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Giguere S.,Laval University | Laviolette F.,Laval University | Marchand M.,Laval University | Tremblay D.,Laval University | And 4 more authors.
PLoS Computational Biology | Year: 2015

The discovery of peptides possessing high biological activity is very challenging due to the enormous diversity for which only a minority have the desired properties. To lower cost and reduce the time to obtain promising peptides, machine learning approaches can greatly assist in the process and even partly replace expensive laboratory experiments by learning a predictor with existing data or with a smaller amount of data generation. Unfortunately, once the model is learned, selecting peptides having the greatest predicted bioactivity often requires a prohibitive amount of computational time. For this combinatorial problem, heuristics and stochastic optimization methods are not guaranteed to find adequate solutions. We focused on recent advances in kernel methods and machine learning to learn a predictive model with proven success. For this type of model, we propose an efficient algorithm based on graph theory, that is guaranteed to find the peptides for which the model predicts maximal bioactivity. We also present a second algorithm capable of sorting the peptides of maximal bioactivity. Extensive analyses demonstrate how these algorithms can be part of an iterative combinatorial chemistry procedure to speed up the discovery and the validation of peptide leads. Moreover, the proposed approach does not require the use of known ligands for the target protein since it can leverage recent multi-target machine learning predictors where ligands for similar targets can serve as initial training data. Finally, we validated the proposed approach in vitro with the discovery of new cationic antimicrobial peptides. Source code freely available at. © 2015 Giguère et al. Source

Fonseca G.P.,Brazilian Nuclear Energy Research Institute (IPEN) | Fonseca G.P.,Maastricht University | Landry G.,Maastricht University | Landry G.,Ludwig Maximilians University of Munich | And 8 more authors.
Physics in Medicine and Biology | Year: 2014

Accounting for brachytherapy applicator attenuation is part of the recommendations from the recent report of AAPM Task Group 186. To do so, model based dose calculation algorithms require accurate modelling of the applicator geometry. This can be non-trivial in the case of irregularly shaped applicators such as the Fletcher Williamson gynaecological applicator or balloon applicators with possibly irregular shapes employed in accelerated partial breast irradiation (APBI) performed using electronic brachytherapy sources (EBS). While many of these applicators can be modelled using constructive solid geometry (CSG), the latter may be difficult and timeconsuming. Alternatively, these complex geometries can be modelled using tessellated geometries such as tetrahedral meshes (mesh geometries (MG)). Recent versions of Monte Carlo (MC) codes Geant4 and MCNP6 allow for the use of MG. The goal of this work was to model a series of applicators relevant to brachytherapy using MG. Applicators designed for 192Ir sources and 50 kV EBS were studied; a shielded vaginal applicator, a shielded Fletcher Williamson applicator and an APBI balloon applicator. All applicators were modelled in Geant4 and MCNP6 using MG and CSG for dose calculations. CSG derived dose distributions were considered as reference and used to validate MG models by comparing dose distribution ratios. In general agreement within 1% for the dose calculations was observed for all applicators between MG and CSG and between codes when considering volumes inside the 25% isodose surface. When compared to CSG, MG required longer computation times by a factor of at least 2 for MC simulations using the same code. MCNP6 calculation times were more than ten times shorter than Geant4 in some cases. In conclusion we presented methods allowing for high fidelity modelling with results equivalent to CSG. To the best of our knowledge MG offers the most accurate representation of an irregular APBI balloon applicator. © 2014 Institute of Physics and Engineering in Medicine. Source

Bernier M.,University LavalQuebec | Fournier V.,University LavalQuebec | Eccles L.,Technology Transfer Team
Canadian Entomologist | Year: 2015

The small hive beetle (SHB), Aethina tumida Murray (Coleoptera: Nitidulidae), is a non-native pest of honey bees (Apis mellifera Linnaeus (Hymenoptera: Apidae)) newly introduced to Canada. The effectiveness of three in-hive traps was tested in springtime in West-Montérégie (southern Québec, Canada) and in late summer in Essex County (southern Ontario, Canada): AJ's Beetle Eater™ (AJ's Beetle Eater), Beetle Barn™ (Rossmann Apiaries), and Hood™ trap (Brushy Mountain Bee Farm). Traps were placed in the brood chamber of 12 colonies in West-Montérégie, and in 48 colonies in the top honey super in Essex County. In-hive traps were effective in reducing SHB populations without compromising the bee population or colony weight gain. In West-Montérégie, the Beetle Barn™ was the most effective trap during the first week, when SHB populations were high. It was less effective when honey bees sealed trap openings with propolis. In Essex County, the AJ's Beetle Eater™ was the most effective throughout the trial. There was no difference in efficacy between the various solutions used in the Hood™ trap (mineral oil versus mineral oil and apple cider vinegar). © Entomological Society of Canada 2014. Source

Celso F.,Sudan University of Science and Technology | Mikhailenko S.D.,Sudan University of Science and Technology | Mikhailenko S.D.,University LavalQuebec | Rodrigues M.A.S.,Sudan University of Science and Technology | And 2 more authors.
Journal of Power Sources | Year: 2016

Composite proton exchange membranes (PEMs) intended for fuel cell applications were prepared by embedding of various amounts of dispersed tri-sulfonic acid ethyl POSS (S-Et-POSS) and tri-sulfonic acid butyl POSS (S-Bu-POSS) in thin films of sulfonated poly ether-ether ketone. The electrical properties of the PEMs were studied by Impedance spectroscopy and it was found that their conductivity σ changes with the filler content following a curve with a maximum. The water uptake of these PEMs showed the same dependence. The investigation of initial isolated S-POSS substances revealed the properties of typical electrolytes, which however in both cases possessed low conductivities of 1. 17 × 10-5 S cm-1 (S-Et-POSS) and 3.52 × 10-5 S cm-1 (S-Bu-POSS). At the same time, the insoluble in water S-POSS was found forming highly conductive interface layer when wetted with liquid water and hence producing a strong positive impact on the conductivity of the composite PEM. Electrical properties of the composites were analysed within the frameworks of effective medium theory and bounding models, allowing to evaluate analytically the range of possible conductivity values. It was found that these approaches produced quite good approximation of the experimental data and constituted a fair basis for interpretation of the observed relationship. © 2015 Elsevier B.V. Source

Bachasson D.,Institute of Myology | Moraux A.,Institute of Myology | Ollivier G.,Institute of Myology | Decostre V.,Institute of Myology | And 11 more authors.
Neuromuscular Disorders | Year: 2016

This study evaluated gait using lower-trunk accelerometry and investigated relationships between gait abnormalities, postural instability, handgrip myotonia, and weakness in lower-limb and axial muscle groups commonly affected in myotonic dystrophy type 1 (DM1). Twenty-two patients (11 men, 11 women; age = 42 years (range: 26–51)) with DM1 and twenty healthy controls (9 men, 11 women; age = 44 years (range: 24–50)) participated in this study. Gait analysis using lower-trunk accelerometry was performed at self-selected walking pace. Postural stability was measured via center of pressure displacement analysis using a force platform during eyes-closed normal stance. Handgrip myotonia was quantified using force-relaxation curve modeling. Patients displayed lower walking speed, stride frequency, stride length, gait regularity, and gait symmetry. Strength of ankle plantar flexors, ankle dorsal flexors and neck flexors correlated with interstride regularity in the vertical direction (ρ = 0.57, ρ = 0.59, and ρ = 0.44, respectively; all P < 0.05). Knee extension strength correlated with gait symmetry in the anteroposterior direction (ρ = 0.45, P < 0.05). Center of pressure velocity was greater in patients and correlated with neck flexion and ankle plantar flexion weakness (ρ = −0.51 and ρ = −0.62, respectively; both P < 0.05), and with interstride regularity in the vertical direction (ρ = −0.58, P < 0.05). No correlation was found between handgrip myotonia and any other variable studied. Lower-trunk accelerometry allows the characterization of gait pattern abnormalities in patients with DM1. Further studies are required to determine the relevance of systematic gait analysis using lower-trunk accelerometry for patient follow-up and intervention planning. © 2016 Elsevier B.V. Source

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