Explore the vast range of titles available.

The Advanced Proton Driven Plasma Wakefield Acceleration Experiment (AWAKE) is a project at CERN aiming to accelerate an electron bunch in a plasma wakefield driven by a proton bunch. The plasma is induced in a 10 m long rubidium vapor cell using a pulsed Ti:Sapphire laser, with the wakefield formed by a proton bunch from the CERN Super Proton Synchrotron (SPS). A 16 MeV electron bunch is simultaneously injected into the plasma cell to be accelerated by the wakefield to energies in the GeV range over this short distance. After successful runs with the proton and laser beams, the electron beam line was installed and commissioned at the end of 2017 to produce and inject a suitable electron bunch into the plasma cell. To achieve the goals of the experiment, it is important to have reliable beam instrumentation measuring the various parameters of the proton, electron and laser beams. This contribution presents the status of the beam instrumentation in AWAKE and reports on the performance achieved during the AWAKE runs in 2017.

With the public’s growing interest in skin whitening, lightening ingredients only used under dermatological supervision until recently, are more and more frequently incorporated into cosmetic formulas. The active agents that lighten skin tone are either natural or synthetic substances, and may act at various levels of melanogenesis. They are used to treat various skin pigmentation disorders or simply to obtain a lighter skin tone as whiter skin may be synonymous of wealth, health, youth, and/or beauty in different cultures. However, recent studies demonstrated the adverse effects of some of these ingredients, leading to their interdiction or restricted use under the European Directive and several other international regulations. After an overview of skin whitening practices and the associated risks, this article provides insight into the mechanisms involved in melanin synthesis and the biological assays available to attest the lightening activity of individual ingredients. The legislation dealing with the use of skin lighteners is then discussed. As traditional depigmenting agents such as hydroquinone and corticosteroids are of safety concern, the potential of natural extracts has been investigated more and more; finally, a synthesis of three years of research in our laboratory for such plant extracts will be given.

The ethical and ecological concerns of today’s consumers looking for both sustainable and efficient ingredients in finished products, put a lot of pressure on the cosmetic market actors who are being driven to profoundly modify the strategies adopted to innovate in terms of actives while notably being urged to switch from petroleum- to plant-based ingredients. To produce such natural cosmetic ingredients, agri-food by-products are advocated as raw material due to their reduced carbon footprint as they actively contribute to the worldwide improvement of waste management. The process to transform plant waste materials into such powerful and objectified “green” cosmetic actives in compliance with circular economy principles is a long-term integrated process. Such a development is thoroughly exemplified in the present paper through the description of the design of liquid anti-age ingredients based on Ribes nigrum L. extract. This was obtained by maceration of blackcurrant pomace. and the embodiment of this extract following its phytochemical analysis notably by HPLC-DAD-ELSD and its bioguided fractionation using in vitro bioassays.

Congenital hepatic fibrosis has been described as a lethal disease with monogenic autosomal recessive inheritance in the Swiss Franches-Montagnes horse breed. We performed a genome-wide association study with 5 cases and 12 controls and detected an association on chromosome 20. Subsequent homozygosity mapping defined a critical interval of 952 kb harboring 10 annotated genes and loci including the polycystic kidney and hepatic disease 1 (autosomal recessive) gene (PKHD1). PKHD1 represents an excellent functional candidate as variants in this gene were identified in human patients with autosomal recessive polycystic kidney and hepatic disease (ARPKD) as well as several mouse and rat mutants. Whereas most pathogenic PKHD1 variants lead to polycystic defects in kidney and liver, a small subset of the human ARPKD patients have only liver symptoms, similar to our horses with congenital hepatic fibrosis. The PKHD1 gene is one of the largest genes in the genome with multiple alternative transcripts that have not yet been fully characterized. We sequenced the genomes of an affected foal and 46 control horses to establish a comprehensive list of variants in the critical interval. We identified two missense variants in the PKHD1 gene which were strongly, but not perfectly associated with congenital hepatic fibrosis. We speculate that reduced penetrance and/or potential epistatic interactions with hypothetical modifier genes may explain the imperfect association of the detected PKHD1 variants. Our data thus indicate that horses with congenital hepatic fibrosis represent an interesting large animal model for the liver-restricted subtype of human ARPKD.

When it comes to the development of new active ingredients for cosmetics, biodiversity is a rich source for inspiration that must be tapped in a sustainable manner to cause no social nor ecological damage. Agri-food by-products are therefore more and more considered as available biomass that can be reused to extract their maximum value to produce new cosmetic ingredients before returning to the biosphere. The process to transform plant waste materials into powerful cosmetic actives is thoroughly described in the present paper via the example of the design of a liquid anti-aging ingredient based on a Prunus domestica L. extract obtained by maceration of plums’ dried leaves in propylene glycol. The subsequent development of an SPE (solid-phase extraction) methodology used to remove the propylene glycol to get access to the extracted molecules is thoroughly described as a means to follow the stability of the ingredient over time once formulated into a finished product.

Melon (Cucumis melo L.) is a global crop in terms of economic importance and nutritional quality. The aim of this study was to explore the variability in metabolite and elemental composition of several commercial varieties of melon in various environmental conditions. Volatile and non-volatile metabolites as well as mineral elements were profiled in the flesh of mature fruit, employing a range of complementary analytical technologies. More than 1,000 metabolite signatures and 19 mineral elements were determined. Data analyses revealed variations related to factors such as variety, growing season, contrasting agricultural management practices (greenhouse vs. field with or without fruit thinning) and planting date. Two hundred and ninety-one analytes discriminated two contrasting varieties, one from the var. inodorous group and the other from the var. cantaloupensis group. Two hundred and eighty analytes discriminated a short shelf-life from a mid-shelf-life variety within the var. cantaloupensis group. Three hundred and twenty-seven analytes discriminated two seasons, and two hundred and fifty-two analytes discriminated two contrasting agricultural management practices. The affected compound families greatly depended on the factor studied. The compositional variability of identified or partially identified compounds was used to study metabolite and mineral element co-regulation using correlation networks. The results confirm that metabolome and mineral element profiling are useful diagnostic tools to characterize the quality of fruits cultivated under commercial conditions. They can also provide knowledge on fruit metabolism and the mechanisms of plant response to environmental modifications, thereby paving the way for metabolomics-guided improvement of cultural practices for better fruit quality.

Skin whitening agents occupy an important part of the dermo-cosmetic market nowadays. They are used to treat various skin pigmentation disorders, or simply to obtain a lighter skin tone. The use of traditional skin bleachers (e.g., hydroquinone, corticoids) is now strictly regulated due to their side effects. When considering this and the growing consumers’ interest for more natural ingredients, plant extracts can be seen as safe and natural alternatives. In this perspective, in vitro bioassays were undertaken to assess cosmetic potential of Reseda luteola, and particularly its promising whitening activities. A bioguided purification procedure employing centrifugal partition chromatography, Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-HRMS) and NMR was developed to isolate and identify the whitening agents (i.e., luteolin and apigenin) from aerial parts of R. luteola. UPLC-HRMS also enabled the characterization of acetylated luteolin- and apigenin-O-glycosides, which occurrence is reported for the first time in R. luteola.

Consumers pay more and more attention not just to the safety and health aspects of ingredients entering their cosmetics’ formulations, but also to their potency, origin, processing, ethical value and environmental footprint. Sustainability of the supply chain, preservation of biodiversity, as well as greener extraction techniques are hence very popular with consumers. Consumers are primarily concerned by the efficacy of the cosmetic products they use and continuously scrutinize product labels, so marketing arguments need to be based on rigorous testing and reliable results to support claims (anti-age, anti-pollution, etc.) displayed on the product’s packaging. As a result, the increasing demand for natural ingredients with assessed bioactivities has profoundly modified the strategies adopted by cosmetic professionals to innovate in terms of actives. Sourcing and developing new natural cosmetic actives is a long-term procedure that is thoroughly described in the present paper, via the example of the design of both liquid and solid ingredients based on Quercus pubescens Willd. leaves extract, for which anti-age properties were assessed by a combination of in vitro assays.

An electro-osmotic model is developed to examine the influence of plasma membrane superficial charges on the regulation of cell ionic composition. Assuming membrane osmotic equilibrium, the ion distribution predicted by Gouy-Chapman-Grahame (GCG) theory is introduced into ion transport equations, which include a kinetic model of the Na/K-ATPase based on the stimulation of this ion pump by internal Na + ions. The algebro-differential equation system describing dynamics of the cell model has a unique resting state, stable with respect to finite-sized perturbations of various types. Negative charges on the membrane are found to greatly enhance relaxation toward steady state following these perturbations. We show that this heightened stability stems from electrostatic interactions at the inner membrane side that shift resting state coordinates along the sigmoidal activation curve of the sodium pump, thereby increasing the pump sensitivity to internal Na + fluctuations. The accuracy of electrostatic potential description with GCG theory is proved using an alternate formalism, based on irreversible thermodynamics, which shows that pressure contribution to ion potential energy is negligible in electrostatic double layers formed at the surfaces of biological membranes. We discuss implications of the results regarding a reliable operation of ionic process coupled to the transmembrane electrochemical gradient of Na + ions.

Congenital hepatic fibrosis has been described as a lethal disease with monogenic autosomal recessive inheritance in the Swiss Franches-Montagnes horse breed. We performed a genome-wide association study with 5 cases and 12 controls and detected an association on chromosome 20. Subsequent homozygosity mapping defined a critical interval of 952 kb harboring 10 annotated genes and loci including the polycystic kidney and hepatic disease 1 (autosomal recessive) gene (PKHD1). PKHD1 represents an excellent functional candidate as variants in this gene were identified in human patients with autosomal recessive polycystic kidney and hepatic disease (ARPKD) as well as several mouse and rat mutants. Whereas most pathogenic PKHD1 variants lead to polycystic defects in kidney and liver, a small subset of the human ARPKD patients have only liver symptoms, similar to our horses with congenital hepatic fibrosis. The PKHD1 gene is one of the largest genes in the genome with multiple alternative transcripts that have not yet been fully characterized. We sequenced the genomes of an affected foal and 46 control horses to establish a comprehensive list of variants in the critical interval. We identified two missense variants in the PKHD1 gene which were strongly, but not perfectly associated with congenital hepatic fibrosis. We speculate that reduced penetrance and/or potential epistatic interactions with hypothetical modifier genes may explain the imperfect association of the detected PKHD1 variants. Our data thus indicate that horses with congenital hepatic fibrosis represent an interesting large animal model for the liver-restricted subtype of human ARPKD.