Search Results (10)

Cav2.1 channels are expressed throughout the brain and are the predominant Ca²⁺ channels in the Purkinje cells. These cerebellar neurons fire spontaneously, and Cav2.1 channels are involved in the regular pacemaking activity. The loss of precision of the firing pattern of Purkinje cells leads to ataxia, a disorder characterized by poor balance and difficulties in performing coordinated movements. In this study, we aimed at characterizing functional and structural consequences of four variations (p.A405T in I-II loop and p.R1359W, p.R1667W and p.S1799L in IIIS4, IVS4, and IVS6 helices, respectively) identified in patients exhibiting a wide spectrum of disorders including ataxia symptoms. Functional analysis using two major Cav2.1 splice variants (Cav2.1+e47 and Cav2.1−e47) in Xenopus laevis oocytes, revealed a lack of effect upon A405T substitution and a significant loss-of-function caused by R1359W, whereas R1667W and S1799L caused both channel gain-of-function and loss-of-function, in a splice variant-dependent manner. Structural analysis revealed the loss of interactions with S1, S2, and S3 helices upon R1359W and R1667W substitutions, but a lack of obvious structural changes with S1799L. Computational modeling suggests that biophysical changes induced by Cav2.1 pathogenic mutations might affect action potential frequency in Purkinje cells. Full article

The susceptibility of plants to burn raises concerns about fire hazard that green roofs may pose to buildings. Main concerns relate to cases when such roofs are poorly maintained or stressed by drought conditions which leads to drying out of plants and the accumulation of dead organic material, greatly increasing the availability of fuel load. Existing standard safety measures aim to prevent the spread of fire through the vegetation cover. However, fire spread by thermal radiation is not considered. In this study, fire risk of exposure of adjacent buildings to radiant heat flux produced by fire on green roofs was assessed. Based on generally accepted maximum tolerable radiant heat flux to exposed facades of 12.5 kW/m², the minimum safe separation distances were obtained for different conditions. Wildland fire behavior model was used to determine flame lengths which is the necessary parameter for a radiation model. Several vegetation types, moisture content scenarios and wind speeds were taken as variables. It was found that by providing the vegetation with reasonably high moisture content the fire risk can be greatly reduced, especially for grass-covered roofs. Since wind also has a strong effect on flame size, considering the exposure of a green roof to wind can bring better understanding of fire risk to adjacent buildings. At no-wind condition and at extremely low moisture content separation distances are as short as 3.1 m for dense shrubs and 2.4 m for tall dense grass. Full article

The number of insect GABA receptors (GABAr) available for expression studies has been recently increased by the cloning of the Acyrthosiphon pisum (pea aphid) RDL subunits. This large number of cloned RDL subunits from pest and beneficial insects opens the door to parallel pharmacological studies on the sensitivity of these different insect GABAr to various agonists or antagonists. The resulting analysis of the molecular basis of the species-specific GABAr responses to insecticides is necessary not only to depict and understand species toxicity, but also to help at the early identification of unacceptable toxicity of insecticides toward beneficial insects such as Apis mellifera (honeybees). Using heterologous expression in Xenopus laevis oocytes, and two-electrode voltage-clamp recording to assess the properties of the GABAr, we performed a comparative analysis of the pharmacological sensitivity of RDL subunits from A. pisum, A. mellifera and Varroa destructor GABAr to three pesticides (fipronil, picrotoxin and dieldrin). These data were compared to similar characterizations performed on two Homo sapiens GABA-A receptors (α₂β₂γ₂ and α₂β₂γ₂). Our results underline a global conservation of the pharmacological profiles of these receptors, with some interesting species specificities, nonetheless, and suggest that this approach can be useful for the early identification of poorly specific molecules. Full article

To answer both the growth of the world’s urban population and the climate changes, new structural systems with high prefabrication levels and renewable materials need to be developed. A novel structural system that could enable the use of modular light-frame construction in high-rise buildings was modeled and analyzed. This system was achieved by having a hyperstructure carrying the loads of four-story light-frame superposed substructures. Two 20-story hyperstructures, one using glulam and another one using reinforced concrete, were designed according to the 2015 National Building Code of Canada and compared. A simplified model for the light-frame modules according to the CSA O86-19 was proposed. The interaction between both systems and the impact on the substructures were analyzed. The results of the response spectrum analysis and dynamic wind analysis show that, with a glulam hyperstructure, modules could be connected to the columns and the floors or only to the floors. With a concrete hyperstructure, the modules must be connected to the columns and the cores. For both systems, the design of shearwalls on the short side of the modules is governed by the lateral deformation imposed by seismic forces, while the design of shearwalls on the long side of the modules is governed by the vertical deformation of the primary beams under gravity loads. Standard shearwall assemblies are sufficient to resist the shear induced by gravitational, wind and seismic loads. The analysis indicates that the system could be viable, but more research should be especially performed on the connections between the substructures and the hyperstructure. Full article

Assessing the fire risk of vegetated roofs includes the determination of their possible contribution to fire. Green roof components such as plants and growing media are organic materials and present a fuel that can catch and support the spread of fire. The flammability characteristics of these components were analyzed and compared to a typical roof covering. Growing media with 15% of organic matter were tested using cone calorimeter apparatus. The fuel load and heat release rate of the growing media were measured in both moist (30%) and dry conditions. It was observed that growing media in a moist condition do not present a fire risk, reaching a maximum heat release rate of 33 kW/m². For dry substrates, a peak heat release rate of 95 kW/m² was recorded in the first minute, which then rapidly decreased to 29 kW/m² in the second minute. Compared to a typical bitumen roof membrane, the green roof showed a better fire performance. The literature data report more severe results for plant behavior, reaching peak heat release rates (HRRs) of 397 kW/m² for dried and 176 kW/m² for a green material. However, a rapid decrease in HRR to much lower values occurs in less than 2 min. The results also show that extensive and intensive types of green roofs present 22% and 95% of the additional fire load density when installed on a modified bitumen membrane, 19.7 and 85.8 MJ/m², respectively. Full article

We examine data assimilation coupling between meteorology and chemistry in the stratosphere from both weak and strong coupling strategies. The study was performed with the Canadian operational weather prediction Global Environmental Multiscale (GEM) model coupled online with the photochemical stratospheric chemistry model developed at the Belgian Institute for Space Aeronomy, described in Part I. Here, the Canadian Meteorological Centre’s operational variational assimilation system was extended to include errors of chemical variables and cross-covariances between meteorological and chemical variables in a 3D-Var configuration, and we added the adjoint of tracer advection in the 4D-Var configuration. Our results show that the assimilation of limb sounding observations from the MIPAS instrument on board Envisat can be used to anchor the AMSU-A radiance bias correction scheme. Additionally, the added value of limb sounding temperature observations on meteorology and transport is shown to be significant. Weak coupling data assimilation with ozone–radiation interaction is shown to give comparable results on meteorology whether a simplified linearized or comprehensive ozone chemistry scheme is used. Strong coupling data assimilation, using static error cross-covariances between ozone and temperature in a 3D-Var context, produced inconclusive results with the approximations we used. We have also conducted the assimilation of long-lived species observations using 4D-Var to infer winds. Our results showed the added value of assimilating several long-lived species, and an improvement in the zonal wind in the Tropics within the troposphere and lower stratosphere. 4D-Var assimilation also induced a correction of zonal wind in the surf zone and a temperature bias in the lower tropical stratosphere. Full article

Currently, green roof fire risks are not clearly defined. This is because the problem is still not well understood, which raises concerns. The possibility of plants catching fire, especially during drought periods, is one of the reasons for necessary protection measures. The potential fire hazard for roof decks covered with vegetation has not yet been fully explored. The present study analyzes the performance of green roofs in extreme heat conditions by simulating a heat transfer process through the assembly. The main objective of this study was to determine the conditions and time required for the roof deck to reach a critical temperature. The effects of growing medium layer thickness (between 3 and 10 cm), porosity (0.5 to 0.7), and heating intensity (50, 100, 150, and 200 kW/m²) were examined. It was found that a green roof can protect a wooden roof deck from igniting with only 3 cm of soil coverage when exposed to severe heat fluxes for at least 25 minutes. The dependency of failure time on substrate thickness decreases with increasing heating load. It was also found that substrate porosity has a low impact on time to failure, and only at high heating loads. Full article

GA101/obinutuzumab is a novel type II anti-CD20 monoclonal antibody (mAb), which is more effective than rituximab (RTX) in preclinical and clinical studies when used in combination with chemotherapy. Ca²⁺ signaling was shown to play a role in RTX-induced cell death. This report concerns the effect of GA101 on Ca²⁺ signaling and its involvement in the direct cell death induced by GA101. We reveal that GA101 triggered an intracellular Ca²⁺ increase by mobilizing intracellular Ca²⁺ stores and activating Orai1-dependent Ca²⁺ influx in non-Hodgkin lymphoma cell lines and primary B-Cell Chronic Lymphocytic Leukemia (B-CLL) cells. According to the cell type, Ca²⁺ was mobilized from two distinct intracellular compartments. In Raji, BL2, and B-CLL cells, GA101 induced a Ca²⁺ release from lysosomes, leading to the subsequent lysosomal membrane permeabilization and cell death. Inhibition of this calcium signaling reduced GA101-induced cell death in these cells. In SU-DHL-4 cells, GA101 mobilized Ca²⁺ from the endoplasmic reticulum (ER). Inhibition of ER replenishment, by blocking Orai1-dependent Ca²⁺ influx, led to an ER stress and unfolded protein response (UPR) which sensitized these cells to GA101-induced cell death. These results revealed the central role of Ca²⁺ signaling in GA101’s action mechanism, which may contribute to designing new rational drug combinations improving its clinical efficacy. Full article

In his short story Pierre Menard, autor del Quijote, Borges describes the extraordinary and paradoxical feat of an imaginary 20th century French writer who recomposes, as it were, part of Cervantes’ early modern masterpiece. Borges’ duplication of the text of the Quijote is meant to give narrative shape to the acknowledgement that a text acquires different meanings in different epochs. This essay first sets Borges’ approach to the construction of the past within a lineage of authors, which harks back to Nietzsche and points to Foucauldian genealogies. It then renews the endeavour of Borges’ character Menard, as it reproduces significant portions of Foucault’s 1971 paper Nietzsche, la généalogie, l’histoire. Whilst the selections of the Foucauldian text are not simply rewritten, as they are given a new English translation, they are also recombined and reconsidered in the light of our contemporary cultural and political context, which underwent significant changes during the apparently short span of time that separates us from the composition of Foucault’s seminal work. Full article

This study evaluates the potential environmental benefits of using an electric over a conventional vehicle in the province of Québec, Canada; a province characterised with an electric grid mix mostly based on hydroelectricity. To do so, we applied an environmental life cycle assessment approach whose results suggest that use of the electric vehicle should be promoted in the province of Québec but only if the vehicle lifetime is optimised. Full article