Calibration and application of the MN2D dynamics model to the avalanches of Las Leñas (Argentina)

During the winters of 1999 and 2000 large avalanches occurred in the ski resort of Las Leñas (Los Andes, Mendoza, Argentina). On 8 September 1999 an avalanche of new, dry snow ran over a path with a 1000 m vertical drop. On 30 June and on 1 July 2000 five avalanches of similar vertical drop, which start with new snow, entrained very wet snow during their descent, and evolved into dense snow avalanches. To use the MN2D dynamics model correctly, calibration of model parameters is necessary. Also, no previous works with the use of dynamics models exist in South America. The events used to calibrate the model occurred during the winters of 1999 and 2000 and are a good sample of the kind of avalanches which can occur in this area of the Andes range. By considering the slope morphology and topography, the snow and meteorological conditions and the results of the model simulations, it was estimated that these avalanches were not extreme events with a return period greater than one hundred years. This implies that, in natural conditions, bigger, extreme avalanches could happen. In this work, the MN2D dynamics model is calibrated with two different avalanches of the same magnitude: dry and wet. The importance of the topographic data in the simulation is evaluated. It is concluded that MN2D dynamics model can be used to simulate dry extreme avalanches in Argentinean Andes but not to simulate extreme wet avalanches, which are much more sensitive to the topography.

Model-based Segmentation and Image Fusion of 3D Computed Tomography and 3D Ultrasound of the Eye for Radiotherapy Planning

For radiotherapy treatment planning of retinoblastoma inchildhood, Computed Tomography (CT) represents thestandard method for tumor volume delineation, despitesome inherent limitations. CT scan is very useful inproviding information on physical density for dosecalculation and morphological volumetric information butpresents a low sensitivity in assessing the tumorviability. On the other hand, 3D ultrasound (US) allows ahigh accurate definition of the tumor volume thanks toits high spatial resolution but it is not currentlyintegrated in the treatment planning but used only fordiagnosis and follow-up. Our ultimate goal is anautomatic segmentation of gross tumor volume (GTV) in the3D US, the segmentation of the organs at risk (OAR) inthe CT and the registration of both. In this paper, wepresent some preliminary results in this direction. Wepresent 3D active contour-based segmentation of the eyeball and the lens in CT images; the presented approachincorporates the prior knowledge of the anatomy by usinga 3D geometrical eye model. The automated segmentationresults are validated by comparing with manualsegmentations. Then, for the fusion of 3D CT and USimages, we present two approaches: (i) landmark-basedtransformation, and (ii) object-based transformation thatmakes use of eye ball contour information on CT and USimages.

Deleterious Actions Of Vegf On The Blood Retinal Barrier And Photoreceptor Survival In The Light-damage Model

Purpose: The retinal balance between pro- and anti-angiogenic factors is critical for angiogenesis control, but is also involved in cell survival. We previously reported upregulation of VEGF and photoreceptor (PR) cell death in the Light-damage (LD) model. Preliminary results showed that anti-VEGF can rescue PR from cell death. Thus, we investigated the role of VEGF on the retina and we herein described the effect of anti-VEGF antibody delivered by lentiviral gene transfer in this model.Methods: To characterize the action of VEGF during the LD, we exposed Balb/c mice subretinally injected with LV-anti-VEGF, or not, to 5'000 lux for 1h. We next evaluated the retinal function, PR survival and protein expression (VEGF, VEGFR1/2, Src, PEDF, p38MAPK, Akt, Peripherin, SWL-opsin) after LD. We analyzed Blood retinal barrier (BRB) integrity on flat-mounted RPE and cryosections stained with β-catenin, ZO-1, N-cadherin and albumin.Results: Results indicate that the VEGF pathway is modulated after LD. LD leads to extravascular albumin leakage and BRB breakdown: β-catenin, ZO-1 and N-cadherin translocate to the cytoplasm of RPE cells showing loss of cell cohesion. This phenomenon is in adequacy with the VEGF time-course expression. Assessment of the retinal function reveals that PR rescue correlates with the level of LV-anti-VEGF expression. Rhodopsin content was higher in the LV-anti-VEGF group than in controls and measures of the ONL thickness indicate that LV-anti-VEGF preserves by 82% the outer nuclear layer from degeneration. Outer segments (OS) appeared well organized with an appropriate length in the LV-anti-VEGF group compared to controls, and the expression of SWL-opsin is maintained in the OS without being mislocalized as in the LV-GFP group. Finally, LV-anti-VEGF treatment prevents BRB breakdown and maintained RPE cell integrity.Conclusions: This study involves VEGF in LD and highlights the prime importance of the BRB integrity for PR survival. Taken together, these results show that anti-VEGF is neuroprotective in this model and maintains functional PR layer in LD-treated mice.

Preclinical evaluation of the immunogenicity of C-type HIV-1-based DNA and NYVAC vaccines in the Balb/C mouse model.

As part of a European initiative (EuroVacc), we report the design, construction, and immunogenicity of two HIV-1 vaccine candidates based on a clade C virus strain (CN54) representing the current major epidemic in Asia and parts of Africa. Open reading frames encoding an artificial 160-kDa GagPolNef (GPN) polyprotein and the external glycoprotein gp120 were fully RNA and codon optimized. A DNA vaccine (DNA-GPN and DNA-gp120, referred to as DNA-C), and a replication-deficient vaccinia virus encoding both reading frames (NYVAC-C), were assessed regarding immunogenicity in Balb/C mice. The intramuscular administration of both plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial T-cell responses against both antigens as well as Env-specific antibodies. Whereas low doses of NYVAC-C failed to induce specific CTL or antibodies, high doses generated cellular as well as humoral immune responses, but these did not reach the levels seen following DNA vaccination. The most potent immune responses were detectable using prime:boost protocols, regardless of whether DNA-C or NYVAC-C was used as the priming or boosting agent. These preclinical findings revealed the immunogenic response triggered by DNA-C and its enhancement by combining it with NYVAC-C, thus complementing the macaque preclinical and human phase I clinical studies of EuroVacc.

Dynamic model of the left ventricle for use in simulation of myocardial perfusion SPECT and gated SPECT

Simulation is a useful tool in cardiac SPECT to assess quantification algorithms. However, simple equation-based models are limited in their ability to simulate realistic heart motion and perfusion. We present a numerical dynamic model of the left ventricle, which allows us to simulate normal and anomalous cardiac cycles, as well as perfusion defects. Bicubic splines were fitted to a number of control points to represent endocardial and epicardial surfaces of the left ventricle. A transformation from each point on the surface to a template of activity was made to represent the myocardial perfusion. Geometry-based and patient-based simulations were performed to illustrate this model. Geometry-based simulations modeled ~1! a normal patient, ~2! a well-perfused patient with abnormal regional function, ~3! an ischaemic patient with abnormal regional function, and ~4! a patient study including tracer kinetics. Patient-based simulation consisted of a left ventricle including a realistic shape and motion obtained from a magnetic resonance study. We conclude that this model has the potential to study the influence of several physical parameters and the left ventricle contraction in myocardial perfusion SPECT and gated-SPECT studies.

Neutron skin thickness in the droplet model with surface width dependence: Indications of softness of the nuclear symmetry energy

We analyze the neutron skin thickness in finite nuclei with the droplet model and effective nuclear interactions. The ratio of the bulk symmetry energy J to the so-called surface stiffness coefficient Q has in the droplet model a prominent role in driving the size of neutron skins. We present a correlation between the density derivative of the nuclear symmetry energy at saturation and the J/Q ratio. We emphasize the role of the surface widths of the neutron and proton density profiles in the calculation of the neutron skin thickness when one uses realistic mean-field effective interactions. Next, taking as experimental baseline the neutron skin sizes measured in 26 antiprotonic atoms along the mass table, we explore constraints arising from neutron skins on the value of the J/Q ratio. The results favor a relatively soft symmetry energy at subsaturation densities. Our predictions are compared with the recent constraints derived from other experimental observables. Though the various extractions predict different ranges of values, one finds a narrow window L∼45-75 MeV for the coefficient L that characterizes the density derivative of the symmetry energy that is compatible with all the different empirical indications.

Synaptic depression and slow oscillatory activity in a biophysical network model of the cerebral cortex

Short-term synaptic depression (STD) is a form of synaptic plasticity that has a large impact on network computations. Experimental results suggest that STD is modulated by cortical activity, decreasing with activity in the network and increasing during silent states. Here, we explored different activity-modulation protocols in a biophysical network model for which the model displayed less STD when the network was active than when it was silent, in agreement with experimental results. Furthermore, we studied how trains of synaptic potentials had lesser decay during periods of activity (UP states) than during silent periods (DOWN states), providing new experimental predictions. We next tackled the inverse question of what is the impact of modifying STD parameters on the emergent activity of the network, a question difficult to answer experimentally. We found that synaptic depression of cortical connections had a critical role to determine the regime of rhythmic cortical activity. While low STD resulted in an emergent rhythmic activity with short UP states and long DOWN states, increasing STD resulted in longer and more frequent UP states interleaved with short silent periods. A still higher synaptic depression set the network into a non-oscillatory firing regime where DOWN states no longer occurred. The speed of propagation of UP states along the network was not found to be modulated by STD during the oscillatory regime; it remained relatively stable over a range of values of STD. Overall, we found that the mutual interactions between synaptic depression and ongoing network activity are critical to determine the mechanisms that modulate cortical emergent patterns.

Monte Carlo thermodynamic and structural properties of the TIP4P water model: dependence on the computational conditions

Classical Monte Carlo simulations were carried out on the NPT ensemble at 25°C and 1 atm, aiming to investigate the ability of the TIP4P water model [Jorgensen, Chandrasekhar, Madura, Impey and Klein; J. Chem. Phys., 79 (1983) 926] to reproduce the newest structural picture of liquid water. The results were compared with recent neutron diffraction data [Soper; Bruni and Ricci; J. Chem. Phys., 106 (1997) 247]. The influence of the computational conditions on the thermodynamic and structural results obtained with this model was also analyzed. The findings were compared with the original ones from Jorgensen et al [above-cited reference plus Mol. Phys., 56 (1985) 1381]. It is notice that the thermodynamic results are dependent on the boundary conditions used, whereas the usual radial distribution functions g(O/O(r)) and g(O/H(r)) do not depend on them.

Drivers and barriers of mobile travel and tourism service adoption : a study of individual perceptions and business model development in a travel and tourism context

The Travel and Tourism field is undergoing changes due to the rapid development of information technology and digital services. Online travel has profoundly changed the way travel and tourism organizations interact with their customers. Mobile technology such as mobile services for pocket devices (e.g. mobile phones) has the potential to take this development even further. Nevertheless, many issues have been highlighted since the early days of mobile services development (e.g. the lack of relevance, ease of use of many services). However, the wide adoption of smartphones and the mobile Internet in many countries as well as the formation of so-called ecosystems between vendors of mobile technology indicate that many of these issues have been overcome. Also when looking at the numbers of downloaded applications related to travel in application stores like Google Play, it seems obvious that mobile travel and tourism services are adopted and used by many individuals. However, as business is expected to start booming in the mobile era, many issues have a tendency to be overlooked. Travelers are generally on the go and thus services that work effectively in mobile settings (e.g. during a trip) are essential. Hence, the individuals’ perceived drivers and barriers to use mobile travel and tourism services in on-site or during trip settings seem particularly valuable to understand; thus this is one primary aim of the thesis. We are, however, also interested in understanding different types of mobile travel service users. Individuals may indeed be very different in their propensity to adopt and use technology based innovations (services). Research is also switching more from investigating issues of mobile service development to understanding individuals’ usage patterns of mobile services. But designing new mobile services may be a complex matter from a service provider perspective. Hence, our secondary aim is to provide insights into drivers and barriers of mobile travel and tourism service development from a holistic business model perspective. To accomplish the research objectives seven different studies have been conducted over a time period from 2002 – 2013. The studies are founded on and contribute to theories within diffusion of innovations, technology acceptance, value creation, user experience and business model development. Several different research methods are utilized: surveys, field and laboratory experiments and action research. The findings suggest that a successful mobile travel and tourism service is a service which supports one or several mobile motives (needs) of individuals such as spontaneous needs, time-critical arrangements, efficiency ambitions, mobility related needs (location features) and entertainment needs. The service could be customized to support travelers’ style of traveling (e.g. organized travel or independent travel) and should be easy to use, especially easy to take into use (access, install and learn) during a trip, without causing security concerns and/or financial risks for the user. In fact, the findings suggest that the most prominent barrier to the use of mobile travel and tourism services during a trip is an individual’s perceived financial cost (entry costs and usage costs). It should, however, be noted that regulations are put in place in the EU regarding data roaming prices between European countries and national telecom operators are starting to see ‘international data subscriptions’ as a sales advantage (e.g. Finnish Sonera provides a data subscription in the Baltic and Nordic region at the same price as in Finland), which will enhance the adoption of mobile travel and tourism services also in international contexts. In order to speed up the adoption rate travel service providers could consider e.g. more local initiatives of free Wi-Fi networks, development of services that can be used, at least to some extent, in an offline mode (do not require costly network access during a trip) and cooperation with telecom operators (e.g. lower usage costs for travelers who use specific mobile services or travel with specific vendors). Furthermore, based on a developed framework for user experience of mobile trip arrangements, the results show that a well-designed mobile site and/or native application, which preferably supports integration with other mobile services, is a must for true mobile presence. In fact, travel service providers who want to build a relationship with their customers need to consider a downloadable native application, but in order to be found through the mobile channel and make contact with potential new customers, a mobile website should be available. Moreover, we have made a first attempt with cluster analysis to identify user categories of mobile services in a travel and tourism context. The following four categories were identified: info-seekers, checkers, bookers and all-rounders. For example “all-rounders”, represented primarily by individuals who use their pocket device for almost any of the investigated mobile travel services, constituted primarily of 23 to 50 year old males with high travel frequency and great online experience. The results also indicate that travel service providers will increasingly become multi-channel providers. To manage multiple online channels, closely integrated and hybrid online platforms for different devices, supporting all steps in a traveler process should be considered. It could be useful for travel service providers to focus more on developing browser-based mobile services (HTML5-solutions) than native applications that work only with specific operating systems and for specific devices. Based on an action research study and utilizing a holistic business model framework called STOF we found that HTML5 as an emerging platform, at least for now, has some limitations regarding the development of the user experience and monetizing the application. In fact, a native application store (e.g. Google Play) may be a key mediator in the adoption of mobile travel and tourism services both from a traveler and a service provider perspective. Moreover, it must be remembered that many device and mobile operating system developers want service providers to specifically create services for their platforms and see native applications as a strategic advantage to sell more devices of a certain kind. The mobile telecom industry has moved into a battle of ecosystems where device makers, developers of operating systems and service developers are to some extent forced to choose their development platforms.

Identification of research trends in the field of separation processes. Application of epidemiological model, citation analysis, text mining, and technical analysis of the financial markets

Choice of industrial development options and the relevant allocation of the research funds become more and more difficult because of the increasing R&D costs and pressure for shorter development period. Forecast of the research progress is based on the analysis of the publications activity in the field of interest as well as on the dynamics of its change. Moreover, allocation of funds is hindered by exponential growth in the number of publications and patents. Thematic clusters become more and more difficult to identify, and their evolution hard to follow. The existing approaches of research field structuring and identification of its development are very limited. They do not identify the thematic clusters with adequate precision while the identified trends are often ambiguous. Therefore, there is a clear need to develop methods and tools, which are able to identify developing fields of research. The main objective of this Thesis is to develop tools and methods helping in the identification of the promising research topics in the field of separation processes. Two structuring methods as well as three approaches for identification of the development trends have been proposed. The proposed methods have been applied to the analysis of the research on distillation and filtration. The results show that the developed methods are universal and could be used to study of the various fields of research. The identified thematic clusters and the forecasted trends of their development have been confirmed in almost all tested cases. It proves the universality of the proposed methods. The results allow for identification of the fast-growing scientific fields as well as the topics characterized by stagnant or diminishing research activity.

Top-down and Bottom-up influences on ACC activation: Evaluation of a proposed model of the feedback-related negativity

The Feedback-Related Negativity (FRN) is thought to reflect the dopaminergic prediction error signal from the subcortical areas to the ACC (i.e., a bottom-up signal). Two studies were conducted in order to test a new model of FRN generation, which includes direct modulating influences of medial PFC (i.e., top-down signals) on the ACC at the time of the FRN. Study 1 examined the effects of one’s sense of control (top-down) and of informative cues (bottom-up) on the FRN measures. In Study 2, sense of control and instruction-based (top-down) and probability-based expectations (bottom-up) were manipulated to test the proposed model. The results suggest that any influences of medial PFC on the activity of the ACC that occur in the context of incentive tasks are not direct. The FRN was shown to be sensitive to salient stimulus characteristics. The results of this dissertation partially support the reinforcement learning theory, in that the FRN is a marker for prediction error signal from subcortical areas. However, the pattern of results outlined here suggests that prediction errors are based on salient stimulus characteristics and are not reward specific. A second goal of this dissertation was to examine whether ACC activity, measured through the FRN, is altered in individuals at-risk for problem-gambling behaviour (PG). Individuals in this group were more sensitive to the valence of the outcome in a gambling task compared to not at-risk individuals, suggesting that gambling contexts increase the sensitivity of the reward system to valence of the outcome in individuals at risk for PG. Furthermore, at-risk participants showed an increased sensitivity to reward characteristics and a decreased response to loss outcomes. This contrasts with those not at risk whose FRNs were sensitive to losses. As the results did not replicate previous research showing attenuated FRNs in pathological gamblers, it is likely that the size and time of the FRN does not change gradually with increasing risk of maladaptive behaviour. Instead, changes in ACC activity reflected by the FRN in general can be observed only after behaviour becomes clinically maladaptive or through comparison between different types of gain/loss outcomes.

Statistical Inference for Computable General Equilibrium Models with Application to a Model of the Moroccan Economy

We study the problem of measuring the uncertainty of CGE (or RBC)-type model simulations associated with parameter uncertainty. We describe two approaches for building confidence sets on model endogenous variables. The first one uses a standard Wald-type statistic. The second approach assumes that a confidence set (sampling or Bayesian) is available for the free parameters, from which confidence sets are derived by a projection technique. The latter has two advantages: first, confidence set validity is not affected by model nonlinearities; second, we can easily build simultaneous confidence intervals for an unlimited number of variables. We study conditions under which these confidence sets take the form of intervals and show they can be implemented using standard methods for solving CGE models. We present an application to a CGE model of the Moroccan economy to study the effects of policy-induced increases of transfers from Moroccan expatriates.

The Exchange Rate in a Dynamic-Optimizing Current Account Model with Nominal Rigidities: a Quantitative Investigation.

This paper studies a dynamic-optimizing model of a semi-small open economy with sticky nominal prices and wages. the model exhibits exchange rate overshooting in response to money supply shocks. the predicted variability of nominal and real exchange rates is roughly consistent with that of G7 effective exchange rates during the post-Bretton Woods era.

Cell lines and animal model in the analysis of pharmacogenomics markers in childhood acute lymphoblastic leukemia

La leucémie aiguë lymphoblastique (LAL) est le cancer pédiatrique le plus fréquent. Elle est la cause principale de mortalité liée au cancer chez les enfants due à un groupe de patient ne répondant pas au traitement. Les patients peuvent aussi souffrir de plusieurs toxicités associées à un traitement intensif de chimiothérapie. Les études en pharmacogénétique de notre groupe ont montré une corrélation tant individuelle que combinée entre les variants génétiques particuliers d’enzymes dépendantes du folate, particulièrement la dihydrofolate réductase (DHFR) ainsi que la thymidylate synthase (TS), principales cibles du méthotrexate (MTX) et le risque élevé de rechute chez les patients atteints de la LAL. En outre, des variations dans le gène ATF5 impliqué dans la régulation de l’asparagine synthetase (ASNS) sont associées à un risque plus élevé de rechute ou à une toxicité ASNase dépendante chez les patients ayant reçu de l’asparaginase d’E.coli (ASNase). Le but principal de mon projet de thèse est de comprendre davantage d’un point de vue fonctionnel, le rôle de variations génétiques dans la réponse thérapeutique chez les patients atteints de la LAL, en se concentrant sur deux composants majeurs du traitement de la LAL soit le MTX ainsi que l’ASNase. Mon objectif spécifique était d’analyser une association trouvée dans des paramètres cliniques par le biais d’essais de prolifération cellulaire de lignées cellulaires lymphoblastoïdes (LCLs, n=93) et d’un modèle murin de xénogreffe de la LAL. Une variation génétique dans le polymorphisme TS (homozygosité de l’allèle de la répétition triple 3R) ainsi que l’haplotype *1b de DHFR (défini par une combinaison particulière d’allèle dérivé de six sites polymorphiques dans le promoteur majeur et mineur de DHFR) et de leurs effets sur la sensibilité au MTX ont été évalués par le biais d’essais de prolifération cellulaire. Des essais in vitro similaires sur la réponse à l’ASNase de E. Coli ont permis d’évaluer l’effet de la variation T1562C de la région 5’UTR de ATF5 ainsi que des haplotypes particuliers du gène ASNS (définis par deux variations génétiques et arbitrairement appelés haplotype *1). Le modèle murin de xénogreffe ont été utilisé pour évaluer l’effet du génotype 3R3R du gène TS. L’analyse de polymorphismes additionnels dans le gène ASNS a révélé une diversification de l’haplotype *1 en 5 sous-types définis par deux polymorphismes (rs10486009 et rs6971012,) et corrélé avec la sensibilité in vitro à l’ASNase et l’un d’eux (rs10486009) semble particulièrement important dans la réduction de la sensibilité in vitro à l’ASNase, pouvant expliquer une sensibilité réduite de l’haplotype *1 dans des paramètres cliniques. Aucune association entre ATF5 T1562C et des essais de prolifération cellulaire en réponse à ASNase de E.Coli n’a été détectée. Nous n’avons pas détecté une association liée au génotype lors d’analyse in vitro de sensibilité au MTX. Par contre, des résultats in vivo issus de modèle murin de xénogreffe ont montré une relation entre le génotype TS 3R/3R et la résistance de manière dose-dépendante au traitement par MTX. Les résultats obtenus ont permis de fournir une explication concernant un haut risque significatif de rechute rencontré chez les patients au génotype TS 3R/3R et suggèrent que ces patients pourraient recevoir une augmentation de leur dose de MTX. À travers ces expériences, nous avons aussi démontré que les modèles murins de xénogreffe peuvent servir comme outil préclinique afin d’explorer l’option d’un traitement individualisé. En conclusion, la connaissance acquise à travers mon projet de thèse a permis de confirmer et/ou d’identifier quelques variants dans la voix d’action du MTX et de l’ASNase qui pourraient faciliter la mise en place de stratégies d’individualisation de la dose, permettant la sélection d’un traitement optimum ou moduler la thérapie basé sur la génétique individuelle.

Some theoretical and methodological considerations for the development of a critical competences model (CCM): an operant approach

This paper develops some theoretical and methodological considerations for the development of a critical competence model (CCM). The model is defined as a set of skills and knowledge functionally organized allowing measurable results with positive consequences for the strategic business objectives. The theoretical approaches of classical model of competences, the contemporary model of competencies and human competencies model were revised for the proposal development. implementation of the model includes 5 steps: 1) conducting a job analysis considering which dimensions or facets are subject to revision, 2) identify people with the opposite performance (the higher performance and lower performance); 3) identify critical incidents most relevant to the job position, 4) develop behavioral expectation scales (bes) and 5) validate BES obtained for experts in the field. As a final consideration, is determined that the competence models require accurate measurement. Approaches considering excessive theoreticism may cause the issue of competence become a fashion business with low or minimal impact, affecting its validity, reliability and deployment in organizations.