Optimization of snowmaking in high mountains ski resort

Ski resorts are deploying more and more systems of artificial snow. These tools are necessary to ensure an important economic activity for the high alpine valleys. However, artificial snow raises important environmental issues that can be reduced by an optimization of its production. This paper presents a software prototype based on artificial intelligence to help ski resorts better manage their snowpack. It combines on one hand a General Neural Network for the analysis of the snow cover and the spatial prediction, with on the other hand a multiagent simulation of skiers for the analysis of the spatial impact of ski practice. The prototype has been tested on the ski resort of Verbier (Switzerland).

Artificial Snow Optimization in Winter Sport Destinations Using a Multi-agent Simulation

This paper presents the Juste-Neige system for predicting the snow height on the ski runs of a resort using a multi-agent simulation software. Its aim is to facilitate snow cover management in order to i) reduce the production cost of artificial snow and to improve the profit margin for the companies managing the ski resorts; and ii) to reduce the water and energy consumption, and thus to reduce the environmental impact, by producing only the snow needed for a good skiing experience. The software provides maps with the predicted snow heights for up to 13 days. On these maps, the areas most exposed to snow erosion are highlighted. The software proceeds in three steps: i) interpolation of snow height measurements with a neural network; ii) local meteorological forecasts for every ski resort; iii) simulation of the impact caused by skiers using a multi-agent system. The software has been evaluated in the Swiss ski resort of Verbier and provides useful predictions.

Automatic measurement of key ski jumping phases and temporal events with a wearable system.

We propose a new method, based on inertial sensors, to automatically measure at high frequency the durations of the main phases of ski jumping (i.e. take-off release, take-off, and early flight). The kinematics of the ski jumping movement were recorded by four inertial sensors, attached to the thigh and shank of junior athletes, for 40 jumps performed during indoor conditions and 36 jumps in field conditions. An algorithm was designed to detect temporal events from the recorded signals and to estimate the duration of each phase. These durations were evaluated against a reference camera-based motion capture system and by trainers conducting video observations. The precision for the take-off release and take-off durations (indoor < 39 ms, outdoor = 27 ms) can be considered technically valid for performance assessment. The errors for early flight duration (indoor = 22 ms, outdoor = 119 ms) were comparable to the trainers' variability and should be interpreted with caution. No significant changes in the error were noted between indoor and outdoor conditions, and individual jumping technique did not influence the error of take-off release and take-off. Therefore, the proposed system can provide valuable information for performance evaluation of ski jumpers during training sessions.

Combinatorial Anti-arenaviral Therapy with the Small Molecule SKI-1/S1P Inhibitor PF-429242 and Ribavirin

Arenaviruses are enveloped negative strand viruses that cause acute and chronic infections. Several Arenaviruses can cause severe hemorrhagic fever in humans. In West Africa Lassa virus causes several hundred thousand infections per year, while Junin, Machupo, Guanarito, and Sabia virus have emerged in South America. So far, only one drug is licensed against arenaviruses, the nucleoside analogue Ribavirin (Rib), which is effective when given early in disease, but shows only minor therapeutic effects in late stages of the infection. Previous works demonstrated that processing of the arenavirus glycoprotein precursor (GPC) by the cellular proprotein convertase site 1 protease (S1P), also known as subtilisin-kexinisozyme 1 (SKI-1), is crucial for cell-to-cell propagation of infectionand production of infectious virus. Recently, the SKI-1/S1P inhibitor PF-429242wasshownto inhibit Old World arenavirusGPCprocessing, cell-to-cell propagation, and infectious virus production. In the present study, we assessed the activity of PF-429242 against processing of the GPCs of the genetically and structurally more distant New World arenaviruses and found potent inhibition of processing of the GPCs of Junin, Machupo, and Guanarito virus. Using the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), we studied the potency of PF-429242 in the context of acute and chronic infection. In line with published data, PF-429242 potently inhibited acute LCMV infection. PF-429242 was also highly active against chronic infection and drug treatment resulted in rapid extinction of the virus without emergence of drug-resistant variants. In a combinatorial drug approach, we found that PF-429242 potentiated the anti-viral effect of Rib in treatment of acute andchronic infection. Taken together, we showed that the SKI-1/S1P inhibitor PF-429242 is broadly active against GPC processing of all major human pathogenic arenaviruses. Apart from being potent in acute infection, the drug is remarkably active in clearing chronic infection and potentiated the anti-arenaviral activity of Rib.

Responses to exercise in normobaric hypoxia: comparison of elite and recreational ski mountaineers.

PURPOSE: Hypoxia is known to reduce maximal oxygen uptake (VO(2max)) more in trained than in untrained subjects in several lowland sports. Ski mountaineering is practiced mainly at altitude, so elite ski mountaineers spend significantly longer training duration at altitude than their lower-level counterparts. Since acclimatization in hypobaric hypoxia is effective, the authors hypothesized that elite ski mountaineers would exhibit a VO2max decrement in hypoxia similar to that of recreational ski mountaineers. METHODS: Eleven elite (E, Swiss national team) and 12 recreational (R) ski mountaineers completed an incremental treadmill test to exhaustion in normobaric hypoxia (H, 3000 m, F(1)O(2) 14.6% ± 0.1%) and in normoxia (N, 485 m, F(1)O(2) 20.9% ± 0.0%). Pulse oxygen saturation in blood (SpO(2)), VO(2max), minute ventilation, and heart rate were recorded. RESULTS: At rest, hypoxic ventilatory response was higher (P < .05) in E than in R (1.4 ± 1.9 vs 0.3 ± 0.6 L · min⁻¹ · kg⁻¹). At maximal intensity, SpO(2) was significantly lower (P < .01) in E than in R, both in N (91.1% ± 3.3% vs 94.3% ± 2.3%) and in H (76.4% ± 5.4% vs 82.3% ± 3.5%). In both groups, SpO(2) was lower (P < .01) in H. Between N and H, VO(2max) decreased to a greater extent (P < .05) in E than in R (-18% and -12%, P < .01). In E only, the VO(2max) decrement was significantly correlated with the SpO(2) decrement (r = .74, P < .01) but also with VO(2max) measured in N (r = .64, P < .05). CONCLUSION: Despite a probable better acclimatization to altitude, VO(2max) was more reduced in E than in R ski mountaineers, confirming previous results observed in lowlander E athletes.

Characterization of SKI-1/S1P-mediated processing of Arenavirus glycoprotein precursors

Arenaviruses are rodent-born world-wide distributed negative strand RNA viruses that comprise a number of important human pathogens including Lassa virus (LASV) which causes more than 3 00'000 infections annually in Western Africa. Lymphocytic choriomeningitis virus (LCMV) is the prototypic member of the arenavirus family, which is divided in two major subgroups according to serological properties and geographical distribution, the Old World and New World arenaviruses. The envelope glycoprotein precursors (GPCs) of arenaviruses have to undergo proteolytic processing to acquire biological function and to be incorporated into progeny virions. A cellular enzyme is responsible for this processing: the Subtilisin Kexin Isozyme-1 or Site-1 protease (SKI- 1/S1P). In this thesis we have studied the relationship between SKI-1/S1P and the envelope GPs of arenaviruses. In a first project, we investigated the molecular interactions between SKI-1/SIP and arenavirus GPCs. Using SKI-1/SIP mutants, we confirmed previously published observations locating LCMV GPC and LASV GPC processing in the Late Golgi/TGN and ER/cis-Golgi, respectively. A single mutation in the cleavage site of LCMV was sufficient to re-locate SKI- 1/SIP-mediated processing from the late Golgi/TGN to the ER/cis-Golgi. We then demonstrated that the transmembrane domain, the C-terminal tail and the phosphorylation sites of SKI-1/S1P are dispensable for GPC processing. Additionally we identified a SKI- 1/S1P mutant defective for autoprocessing at site Β, B' that was selectively impaired in processing of viral GPCs but not cellular substrates. We also showed that a soluble variant of SKI-1/SIΡ was unable to cleave envelope GPs at the cell surface when added in the culture medium. This study highlighted a new target for small molecule inhibitors that would specifically impair GPC but not cellular substrate processing. In a second project, we identified and characterized two residues: LASV GPC Y253 and SKI-1/S1P Y285 that are important for the SKI-1/SIP-mediated LASV GPC cleavage. An alignment of GPC sequences revealed a conserved aromatic residue in P7 position in the GPCs of Old World and Clade C of New World arenaviruses. Mutations in GPC at position P7 impaired processing efficiency. In SKI-1/S1P, mutating Y285 into A negatively affected processing of substrates containing aromatic residues in P7, without affecting others. This property could be used to develop specific drugs targeting SKI-1/SIP-mediated cleavage of LASV GPC without affecting cellular substrates. As a third project we studied the role of the SKI-1/SIP-mediated processing and the unusual stable signal peptide (SSP) for the folding and secretion of soluble forms of the ectodomain of LASV and LCMV glycoproteins. We provide evidence that the transmembrane domain and the cytosolic tail are crucial for the stability of the prefusion conformation of arenavirus GP and that the SSP is required for transport and processing of full-length GP, but not the soluble ectodomain per se. Taken together, these results will lead to a better understanding of the complex interactions between arenavirus GPCs and SKI-1/S IP, paving the avenue for the development of novel anti-arenaviral therapeutics. - Les Arenavirus sont des virus à ARN négatif distribués mondialement et portés par les rongeurs. Cette famille de virus comprend des virus hautement pathogènes pour l'homme comme le virus de Lassa (LASV) qui cause plus de 300Ό00 infections par année en Afrique de l'Ouest. Le virus de la chorioméningite lymphocytaire (LCMV) est le représentant de cette famille qui est divisée en deux sous-groupes selon des critères sérologiques et de distributions géographiques: arenavirus du Nouveau et de l'Ancien monde. Les glycoprotéines d'enveloppe de ces virus (GPCs) doivent être clivées pour être incorporées dans le virus et ainsi lui permettre d'être infectieux. Une enzyme cellulaire est responsable de ce clivage : la Subtilisin Kexin Isozyme-1 ou protéase Site-1 (SKI-l/SlP). Dans cette thèse, nous avons étudié la relation entre cette enzyme cellulaire et les GPs des arenavirus. Dans un premier temps, nous avons étudié les interactions moléculaires entre SKI- 1/S1P et GPC. A l'aide de mutants de SKI-l/SlP, nous avons confirmé des résultats précédemment publiés montrant que les glycoprotéines d'enveloppe de LASV sont clivés dans le réticulum endoplasmique/cis-Golgi alors que celles de LCMV sont clivées dans le Golgi tardif/TGN. Une seule mutation dans le site de clivage de la glycoprotéine de LCMV est suffisante pour changer le compartiment cellulaire dans lequel est clivée cette glycoprotéine. Ensuite, nous avons démontré que le domaine transmembranaire, la partie cytosolique C-terminale ainsi que les sites de phosphorylations de cette enzyme ne sont pas indispensables pour permettre le clivage de GPC. De plus, nous avons identifié un mutant de SKI-l/SlP dans lequel Γ autoprocessing au site B,B' est impossible, incapable de cliver GPC mais toujours pleinement fonctionnelle envers ses substrats cellulaires. Nous avons également démontré qu'une forme soluble de SKI-l/SlP ajoutée dans le milieu de culture n'est pas capable de couper GPC à la surface de la cellule. Cette étude a défini une nouvelle cible potentielle pour un médicament qui inhiberait le clivage des glycoprotéines des arenavirus sans affecter les processus normaux de la cellule. Dans un second project, nous avons identifié deux acides aminés, LASV GPC Y253 et SKI-l/SlP Y285, qui sont important pour le clivage de LASV GPC. Un alignement des séquences de clivage des GPCs a montré qu'un résidu aromatique est conservé en position P7 du site de clivage chez tous les arenavirus de l'Ancien monde et dans le clade C des arenavirus du Nouveau monde. Une mutation de cet acide aminée dans GPC réduit l'efficacité de clivage par SKI-l/SlP. Mutation de la tyrosine 285 de SKI-l/SlP en alanine affecte négativement le clivage des substrats contenant un résidu aromatique en position P7 sans affecter les autres. Cette propriété pourrait être utilisée pour le développement de médicaments spécifiques ciblant le clivage de GPC. Finalement, nous avons étudié le rôle du processing accomplit par SKI-l/SlP et du signal peptide pour le pliage et la sécrétion de formes solubles des glycoprotéines de LASV et LCMV. Nous avons montré que le domaine transmembranaire et la partie cytosolique de GP sont crucials pour la stabilité de la conformation pre-fusionnelle des GPs et que SSP est nécessaire pour le transport et le processing de GP, mais pas de son ecto-domaine soluble. En conclusion, les résultats obtenus durant cette thèse permettrons de mieux comprendre les interactions complexes entre SKI-l/SlP et les glycoprotéines des arenavirus, ouvrant le chemin pour le développement de nouveaux médicaments anti-arénaviraux.

Measurement of the dynamics in ski jumping using a wearable inertial sensor-based system.

Abstract Dynamics is a central aspect of ski jumping, particularly during take-off and stable flight. Currently, measurement systems able to measure ski jumping dynamics (e.g. 3D cameras, force plates) are complex and only available in few research centres worldwide. This study proposes a method to determine dynamics using a wearable inertial sensor-based system which can be used routinely on any ski jumping hill. The system automatically calculates characteristic dynamic parameters during take-off (position and velocity of the centre of mass perpendicular to the table, force acting on the centre of mass perpendicular to the table and somersault angular velocity) and stable flight (total aerodynamic force). Furthermore, the acceleration of the ski perpendicular to the table was quantified to characterise the skis lift at take-off. The system was tested with two groups of 11 athletes with different jump distances. The force acting on the centre of mass, acceleration of the ski perpendicular to the table, somersault angular velocity and total aerodynamic force were different between groups and correlated with the jump distances. Furthermore, all dynamic parameters were within the range of prior studies based on stationary measurement systems, except for the centre of mass mean force which was slightly lower.

Differential Recognition of Old World and New World Arenavirus Envelope Glycoproteins by Subtilisin Kexin Isozyme 1 (SKI-1)/Site 1 Protease (S1P).

The arenaviruses are an important family of emerging viruses that includes several causative agents of severe hemorrhagic fevers in humans that represent serious public health problems. A crucial step of the arenavirus life cycle is maturation of the envelope glycoprotein precursor (GPC) by the cellular subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P). Comparison of the currently known sequences of arenavirus GPCs revealed the presence of a highly conserved aromatic residue at position P7 relative to the SKI-1/S1P cleavage side in Old World and clade C New World arenaviruses but not in New World viruses of clades A and B or cellular substrates of SKI-1/S1P. Using a combination of molecular modeling and structure-function analysis, we found that residueY285 of SKI-1/S1P, distal from the catalytic triad, is implicated in the molecular recognition of the aromatic "signature residue" at P7 in the GPC of Old World Lassa virus. Using a quantitative biochemical approach, we show that Y285 of SKI-1/S1P is crucial for the efficient processing of peptides derived from Old World and clade C New World arenavirus GPCs but not of those from clade A and B New World arenavirus GPCs. The data suggest that during coevolution with their mammalian hosts, GPCs of Old World and clade C New World viruses expanded the molecular contacts with SKI-1/S1P beyond the classical four-amino-acid recognition sequences and currently occupy an extended binding pocket.

A system to measure the kinematics during the entire ski jump sequence using inertial sensors.

Three-dimensional analysis of the entire sequence in ski jumping is recommended when studying the kinematics or evaluating performance. Camera-based systems which allow three-dimensional kinematics measurement are complex to set-up and require extensive post-processing, usually limiting ski jumping analyses to small numbers of jumps. In this study, a simple method using a wearable inertial sensors-based system is described to measure the orientation of the lower-body segments (sacrum, thighs, shanks) and skis during the entire jump sequence. This new method combines the fusion of inertial signals and biomechanical constraints of ski jumping. Its performance was evaluated in terms of validity and sensitivity to different performances based on 22 athletes monitored during daily training. The validity of the method was assessed by comparing the inclination of the ski and the slope at landing point and reported an error of -0.2±4.8°. The validity was also assessed by comparison of characteristic angles obtained with the proposed system and reference values in the literature; the differences were smaller than 6° for 75% of the angles and smaller than 15° for 90% of the angles. The sensitivity to different performances was evaluated by comparing the angles between two groups of athletes with different jump lengths and by assessing the association between angles and jump lengths. The differences of technique observed between athletes and the associations with jumps length agreed with the literature. In conclusion, these results suggest that this system is a promising tool for a generalization of three-dimensional kinematics analysis in ski jumping.

Characterization of lower-limbs inter-segment coordination during the take-off extension in ski jumping.

Take-off, the most important phase in ski jumping, has been primarily studied in terms of spatio-temporal parameters; little is known about its motor control aspects. This study aims to assess the inter-segment coordination of the shank-thigh and thigh-sacrum pairs using the continuous relative phase (CRP). In total 87 jumps were recorded from 33 athletes with an inertial sensor-based system. The CRP curves indicated that the thighs lead the shanks during the first part of take-off extension and that the shanks rotated faster at the take-off extension end. The thighs and sacrum first rotated synchronously, with the sacrum then taking lead, with finally the thighs rotating faster. Five characteristic features were extracted from the CRP and their relationship with jump length was tested. Three features of the shank-thigh pair and one of the thigh-sacrum pair reported a significant association with jump length. It was observed that athletes who achieved longer jumps had their thighs leading their shanks during a longer time, with these athletes also having a more symmetric movement between thighs and sacrum. This study shows that inter-segment coordination during the take-off extension is related to performance and further studies are necessary to contrast its importance with other ski jumping aspects.