A method for assessing the scientific and additional values of geomorphosites

Abstract. Over the last two decades, several methods have been developed to reduce subjectivity of geomorphosite selection through use of transparent assessment criteria. Most of these methods propose criteria such as integrity, rarity, representativeness and palaeogeographical importance for the evaluation of the «scientific value» of sites. For the assessment of their global quality, «additional values» of ecological, cultural, aesthetic and economic nature have, at times, been taken into consideration. This paper proposes a new assessment method that integrates both sets of values into the evaluation of geomorphosites. The method is described and its implementation in two different cases presented: compilation of an inventory of geomorphosites in the National Park of Adula (Ticino, Switzerland) and evaluation of the geocultural heritage of the Trient area (Valais, Switzerland). </jats:p

Prospection géophysique multi-méthodes du pergélisol alpin dans le Sud des Alpes Suisses

La prospection géophysique multi-méthodes du pergélisol alpin dans la Valle di Sceru (sud des Alpes suisses, Canton du Tessin) à l’aide de méthodes thermiques (température des sources et de la surface du sol), à l’aide de méthodes thermiques (température des sources et de la surface du sol), de résistivité (sondage géoélectrique) et électromagnétiques (VLF-R et conductivimètre EM31) a permis de déterminer la répartition et les caractéristiques du pergélisol dans les glaciers rocheux et les éboulis étudiés. La répartition du pergélisol dans les glaciers rocheux est assez homogène et généralement contrôlée par les conditions topoclimatiques du site. Pour les éboulis, au contraire, l’extension spatiale du pergélisol est le plus souvent hétérogène et la probabilité d’occurrence du pergélisol diminue en direction du haut du versant. Les processus qui semblent contrôler la répartition du pergélisol dans les éboulis sont les échanges d’air advectifs, la redistribution de la neige (par le vent et les avalanches) et le granoclassement longitudinal. L’étude a également permis de tester les méthodes électromagnétiques utilisées et de les valider pour la prospection du pergélisol alpin.The multi-method geophysical prospecting of alpine permafrost in the Sceru Valley (southern Swiss Alps, Ticino Canton) with thermal methods (spring temperature and ground surface temperature monitoring), DC-resistivity method (Vertical Electrical Sounding) and electromagnetic methods (VLF-R and conductivity-meter EM 31), allowed determining the permafrost distribution and characteristics in the investigated rockglaciers and talus slopes. The permafrost distribution is quite homogeneous in the rockglaciers, where it is generally controlled by the topoclimatic conditions of the site. In the talus slopes, the permafrost distribution is quite heterogeneous and the probability of permafrost occurrence decreases upslope. The main processes controlling this particular permafrost distribution are the chimney effect, the redistribution of snow by wind and avalanches and, finally, the increase of grain size downslope. The study also allowed testing electromagnetic methods and to validating their application in the prospecting of alpine permafrost

Homology modeling and dynamics of the extracellular domain of rat and human neuronal nicotinic acetylcholine receptor subtypes α4β2 and α7

In recent years, it has become clear that the neuronal nicotinic acetylcholine receptor (nAChR) is a valid target in the treatment of a variety of diseases, including Alzheimer's disease, anxiety, and nicotine addiction. As with most membrane proteins, information on the three-dimensional (3D) structure of nAChR is limited to data from electron microscopy, at a resolution that makes the application of structure-based design approaches to develop specific ligands difficult. Based on a high-resolution crystal structure of AChBP, homology models of the extracellular domain of the neuronal rat and human nAChR subtypes α4β2 and α7 (the subtypes most abundant in brain) were built, and their stability assessed with molecular dynamics (MD). All models built showed conformational stability over time, confirming the quality of the starting 3D model. Lipophilicity and electrostatic potential studies performed on the rat and human α4β2 and α7 nicotinic models were compared to AChBP, revealing the importance of the hydrophobic aromatic pocket and the critical role of the α-subunit Trp—the homolog of AChBP-Trp 143—for ligand binding. The models presented provide a valuable framework for the structure-based design of specific α4β2 nAChR subtype ligands aimed at improving therapeutic and diagnostic applications. Figure Electrostatic surface potential of the binding site cavity of the neuronal nicotinic acetylcholine receptor (nAChR). Nicotinic models performed with the MOLCAD program: a rat α7, b rat α4β2, c human α7, d human α4β2. All residues labeled are part of the α7 (a,c) or α4 (b,d) subunit with the exception of Phe 117, which belongs to subunit β2 (d). Violet Very negative, blue negative, yellow neutral, red very positiv

Breaking the Aggregation of the Monoclonal Antibody Bevacizumab (Avastin®) by Dexamethasone Phosphate: Insights from Molecular Modelling and Asymmetrical Flow Field-Flow Fractionation

ABSTRACT: Purpose: To investigate the mechanism behind the aggregation breaking properties of dexamethasone phosphate and related corticosteroids on the IgG1 antibody bevacizumab (Avastin®). Methods: An in silico 3D dimer model is developed to identify the bevacizumab-bevacizumab interface, and different corticosteroids are docked onto the model to distinguish preferred binding sites. In silico predictions are validated by in vitro stability studies, where the antibody is stressed in presence or absence of each corticosteroid and formed aggregates are quantified by asymmetrical flow field-flow fractionation. Results: The dimer model features one close crystal contact area: Lys445 on the Fc region interacts with one Fab arm of the second bevacizumab. Docking reveals an interaction between the phosphate group of dexamethasone phosphate and Lys445, while the rest of the molecule is hindering dimer formation. Predictions are confirmed in vitro, demonstrating that dexamethasone phosphate and betamethasone phosphate partly prevent antibody aggregation, whereas triamcinolone acetonide phosphate does not. Conclusions: Results suggest that bevacizumab monomers follow a specific mechanism to form dimers in which a protein-protein interaction hotspot can be distinguished. The dimer formation can be hindered by corticosteroids in a specific way. This approach allows a simple way to stabilize IgG1 antibodie