Instructional and Technological Design of E-Learning Courses

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Phenotypic Screens, Chemical Genomics, and Antimalarial Lead Discovery

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A novel validated assay to support the discovery of new anti-malarial gametocytocidal agents

Additional file 1. Graphical representation of the expression of 12 selected genes throughout the 30 days of gametocytogenesis. Y-axis shows the gene expression represented as (Ctgene−Ct18S rRNA)Ttime × −(Ctgene−Ct18S rRNA)T0, considering the time 0 as the basal expression. Although only the gametocytogenesis during 30 days is presented, similar results were obtained from day 0 to day 15 in both assays

Machine learning-based phenotypic imaging to characterise the targetable biology of <i>Plasmodium falciparum</i> male gametocytes for the development of transmission-blocking antimalarials

Preventing parasite transmission from humans to mosquitoes is recognised to be critical for achieving elimination and eradication of malaria. Consequently developing new antimalarial drugs with transmission-blocking properties is a priority. Large screening campaigns have identified many new transmission-blocking molecules, however little is known about how they target the mosquito-transmissible Plasmodium falciparum stage V gametocytes, or how they affect their underlying cell biology. To respond to this knowledge gap, we have developed a machine learning image analysis pipeline to characterise and compare the cellular phenotypes generated by transmission-blocking molecules during male gametogenesis. Using this approach, we studied 40 molecules, categorising their activity based upon timing of action and visual effects on the organisation of tubulin and DNA within the cell. Our data both proposes new modes of action and corroborates existing modes of action of identified transmission-blocking molecules. Furthermore, the characterised molecules provide a new armoury of tool compounds to probe gametocyte cell biology and the generated imaging dataset provides a new reference for researchers to correlate molecular target or gene deletion to specific cellular phenotype. Our analysis pipeline is not optimised for a specific organism and could be applied to any fluorescence microscopy dataset containing cells delineated by bounding boxes, and so is potentially extendible to any disease model

Drug Screen Targeted at Plasmodium Liver Stages Identifies a Potent Multistage Antimalarial Drug

Plasmodium parasites undergo a clinically silent and obligatory developmental phase in the host’s liver cells before they are able to infect erythrocytes and cause malaria symptoms. To overcome the scarcity of compounds targeting the liver stage of malaria, we screened a library of 1037 existing drugs for their ability to inhibit Plasmodium hepatic development. Decoquinate emerged as the strongest inhibitor of Plasmodium liver stages, both in vitro and in vivo. Furthermore, decoquinate kills the parasite’s replicative blood stages and is active against developing gametocytes, the forms responsible for transmission. The drug acts by selectively and specifically inhibiting the parasite’s mitochondrial $bc_1$ complex, with little cross-resistance with the antimalarial drug atovaquone. Oral administration of a single dose of decoquinate effectively prevents the appearance of disease, warranting its exploitation as a potent antimalarial compound

Computational modelling of the local structure and thermophysical properties of ternary MgCl2-NaCl-KCl salt for thermal energy storage applications

Molten salts as heat transfer fluids (HTF) for concentrated solar power (CSP) plant application are considered as the best thermal storage medium, and more precisely molten chlorides, presenting a wide operating range and coupled with competitive cost. Furthermore, MgCl2-NaCl-KCl (MgNaK) mixture appeared as the most promising one but need further studies to better understand its thermophysical properties. Indeed, its hydrated form leads to the formation of corrosive compounds. In this research, two different methods are used to model the ternary mixture. The dehydration process is evaluated by thermodynamical calculations with Thermocalc software. Then, the local structure, thermal conductivity and viscosity are estimated by means of molecular dynamics simulation, with LAMMPS package. The results were close to past simulations studies and experimental references, but discrepancies need to be further minimized regarding some variable fluctuations

Corrosion study of Ni-based alloy in ternary chloride salt for thermal storage application

MgCl2/NaCl/KCl salt appeared as a high-potential heat transfer fluid for concentrated solar application, offering a wide operating range and low cost. Nevertheless, MgCl2 hydrates and atmosphere relative humidity are the limiting factors for a real scale CSP plant, leading to severe corrosion. Thus, Inconel 617 was tested at 700ºC up to 24 h in air atmosphere to simulate a punctual failure in the inertization system of a plant. XRD and SEM-EDX analysis showed unstable multilayers growing in cascade, highlighting chromium, aluminum, magnesium, and oxygen activities. Additionally, A radial growth of MgCr2O4 at the expense of MgO grains was visualized

Drug Screen Targeted at Plasmodium Liver Stages Identifies a Potent Multistage Antimalarial Drug

Plasmodium parasites undergo a clinically silent and obligatory developmental phase in the host's liver cells before they are able to infect erythrocytes and cause malaria symptoms. To overcome the scarcity of compounds targeting the liver stage of malaria, we screened a library of 1037 existing drugs for their ability to inhibit Plasmodium hepatic development. Decoquinate emerged as the strongest inhibitor of Plasmodium liver stages, both in vitro and in vivo. Furthermore, decoquinate kills the parasite's replicative blood stages and is active against developing gametocytes, the forms responsible for transmission. The drug acts by selectively and specifically inhibiting the parasite's mitochondrial bc1 complex, with little cross-resistance with the antimalarial drug atovaquone. Oral administration of a single dose of decoquinate effectively prevents the appearance of disease, warranting its exploitation as a potent antimalarial compoun

Experimental study on steam oxidation resistance at 600 °C of Inconel 625 coatings deposited by HVOF and laser cladding

Inconel 625 (IN625) coatings were deposited by High-Velocity Oxy-fuel (HVOF) and laser cladding, on a 10.50–12%Cr steel to improve its oxidation resistance. Both as-deposited coatings exhibited a γ-Ni-Cr matrix and two protective oxides (Cr2O3 and NiCr2O4). In addition, laser cladding as-deposited coatings also presented precipitates A2B-type Laves phases due to the dilution effect from laser cladding technique. Coated and uncoated steel were oxidized under isothermal conditions at 600 ◦C for 2000 h and subsequently analyzed using gravimetry, SEM-EDS and XRD techniques. The application of IN625 coatings revealed a weight gain ten times lower than that registered for the uncoated steel, this improvement being mainly due to the presence of protective and stable Cr2O3 and NiCr2O4 oxides. Additionally, the XRD analysis showed that the initial Laves phases present in the laser cladding coating, were re-dissolved and transformed in δ-Ni3Nb compound suggesting that that the temperature and exposure time are enough to induce this transformation