Approche géographique du terroir du Kirsch à Fougerolles

National audienceA la frontière de la Franche-Comté et de la Lorraine, la localité de Fougerolles et le finage qui l'entoure sont le lieu d'une production originale : la culture de cerisiers, dont les fruits, après fermentation et distillation, donnent naissance à une eau de vie de cerises de bonne réputatio

The drug development pipeline for glioblastoma: a cross sectional assessment of the FDA orphan drug product designation database

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumour among adult patients and represents an almost universally fatal disease. Novel therapies for GBM are being developed under the orphan drug legislation and the knowledge on the molecular makeup of this disease has been increasing rapidly. However, the clinical outcomes in GBM patients with currently available therapies are still dismal. An insight into the current drug development pipeline for GBM is therefore of particular interest. OBJECTIVES: To provide a quantitative clinical-regulatory insight into the status of FDA orphan drug designations for compounds intended to treat GBM. METHODS: Quantitative cross-sectional analysis of the U.S. Food and Drug Administration Orphan Drug Product database between 1983 and 2020. STROBE criteria were respected. RESULTS: Four orphan drugs out of 161 (2,4%) orphan drug designations were approved for the treatment for GBM by the FDA between 1983 and 2020. Fourteen orphan drug designations were subsequently withdrawn for unknown reasons. The number of orphan drug designations per year shows a growing trend. In the last decade, the therapeutic mechanism of action of designated compounds intended to treat glioblastoma shifted from cytotoxic drugs (median year of designation 2008) to immunotherapeutic approaches and small molecules (median year of designation 2014 and 2015 respectively) suggesting an increased focus on precision in the therapeutic mechanism of action for compounds the development pipeline. CONCLUSION: Despite the fact that current pharmacological treatment options in GBM are sparse, the drug development pipeline is steadily growing. In particular, the surge of designated immunotherapies detected in the last years raises the hope that elaborate combination possibilities between classical therapeutic backbones (radiotherapy and chemotherapy) and novel, currently experimental therapeutics may help to provide better therapies for this deadly disease in the future

Degenerate epitaxy-driven defects in monolayer silicon oxide onto ruthenium

The structure of the ultimately-thin crystalline allotrope of silicon oxide, prepared onto a ruthenium surface, is unveiled down to atomic scale with chemical sensitivity, thanks to high resolution scanning tunneling microscopy and first principle calculations. An ordered oxygen lattice is imaged which coexists with the two-dimensional monolayer oxide. This coexistence signals a displacive transformation from an oxygen reconstructed-Ru(0001) to silicon oxide, along which latterally-shifted domains form, each with equivalent and degenerate epitaxial relationships with the substrate. The unavoidable character of defects at boundaries between these domains appeals for the development of alternative methods capable of producing single-crystalline two-dimensional oxides

Decentralized energy-saving hydraulic concepts for mobile working machines

The high price of batteries in working machines with electric drives offer a potential for investment in energy-saving hydraulic systems. The decentralized power network opens up new approaches for hydraulic- and hybrid circuits. In addition, the regeneration of energy can be used at any point of the machine. For the example of an excavator arm drive with a double cylinder two compact hydraulic circuits are presented, which relieve a central hydraulic system

The Early Aptian Grünten Member: Description of a new lithostratigraphic unit of the helvetic Garschella Formation

Abstract.: Early Aptian sediments mostly referred to as "upper Orbitolina beds” are known from a relatively small number of outcrop areas throughout the distal part of the Helvetic Zone of Switzerland, Austria and Germany. These sediments are here formally defined as a new, basal member of the Garschella Formation; the Grünten Member. Equivalent and correlatable sediments also exist in the Vercors region of the French Dauphinée Zone. The historical type section (holostratotype) of the Grünten Member is situated on the Grünten Mountain in southern Germany. A new type section (lectostratotype) for the Grünten Member is chosen in the better suited Bauen-Brisen area of Central Switzerland and an additional reference section (hypostratotype) is defined near the Rawil Pass in the Bernese Oberland of Switzerland. In relatively proximal settings, the Grünten Member overlies Early Aptian limestones of the Urgonian Carbonate Platform (Schrattenkalk Formation), documenting its demise and early "drowning”. In relatively distal settings, it overlies the contemporary hemipelagic sediments of the Drusberg and Mittagspitz Formations. In complete successions, the Grünten Member is in turn overlain by the basal, phosphoritic Luitere Bed of the Brisi Member (Garschella Formation) documenting the continuing "drowning” of the Urgonian Carbonate Platform in the Late Aptian. The Grünten Member essentially consists of a single stratigraphic sequence, beginning with a marly base and gradually passing to crinoidal limestones at its top. Rare ammonite finds as well as sequence stratigraphic correlations suggest a late Early Aptian age (parts of the Deshayesi and Furcata Ammonite Zones). In the relatively proximal reference section of Rawil, the Grünten Member contains two phosphoritic horizons. Phosphateenriched horizons are also known from other proximal sections of the Grünten Membe

Circuitry rewiring directly couples competence to predation in the gut dweller Streptococcus salivarius

Small distortions in transcriptional networks might lead to drastic phenotypical changes, especially in cellular developmental programs such as competence for natural transformation. Here, we report a pervasive circuitry rewiring for competence and predation interplay in commensal streptococci. Canonically, in streptococci paradigms such as Streptococcus pneumoniae and Streptococcus mutans, the pheromone-based two-component system BlpRH is a central node that orchestrates the production of antimicrobial compounds (bacteriocins) and incorporates signal from the competence activation cascade. However, the human commensal Streptococcus salivarius does not contain a functional BlpRH pair, while the competence signaling system ComRS directly couples bacteriocin production and competence commitment. This network shortcut might underlie an optimal adaptation against microbial competitors and explain the high prevalence of S. salivarius in the human digestive tract. Moreover, the broad spectrum of bacteriocin activity against pathogenic bacteria showcases the commensal and genetically tractable S. salivarius species as a user-friendly model for competence and bacterial predation

Electrically Driven Varifocal Silicon Metalens

Optical metasurfaces have shown to be a powerful approach to planar optical elements, enabling an unprecedented control over light phase and amplitude. At that stage, where a wide variety of static functionalities have been accomplished, most efforts are being directed toward achieving reconfigurable optical elements. Here, we present our approach to an electrically controlled varifocal metalens operating in the visible frequency range. It relies on dynamically controlling the refractive index environment of a silicon metalens by means of an electric resistor embedded into a thermo-optical polymer. We demonstrate precise and continuous tuneability of the focal length and achieve focal length variation larger than the Rayleigh length for voltage as small as 12 V. The system time-response is of the order of 100 ms, with the potential to be reduced with further integration. Finally, the imaging capability of our varifocal metalens is successfully validated in an optical microscopy setting. Compared to conventional bulky reconfigurable lenses, the presented technology is a lightweight and compact solution, offering new opportunities for miniaturized smart imaging devices.Peer ReviewedPostprint (author's final draft

Insertion sequence content reflects genome plasticity in strains of the root nodule actinobacterium Frankia

<p>Abstract</p> <p>Background</p> <p>Genome analysis of three <it>Frankia sp. </it>strains has revealed a high number of transposable elements in two of the strains. Twelve out of the 20 major families of bacterial Insertion Sequence (IS) elements are represented in the 148 annotated transposases of <it>Frankia </it>strain HFPCcI3 (CcI3) comprising 3% of its total coding sequences (CDS). EAN1pec (EAN) has 183 transposase ORFs from 13 IS families comprising 2.2% of its CDS. Strain ACN14a (ACN) differs significantly from the other strains with only 33 transposase ORFs (0.5% of the total CDS) from 9 IS families.</p> <p>Results</p> <p>Insertion sequences in the <it>Frankia </it>genomes were analyzed using BLAST searches, PHYML phylogenies and the IRF (Inverted Repeat Finder) algorithms. To identify putative or decaying IS elements, a PSI-TBLASTN search was performed on all three genomes, identifying 36%, 39% and 12% additional putative transposase ORFs than originally annotated in strains CcI3, EAN and ACN, respectively. The distribution of transposase ORFs in each strain was then analysed using a sliding window, revealing significant clustering of elements in regions of the EAN and CcI3 genomes. Lastly the three genomes were aligned with the MAUVE multiple genome alignment tool, revealing several Large Chromosome Rearrangement (LCR) events; many of which correlate to transposase clusters.</p> <p>Conclusion</p> <p>Analysis of transposase ORFs in <it>Frankia </it>sp. revealed low inter-strain diversity of transposases, suggesting that the majority of transposase proliferation occurred without recent horizontal transfer of novel mobile elements from outside the genus. Exceptions to this include representatives from the IS3 family in strain EAN and seven IS4 transposases in all three strains that have a lower G+C content, suggesting recent horizontal transfer. The clustering of transposase ORFs near LCRs revealed a tendency for IS elements to be associated with regions of chromosome instability in the three strains. The results of this study suggest that IS elements may help drive chromosome differences in different <it>Frankia </it>sp. strains as they have adapted to a variety of hosts and environments.</p