Exploration de différentes architectures de réseaux de neurones pour la prédiction de la glace atmosphérique sur les conducteurs des réseaux électriques

Dans le but d'établir un modèle informatique empirique visant à prédire l'évolution temporelle des charges mécaniques dues à l'accumulation de la glace atmosphérique sur les conducteurs de transport d'énergie électrique, cinq architectures de réseaux de neurones artificiels ont été étudiées et comparées. Deux réseaux de nature statique, soit le Perceptron multicouches (MLP) et le réseau à fonctions de base radiales (RBF), ainsi que deux réseaux orientés vers le traitement temporel, soit le réseau à réponse impulsionnelle finie (FIR) et le réseau récurrent Elman, ont été comparés à la régression linéaire multiple (ADALINE). Les données utilisées pour faire l'entraînement des modèles basés sur les réseaux de neurones proviennent du site instrumenté du Mont-Bélair qui fait partie du système de surveillance en temps réel SYGIVRE d'Hydro-Québec. On retrouve sur ce site une ligne de 315 kV dotée d'un capteur de force pour la mesure des forces mécaniques, plusieurs instruments météorologiques standards ainsi qu'un givromètre permettant d'évaluer l'intensité des conditions givrantes environnantes. Les modèles créés dans le cadre de cette recherche utilisèrent la température ambiante, la vitesse normale du vent et le signal du givromètre comme paramètres d'entrée et le signal de charge (ou son taux de variation) comme paramètre de sortie. Les résultats indiquent que les réseaux de neurones (le FIR par exemple) constituent un outil prédictif potentiellement avantageux ayant une puissance de représentation supérieure à des techniques statistiques simples comme la régression linéaire multiple. Les réseaux de neurones de nature statique donnent généralement de moins bons résultats que les réseaux orientés vers le traitement temporel et semblent donc moins adéquats. Toutefois, les performances affichées par les modèles montrent bien que la problématique de la prédiction des charges mécaniques de glace atmosphérique est plutôt difficile et qu'il ne faut pas considérer les réseaux de neurones comme une solution magique. L'utilisation de l'historique passé du signal de sortie comme variable d'entrée supplémentaire améliore notablement la situation cependant dans le cadre d'une prédiction en avance. Dans ce cas, les modèles fournissent une prédiction raisonnablement précise

A multimodal endoscopic approach for characterizing sea-ice optics, physics, biology and biogeochemistry at small scale

Sea ice is a complex and heterogeneous medium that hosts a rich community of microbial organisms and small invertebrates. This ecosystem is shaped by a network of inhabitable spaces where the upward and downward fluxes of solutes and light support primary production, and ultimately the whole sea-ice trophic network. Describing the optical, physical, biological and biogeochemical processes that drive the functioning of the sea-ice ecosystem at the appropriate, i.e. small scale (micro- to centimeter), is very challenging. This medium is solid, fragile and highly heterogeneous. Traditional sea-ice sampling methods based on coring are most often coarse and destructive. Not only do they not allow the small scale to be explored, they generally alter the material to be analyzed. Here, we present a new approach for measuring relevant variables of the sea-ice ecosystem at small scale and, as much as possible, non-destructively. Inspired by medical endoscopes, the custom-built platform is intended to carry various types of miniaturized optical sensors for radiometry, chemistry and high-resolution imaging of the sea-ice interior. In this presentation, we will describe the concept and present the progress made to date

Identification of PP2A-B55 targets uncovers regulation of emerin during nuclear envelope reassembly in Drosophila

Mitotic exit requires the dephosphorylation of many proteins whose phosphorylation was needed for mitosis. Protein phosphatase 2A with its B55 regulatory subunit (PP2A-B55) promotes this transition. However, the events and substrates that it regulates are incompletely understood. We used proteomic approaches in Drosophila to identify proteins that interact with and are dephosphorylated by PP2A-B55. Among several candidates, we identified emerin (otefin in Drosophila). Emerin resides in the inner nuclear membrane and interacts with the DNA-binding protein barrier-to-autointegration factor (BAF) via a LEM domain. We found that the phosphorylation of emerin at Ser50 and Ser54 near its LEM domain negatively regulates its association with BAF, lamin and additional emerin in mitosis. We show that dephosphorylation of emerin at these sites by PP2A-B55 determines the timing of nuclear envelope reformation. Genetic experiments indicate that this regulation is required during embryonic development. Phosphoregulation of the emerin–BAF complex formation by PP2A-B55 appears as a key event of mitotic exit that is likely conserved across species

A phase 2 study of trametinib for patients with pediatric glioma or plexiform neurofibroma with refractory tumor and activation of the MAPK/ERK pathway: TRAM-01

Background: Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children. Up to 50% will be refractory to conventional chemotherapy. It is now known that the majority of PLGG have activation of the MAPK/ERK pathway. The same pathway is also activated in plexiform neurofibromas (PNs) which are low-grade tumors involving peripheral nerves in patients with neurofibromatosis type 1 (NF1). These lesions are known to be refractory to chemotherapy. Specific MEK inhibitors such as trametinib are now available and have been approved for other cancers harboring mutations in the MAPK/ERK pathway such as melanoma. We have observed significant responses to trametinib in patients with refractory PLGG in our institutions and results from the phase I study are promising. The treatment appears not only efficacious but is also usually well tolerated. We hypothesize that we will observe responses in the majority of refractory PLGG and PN treated with trametinib in this phase 2 study. Methods: The primary objective is to determine the objective response rate of trametinib as a single agent for treatment of progressing/refractory tumors with MAPK/ERK pathway activation. The TRAM-01 study is a phase II multicentric open-label basket trial including four groups. Group 1 includes NF1 patients with progressing/refractory glioma. Group 2 includes NF1 patients with plexiform neurofibroma. Group 3 includes patients with progressing/refractory glioma with KIAA1549-BRAF fusion. Group 4 includes other patients with progressing/refractory glioma with activation of the MAPK/ERK pathway. Eligible patients for a given study group will receive daily oral trametinib at full dose for a total of 18 cycles of 28 days. A total of 150 patients will be enrolled in seven Canadian centers. Secondary objectives include the assessment of progression-free survival, overall survival, safety and tolerability of trametinib, serum levels of trametinib and evaluation of quality of life during treatment. Discussion: Trametinib will allow us to target directly and specifically the MAPK/ERK pathway. We expect to observe a significant response in most patients. Following our study, trametinib could be integrated into standard treatment of PLGG and PN. Trial registration: ClinicalTrials.gov Identifier: NCT03363217 December 6, 2017.Other UBCNon UBCReviewedFacult

Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission

<div><h3>Background</h3><p>Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Dendritic cell–specific ICAM-3 grabbing-nonintegrin (DC-SIGN, also known as CD209) is an HIV-1 receptor that enhances its transmission to T cells and is expressed on placental macrophages.</p> <h3>Methods and Findings</h3><p>We have investigated the association between DC-SIGN genetic variants and risk of MTCT of HIV-1 among Zimbabwean infants and characterized the impact of the associated mutations on DC-SIGN expression and interaction with HIV-1. DC-SIGN promoter (p-336C and p-201A) and exon 4 (198Q and 242V) variants were all significantly associated with increased risk of intrauterine (IU) HIV-1 infection. Promoter variants decreased DC-SIGN expression both in vitro and in placental CD163⁺ macrophages (Hofbauer cells) of HIV-1 unexposed infants but not of HIV-1 exposed infants. The exon 4 protein-modifying mutations increased HIV-1 capture and transmission to T cells in vitro.</p> <h3>Conclusion</h3><p>This study provides compelling evidence to support an important role of DC-SIGN in IU HIV-1 infection.</p> </div

DC-SIGN promoter variants reduced transcriptional activity <i>in vitro</i> and reduced DC-SIGN expression in placental macrophages.

<p>(A, B) Transcriptional activity <i>in vitro</i> (A) Schematic representation of reporter gene constructs corresponding to the DC-SIGN promoter region from positions −507 to −1 with or without promoter variants −336C and −201A. (B) Relative luciferase expression from pGL2-Basic, the parental vector without a promoter. Expression of the DC-SIGN promoter constructs was calculated relative to this value. Results are mean ± S.E.M. values of three independent experiments performed in triplicates and differences in relative luciferase expression between variants and wild-type were examined with Student’s t test. (C) Hofbauer-like cells were analysed by flow cytometry to measure DC-SIGN expression in infants bearing or not promoter variants. Dead cells and Lin⁺ (CD3; CD19; CD56) cells were excluded and subsets were identified for their side scatter (SSC-A) properties and their level of CD14 expression. Placental macrophages were selected for high granularity and CD14 expression (CD14⁺ subset). DC-SIGN was expressed on CD163⁺ and CD163⁻ subsets. Dot plots and flow cytometry histograms are representative experiments of all patients. Mean fluorescence intensity (MFI) of DC-SIGN, HLA-DR and CD68 was compared between both subsets for infants bearing or not promoter variants and born from HIV-1-negative mothers (p-336T/p-201C group n = 4; p-336C or p-336C/p-201A group n = 11). (D) DC-SIGN, HLA-DR and CD68 expression was compared in CD163+ and CD163− subsets from infants bearing or not promoter variants and born from HIV-1-negative mothers (HIV-1 Unexposed; p-336T/p-201C group n = 4; p-336C or p-336C/p-201A group n = 11) or from HIV-1-positive mothers (HIV-1 Exposed; p-336T/p-201C group n = 3; p-336C or p-336C/p-201A group n = 6). Results in C and D are mean ± S.E.M. values of MFI and difference between subsets or variants was calculated with Student’s t test.</p