On the active guidance of railway vehicles

The conflict between stability and curving has been well documented since the dawn of the railways. Advances in computer technology and deeper understanding of the complex mechanics of the wheel-rail interface have led to the study of innovative designs. This thesis outlines the need for steering systems for railway applications. A number of innovative passive solutions have been proposed to reduce the conflict between stability and curving. Comparisons of some of these solutions show that significant benefits can be obtained by using uncommon configurations. [Continues.

Faith in the times of corona: behaviour change communication with faith actors in displacement settings

This record includes an extended abstract and MP4 presentation. Presented at the 42nd WEDC International Conference.</div

Marceline Desbordes-Valmore : de poète maudit à écrivain de contes pour enfants, étude de la subversion d'un genre

Qu’est-ce qui distingue les Contes et scènes de la vie de famille (1865) de Marceline Desbordes-Valmore (1786-1859) des contes moraux de la même époque ? Quelle idéologie est véhiculée dans ces contes et à qui est-elle destinée ? Pour répondre à ces questions, j’établis d’abord l’horizon d’attente des lecteurs de contes moraux au XIXe siècle. De cette façon, il est possible de comprendre dans quel espace social et littéraire Desbordes-Valmore conçoit son projet d’écriture et de quelle façon elle applique, interprète et contourne les règles qui régissent l’écriture du conte moral pour enfants. Pour voir l’effet-idéologie qui parcourt les récits de Desbordes-Valmore, j’analyse chacun des contes en fonction de la poétique de la norme établie par Philippe Hamon dans Texte et idéologie. En étudiant de près les foyers normatifs et les évaluations des différents savoirs des personnages, je suis en mesure de constater que Desbordes-Valmore présente une écriture subversive qui, pour reprendre les mots de Pierre Bourdieu dans Langage et pouvoir symbolique, a « la possibilité de changer le monde social en changeant la représentation de ce monde qui contribue à sa réalité ou, plus précisément, en opposant une pré-vision paradoxale, utopie, projet, programme, à la vision ordinaire, qui appréhende le monde social comme monde naturel ». Ce qu’elle propose par son écriture, c’est un altruisme porté par une voix maternelle forte qui vient faire front à l’individualisme bourgeois patriarcal qui domine la société dans laquelle elle vit et écrit

NCL812 compounds exert their antibacterial action on the cell membrane of <i>S</i>. <i>pneumoniae</i> and <i>S</i>. <i>aureus</i>.

<p>(<b>A and B</b>), <i>S</i>. <i>pneumoniae</i> strain D39 exposed to 16 μg/ml NCL812 for 6 h exhibited significantly thicker cell membranes compared to untreated samples (<b>A</b>) (<i>p</i> < 0.0001; two-tailed unpaired <i>t</i>-test) and displayed significantly wider periplasmic space compared to untreated samples (<b>B</b>) (<i>p</i> < 0.001; two-tailed unpaired <i>t</i>-test. Data presented are an example from 12 different bacterial cells, each with at least 10 measurements per bacteria for both treated and untreated samples. (<b>C and D</b>) NCL812 affects macromolecular synthesis (<b>c</b>) and ATP release (<b>D</b>) in <i>S</i>. <i>aureus</i>. (<b>E and F</b>), NCL Compounds dissipate the membrane potential of <i>S</i>. <i>pneumoniae</i> and <i>S</i>. <i>aureus</i>. Membrane potential measurements of <i>S</i>. <i>pneumoniae</i> D39 (<b>E</b>) and <i>S</i>. <i>aureus</i> ATCC49775 (<b>F</b>). Bacterial suspensions were exposed to 16 μg/ml NCL812, NCL195, NCL219, or ampicillin (control) for 5 min after which DiOC₂(3) was added and the fluorescence monitored until it plateaued. Cells were then re-energized with 0.5% glucose and the establishment of a membrane potential was measured as an increase in fluorescence until it plateaued. The membrane potential was then disrupted by the addition of the proton ionophore (CCCP). Data presented is representative of two experiments. For full description, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0183457#sec002" target="_blank">Materials and Methods</a>.</p

Antimicrobial activity of NCL195 against Gram-negative bacteria alone and in combination with EDTA or polymyxin B.

<p>Antimicrobial activity of NCL195 against Gram-negative bacteria alone and in combination with EDTA or polymyxin B.</p

Structure activity relationship between NCL812, NCL195 and NCL219.

<p>Installation of a 4-<i>tert</i>-butyl and a C-methyl imine moiety provided NCL219 with considerably enhanced hydrolytic stability while retaining the excellent antimicrobial activity of NCL812, while guanidine to 2,4,6-triaminopyrimindine bioisosteric modification yielded NCL195, which allowed potency and drug-like character enhancement.</p

NCL812 and NCL195 exhibit high plasma concentration and low plasma clearance rates.

<p>Pharmacokinetic parameters for NCL812 (<b>A</b>) and NCL195 (<b>B</b>) after IV administration at a dose of 5 mg/kg to male CD1 mice (n = 8 per compound), indicating that both compounds exhibited high plasma concentrations and long apparent terminal elimination half-lives. (<b>C</b>), Pharmacokinetic parameters for NCL195 after IP administration at a dose of 43 mg/kg to male CD1 mice (n = 2 per time point), indicating that NCL195 was rapidly absorbed after dosing, and plasma concentrations remained above 3–4 μg/ml for the initial 7.5 h post-dose period.</p

MIC range values for NCL812, NCL195 and NCL219 compared to MIC₉₀ values for daptomycin and ampicillin against <i>S</i>. <i>pneumoniae</i>, <i>S</i>. <i>aureus</i> and vancomycin resistant enterococci (VRE).

<p>MIC range values for NCL812, NCL195 and NCL219 compared to MIC₉₀ values for daptomycin and ampicillin against <i>S</i>. <i>pneumoniae</i>, <i>S</i>. <i>aureus</i> and vancomycin resistant enterococci (VRE).</p

NCL195 demonstrates limited cytotoxicity to mammalian cell lines.

<p>Real-time cell viability measurements for Hep G2 (<b>A, B, C</b>) and MDBK (<b>D, E, F</b>) cells after treatment with 2 or 8 μg/ml NCL812, NCL195 or NCL219. Cell viability was measured every 60 min for 20 h at 37°C and 5% CO₂ on a Cytation 5 Cell Imaging Multi-Mode Reader (BioTek) using the RealTime-Glo MT Cell Viability Assay reagent (Promega). Data are means (± s.e.m.) relative light units (RLU) for each treatment per time point (in duplicate).</p

Physicochemical and metabolism parameters for NCL812, NCL195 and NCL219 in human and mouse liver microsomes.

<p>Physicochemical and metabolism parameters for NCL812, NCL195 and NCL219 in human and mouse liver microsomes.</p