Synthesis of novel pyrophosphorothiolate-linked dinucleoside cap analogues in a ball mill

Michaelis–Arbuzov reactions of S-aryl disulfide derivatives of 3′-thiothymidine or 5′-thioadenosine with tris(trimethylsilyl) phosphite proceeded in high yields to the corresponding phosphorothiolate monoesters. Subsequent hydrolytic desilylation and phosphate coupling were effected in one-pot using liquid-assisted grinding in a vibration ball mill. Novel 3′,5′- and 5′,5′-pyrophosphorothiolate-linked dinucleoside cap analogues were thereby prepared.

A novel inhibitor of channel activating proteases: Putting the CAP on ENaC

Background: Excessive activation of epithelial sodium channels (ENaC) contributes to CF lung pathophysiology due to the resultant dehydration of the airway surface liquid (ASL) and impaired mucociliary clearance. Regulated proteolysis of the endogenous α and γ subunits of ENaC by apical membrane-bound Channel Activating Proteases (CAPs) is a fundamental regulatory mechanism for channel activity. In the CF lung a stark imbalance between the levels of CAPs and their natural inhibitors drives the activation of normally inactive ENaC. On this basis inhibition of CAPs-ENaC signalling represents a potential therapeutic intervention. To this end we have developed a novel cell impermeable active-site directed compound (QUB-TL1) designed to inactivate key trypsin-like CAPs highly relevant in this regard. Objectives & Methods: Utilize differentiated non-CF and CF human airway epithelial cells to assess the impact of QUB-TL1 on a range of parameters including surface CAP activities, ENaC subunit processing/channel activity, ASL height and mucociliary clearance. Results: Treatment of airway epithelial cells with QUB-TL1 results in the significant downregulation of key endogenous CAP activities found to be excessively active at the surface of CF cultures. QUB-TL1-mediated CAP inhibition subsequently causes the internalisation of a pool of processed (active) ENaCγ prominent at the apical surface of CF cultures which correlates with a decline in channel activity. This downregulation of ENaC activity results in an increase in ASL height and improved mucociliary clearance in CF cells. We further find QUB-TL1 uniquely inhibits the ENaC activating enzyme furin, which is in contrast to the alternate trypsin-like CAP inhibitors camostat mesylate and aprotinin. QUB-TL1-mediated furin inhibition correlates with a reduction in neutrophil elastase-induced ENaC activation. Moreover we find QUB-TL1 treatment protects CF cultures from Pseudomonas aeruginosa exotoxin A-induced cytotoxicity. Pseudomonas aeruginosa exotoxin A is a major toxic product activated by furin and positively associated with mortality. Conclusion: The novel inhibitor (QUB-TL1) dampens CAPs-ENaC signalling which improves hydration status mucociliary clearance in CF airway epithelial cell cultures. Moreover this compound provides additional benefit by preventing Pseudomonas aeruginosa exotoxin A-induced cytotoxicity.

Detecting Submerged Macrophytes in a UK Chalk Stream Using Field Spectroscopy

Various studies using optical remote sensing in the marine environment have shown the possibilities of spectral discrimination of benthic macro and micro-algae. For in-land water bodies only very recently studies of have explored similar use of optical remote sensing to identify the taxonomic composition of algae and rooted plant communities. The importance of these communities for the functioning of river ecosystems warrants further research. In the study presented here, field spectroscopy is used to assess the possibilities of optically detecting macrophytes in a UK chalk streams. Spectral signatures of four common macrophytes were measured using a hand-held GER1500 spectroradiometer. Despite the strong absorption of near infrared in water, the results show that information on NIR can clearly contribute to the detection of submerged vegetation in shallow UK chalk stream environments. Observed spectra compare well with simulated submerged vegetation spectra, based on water absorption coefficients only. The field investigations, which were performed in the river Wylye, also indicate the confounding effects of specular reflection from riparian vegetation. The results of this study can inform remote sensing studies of the riverine environment using multi-spectral/low altitude sensors. Such larger scale studies will be highly beneficial for monitoring variation in chalk stream bioindicators, such as ranunculus.

Quantifying Submerged Fluvial Topography Using Hyperspatial Resolution UAS Imagery and Structure From Motion Photogrammetry.

Quantifying the topography of rivers and their associated bedforms has been a fundamental concern of fluvial geomorphology for decades. Such data, acquired at high temporal and spatial resolutions, are increasingly in demand for process-oriented investigations of flow hydraulics, sediment dynamics and in-stream habitat. In these riverine environments, the most challenging region for topographic measurement is the wetted, submerged channel. Generally, dry bed topography and submerged bathymetry are measured using different methods and technology. This adds to the costs, logistical challenges and data processing requirements of comprehensive river surveys. However, some technologies are capable of measuring the submerged topography. Through-water photogrammetry and bathymetric LiDAR are capable of reasonably accurate measurements of channel beds in clear water. Whilst the cost of bathymetric LiDAR remains high and its resolution relatively coarse, the recent developments in photogrammetry using Structure from Motion (SfM) algorithms promise a fundamental shift in the accessibility of topographic data for a wide range of settings. Here we present results demonstrating the potential of so called SfM-photogrammetry for quantifying both exposed and submerged fluvial topography at the mesohabitat scale. We show that imagery acquired from a rotary-winged Unmanned Aerial System (UAS) can be processed in order to produce digital elevation models (DEMs) with hyperspatial resolutions (c. 0.02 m) for two different river systems over channel lengths of 50-100 m. Errors in submerged areas range from 0.016 m to 0.089 m, which can be reduced to between 0.008 m and 0.053 m with the application of a simple refraction correction. This work therefore demonstrates the potential of UAS platforms and SfM-photogrammetry as a single technique for surveying fluvial topography at the mesoscale (defined as lengths of channel from c.10 m to a few hundred metres). This article is protected by copyright. All rights reserved.

Stade Bergeyre, [football] association, 7/3/20, équipe CAP [Cercle athlétique de Paris] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58359

9/5/20, stade Bergeyre, [football] association, équipe [du] CAP [Club Athlétique de Paris] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59211

Boethius, De institutione arithmetica, cum commentariis (2-36). - Gerbertus Remensis, Scholium ad Boethii Arithmeticam Institutionem, lib. II, cap. 1 (36) [fragment].

Au f. 36, une main du XIIIe s. a ajouté un passage du traité de Gerbert intitulé "Scholium ad Boethii Arithmeticam Institutionem".

Chronica Caroli sexti, l. XXXIX, cap. 8 - l. XLIII [chronique latine du religieux de Saint-Denis, 1418-1422].

D'après L. Delisle, ce ms. a appartenu à Antoine Lancelot, inspecteur du collège royal en 1732, qui fit don de ses livres à la Bibliothèque royale en 1733. Lancelot.

1.° De miraculis sanctissimae Dei genitricis Virginis Mariae liber, qui à Caesario lib. 7. cap. 44. annotante Petro Francisco Chiffletio, laudatur sub nomine libri miraculorum Claraevallis, videturque pars esse libri miraculorum jussu Joannis, Prioris Claraevallis, conscripti. — 2.° Libri tres de miraculis diversis : authore Herberto, primùm Monacho Claraevallensi, postea Turrium in Sardinia Episcopo.

Colbertinus