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The voltage-gated sodium channel Nav1.7 is encoded by

The French mouse clinic (Institut Clinique de la Souris; ICS) has produced more than 2000 targeting vectors for ‘à la carte’ mutagenesis in C57BL/6N mice. Although most of the vectors were used successfully for homologous recombination in murine embryonic stem cells (ESCs), a few have failed to target a specific locus after several attempts. We show here that co-electroporation of a CRISPR plasmid with the same targeting construct as the one that failed previously allows the systematic achievement of positive clones. A careful validation of these clones is, however, necessary as a significant number of clones (but not all) show a concatemerization of the targeting plasmid at the locus. A detailed Southern blot analysis permitted characterization of the nature of these events as standard long-range 5′ and 3′ PCRs were not able to distinguish between correct and incorrect alleles. We show that a simple and inexpensive PCR performed prior to ESC amplification allows detection and elimination of those clones with concatemers. Finally, although we only tested murine ESCs, our results highlight the risk of mis-validation of any genetically modified cell line (such as established lines, induced pluripotent stem cells or those used for ex vivo gene therapy) that combines the use of CRISPR/Cas9 and a circular double-stranded donor. We strongly advise the CRISPR community to perform a Southern blot with internal probes when using CRISPR to enhance homologous recombination in any cell type, including fertilized oocytes.

This work aims at describing the synthesis under mild conditions of amphiphilic aluminium/calcium organosilicate particles using a mixture of three organosilanes as starting material: tetraethoxysilane (TEOS), octyltriethoxysilane (OCTEO) and 3-[hydroxy(polyethyleneoxy)propyl]trimethoxysilane (4140). As opposed to the conventional synthesis, the method described here introduces a double functionalization of organosilicate particles with a tailored hydrophilic/hydrophobic ratio containing both aluminium and calcium within the inorganic layer. To investigate the influence of silane precursor ratio on the size of the particles and their ability to stabilize Pickering emulsions, we used a D-optimal mixture design methodology. The granulometric analysis revealed that the amount of OCTEO had a significant influence on obtaining visible particles, whereas successful syntheses presented a unimodal sub-micron mean distribution ranging from 650 nm to 3 μm. Elemental analysis, infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to more accurately characterize the organosilicates produced. Our results showed that a high concentration of hydrophobic silane led to particles that could stabilize concentrated water-in-silicone (W/Si) Pickering emulsions whereas more hydrophilic particles resulted in unstable silicone-in-water (Si/W) emulsions.

Birth-related torts take several forms and may be distinguished, on the one hand, according to the type of plaintiff and, on the other, according to whether the child is born healthy or handicapped. Through a study of German, American, English, and French statutes and judicial decisions, one may observe that ethical and moral considerations often interfere with the legal reasoning. Taking into account non-legal criteria sometimes leads to exonerating medical professionals from liability where this cannot be legally justified when others, whose faults are objectively less serious but without any relation to the birth of a child, are held liable without hesitation. This situation is all the more unfortunate in that it denies compensation to a whole category of victims whose damages are nevertheless very real. It is therefore left to the legal community to find realistic and reasonable solutions that are based on the law., La responsabilité civile liée à la naissance d’un enfant recouvre plusieurs hypothèses que l’on peut distinguer, d’une part, en fonction du demandeur à l’action et, d’autre part, selon que l’enfant est né sain ou handicapé. Au travers d’une étude des ordres juridiques allemand, américain, anglais et français, l’on peut constater qu’en la matière, des considérations éthiques et morales viennent bien souvent interférer avec le raisonnement juridique. La prise en compte de critères périjuridiques conduit parfois à accorder au corps médical une exonération de responsabilité, laquelle, juridiquement, ne se justifie pas, alors que d’autres fautes, objectivement moins graves mais sans lien avec la naissance d’un enfant, sont sanctionnées sans aucune hésitation. Cette situation est regrettable, d’autant plus qu’elle conduit à priver d’indemnisation toute une catégorie de victimes dont le préjudice est pourtant réel. Il s’agit donc pour le juriste de trouver des solutions réalistes et raisonnables fondées sur le droit., Demme Géraldine, Lorentz Romain. Responsabilité civile et naissance d’un enfant. Aperçu comparatif. In: Revue internationale de droit comparé. Vol. 57 N°1,2005. pp. 103-139.

This study investigates the performance of new innovation intermediaries in an open innovation framework. One promising way to open up the innovation process is to interact with innovation intermediaries either to find new co-development partners or to promote new technologies. However, the extensive literature dealing with open innovation needs to be enriched by studies highlighting the role of new innovation intermediaries at the new product development (NPD) level. To do so, this paper presents a concrete technological case study to illustrate the mechanism of innovation intermediaries in promoting under-development technologies. A qualitative research approach was used to analyse the performance of classical innovation consulting approaches when compared with web-based intermediaries also known as 'markets for technology' or 'open innovation accelerators'. The findings give a better understanding of the intrinsic performance and the added value of new intermediaries in order to open up the innovation process in the bio-industrial sectors.

Lorentz Romain. Dommage purement patrimonial, rapport français . In: Revue internationale de droit comparé. Vol. 58 N°2,2006. pp. 393-407.