Modelling the influence of change in fire regime on the local distribution of a Mediterranean pyrophytic plant species (Cistus salviifolius) at its northern range limit

Aims: To assess the potential distribution of an obligate seeder and active pyrophyte, Cistus salviifolius, a vulnerable species in the Swiss Red List; to derive scenarios by changing the fire return interval; and to discuss the results from a conservation perspective. A more general aim is to assess the impact of fire as a natural factor influencing the vegetation of the southern slopes of the Alps. Locations: Alps, southern Switzerland. Methods: Presence-absence data to fit the model were obtained from the most recent field mapping of C. salviifolius. The quantitative environmental predictors used in this study include topographic, climatic and disturbance (fire) predictors. Models were fitted by logistic regression and evaluated by jackknife and bootstrap approaches. Changes in fire regime were simulated by increasing the time-return interval of fire (simulating longer periods without fire). Two scenarios were considered: no fire in the past 15 years; or in the past 35 years. Results: Rock cover, slope, topographic position, potential evapotranspiration and time elapsed since the last fire were selected in the final model. The Nagelkerke R-2 of the model for C. salviifolius was 0.57 and the Jackknife area under the curve evaluation was 0.89. The bootstrap evaluation revealed model robustness. By increasing the return interval of fire by either up to 15 years, or 35 years, the modelled C. salviifolius population declined by 30-40%, respectively. Main conclusions: Although fire plays a significant role, topography and rock cover appear to be the most important predictors, suggesting that the distribution of C. salviifolius in the southern Swiss Alps is closely related to the availability of supposedly competition-free sites, such as emerging bedrock, ridge locations or steep slopes. Fire is more likely to play a secondary role in allowing C. salviifolius to extend its occurrence temporarily, by increasing germination rates and reducing the competition from surrounding vegetation. To maintain a viable dormant seed bank for C. salviifolius, conservation managers should consider carrying out vegetation clearing and managing wild fire propagation to reduce competition and ensure sufficient recruitment for this species.

DISTRIBUTION OF ORGANIC CARBON IN DIFFERENT SOIL FRACTIONS IN ECOSYSTEMS OF CENTRAL AMAZONIA

Organic matter plays an important role in many soil properties, and for that reason it is necessary to identify management systems which maintain or increase its concentrations. The aim of the present study was to determine the quality and quantity of organic C in different compartments of the soil fraction in different Amazonian ecosystems. The soil organic matter (FSOM) was fractionated and soil C stocks were estimated in primary forest (PF), pasture (P), secondary succession (SS) and an agroforestry system (AFS). Samples were collected at the depths 0-5, 5-10, 10-20, 20-40, 40-60, 60-80, 80-100, 100-160, and 160-200 cm. Densimetric and particle size analysis methods were used for FSOM, obtaining the following fractions: FLF (free light fraction), IALF (intra-aggregate light fraction), F-sand (sand fraction), F-clay (clay fraction) and F-silt (silt fraction). The 0-5 cm layer contains 60 % of soil C, which is associated with the FLF. The F-clay was responsible for 70 % of C retained in the 0-200 cm depth. There was a 12.7 g kg-1 C gain in the FLF from PF to SS, and a 4.4 g kg-1 C gain from PF to AFS, showing that SS and AFS areas recover soil organic C, constituting feasible C-recovery alternatives for degraded and intensively farmed soils in Amazonia. The greatest total stocks of carbon in soil fractions were, in decreasing order: (101.3 Mg ha-1 of C - AFS) > (98.4 Mg ha-1 of C - FP) > (92.9 Mg ha-1 of C - SS) > (64.0 Mg ha-1 of C - P). The forms of land use in the Amazon influence C distribution in soil fractions, resulting in short- or long-term changes.

Test of the fluctuation theorem for stochastic entropy production in a nonequilibrium steady state

We derive a simple closed analytical expression for the total entropy production along a single stochastic trajectory of a Brownian particle diffusing on a periodic potential under an external constant force. By numerical simulations we compute the probability distribution functions of the entropy and satisfactorily test many of the predictions based on Seiferts integral fluctuation theorem. The results presented for this simple model clearly illustrate the practical features and implications derived from such a result of nonequilibrium statistical mechanics.

Preparation, maintenance, and use of serum-free aggregating brain cell cultures.

Serum-free aggregating brain cell cultures are free-floating three-dimensional primary cell cultures able to reconstitute spontaneously a histotypic brain architecture to reproduce critical steps of brain development and to reach a high level of structural and functional maturity. This culture system offers, therefore, a unique model for neurotoxicity testing both during the development and at advanced cellular differentiation, and the high number of aggregates available combined with the excellent reproducibility of the cultures facilitates routine test procedures. This chapter presents a detailed description of the preparation, maintenance, and use of these cultures for neurotoxicity studies and a comparison of the developmental characteristics between cultures derived from the telencephalon and cultures derived from the whole brain. For culture preparation, mechanically dissociated embryonic brain tissue is used. The initial cell suspension, composed of neural stem cells, neural progenitor cells, immature postmitotic neurons, glioblasts, and microglial cells, is kept in a serum-free, chemically defined medium under continuous gyratory agitation. Spherical aggregates form spontaneously and are maintained in suspension culture for several weeks. Within the aggregates, the cells rearrange and mature, reproducing critical morphogenic events, such as migration, proliferation, differentiation, synaptogenesis, and myelination. For experimentation, replicate cultures are prepared by the randomization of aggregates from several original flasks. The high yield and reproducibility of the cultures enable multiparametric endpoint analyses, including "omics" approaches.

Testing the bivariate distribution of daily equity returns using copulas: an application to the Spanish stock market

In this paper we deal with the identification of dependencies between time series of equity returns. Marginal distribution functions are assumed to be known, and a bivariate chi-square test of fit is applied in a fully parametric copula approach. Several families of copulas are fitted and compared with Spanish stock market data. The results show that the t-copula generally outperforms other dependence structures, and highlight the difficulty in adjusting a significant number of bivariate data series

Niche, distribution and global change : modeling insights into biogeography and conservation biology Olivier Broennimann

RESUME Les évidences montrant que les changements globaux affectent la biodiversité s'accumulent. Les facteurs les plus influant dans ce processus sont les changements et destructions d'habitat, l'expansion des espèces envahissantes et l'impact des changements climatiques. Une évaluation pertinente de la réponse des espèces face à ces changements est essentielle pour proposer des mesures permettant de réduire le déclin actuel de la biodiversité. La modélisation de la répartition d'espèces basée sur la niche (NBM) est l'un des rares outils permettant cette évaluation. Néanmoins, leur application dans le contexte des changements globaux repose sur des hypothèses restrictives et demande une interprétation critique. Ce travail présente une série d'études de cas investiguant les possibilités et limitations de cette approche pour prédire l'impact des changements globaux. Deux études traitant des menaces sur les espèces rares et en danger d'extinction sont présentées. Les caractéristiques éco-géographiques de 118 plantes avec un haut degré de priorité de conservation sont revues. La prévalence des types de rareté sont analysées en relation avec leur risque d'extinction UICN. La revue souligne l'importance de la conservation à l'échelle régionale. Une évaluation de la rareté à échelle globale peut être trompeuse pour certaine espèces car elle ne tient pas en compte des différents degrés de rareté que présente une espèce à différentes échelles spatiales. La deuxième étude test une approche pour améliorer l'échantillonnage d'espèces rares en incluant des phases itératives de modélisation et d'échantillonnage sur le terrain. L'application de l'approche en biologie de la conservation (illustrée ici par le cas du chardon bleu, Eryngium alpinum), permettrait de réduire le temps et les coûts d'échantillonnage. Deux études sur l'impact des changements climatiques sur la faune et la flore africaine sont présentées. La première étude évalue la sensibilité de 227 mammifères africains face aux climatiques d'ici 2050. Elle montre qu'un nombre important d'espèces pourrait être bientôt en danger d'extinction et que les parcs nationaux africains (principalement ceux situé en milieux xériques) pourraient ne pas remplir leur mandat de protection de la biodiversité dans le futur. La seconde étude modélise l'aire de répartition en 2050 de 975 espèces de plantes endémiques du sud de l'Afrique. L'étude propose l'inclusion de méthodes améliorant la prédiction des risques liés aux changements climatiques. Elle propose également une méthode pour estimer a priori la sensibilité d'une espèce aux changements climatiques à partir de ses propriétés écologiques et des caractéristiques de son aire de répartition. Trois études illustrent l'utilisation des modèles dans l'étude des invasions biologiques. Une première étude relate l'expansion de la laitue sáuvage (Lactuca serriola) vers le nord de l'Europe en lien avec les changements du climat depuis 250 ans. La deuxième étude analyse le potentiel d'invasion de la centaurée tachetée (Centaures maculosa), une mauvaise herbe importée en Amérique du nord vers 1890. L'étude apporte la preuve qu'une espèce envahissante peut occuper une niche climatique différente après introduction sur un autre continent. Les modèles basés sur l'aire native prédisent de manière incorrecte l'entier de l'aire envahie mais permettent de prévoir les aires d'introductions potentielles. Une méthode alternative, incluant la calibration du modèle à partir des deux aires où l'espèce est présente, est proposée pour améliorer les prédictions de l'invasion en Amérique du nord. Je présente finalement une revue de la littérature sur la dynamique de la niche écologique dans le temps et l'espace. Elle synthétise les récents développements théoriques concernant le conservatisme de la niche et propose des solutions pour améliorer la pertinence des prédictions d'impact des changements climatiques et des invasions biologiques. SUMMARY Evidences are accumulating that biodiversity is facing the effects of global change. The most influential drivers of change in ecosystems are land-use change, alien species invasions and climate change impacts. Accurate projections of species' responses to these changes are needed to propose mitigation measures to slow down the on-going erosion of biodiversity. Niche-based models (NBM) currently represent one of the only tools for such projections. However, their application in the context of global changes relies on restrictive assumptions, calling for cautious interpretations. In this thesis I aim to assess the effectiveness and shortcomings of niche-based models for the study of global change impacts on biodiversity through the investigation of specific, unsolved limitations and suggestion of new approaches. Two studies investigating threats to rare and endangered plants are presented. I review the ecogeographic characteristic of 118 endangered plants with high conservation priority in Switzerland. The prevalence of rarity types among plant species is analyzed in relation to IUCN extinction risks. The review underlines the importance of regional vs. global conservation and shows that a global assessment of rarity might be misleading for some species because it can fail to account for different degrees of rarity at a variety of spatial scales. The second study tests a modeling framework including iterative steps of modeling and field surveys to improve the sampling of rare species. The approach is illustrated with a rare alpine plant, Eryngium alpinum and shows promise for complementing conservation practices and reducing sampling costs. Two studies illustrate the impacts of climate change on African taxa. The first one assesses the sensitivity of 277 mammals at African scale to climate change by 2050 in terms of species richness and turnover. It shows that a substantial number of species could be critically endangered in the future. National parks situated in xeric ecosystems are not expected to meet their mandate of protecting current species diversity in the future. The second study model the distribution in 2050 of 975 endemic plant species in southern Africa. The study proposes the inclusion of new methodological insights improving the accuracy and ecological realism of predictions of global changes studies. It also investigates the possibility to estimate a priori the sensitivity of a species to climate change from the geographical distribution and ecological proprieties of the species. Three studies illustrate the application of NBM in the study of biological invasions. The first one investigates the Northwards expansion of Lactuca serriola L. in Europe during the last 250 years in relation with climate changes. In the last two decades, the species could not track climate change due to non climatic influences. A second study analyses the potential invasion extent of spotted knapweed, a European weed first introduced into North America in the 1890s. The study provides one of the first empirical evidence that an invasive species can occupy climatically distinct niche spaces following its introduction into a new area. Models fail to predict the current full extent of the invasion, but correctly predict areas of introduction. An alternative approach, involving the calibration of models with pooled data from both ranges, is proposed to improve predictions of the extent of invasion on models based solely on the native range. I finally present a review on the dynamic nature of ecological niches in space and time. It synthesizes the recent theoretical developments to the niche conservatism issues and proposes solutions to improve confidence in NBM predictions of the impacts of climate change and species invasions on species distributions.

Interhemispheric distribution of Alzheimer disease and vascular pathology in brain aging

BACKGROUND AND PURPOSE: Most of the neuropathological studies in brain aging were based on the assumption of a symmetrical right-left hemisphere distribution of both Alzheimer disease and vascular pathology. To explore the impact of asymmetrical lesion formation on cognition, we performed a clinicopathological analysis of 153 cases with mixed pathology except macroinfarcts. METHODS: Cognitive status was assessed prospectively using the Clinical Dementia Rating scale; neuropathological evaluation included assessment of Braak neurofibrillary tangle and Ass deposition staging, microvascular pathology, and lacunes. The right-left hemisphere differences in neuropathological scores were evaluated using the Wilcoxon signed rank test. The relationship between the interhemispheric distribution of lesions and Clinical Dementia Rating scores was assessed using ordered logistic regression. RESULTS: Unlike Braak neurofibrillary tangle and Ass deposition staging, vascular scores were significantly higher in the left hemisphere for all Clinical Dementia Rating scores. A negative relationship was found between Braak neurofibrillary tangle, but not Ass staging, and vascular scores in cases with moderate to severe dementia. In both hemispheres, Braak neurofibrillary tangle staging was the main determinant of cognitive decline followed by vascular scores and Ass deposition staging. The concomitant predominance of Alzheimer disease and vascular pathology in the right hemisphere was associated with significantly higher Clinical Dementia Rating scores. CONCLUSIONS: Our data show that the cognitive impact of Alzheimer disease and vascular lesions in mixed cases may be assessed unilaterally without major information loss. However, interhemispheric differences and, in particular, increased vascular and Alzheimer disease burden in the right hemisphere may increase the risk for dementia in this group.

Development of a Conductometric Test for Frost Resistance of Concrete, HR-272, 1988

Research is described that was aimed at developing a test method which can be reasonably and rapidly performed in the laboratory and in the field to predict, with a high degree of certainty, the behavior of concrete subjected to the action of alternate freezing and thawing. The conductometric evaluation of concrete durability was explored with 3 different test methods: conductometric evaluation of the resistance of concrete to rapid freezing and thawing; conductomtric evaluation of the resistance of concrete to natural freezing and thawing, and conductometric evaluation of the pore size distribution of concrete and its correlation to concrete durability. The study showed that conductance could be used as a viable method for determining the durability of portland cement concrete. This would also allow the continuous monitoring of concrete durability without the removal twice per week from the freeze/thaw chamber. Recommendations for the continued development of these test methods are also included.

Patterns of pain-free response in 497 cases of classic trigeminal neuralgia treated with Gamma Knife surgery and followed up for least 1 year.

Object The goal of this study was to establish whether clear patterns of initial pain freedom could be identified when treating patients with classic trigeminal neuralgia (TN) by using Gamma Knife surgery (GKS). The authors compared hypesthesia and pain recurrence rates to see if statistically significant differences could be found. Methods Between July 1992 and November 2010, 737 patients presenting with TN underwent GKS and prospective evaluation at Timone University Hospital in Marseille, France. In this study the authors analyzed the cases of 497 of these patients, who participated in follow-up longer than 1 year, did not have megadolichobasilar artery- or multiple sclerosis-related TN, and underwent GKS only once; in other words, the focus was on cases of classic TN with a single radiosurgical treatment. Radiosurgery was performed with a Leksell Gamma Knife (model B, C, or Perfexion) using both MR and CT imaging targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.8 mm (range 4.5-14 mm) anterior to the emergence of the nerve. A median maximum dose of 85 Gy (range 70-90 Gy) was delivered. Using empirical methods and assisted by a chart with clear cut-off periods of pain free distribution, the authors were able to divide patients who experienced freedom from pain into 3 separate groups: patients who became pain free within the first 48 hours post-GKS; those who became pain free between 48 hours and 30 days post-GKS; and those who became pain free more than 30 days after GKS. Results The median age in the 497 patients was 68.3 years (range 28.1-93.2 years). The median follow-up period was 43.75 months (range 12-174.41 months). Four hundred fifty-four patients (91.34%) were initially pain free within a median time of 10 days (range 1-459 days) after GKS. One hundred sixty-nine patients (37.2%) became pain free within the first 48 hours (Group PF(≤ 48 hours)), 194 patients (42.8%) between posttreatment Day 3 and Day 30 (Group PF((>48 hours, ≤ 30 days))), and 91 patients (20%) after 30 days post-GKS (Group PF(>30 days)). Differences in postoperative hypesthesia were found: in Group PF(≤ 48 hours) 18 patients (13.7%) developed postoperative hypesthesia, compared with 30 patients (19%) in Group PF((>48 hours, ≤ 30 days)) and 22 patients (30.6%) in Group PF(>30 days) (p = 0.014). One hundred fifty-seven patients (34.4%) who initially became free from pain experienced a recurrence of pain with a median delay of 24 months (range 0.62-150.06 months). There were no statistically significant differences between the patient groups with respect to pain recurrence: 66 patients (39%) in Group PF(≤ 48 hours) experienced pain recurrence, compared with 71 patients (36.6%) in Group PF((>48 hours, ≤ 30 days)) and 27 patients (29.7%) in Group PF(>30 days) (p = 0.515). Conclusions A substantial number of patients (169 cases, 37.2%) became pain free within the first 48 hours. The rate of hypesthesia was higher in patients who became pain free more than 30 days after GKS, with a statistically significant difference between patient groups (p = 0.014).

Dynamic Pavement Deflection Measurements, Progress Report, HR-178, 1977

The Road Rater is a dynamic deflection measuring appa-ratus for flexible base pavements. The basic operating principle of the Road Rater is to impart a dynamic loading and measure the resultant movement of the pavement with velocity sensors. This data, when properly adjusted for temperature by use of a nomograph included in this report, can be used to determine pavement life expectancy and estimate overlay thickness required. Road Rater testing will be conducted in the spring, when pave-ments are in their weakest condition, until seasonal correction factors can be developed. The Road Rater does not have sufficient ram weight to effectively evaluate load carrying capacity of rigid pavements. All rigid pavements react similarly to Road Rater testing and generally deflect from 0.65 to 1.30 mils. Research will be continued to evaluate rigid pavements with the Road Rater, however. The Road Rater has proven to be a reliable, trouble free pavement evaluation machine. The deflection apparatus was originally front-mounted, but was rear-mounted during the winter of 1977-78. Since that time, van handling has greatly improved, and front suspension parts are no longer overstressed due to improper weight distribution. The Road Rater provides a fast, economical, nondestructive test method to evaluate flexible pavements. Road Rater test data can be used to predict pavement life, set priorities for asphaltic concrete resurfacing, and design asphaltic concrete overlays. Temperature and seasonal variations significantly affect Road Rater deflection readings and must be considered. A nomograph included in this report adjusts for temperature, but does not correct for seasonal effect. Road Rater testing will be conducted in the spring until seasonal correction factors can be developed. The Road Rater has not successfully evaluated rigid pavements, but research will continue in this area. 1. Recommendations for continuing Road Rater research, evaluation and application are as follows:A computer program should be established to reduce Road Rater raw data (Range and Sensor reading) to HR-178 Road Rater Dynamic Deflections For Determining Structural Rating Of Flexible Pavements mean deflection (mils) and/or structural rating. This computer printout would be similar to present friction testing printouts, and would greatly reduce Road Rater data reduction manpower needs and costs. 2. Seasonal variation study should continue to develop seasonal correction factors. Seasonal test roads will be studied concurrently with routine testing during 1979 to develop this relationship. All Road Rater testing will be conducted in the spring until the seasonal relationship is established. 3. An asphaltic concrete overlay design method should be established based on Road Rater de-flection readings. The AASHTO Interim Guide for Design of Pavement Structures 1972 will be used as a base document for this study. 4. AASHTO Structural numbers should be compared to Road Rater Structural Ratings during 1979 on asphaltic concrete overlay projects. This analysis will enable us to refine Road Rater evaluation of flexible pavements. Roads will be tested before resurfacing and several months

Correlation of photodynamic activity and fluorescence signaling for free and pegylated mTHPC in mesothelioma xenografts

Rapport de synthèse : Introduction : Les premières applications cliniques de la thérapie photodynamique (PDT) remontent à plus d'une vingtaine d'années. Basée sur l'activation d'un médicament photosensibilisateur par une source lumineuse à une longueur d'onde spécifique, la PDT permet la destruction sélective de tissus contenant le produit actif. Ce procédé a été expérimenté dans le traitement de cancers en raison de la propriété du médicament à se concentrer dans les tumeurs tout en épargnant les structures normales contigües. Cependant, les photosensibilisateurs utilisés jusqu'à ce jour n'ont pas démontré une accumulation exclusive dans les tissus néoplasiques mais également dans les structures saines avoisinantes induisant une destruction tissulaire non sélective. Notamment, d'importantes complications ont été rapportées suite à l'utilisation de la PDT dans la cavité thoracique après la résection de mésothéliomes pleuraux, et ce malgré l'arrivée de photosensibilisateurs de secondes générations. De ce fait, plusieurs études expérimentales ont été menées afin d'améliorer la sélectivité tumorale du médicament en modulant différentes conditions de traitement et en modifiant la structure du photosensibilisateur par pégylation. Le but de cette étude expérimentale est de corréler l'activité photodynamique, la phototoxicité et la distribution du m-tetrahydroxyphenylchlorin (mTHPC) et de sa forme pégylée, le PEG-mTHPC. De ce fait, un modèle de souris nues porteur de xenogreffes de mésothéliome humain a été utilisé pour étudier les deux photosensibilisateurs. De récents travaux avec ce modèle ont montré que la mesure de la concentration tissulaire du mTHPC et de sa forme pégylée par HPLC restait limitée afin de prédire l'activité photodynamique. De ce fait, nous pensons que les mesures de fluorescence peuvent être plus appropriée. Le signalement fluorescent est mesuré dans le tissu tumoral et dans une région contrôle de la peau afin d'étudier la distribution et l'intensité des deux sensibilisateurs. Méthode : Des souris nues (cd1nu/nu mice) de 8 semaines ont été transplantées avec des fragments de mésothéliome malin humain (H-meso-1). Ces derniers ont été obtenus à partir d'une suspension cellulaire. Au moins trois passages ont été faits dans les animaux, avant que le traitement soit initié. Deux groupes de 6 souris chacun ont été utilisés pour l'injection intraveineuse par la queue du mTHPC à 0.15 mg/kg et du PEG-mTHPC à dose équimolaire. Après trois jour, la tumeur ainsi qu'une région contrôle de la cuisse ont été illuminées sur une surface d'un diamètre de 1.2 cm et pendant 133 secondes avec un laser à une longueur d'onde à 652 nm (fluence 20 J/cm2, fluence rate 150 mW/cm2). Les animaux ont été ensuite sacrifiés 72 heures après l'illumination. L'étendue de la nécrose tumorale et de la région contrôle ont été déterminées en aveugle par histomorphometrie par un pathologue (HJA). La fluorescence microscopique a été évaluée dans 12 souris à une concentration de 0.15 et 0.5 mg/kg pour le mTHPC, et à doses équimolaires pour le PEG-mTHPC. Trois animaux ont été injectés avec le mTHPC à 0.15 mg/kg, 3 autres à dose équimolaire avec la forme pégylée et 6 souris avec le mTHPC à 0.5 mg/kg et à dose équimolaire. Les animaux ont été sacrifiés 72 heures après injection. L'intensité fluorescente des sensibilisateurs a été mesurée dans la tumeur et la région contrôle. Suite à cela, les coupes ont été fixées par H&E et superposées aux images fluorescentes, afin de localiser la distribution des deux photosensibilisateurs dans les différents compartiments tissulaires. Six souris transplantées n'ayant ni été injectées avec les sensibilisateurs ou illuminées ont servi de groupe contrôle. Résultats : Trois jours après l'illumination, la PDT provoque une nécrose tumorale de 10 ±5.4 mm2 pour le mTHPC à 0.15mg/kg et 5.2 ± 4.6 mm2 pour sa forme pégylée à dose équimolaire. Cependant, la nécrose tumorale induite par les deux formulations du sensibilisateur est significativement plus élevée que dans le groupe contrôle (0.33 ± 0.58 mm2) (P=0.02). Toutefois, le mTHPC pégylé provoque une photosensibilité cutanée moins importante que la forme non-pegylée. Dans les deux groupes, aucune nécrose n'a été observée dans la cuisse des animaux. Trois jours après l'injection du mTHPC et de la forme pégylée à 0.15 mg/kg, aucune activité fluorescente n'a été détectée. Cependant, à 0.5 mg/kg, la fluorescence microscopique révèle une distribution hétérogène des deux photo-sensibilisateurs dans le tissu tumoral avec une accumulation prédominante dans les régions peri-vasculaires. Les deux médicaments montrent une distribution intracellulaire homogène dans le cytoplasme et une absence de signalement dans le nucleus. La mesure de l'intensité fluorescente du mTHPC à 0.5mg/kg ne montre pas de différence significative entre le tissu tumoral et la région contrôle. Par contre, le PEG-mTHPC montre une intensité fluorescente supérieure dans le tissu tumoral que dans la peau (ratio tumeur- peau 0.94 pour le mTHPC et 1.73 pour le PEG-mTHPC). Conclusion : L'utilisation du mTHPC à 0.15mg/kg induit une nécrose tumorale similaire à celle du PEG-mTHPC à dose équimolaire. Cependant, ce dernier démontre une photo-toxicité plus atténuée de la peau. La fluorescence microscopique permet de localiser les deux sensibilisateurs dans les différents compartiments tissulaires à partir d'une dose de 0.5 mg/kg. Le PEG-mTHPC induit un signalement fluorescent supérieur dans le tissu tumoral par rapport à la peau. La mesure du signalement fluorescent a le potentiel de prédire l'activité photodynamique du mTHPC et de sa forme pégylée dans les xénogreffes de mésothéliome humain dans un modèle de souris nue.

Lack of the alanine-serine-cysteine transporter 1 causes tremors, seizures, and early postnatal death in mice.

The Na(+)-independent alanine-serine-cysteine transporter 1 (Asc-1) is exclusively expressed in neuronal structures throughout the central nervous system (CNS). Asc-1 transports small neutral amino acids with high affinity especially for D-serine and glycine (K(i): 8-12 microM), two endogenous glutamate co-agonists that activate N-methyl-D-aspartate (NMDA) receptors through interacting with the strychnine-insensitive glycine binding-site. By regulating D-serine (and possibly glycine) levels in the synaptic cleft, Asc-1 may play an important role in controlling neuronal excitability. We generated asc-1 gene knockout (asc-1(-/-)) mice to test this hypothesis. Behavioral phenotyping combined with electroencephalogram (EEG) recordings revealed that asc-1(-/-) mice developed tremors, ataxia, and seizures that resulted in early postnatal death. Both tremors and seizures were reduced by the NMDA receptor antagonist MK-801. Extracellular recordings from asc-1(-/-) brain slices indicated that the spontaneous seizure activity did not originate in the hippocampus, although, in this region, a relative increase in evoked synaptic responses was observed under nominal Mg(2+)-free conditions. Taken together with the known neurochemistry and neuronal distribution of the Asc-1 transporter, these results indicate that the mechanism underlying the behavioral hyperexcitability in mutant mice is likely due to overactivation of NMDA receptors, presumably resulting from elevated extracellular D-serine. Our study provides the first evidence to support the notion that Asc-1 transporter plays a critical role in regulating neuronal excitability, and indicate that the transporter is vital for normal CNS function and essential to postnatal survival of mice.

Atmospheric deposition and migration of artificial radionuclides in Alpine soils (Val Piora, Switzerland) compared to the distribution of selected major and trace elements.

Artificial radionuclides ((137)Cs, (90)Sr, Pu, and (241)Am) are present in soils because of Nuclear Weapon Tests and accidents in nuclear facilities. Their distribution in soil depth varies according to soil characteristics, their own chemical properties, and their deposition history. For this project, we studied the atmospheric deposition of (137)Cs, (90)Sr, Pu, (241)Am, (210)Pb, and stable Pb. We compared the distribution of these elements in soil profiles from different soil types from an alpine Valley (Val Piora, Switzerland) with the distribution of selected major and trace elements in the same soils. Our goals were to explain the distribution of the radioisotopes as a function of soil parameters and to identify stable elements with analogous behaviors. We found that Pu and (241)Am are relatively immobile and accumulate in the topsoil. In all soils, (90)Sr is more mobile and shows some accumulations at depth into Fe-Al rich horizons. This behavior is also observed for Cu and Zn, indicating that these elements may be used as chemical analogues for the migration of (90)Sr into the soil.

Développement d'un Test Sérologique Contre le Virus de la Chorioméningite Lymphocytaire

Les Arenavirus sont une famille de virus à ARN très diversifiée avec plus de 23 espèces recensées dans le monde, divisées en deux Clades majeures (Emonet et al., 2009). Ils sont classifiés en Arenavirus du Nouveau Monde versus de l'Ancien Monde (Buchmeier, de la Torre, and Peters, 2007) (Fig. 1). Parmi les Arenavirus, sept sont connus pour être les agents causales de fièvres hémorragiques foudroyantes : Les virus Lassa, Junin, Machupo, Guanarito, Sabia, Chapare et Lujo. Les Arenavirus infectent, de façon spécifique, des espèces de rongeurs qui sont le réservoir naturel déterminant ainsi leur distribution géographique (Clegg, 2002). On retrouve le virus de la chorioméningite lymphocytaire (LCMV) à la fois en Europe et aux Amériques. Le rongeur infecté est le vecteur de transmission à l'Homme. Les maladies associées aux infections par les Arenavirus hémorragiques ont un haut taux de mortalité allant de 15 à 30% et sont à haut risque épidémiologique en raison de l'absence de vaccin et de traitement efficace. Pour ces raisons, ces Arenavirus sont classifiés comme pathogènes à haut risque par le centre pour le contrôle des maladies (CDC) (Borio et al., 2002).

Are niche-based species distribution models transferable in space?

Aim To assess the geographical transferability of niche-based species distribution models fitted with two modelling techniques. Location Two distinct geographical study areas in Switzerland and Austria, in the subalpine and alpine belts. Methods Generalized linear and generalized additive models (GLM and GAM) with a binomial probability distribution and a logit link were fitted for 54 plant species, based on topoclimatic predictor variables. These models were then evaluated quantitatively and used for spatially explicit predictions within (internal evaluation and prediction) and between (external evaluation and prediction) the two regions. Comparisons of evaluations and spatial predictions between regions and models were conducted in order to test if species and methods meet the criteria of full transferability. By full transferability, we mean that: (1) the internal evaluation of models fitted in region A and B must be similar; (2) a model fitted in region A must at least retain a comparable external evaluation when projected into region B, and vice-versa; and (3) internal and external spatial predictions have to match within both regions. Results The measures of model fit are, on average, 24% higher for GAMs than for GLMs in both regions. However, the differences between internal and external evaluations (AUC coefficient) are also higher for GAMs than for GLMs (a difference of 30% for models fitted in Switzerland and 54% for models fitted in Austria). Transferability, as measured with the AUC evaluation, fails for 68% of the species in Switzerland and 55% in Austria for GLMs (respectively for 67% and 53% of the species for GAMs). For both GAMs and GLMs, the agreement between internal and external predictions is rather weak on average (Kulczynski's coefficient in the range 0.3-0.4), but varies widely among individual species. The dominant pattern is an asymmetrical transferability between the two study regions (a mean decrease of 20% for the AUC coefficient when the models are transferred from Switzerland and 13% when they are transferred from Austria). Main conclusions The large inter-specific variability observed among the 54 study species underlines the need to consider more than a few species to test properly the transferability of species distribution models. The pronounced asymmetry in transferability between the two study regions may be due to peculiarities of these regions, such as differences in the ranges of environmental predictors or the varied impact of land-use history, or to species-specific reasons like differential phenotypic plasticity, existence of ecotypes or varied dependence on biotic interactions that are not properly incorporated into niche-based models. The lower variation between internal and external evaluation of GLMs compared to GAMs further suggests that overfitting may reduce transferability. Overall, a limited geographical transferability calls for caution when projecting niche-based models for assessing the fate of species in future environments.