VLA multifrequency observations of RSCVn binaries

We present multiepoch Very Large Array (VLA) observations at 1.4 GHz, 4.9 GHz, 8.5 GHz and 14.9 GHz for a sample of eight RS CVn binary systems. Circular polarization measurements of these systems are also reported. Most of the fluxes observed are consistent with incoherent emission from mildly relativistic electrons. Several systems show an increase of the degree of circular polarization with increasing frequency in the optically thin regime, in conflict with predictions by gyrosynchrotron models. We observed a reversal in the sense of circular polarization with increasing frequency in three non-eclipsing systems: EI Eri, DM Uma and HD 8358. We find clear evidence for coherent plasma emission at 1.4 GHz in the quiescent spectrum of HD 8358 during the helicity reversal. The degrees of polarization of the other two systems could also be accounted for by a coherent emission process. The observations of ER Vul revealed two U-shaped flux spectra at the highest frequencies. The U-shape of the spectra may be accounted for by an optically thin gyrosynchrotron source for the low frequency part whereas the high frequency part is dominated by a thermal emission component.

Search for very high energy gamma-ray emission from pulsar-pulsar wind nebula systems with the MAGIC telescope

The MAGIC collaboration has searched for high-energy gamma-ray emission of some of the most promising pulsar candidates above an energy threshold of 50 GeV, an energy not reachable up to now by other ground-based instruments. Neither pulsed nor steady gamma-ray emission has been observed at energies of 100 GeV from the classical radio pulsars PSR J0205+6449 and PSR J2229+6114 (and their nebulae 3C58 and Boomerang, respectively) and the millisecond pulsar PSR J0218+4232. Here, we present the flux upper limits for these sources and discuss their implications in the context of current model predictions.

Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4-2.

Nedd4-2 has been proposed to play a critical role in regulating epithelial Na+ channel (ENaC) activity. Biochemical and overexpression experiments suggest that Nedd4-2 binds to the PY motifs of ENaC subunits via its WW domains, ubiquitinates them, and decreases their expression on the apical membrane. Phosphorylation of Nedd4-2 (for example by Sgk1) may regulate its binding to ENaC, and thus ENaC ubiquitination. These results suggest that the interaction between Nedd4-2 and ENaC may play a crucial role in Na+ homeostasis and blood pressure (BP) regulation. To test these predictions in vivo, we generated Nedd4-2 null mice. The knockout mice had higher BP on a normal diet and a further increase in BP when on a high-salt diet. The hypertension was probably mediated by ENaC overactivity because 1) Nedd4-2 null mice had higher expression levels of all three ENaC subunits in kidney, but not of other Na+ transporters; 2) the downregulation of ENaC function in colon was impaired; and 3) NaCl-sensitive hypertension was substantially reduced in the presence of amiloride, a specific inhibitor of ENaC. Nedd4-2 null mice on a chronic high-salt diet showed cardiac hypertrophy and markedly depressed cardiac function. Overall, our results demonstrate that in vivo Nedd4-2 is a critical regulator of ENaC activity and BP. The absence of this gene is sufficient to produce salt-sensitive hypertension. This model provides an opportunity to further investigate mechanisms and consequences of this common disorder.

Improving QPF by blending techniques at the Meteorological Service of Catalonia

The current operational very short-term and short-term quantitative precipitation forecast (QPF) at the Meteorological Service of Catalonia (SMC) is made by three different methodologies: Advection of the radar reflectivity field (ADV), Identification, tracking and forecasting of convective structures (CST) and numerical weather prediction (NWP) models using observational data assimilation (radar, satellite, etc.). These precipitation forecasts have different characteristics, lead time and spatial resolutions. The objective of this study is to combine these methods in order to obtain a single and optimized QPF at each lead time. This combination (blending) of the radar forecast (ADV and CST) and precipitation forecast from NWP model is carried out by means of different methodologies according to the prediction horizon. Firstly, in order to take advantage of the rainfall location and intensity from radar observations, a phase correction technique is applied to the NWP output to derive an additional corrected forecast (MCO). To select the best precipitation estimation in the first and second hour (t+1 h and t+2 h), the information from radar advection (ADV) and the corrected outputs from the model (MCO) are mixed by using different weights, which vary dynamically, according to indexes that quantify the quality of these predictions. This procedure has the ability to integrate the skill of rainfall location and patterns that are given by the advection of radar reflectivity field with the capacity of generating new precipitation areas from the NWP models. From the third hour (t+3 h), as radar-based forecasting has generally low skills, only the quantitative precipitation forecast from model is used. This blending of different sources of prediction is verified for different types of episodes (convective, moderately convective and stratiform) to obtain a robust methodology for implementing it in an operational and dynamic way.

Mutational and computational analysis of the alpha(1b)-adrenergic receptor. Involvement of basic and hydrophobic residues in receptor activation and G protein coupling.

To investigate their role in receptor coupling to G(q), we mutated all basic amino acids and some conserved hydrophobic residues of the cytosolic surface of the alpha(1b)-adrenergic receptor (AR). The wild type and mutated receptors were expressed in COS-7 cells and characterized for their ligand binding properties and ability to increase inositol phosphate accumulation. The experimental results have been interpreted in the context of both an ab initio model of the alpha(1b)-AR and of a new homology model built on the recently solved crystal structure of rhodopsin. Among the twenty-three basic amino acids mutated only mutations of three, Arg(254) and Lys(258) in the third intracellular loop and Lys(291) at the cytosolic extension of helix 6, markedly impaired the receptor-mediated inositol phosphate production. Additionally, mutations of two conserved hydrophobic residues, Val(147) and Leu(151) in the second intracellular loop had significant effects on receptor function. The functional analysis of the receptor mutants in conjunction with the predictions of molecular modeling supports the hypothesis that Arg(254), Lys(258), as well as Leu(151) are directly involved in receptor-G protein interaction and/or receptor-mediated activation of the G protein. In contrast, the residues belonging to the cytosolic extensions of helices 3 and 6 play a predominant role in the activation process of the alpha(1b)-AR. These findings contribute to the delineation of the molecular determinants of the alpha(1b)-AR/G(q) interface.

MIGCLIM: Predicting plant distribution and dispersal in a changing climate

Many studies have forecasted the possible impact of climate change on plant distribution using models based on ecological niche theory. In their basic implementation, niche-based models do not constrain predictions by dispersal limitations. Hence, most niche-based modelling studies published so far have assumed dispersal to be either unlimited or null. However, depending on the rate of climatic change, the landscape fragmentation and the dispersal capabilities of individual species, these assumptions are likely to prove inaccurate, leading to under- or overestimation of future species distributions and yielding large uncertainty between these two extremes. As a result, the concepts of "potentially suitable" and "potentially colonisable" habitat are expected to differ significantly. To quantify to what extent these two concepts can differ, we developed MIGCLIM, a model simulating plant dispersal under climate change and landscape fragmentation scenarios. MIGCLIM implements various parameters, such as dispersal distance, increase in reproductive potential over time, barriers to dispersal or long distance dispersal. Several simulations were run for two virtual species in a study area of the western Swiss Alps, by varying dispersal distance and other parameters. Each simulation covered the hundred-year period 2001-2100 and three different IPCC-based temperature warming scenarios were considered. Our results indicate that: (i) using realistic parameter values, the future potential distributions generated using MIGCLIM can differ significantly (up to more than 95% decrease in colonized surface) from those that ignore dispersal; (ii) this divergence increases both with increasing climate warming and over longer time periods; (iii) the uncertainty associated with the warming scenario can be nearly as large as the one related to dispersal parameters; (iv) accounting for dispersal, even roughly, can importantly reduce uncertainty in projections.

Novel methods improve prediction of species' distributions from occurrence data

Prediction of species' distributions is central to diverse applications in ecology, evolution and conservation science. There is increasing electronic access to vast sets of occurrence records in museums and herbaria, yet little effective guidance on how best to use this information in the context of numerous approaches for modelling distributions. To meet this need, we compared 16 modelling methods over 226 species from 6 regions of the world, creating the most comprehensive set of model comparisons to date. We used presence-only data to fit models, and independent presence-absence data to evaluate the predictions. Along with well-established modelling methods such as generalised additive models and GARP and BIOCLIM, we explored methods that either have been developed recently or have rarely been applied to modelling species' distributions. These include machine-learning methods and community models, both of which have features that may make them particularly well suited to noisy or sparse information, as is typical of species' occurrence data. Presence-only data were effective for modelling species' distributions for many species and regions. The novel methods consistently outperformed more established methods. The results of our analysis are promising for the use of data from museums and herbaria, especially as methods suited to the noise inherent in such data improve.

The effects of dominance, regular inbreeding and sampling design on Q(ST), an estimator of population differentiation for quantitative traits.

To test whether quantitative traits are under directional or homogenizing selection, it is common practice to compare population differentiation estimates at molecular markers (F(ST)) and quantitative traits (Q(ST)). If the trait is neutral and its determinism is additive, then theory predicts that Q(ST) = F(ST), while Q(ST) > F(ST) is predicted under directional selection for different local optima, and Q(ST) < F(ST) is predicted under homogenizing selection. However, nonadditive effects can alter these predictions. Here, we investigate the influence of dominance on the relation between Q(ST) and F(ST) for neutral traits. Using analytical results and computer simulations, we show that dominance generally deflates Q(ST) relative to F(ST). Under inbreeding, the effect of dominance vanishes, and we show that for selfing species, a better estimate of Q(ST) is obtained from selfed families than from half-sib families. We also compare several sampling designs and find that it is always best to sample many populations (>20) with few families (five) rather than few populations with many families. Provided that estimates of Q(ST) are derived from individuals originating from many populations, we conclude that the pattern Q(ST) > F(ST), and hence the inference of directional selection for different local optima, is robust to the effect of nonadditive gene actions.

Molecular modeling of peptide-MHC class I complexes : applications to peptide based immunotherapy

Summary The specific CD8+ T cell immune response against tumors relies on the recognition by the T cell receptor (TCR) on cytotoxic T lymphocytes (CTL) of antigenic peptides bound to the class I major histocompatibility complex (MHC) molecule. Such tumor associated antigenic peptides are the focus of tumor immunotherapy with peptide vaccines. The strategy for obtaining an improved immune response often involves the design of modified tumor associated antigenic peptides. Such modifications aim at creating higher affinity and/or degradation resistant peptides and require precise structures of the peptide-MHC class I complex. In addition, the modified peptide must be cross-recognized by CTLs specific for the parental peptide, i.e. preserve the structure of the epitope. Detailed structural information on the modified peptide in complex with MHC is necessary for such predictions. In this thesis, the main focus is the development of theoretical in silico methods for prediction of both structure and cross-reactivity of peptide-MHC class I complexes. Applications of these methods in the context of immunotherapy are also presented. First, a theoretical method for structure prediction of peptide-MHC class I complexes is developed and validated. The approach is based on a molecular dynamics protocol to sample the conformational space of the peptide in its MHC environment. The sampled conformers are evaluated using conformational free energy calculations. The method, which is evaluated for its ability to reproduce 41 X-ray crystallographic structures of different peptide-MHC class I complexes, shows an overall prediction success of 83%. Importantly, in the clinically highly relevant subset of peptide-HLAA*0201 complexes, the prediction success is 100%. Based on these structure predictions, a theoretical approach for prediction of cross-reactivity is developed and validated. This method involves the generation of quantitative structure-activity relationships using three-dimensional molecular descriptors and a genetic neural network. The generated relationships are highly predictive as proved by high cross-validated correlation coefficients (0.78-0.79). Together, the here developed theoretical methods open the door for efficient rational design of improved peptides to be used in immunotherapy. Résumé La réponse immunitaire spécifique contre des tumeurs dépend de la reconnaissance par les récepteurs des cellules T CD8+ de peptides antigéniques présentés par les complexes majeurs d'histocompatibilité (CMH) de classe I. Ces peptides sont utilisés comme cible dans l'immunothérapie par vaccins peptidiques. Afin d'augmenter la réponse immunitaire, les peptides sont modifiés de façon à améliorer l'affinité et/ou la résistance à la dégradation. Ceci nécessite de connaître la structure tridimensionnelle des complexes peptide-CMH. De plus, les peptides modifiés doivent être reconnus par des cellules T spécifiques du peptide natif. La structure de l'épitope doit donc être préservée et des structures détaillées des complexes peptide-CMH sont nécessaires. Dans cette thèse, le thème central est le développement des méthodes computationnelles de prédiction des structures des complexes peptide-CMH classe I et de la reconnaissance croisée. Des applications de ces méthodes de prédiction à l'immunothérapie sont également présentées. Premièrement, une méthode théorique de prédiction des structures des complexes peptide-CMH classe I est développée et validée. Cette méthode est basée sur un échantillonnage de l'espace conformationnel du peptide dans le contexte du récepteur CMH classe I par dynamique moléculaire. Les conformations sont évaluées par leurs énergies libres conformationnelles. La méthode est validée par sa capacité à reproduire 41 structures des complexes peptide-CMH classe I obtenues par cristallographie aux rayons X. Le succès prédictif général est de 83%. Pour le sous-groupe HLA-A*0201 de complexes de grande importance pour l'immunothérapie, ce succès est de 100%. Deuxièmement, à partir de ces structures prédites in silico, une méthode théorique de prédiction de la reconnaissance croisée est développée et validée. Celle-ci consiste à générer des relations structure-activité quantitatives en utilisant des descripteurs moléculaires tridimensionnels et un réseau de neurones couplé à un algorithme génétique. Les relations générées montrent une capacité de prédiction remarquable avec des valeurs de coefficients de corrélation de validation croisée élevées (0.78-0.79). Les méthodes théoriques développées dans le cadre de cette thèse ouvrent la voie du design de vaccins peptidiques améliorés.

Extra-pair paternity, testes size and testosterone level in relation to colour polymorphism in the barn owl Tyto alba

In many bird populations, individuals display one of several genetically inherited colour morphs. Colour polymorphism can be maintained by several mechanisms one of which being frequency-dependent selection with colour morphs signalling alternative mating strategies. One morph may be dominant and territorial, and another one adopt a sneaky behaviour to gain access to fertile females. We tested this hypothesis in the barn owl Tyto alba in which coloration varies from reddish-brown to white. This trait is heritable and neither sensitive to the environment in which individuals live nor to body condition. In Switzerland, reddish-brown males were observed to feed their brood at a higher rate and to produce more offspring than white males. This observation lead us to hypothesize that white males may equalise fitness by investing more effort in extra-pair copulations. This hypothesis predicts that lighter Coloured males produce more extra-pair young, have larger testes and higher levels of circulating testosterone. However, our results are not consistent with these three predictions. First, paternity analyses of 54 broods with a total of 211 offspring revealed that only one young was not sired by the male that was feeding it. Second, testes size was not correlated with male plumage coloration suggesting that white males are not sexually more active. Finally, in nestlings at the time of feather growth testosterone level was not related to plumage coloration suggesting that this androgen is not required for the expression of this plumage trait. Our study therefore indicates that in the barn owl colour polymorphism plays no role in the probability of producing extra-pair young.

Vascular continuity, cell axialization and auxin.

Phytohormones have been implicated in vascular development in various ways, but their precise function and the extent of their influence is still controversial. Recent results from experimental manipulation of developing organs and Arabidopsis developmental genetics support a role for polar auxin flow in cell axis formation within the vascular system and, interestingly, also in the embryonic establishment of the plant body axis. Vascular responses to auxin transport inhibition indicate patterns of auxin distribution during leaf development and new technologies may enable these predictions to be tested within the near future. Moreover, recently discovered Arabidopsis axialisation mutants seem to identify essential genes that relay auxin signals in vascular development. A first gene in this class, MONOPTEROS (MP) has been cloned and encodes a transcription factor capable of binding to auxin response elements in the control regions of auxin regulated genes. Molecular identification of further axialisation genes may provide access to a mechanistic understanding of plant cell axis formation.

Improving the prediction of plant species distribution and community composition by adding edaphic to topo-climatic variables

Questions Soil properties have been widely shown to influence plant growth and distribution. However, the degree to which edaphic variables can improve models based on topo-climatic variables is still unclear. In this study, we tested the roles of seven edaphic variables, namely (1) pH; (2) the content of nitrogen and of (3) phosphorus; (4) silt; (5) sand; (6) clay and (7) carbon-to-nitrogen ratio, as predictors of species distribution models in an edaphically heterogeneous landscape. We also tested how the respective influence of these variables in the models is linked to different ecological and functional species characteristics. Location The Western Alps, Switzerland. Methods With four different modelling techniques, we built models for 115 plant species using topo-climatic variables alone and then topo-climatic variables plus each of the seven edaphic variables, one at a time. We evaluated the contribution of each edaphic variable by assessing the change in predictive power of the model. In a second step, we evaluated the importance of the two edaphic variables that yielded the largest increase in predictive power in one final set of models for each species. Third, we explored the change in predictive power and the importance of variables across plant functional groups. Finally, we assessed the influence of the edaphic predictors on the prediction of community composition by stacking the models for all species and comparing the predicted communities with the observed community. Results Among the set of edaphic variables studied, pH and nitrogen content showed the highest contributions to improvement of the predictive power of the models, as well as the predictions of community composition. When considering all topo-climatic and edaphic variables together, pH was the second most important variable after degree-days. The changes in model results caused by edaphic predictors were dependent on species characteristics. The predictions for the species that have a low specific leaf area, and acidophilic preferences, tolerating low soil pH and high humus content, showed the largest improvement by the addition of pH and nitrogen in the model. Conclusions pH was an important predictor variable for explaining species distribution and community composition of the mountain plants considered in our study. pH allowed more precise predictions for acidophilic species. This variable should not be neglected in the construction of species distribution models in areas with contrasting edaphic conditions.

Applicability of a distributed watershed pollution model in a data-poor environment in Santa Catarina State, Brazil

Intensification of agricultural production without a sound management and regulations can lead to severe environmental problems, as in Western Santa Catarina State, Brazil, where intensive swine production has caused large accumulations of manure and consequently water pollution. Natural resource scientists are asked by decision-makers for advice on management and regulatory decisions. Distributed environmental models are useful tools, since they can be used to explore consequences of various management practices. However, in many areas of the world, quantitative data for model calibration and validation are lacking. The data-intensive distributed environmental model AgNPS was applied in a data-poor environment, the upper catchment (2,520 ha) of the Ariranhazinho River, near the city of Seara, in Santa Catarina State. Steps included data preparation, cell size selection, sensitivity analysis, model calibration and application to different management scenarios. The model was calibrated based on a best guess for model parameters and on a pragmatic sensitivity analysis. The parameters were adjusted to match model outputs (runoff volume, peak runoff rate and sediment concentration) closely with the sparse observed data. A modelling grid cell resolution of 150 m adduced appropriate and computer-fit results. The rainfall runoff response of the AgNPS model was calibrated using three separate rainfall ranges (< 25, 25-60, > 60 mm). Predicted sediment concentrations were consistently six to ten times higher than observed, probably due to sediment trapping along vegetated channel banks. Predicted N and P concentrations in stream water ranged from just below to well above regulatory norms. Expert knowledge of the area, in addition to experience reported in the literature, was able to compensate in part for limited calibration data. Several scenarios (actual, recommended and excessive manure applications, and point source pollution from swine operations) could be compared by the model, using a relative ranking rather than quantitative predictions.

Semi-supervised remote sensing image classification with cluster kernels

A semisupervised support vector machine is presented for the classification of remote sensing images. The method exploits the wealth of unlabeled samples for regularizing the training kernel representation locally by means of cluster kernels. The method learns a suitable kernel directly from the image and thus avoids assuming a priori signal relations by using a predefined kernel structure. Good results are obtained in image classification examples when few labeled samples are available. The method scales almost linearly with the number of unlabeled samples and provides out-of-sample predictions.

Melanin-based coloration is a nondirectionally selected sex-specific signal of offspring development in the Alpine swift

Two mutually exclusive hypotheses have been put forward to explain the evolution and adaptive function of melanin-based color traits. According to sexual selection theory melanism is a directionally selected signal of individual quality, whereas theory on the maintenance of genetic polymorphism proposes that alternative melanin-based variants achieve equal fitness. Alpine swift (Apus melba) males and females have a conspicuous patch of white feathers on the breast with their rachis varying continuously from white to black, and hence the breast varies from white to striated. If this trait is a sexually selected signal of quality, its expression should be condition dependent and the degree of melanism directionally selected. If variation in melanism is a polymorphism, its expression should be genetically determined and fitness of melanin-based variants equal. We experimentally tested these predictions by exchanging eggs or hatchlings between randomly chosen nests and by estimating survival and reproduction in relation to melanism. We found that breast melanism is heritable and that the environment and body condition do not significantly influence its expression. Between 5 and 50 days of age nestlings were heavier and their wings longer when breast feathers of their biological father were blacker, and they also fledged at a younger age. This shows that aspects of offspring quality covary positively with the degree of melanism. However, this did not result in directional selection because nestling survival and recruitment in the local breeding population were not associated with father breast melanism. Furthermore, adult survival, age at first reproduction and probability of skipping reproduction did not covary with the degree of melanism. Genetic variation in breast melanism is therefore maintained either because nonmelanic males achieve fitness similar to melanic males via a different route than producing fast-growing offspring, or because the advantage of producing fast-growing offspring is not sufficiently pronounced to result in directional selection.