Mesure du rendement absolu de radioluminescence des scintillateurs liquides à base de benzène et de ses dérivés méthylés

On décrit une méthode expérimentale permettant d'évaluer le rendement absolu de scintillation et on présente les résultats obtenus avec des solutions de α-naphtyl-2 phényl-5 oxazole (α-NPO) à 5 g/1 dans le benzène et ses dérivés méthylés. Les valeurs trouvées (0,020 ± 0,002 dans le cas du benzène privé d'oxygène) sont notablement inférieures à celles antérieurement rapportées dans la littérature. On indique également les rendements radiolytiques de formation des états excités singulets du solvant (Gs1 = 0,98 pour le benzène) que l'on déduit de ces mesures

The mutational impact of culturing human pluripotent and adult stem cells

Genetic changes acquired during in vitro culture pose a risk for the successful application of stem cells in regenerative medicine. To assess the genetic risks induced by culturing, we determined all mutations in individual human stem cells by whole genome sequencing. Individual pluripotent, intestinal, and liver stem cells accumulate 3.5 ± 0.5, 7.2 ± 1.1 and 8.3 ± 3.6 base substitutions per population doubling, respectively. The annual in vitro mutation accumulation rate of adult stem cells is nearly 40-fold higher than the in vivo mutation accumulation rate. Mutational signature analysis reveals that in vitro induced mutations are caused by oxidative stress. Reducing oxygen tension in culture lowers the mutational load. We use the mutation rates, spectra, and genomic distribution to model the accumulation of oncogenic mutations during typical in vitro expansion, manipulation or screening experiments using human stem cells. Our study provides empirically defined parameters to assess the mutational risk of stem cell based therapies

Photochemical activation of TRPA1 channels in neurons and animals

Optogenetics is a powerful research tool because it enables high-resolution optical control of neuronal activity. However, current optogenetic approaches are limited to transgenic systems expressing microbial opsins and other exogenous photoreceptors. Here, we identify optovin, a small molecule that enables repeated photoactivation of motor behaviors in wild type animals. Surprisingly, optovin's behavioral effects are not visually mediated. Rather, photodetection is performed by sensory neurons expressing the cation channel TRPA1. TRPA1 is both necessary and sufficient for the optovin response. Optovin activates human TRPA1 via structure-dependent photochemical reactions with redox-sensitive cysteine residues. In animals with severed spinal cords, optovin treatment enables control of motor activity in the paralyzed extremities by localized illumination. These studies identify a light-based strategy for controlling endogenous TRPA1 receptors in vivo, with potential clinical and research applications in non-transgenic animals, including humans

Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed

Radioluminescence des milieux organiques I. Étude cinétique

A description is given of the formation, the evolution and the spatial arrangement of activated molecules in organic scintillators excited by high energy particles. The kinetics of the prompt and the delayed scintillation components are described. The prompt emission is shown to result from molecular excitation in upper singlet states, followed by internal conversion to the lowest singlet level responsible for fluorescence emission. The delayed component is attributed to emission from singlet states formed during the encounter of two triplet excitons in the particle track. Equations are obtained defining the time dependence of intensity and the integrated intensities of both components, in the case of pure or binary systems containing or not quenching substances like molecular oxygen.Afin de préciser l'origine des deux composantes de la radioluminescence des milieux organiques, on analyse l'ensemble des processus élémentaires conduisant à la formation des états excités moléculaires responsables de l'émission de lumière dans les scintillateurs organiques soumis à des rayonnements corpusculaires de grande énergie. On est ainsi amené à attribuer l'émission prompte à la désactivation radiative de molécules excitées directement dans un état singulet lors du passage des particules ionisantes. L'émission différée est due aux états singulets résultant de l'interaction de deux excitons triplets dans la trace des corpuscules chargés. On établit les expressions théoriques des intensités instantanée et intégrée de la radioluminescence de milieux aromatiques purs et de systèmes binaires, contenant ou non des substances inhibitrices comme l'oxygène

Influence de la température sur les photomultiplicateurs

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