and open-ended questions examined the presence of pain/discomfort, its severity, minimizing and aggravating factors, particularly in relation to the EPIOC and its use. Results: Most EPIOC users described experiences of pain with 17% reporting severe pain. Over half felt their pain was influenced by the wheelchair and few (25%) considered their chair eased their symptoms. The most common strategy for pain relief was taking medication. Other self-help strategies included changing position, exercise and complementary therapies. Respondents emphasized the provision of backrests, armrests, footrests and cushions which might alleviate or exacerbate pain, highlighting the importance of appropriate assessment for this high dependency group. Conclusions: Users related pain to their underlying medical condition, their wheelchair or a combination of the two. User feedback is essential to ensure that the EPIOC meets health needs with minimal pain. This becomes more important as the health condition of users changes over time