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71.
Dr. Sophie Vichier-Guerre Dr. Therese C. Ku Dr. Sylvie Pochet Prof. Katherine L. Seley-Radtke 《Chembiochem : a European journal of chemical biology》2020,21(10):1412-1417
The structurally unique “fleximer” nucleosides were originally designed to investigate how flexibility in a nucleobase could potentially affect receptor–ligand recognition and function. Recently they have been shown to have low-to-sub-micromolar levels of activity against a number of viruses, including coronaviruses, filoviruses, and flaviviruses. However, the synthesis of distal fleximers in particular has thus far been quite tedious and low yielding. As a potential solution to this issue, a series of proximal fleximer bases (flex-bases) has been successfully coupled to both ribose and 2′-deoxyribose sugars by using the N-deoxyribosyltransferase II of Lactobacillus leichmannii (LlNDT) and Escherichia coli purine nucleoside phosphorylase (PNP). To explore the range of this facile approach, transglycosylation experiments on a thieno-expanded tricyclic heterocyclic base, as well as several distal and proximal flex-bases were performed to determine whether the corresponding fleximer nucleosides could be obtained in this fashion, thus potentially significantly shortening the route to these biologically significant compounds. The results of those studies are reported herein. 相似文献
72.
73.
Oxana Kazakova Irina Smirnova Elena Tretyakova Ren Csuk Sophie Hoenke Lucie Fischer 《International journal of molecular sciences》2021,22(4)
Semi-synthetic triterpenoids, holding an amino substituted seven-membered A-ring (azepano-ring), which could be synthesized from triterpenic oximes through a Beckmann type rearrangement followed by a reduction of lactame fragment, are considered to be novel promising agents exhibiting anti-microbial, alpha-glucosidase, and butyrylcholinesterase inhibitory activities. In this study, in an attempt to develop new antitumor candidates, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives of betulin, oleanolic, ursolic, and glycyrrhetinic acids were evaluated for their cytotoxic activity against five human cancer cell lines and non-malignant mouse fibroblasts by means of a colorimetric sulforhodamine assay. Azepanoallobetulinic acid amide derivative 11 was the most cytotoxic compound of this series but showed little selectivity between the different human tumor cell lines. Flow cytometry experiments showed compound 11 to act mainly by apoptosis (44.3%) and late apoptosis (21.4%). The compounds were further screened at the National Cancer Institute towards a panel of 60 cancer cell lines. It was found that compounds 3, 4, 7, 8, 9, 11, 15, 16, 19, and 20 showed growth inhibitory (GI50) against the most sensitive cell lines at submicromolar concentrations (0.20–0.94 μM), and their cytotoxic activity (LC50) was also high (1–6 μM). Derivatives 3, 8, 11, 15, and 16 demonstrated a certain selectivity profile at GI50 level from 5.16 to 9.56 towards K-562, CCRF-CEM, HL-60(TB), and RPMI-8226 (Leukemia), HT29 (Colon cancer), and OVCAR-4 (Ovarian cancer) cell lines. Selectivity indexes of azepanoerythrodiol 3 at TGI level ranged from 5.93 (CNS cancer cell lines SF-539, SNB-19 and SNB-75) to 14.89 for HCT-116 (colon cancer) with SI 9.56 at GI50 level for the leukemia cell line K-562. The present study highlighted the importance of A-azepano-ring in the triterpenic core for the development of novel antitumor agents, and a future aim to increase the selectivity profile will thus lie in the area of modifications of azepano-triterpenic acids at their carboxyl group. 相似文献
74.
Daniel J. Owens Julien Messant Sophie Moog Mark Viggars Arnaud Ferry Kamel Mamchaoui Emmanuelle Lacne Norma Romro Astrid Brull Gisle Bonne Gillian Butler-Browne Catherine Coirault 《International journal of molecular sciences》2021,22(1)
Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the LMNA gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with LMNA mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery–Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and LMNA-related congenital muscular dystrophy (LMNA-CMD). Although the exact pathophysiological mechanisms responsible for LMNA-CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth. Using human muscle stem cells (MuSCs) carrying LMNA-CMD mutations, we observe impaired myogenic fusion with disorganized cadherin/β catenin adhesion complexes. We show that skeletal muscle from Lmna-CMD mice is unable to hypertrophy in response to functional overload, due to defective fusion of activated MuSCs, defective protein synthesis and defective remodeling of the neuromuscular junction. Moreover, stretched myotubes and overloaded muscle fibers with LMNA-CMD mutations display aberrant mechanical regulation of the yes-associated protein (YAP). We also observe defects in MuSC activation and YAP signaling in muscle biopsies from LMNA-CMD patients. These phenotypes are not recapitulated in closely related but less severe EDMD models. In conclusion, combining studies in vitro, in vivo, and patient samples, we find that LMNA-CMD mutations interfere with mechanosignaling pathways in skeletal muscle, implicating A-type lamins in the regulation of skeletal muscle growth. 相似文献
75.
Sophie Bresch Björn Mieller Daniela Schönauer-Kamin Ralf Moos Timmy Reimann Fabien Giovannelli Torsten Rabe 《Journal of the American Ceramic Society》2021,104(2):917-927
Calcium cobaltite Ca3Co4O9, abbreviated Co349, is a promising thermoelectric material for high-temperature applications in air. Its anisotropic properties can be assigned to polycrystalline parts by texturing. Tape casting and pressure-assisted sintering (PAS) are a possible future way for a cost-effective mass-production of thermoelectric generators. This study examines the influence of pressure and dwell time during PAS at 900°C of tape-cast Co349 on texture and thermoelectric properties. Tape casting aligns lentoid Co349. PAS results in a textured Co349 microstructure with the thermoelectrically favorable ab-direction perpendicular to the pressing direction. By pressure variation during sintering, the microstructure of Co349 can be tailored either toward a maximum figure of merit as required for energy harvesting or toward a maximum power factor as required for energy harvesting. Moderate pressure of 2.5 MPa results in 25% porosity and a textured microstructure with a figure of merit of 0.13 at 700°C, two times higher than the dry-pressed, pressureless-sintered reference. A pressure of 7.5 MPa leads to 94% density and a high power factor of 326 µW/mK2 at 800°C, which is 11 times higher than the dry-pressed reference (30 MPa) from the same powder. 相似文献
76.
77.
Fire hazard in nuclear power plants (NPPs) is particularly often investigated as potential cause of safety equipment failure and confinement loss. Many fire events recorded in NPPs involve electric cables, widely used throughout facilities. IRSN is developing the CALIF3S/ISIS computational fluid dynamics software devoted to fire simulation in large‐scale confined and mechanically ventilated compartments. This paper presents two aspects of the CALIF3S/ISIS code ability to simulate fires. The first one concerns vertical and horizontal spreading of a cable tray fire in open atmosphere using an approach based on the FLASH‐CAT cable fire spread model. Resorting to the suitable parameters of the FLASH‐CAT model based on video fire analyses of tests enables to properly compute the heat release rate of the fire. The second aspect concerns the ability to simulate the evolution and consequences of fires in confined and mechanically ventilated compartments. For these cases, the heat release rate measured during the corresponding experiment is used as input data for the calculations. The predicted evolutions of pressure or gas temperatures are in relatively good accordance with the experiments. The major discrepancy concerns gas concentrations in the fire room which is attributed to a lack of information about the properties of the fuel material. 相似文献
78.
Scott Kroeker Sophie Schuller John E. C. Wren Brandon J. Greer Adel Mesbah 《Journal of the American Ceramic Society》2016,99(5):1557-1564
Sodium borosilicate base glasses modeled on French nuclear waste materials were prepared to test the dependence of crystallization product quantity and distribution on cesium‐ and molybdenum‐loading and glass cooling rate. Scanning electron microscopy shows the presence of micrometer‐sized domains of Mo‐rich crystalline precipitates. X‐ray diffraction patterns are complex but reveal the presence of sodium molybdates and CsNaMoO4·2H2O. 133Cs and 23Na magic‐angle spinning NMR spectroscopy exhibit distinct peaks for glassy and crystalline phases which can be quantified to obtain the identities of the individual compounds that are formed as well as the fractions of these nuclei in particular crystalline phases. In these model systems, 1 mol% Mo can be entirely incorporated into the glassy network whereas 2.5 and 5 mol% Mo produce significant quantities of crystalline phases, with little dependence on cooling rate. Cesium content appears to have a weak influence on crystallization behavior. Sodium molybdate and sodium‐cesium molybdate hydrate are the dominant devitrification phases in all cases. 相似文献
79.
Michaela Schubert Christian Münch Sophie Schuurman Véronique Poulain Jaroslaw Kita Ralf Moos 《Journal of the European Ceramic Society》2018,38(2):613-619
NiMn2O4+δ thermistor thick films have been successfully deposited by the so-called Aerosol Deposition Method (ADM) at room temperature on alumina substrates, Si-wafers, as well as on special planar four-wire interdigital electrode structures for high-precision electrical characterization. The NTCR films are homogeneous, completely dense and scratch resistant. Both as-deposited and tempered, the NTCR films exhibit a cubic spinel structure. Between 25 °C and 90 °C, the NTCR film resistance behaves as it is typical for variable range hopping (VRH) with parabolic density of states. As a result of moderate film tempering, the thermistor constant B and the specific resistance at 25 °C (ρ25) decrease from 4250 K to 4020 K and 65 Ω·m to 40 Ω·m respectively, and are close to bulk values. In combination with the excellent reproducibility of the ρ25 and B values, AD processing of films appears to be a promising alternative for classical ceramic bulk processes. 相似文献
80.
Alexandre Ruellan Violette Ducruet Audrey Gratia Lidia Saelices Jimenez Alain Guinault Cyrille Sollogoub Guillaume Chollet Sandra Domenek 《Polymer International》2016,65(6):683-690
Polylactide (PLA) is the most used biodegradable and biobased food packaging polymer for rigid containers and films. However, its low ductility is a hurdle for increasing its applications in flexible food packaging. A solution is the use of additives. Palm oil deodorizer distillate (PODC) is revealed to be an excellent additive promoting PLA ductility. PODC is a by‐product of vegetable oil refining, which is available in stable quality and in sufficient amounts. Amorphous PLA/PODC blends had an elongation at break of around 130% and that of semi‐crystalline blends was still around 55% compared to the initial 5% of neat PLA. At the same time the PLA rigidity and high glass transition temperatures were kept. PODC was also a very efficient processing aid, allowing for film blow extrusion. The blends were stable in properties during six months without exudation. They complied with legal norms of Food Contact Materials (EU 10/2011) and induced no sensorial alteration of packed food. Therefore PODC is a very interesting alternative to common plasticizers for the production of flexible PLA packaging films. © 2016 Society of Chemical Industry 相似文献