The Application of New Molecular Methods in the Investigation of a Waterborne Outbreak of Norovirus in Denmark, 2012

In December 2012, an outbreak of acute gastrointestinal illness occurred in a geographical distinct area in Denmark covering 368 households. A combined microbiological, epidemiological and environmental investigation was initiated to understand the outbreak magnitude, pathogen(s) and vehicle in order to control the outbreak. Norovirus GII.4 New Orleans 2009 variant was detected in 15 of 17 individual stool samples from 14 households. Norovirus genomic material from water samples was detected and quantified and sequencing of longer parts of the viral capsid region (>1000 nt) were applied to patient and water samples. All five purposely selected water samples tested positive for norovirus GII in levels up to 1.8×10(4) genomic units per 200 ml. Identical norovirus sequences were found in all 5 sequenced stool samples and 1 sequenced water sample, a second sequenced water sample showed 1 nt (<0.1%) difference. In a cohort study, including 256 participants, cases were defined as residents of the area experiencing diarrhoea or vomiting onset on 12-14 December 2012. We found an attack rate of 51%. Being a case was associated with drinking tap-water on 12-13 December (relative risk = 6.0, 95%CI: 1.6-22) and a dose-response relation for the mean glasses of tap-water consumed was observed. Environmental investigations suggested contamination from a sewage pipe to the drinking water due to fall in pressure during water supply system renovations. The combined microbiological, epidemiological and environmental investigations strongly indicates the outbreak was caused by norovirus contamination of the water supply system

Template-free 13-protofilament microtubule–MAP assembly visualized at 8 A resolution

Microtubule-associated proteins (MAPs) are essential for regulating and organizing cellular microtubules (MTs). However, our mechanistic understanding of MAP function is limited by a lack of detailed structural information. Using cryo-electron microscopy and single particle algorithms, we solved the 8 Å structure of doublecortin (DCX)-stabilized MTs. Because of DCX’s unusual ability to specifically nucleate and stabilize 13-protofilament MTs, our reconstruction provides unprecedented insight into the structure of MTs with an in vivo architecture, and in the absence of a stabilizing drug. DCX specifically recognizes the corner of four tubulin dimers, a binding mode ideally suited to stabilizing both lateral and longitudinal lattice contacts. A striking consequence of this is that DCX does not bind the MT seam. DCX binding on the MT surface indirectly stabilizes conserved tubulin–tubulin lateral contacts in the MT lumen, operating independently of the nucleotide bound to tubulin. DCX’s exquisite binding selectivity uncovers important insights into regulation of cellular MTs

Eliciting Awe in the Spectator: The Case of a Dhrupad-Based Dance Performance

This paper describes “Kalos, eîdos, skopeîn,” an immersive Dhrupad-based dance installation designed to elicit feelings of awe in the spectators, in a real-life artistic context. This study used a mixed-methods approach in order to explore spectators’ awe experience (N=45), using specific scales and interpretative phenomenological analysis. Results suggested that “Kalos, eîdos, skopeîn,” with its combination of nature motifs and the slow dance-walk associated with the Dhrupad music in the choreography, was able to produce awe-related moments in some spectators and inspire a degree of positive emotions. Our qualitative results viewed awe explicitly as a positive emotion and showed that generally the spectator narratives, involving the whole performance, were based on modified states of consciousness. Three themes emerged: the main theme is “A rich experience of modified states of consciousness” involving the whole performance, and two interconnected sub-themes “Captivated by the slowness of the dancers” associated with the slow movement and “I can still hear the mantra in my head” in rapport with Dhrupad music. This study was carried out as part of the Canadian FRQSC/FCI Project (2019-RC2-260306)

Eliciting Awe in the Spectator: The Case of a Dhrupad-Based Dance Performance

This paper describes “Kalos, eîdos, skopeîn,” an immersive Dhrupad-based dance installation designed to elicit feelings of awe in the spectators, in a real-life artistic context. This study used a mixed-methods approach in order to explore spectators’ awe experience (N=45), using specific scales and interpretative phenomenological analysis. Results suggested that “Kalos, eîdos, skopeîn,” with its combination of nature motifs and the slow dance-walk associated with the Dhrupad music in the choreography, was able to produce awe-related moments in some spectators and inspire a degree of positive emotions. Our qualitative results viewed awe explicitly as a positive emotion and showed that generally the spectator narratives, involving the whole performance, were based on modified states of consciousness. Three themes emerged: the main theme is “A rich experience of modified states of consciousness” involving the whole performance, and two interconnected sub-themes “Captivated by the slowness of the dancers” associated with the slow movement and “I can still hear the mantra in my head” in rapport with Dhrupad music. This study was carried out as part of the Canadian FRQSC/FCI Project (2019-RC2-260306)

Real-Time Assessment of Health-Care Requirements During the Zika Virus Epidemic in Martinique.

The spread of Zika virus in the Americas has been associated with a surge in Guillain-Barré syndrome (GBS) cases. Given the severity of GBS, territories affected by Zika virus need to plan health-care resources to manage GBS patients. To inform such planning in Martinique, we analyzed Zika virus surveillance and GBS data from Martinique in real time with a modeling framework that captured dynamics of the Zika virus epidemic, the risk of GBS in Zika virus-infected persons, and the clinical management of GBS cases. We compared our estimates with those from the 2013-2014 Zika virus epidemic in French Polynesia. We were able to predict just a few weeks into the epidemic that, due to lower transmission potential and lower probability of developing GBS following infection in Martinique, the total number of GBS cases in Martinique would be substantially lower than suggested by simple extrapolations from French Polynesia. We correctly predicted that 8 intensive-care beds and 7 ventilators would be sufficient to treat GBS cases. This study showcased the contribution of modeling to inform local health-care planning during an outbreak. Timely studies that estimate the proportion of infected persons that seek care are needed to improve the predictive power of such approaches

Pregled lijekova protiv raka koji ciljano djeluju na mikrotubule

The entire world is looking for effective cancer therapies whose benefits would outweigh their toxicity. One way to reduce resistance to chemotherapy and its adverse effects is the so called targeted therapy, which targets specific molecules (“molecular targets”) that play a critical role in cancer growth, progression, and metastasis. One such specific target are microtubules. In this review we address the current knowledge about microtubule-targeting agents or drugs (MTAs/MTDs) used in cancer therapy from their synthesis to toxicities. Synthetic and natural MTAs exhibit antitumor activity, and preclinical and clinical studies have shown that their anticancer effectiveness is higher than that of traditional drug therapies. Furthermore, MTAs involve a lower risk of adverse effects such as neurotoxicity and haemotoxicity. Several new generation MTAs are currently being evaluated for clinical use. This review brings updated information on the benefits of MTAs, therapeutic approaches, advantages, and challenges in their research.U cijelome se svijetu traga za djelotvornim liječenjem protiv raka čije bi koristi prevagnule nad štetnim djelovanjem. Jedan od načina da se smanji otpornost na kemoterapiju i njezine štetne učinke svakako je takozvano ciljano liječenje, usmjereno na pojedine molekule (molekulske ciljeve) koje imaju važnu ulogu u rastu, napredovanju i metastaziranju raka. Primjer takvih specifičnih ciljeva su mikrotubuli. U ovom se preglednom radu osvrćemo na najnovije spoznaje o lijekovima koji ciljano djeluju na mikrotubule (engl. microtubule-targeting agents/drugs, krat. MTA/MTD), a rabe se u liječenju raka. Takvi prirodni i sintetizirani lijekovi djeluju protutumorski, a pretklinička istraživanja i klinička ispitivanja pokazuju da je njihova djelotvornost veća nego ona tradicionalnih lijekova. Osim toga, ti lijekovi donose manji rizik od štetnih učinaka poput neurotoksičnosti i hemotoksičnosti. Upravo se klinički ocjenjuju nove generacije nekoliko lijekova koji ciljano djeluju na mikrotubule. Ovdje donosimo najnovije spoznaje o njihovim koristima, pristupima liječenju, prednostima i izazovima u istraživanju

Tubulin-binding dibenz[c,e]oxepines: Part 2 Structural variation and biological evaluation as tumour vasculature disrupting agents

5,7-Dihydro-3,9,10,11-tetramethoxybenz[c,e]oxepin-4-ol 1, prepared from a dibenzyl ether precursor via Pd-catalysed intramolecular direct arylation, possesses broad-spectrum in vitro cytotoxicity towards various tumour cell lines, and induces vascular shutdown, necrosis and growth delay in tumour xenografts in mice at sub-toxic doses. The biological properties of 1 and related compounds can be attributed to their ability to inhibit microtubule assembly at the micromolar level, by binding reversibly to the same site of the tubulin αβ-heterodimer as colchicine 2 and the allocolchinol, N-acetylcolchinol 4

Guillaume Des Autels, "J'ayme ma Sainte en tout bien et honneur", 1550

"De son amour[1]." Texte J’ayme ma Sainte[2] en tout bien et honneur, Et ne pretends rien, sinon qu’elle m’ayme, Je ne veuil[3] point avoir d’autre bonheur Pour satisfaire à mon amour extreme.  Mais si un autre est aymé d’elle mesme[4], Et peult au bien que je n’espere atteindre[5], Vien t’en, ô Mort, soudain ma vie estreindre, Car de regret je languiray aussi. Je crains cela et ce qui me fait craindre Est que souvent Amour se joue ainsi. Source : Repos de plus grand travail, 1550. Notes [1..

Characterization and modeling of the behaviour and the failure of thermoplastics in a wide strain-rate range and temperature

De nos jours les matériaux polymères sont omniprésents dans l’habitacle d’un véhicule. C’est le cas notamment pour les composants comme la planche de bord ou les panneaux de portes. Ces éléments sont soumis à des cahiers des charges imposés par les réglementations internationales pour minimiser les blessures occasionnées à l’occupant en cas d’accident. Il est donc indispensable de caractériser les propriétés mécaniques de ces matériaux par des essais physiques impliquant différents cas de chargement sur de larges gammes de vitesse de sollicitation et de température. Les données recueillies permettent ainsi d’alimenter des modèles de comportement numériques censés reproduire avec fidélité le comportement complet d’un polymère, si possible jusqu’à rupture, en prenant en compte toutes ses spécificités. En effet, dans un souci d’optimisation des coûts de développement, la simulation numérique est aujourd’hui un outil incontournable dans la conception et le dimensionnement de composants. Ainsi dans le cadre de ces travaux, il est proposé de caractériser le comportement complet d’un polymère semi-cristallin jusqu’à la rupture pour une gamme étendue de vitesse de déformation et de température. Dans un premier temps, des DMA et des essais de traction sont réalisés pour caractériser les propriétés viscoélastiques-viscoplastiques du matériau. Puis la notion de principe d’équivalence temps/température est introduite et vérifiée expérimentalement dans les deux domaines. Un modèle basé sur les équations constitutives développées par Balieu et al. et enrichi grâce à ce principe est alors identifié puis implémenté dans le code de calcul Ls Dyna. Il est validé par comparaison à divers résultats expérimentaux. Dans un second temps, les travaux portent sur la caractérisation expérimentale et la modélisation de la rupture. Après avoir défini des géométries d’éprouvettes permettant d’atteindre des taux de triaxialité variés, des essais à rupture sont réalisés à différentes vitesses de déformation pour deux températures +23 et -30°C. Une surface de comportement à rupture est ainsi identifiée et introduite dans le modèle de rupture GISSMO. Le modèle complet, i.e. associant les lois de comportement et de rupture, et ensuite validé en comparaison à des résultats expérimentaux sur éprouvettes, mais également sur démonstrateur industriel.Nowadays, polymers are used for the interior parts of vehicles. It is particularly the case for components such as dashboards and door panels. These elements are submitted to requirements imposed by international regulations in order to minimize the injuries of the passengers in case of a car crash. It is therefore essential to characterize the mechanical properties of those polymeric materials for several load cases on a wide range of strain-rate and temperature. The collected data can be used to fill numerical behavior models supposed to accurately predict the whole behavior of a polymer, if possible up the failure, taking all polymer behavior specificities into account. Indeed, aiming at optimizing development costs, numerical simulation is currently a key tool in the design of engineering components. Thus, in this thesis work, it is proposed to characterize the complete whole behavior of a semi-crystalline polymer in a wide range of strain-rate and temperature until failure. First, some DMA and tensile tests are carried out in order to characterize the viscoelastic and viscoplastic properties of the material. Then, time-temperature-superposition principle is introduced and validated in the two domains. A model based on the constitutive equations developed by Balieu and al. and enriched thanks to this principle is identified and implemented in the Ls Dyna code. It is validated by comparison with experimental results. Secondly, the work focusses on the experimental characterization and the modelling of failure. Several specimen geometries are designed to reach some specific triaxiality ratios and are tested at different strain-rates and two temperatures +23 and -30°C. A failure behavior surface is thus identified and introduced in the GISSMO failure model. The complete model of behavior, i.e. constituted of behavior laws and failure criterion, is then validated based on comparison with experimental data extracted from tests on specimens, but also on an industrial demonstrator