Kernel-based Mapping of Meteorological Fields in Complex Orography

Due to the advances in sensor networks and remote sensing technologies, the acquisition and storage rates of meteorological and climatological data increases every day and ask for novel and efficient processing algorithms. A fundamental problem of data analysis and modeling is the spatial prediction of meteorological variables in complex orography, which serves among others to extended climatological analyses, for the assimilation of data into numerical weather prediction models, for preparing inputs to hydrological models and for real time monitoring and short-term forecasting of weather.In this thesis, a new framework for spatial estimation is proposed by taking advantage of a class of algorithms emerging from the statistical learning theory. Nonparametric kernel-based methods for nonlinear data classification, regression and target detection, known as support vector machines (SVM), are adapted for mapping of meteorological variables in complex orography.With the advent of high resolution digital elevation models, the field of spatial prediction met new horizons. In fact, by exploiting image processing tools along with physical heuristics, an incredible number of terrain features which account for the topographic conditions at multiple spatial scales can be extracted. Such features are highly relevant for the mapping of meteorological variables because they control a considerable part of the spatial variability of meteorological fields in the complex Alpine orography. For instance, patterns of orographic rainfall, wind speed and cold air pools are known to be correlated with particular terrain forms, e.g. convex/concave surfaces and upwind sides of mountain slopes.Kernel-based methods are employed to learn the nonlinear statistical dependence which links the multidimensional space of geographical and topographic explanatory variables to the variable of interest, that is the wind speed as measured at the weather stations or the occurrence of orographic rainfall patterns as extracted from sequences of radar images. Compared to low dimensional models integrating only the geographical coordinates, the proposed framework opens a way to regionalize meteorological variables which are multidimensional in nature and rarely show spatial auto-correlation in the original space making the use of classical geostatistics tangled.The challenges which are explored during the thesis are manifolds. First, the complexity of models is optimized to impose appropriate smoothness properties and reduce the impact of noisy measurements. Secondly, a multiple kernel extension of SVM is considered to select the multiscale features which explain most of the spatial variability of wind speed. Then, SVM target detection methods are implemented to describe the orographic conditions which cause persistent and stationary rainfall patterns. Finally, the optimal splitting of the data is studied to estimate realistic performances and confidence intervals characterizing the uncertainty of predictions.The resulting maps of average wind speeds find applications within renewable resources assessment and opens a route to decrease the temporal scale of analysis to meet hydrological requirements. Furthermore, the maps depicting the susceptibility to orographic rainfall enhancement can be used to improve current radar-based quantitative precipitation estimation and forecasting systems and to generate stochastic ensembles of precipitation fields conditioned upon the orography.

Numerous potentially functional but non-genic conserved sequences on human chromosome 21.

The use of comparative genomics to infer genome function relies on the understanding of how different components of the genome change over evolutionary time. The aim of such comparative analysis is to identify conserved, functionally transcribed sequences such as protein-coding genes and non-coding RNA genes, and other functional sequences such as regulatory regions, as well as other genomic features. Here, we have compared the entire human chromosome 21 with syntenic regions of the mouse genome, and have identified a large number of conserved blocks of unknown function. Although previous studies have made similar observations, it is unknown whether these conserved sequences are genes or not. Here we present an extensive experimental and computational analysis of human chromosome 21 in an effort to assign function to sequences conserved between human chromosome 21 (ref. 8) and the syntenic mouse regions. Our data support the presence of a large number of potentially functional non-genic sequences, probably regulatory and structural. The integration of the properties of the conserved components of human chromosome 21 to the rapidly accumulating functional data for this chromosome will improve considerably our understanding of the role of sequence conservation in mammalian genomes.

To differentiate complementary mri sequences to standard protocol in detecting degenerative inflammatory lumbar spine lesions

Purpose: To compare the additional informations obtainedwith axial and sagittal T2 weighted with fat saturation(T2FS) and T1 weighted with Gadolinium iv sequenceswith fat saturation (T1FSGd) to detect degenerativeinflammatory lumbar spine lesions.Materials and Methods: Our retrospective study included73 patients (365 lumbar levels) with lumbar spinedegenerative disease (25 males, 48 females, mean age56 years). MRI protocol was performed with T1 and T2weighted sagittal and T2 weighted axial sequences(standard protocol), axial and sagittal T2FS and T1FSGd.Images were independently analyzed by two musculoskeletalradiologists and a neurosurgeon. Two groups ofsequences were analyzed: standard + T2FS sequences(group 1), standard + T1FSGd sequences (group 2).Degenerative inflammatory lumbar spine lesions werenoted at each level in: anterior column (vertebralendplate), spinal canal (epidural and peri-radicular fat)and posterior column (facet joint with capsular recessand subchondral bone).Results: Degenerative inflammatory lesions were present in18% (66/365) of levels in group 1, and 48% (175/365) oflevels in group 2. In details, lesions were noted in group 1 and2 respectively:-in 44 and 66 levels for anterior column,-in22 and 131 levels for posterior column,-in 0 and 36 levelsfor spinal canal. All these differences were statisticallysignificant. Intra and Interobserver agreements were good.Conclusion: The T1FSGd sequence is more sensitive thanT2FS to show the degenerative inflammatory lumbar spinelesions, especially in spinal canal and posterior column.

Phylogenetics of Olea (Oleaceae) based on plastid and nuclear ribosomal DNA sequences: tertiary climatic shifts and lineage differentiation times.

BACKGROUND AND AIMS: The genus Olea (Oleaceae) includes approx. 40 taxa of evergreen shrubs and trees classified in three subgenera, Olea, Paniculatae and Tetrapilus, the first of which has two sections (Olea and Ligustroides). Olive trees (the O. europaea complex) have been the subject of intensive research, whereas little is known about the phylogenetic relationships among the other species. To clarify the biogeographical history of this group, a molecular analysis of Olea and related genera of Oleaceae is thus necessary. METHODS: A phylogeny was built of Olea and related genera based on sequences of the nuclear ribosomal internal transcribed spacer-1 and four plastid regions. Lineage divergence and the evolution of abaxial peltate scales, the latter character linked to drought adaptation, were dated using a Bayesian method. KEY RESULTS: Olea is polyphyletic, with O. ambrensis and subgenus Tetrapilus not sharing a most recent common ancestor with the main Olea clade. Partial incongruence between nuclear and plastid phylogenetic reconstructions suggests a reticulation process in the evolution of subgenus Olea. Estimates of divergence times for major groups of Olea during the Tertiary were obtained. CONCLUSIONS: This study indicates the necessity of revising current taxonomic boundaries in Olea. The results also suggest that main lines of evolution were promoted by major Tertiary climatic shifts: (1) the split between subgenera Olea and Paniculatae appears to have taken place at the Miocene-Oligocene boundary; (2) the separation of sections Ligustroides and Olea may have occurred during the Early Miocene following the Mi-1 glaciation; and (3) the diversification within these sections (and the origin of dense abaxial indumentum in section Olea) was concomitant with the aridification of Africa in the Late Miocene.

Outcome evaluation of ankle osteoarthritis treatments using spatio-temporal gait parameters and plantar pressure during unconstrained long distance walking : P25

Introduction: Ankle arthrodesis (AD) and total ankle replacement (TAR) are typical treatments for ankle osteoarthritis (AO). Despite clinical interest, there is a lack of their outcome evaluation using objective criteria. Gait analysis and plantar pressure assessment are appropriate to detect pathologies in orthopaedics but they are mostly used in lab with few gait cycles. In this study, we propose an ambulatory device based on inertial and plantar pressure sensors to compare the gait during long-distance trials between healthy subjects (H) and patients with AO or treated by AD and TAR. Methods: Our study included four groups: 11 patients with AO, 9 treated by TAR, 7 treated by AD and 6 control subjects. An ambulatory system (Physilog®, CH) was used for gait analysis; plantar pressure measurements were done using a portable insole (Pedar®-X, DE). The subjects were asked to walk 50 meters in two trials. Mean value and coefficient of variation of spatio-temporal gait parameters were calculated for each trial. Pressure distribution was analyzed in ten subregions of foot. All parameters were compared among the four groups using multi-level model-based statistical analysis. Results: Significant difference (p <0.05) with control was noticed for AO patients in maximum force in medial hindfoot and forefoot and in central forefoot. These differences were no longer significant in TAR and AD groups. Cadence and speed of all pathologic groups showed significant difference with control. Both treatments showed a significant improvement in double support and stance. TAR decreased variability in speed, stride length and knee ROM. Conclusions: In spite of a small sample size, this study showed that ankle function after AO treatments can be evaluated objectively based on plantar pressure and spatio-temporal gait parameters measured during unconstrained walking outside the lab. The combination of these two ambulatory techniques provides a promising way to evaluate foot function in clinics.

Auditory spatio-temporal brain dynamics and their consequences for multisensory interactions in humans.

Recent multisensory research has emphasized the occurrence of early, low-level interactions in humans. As such, it is proving increasingly necessary to also consider the kinds of information likely extracted from the unisensory signals that are available at the time and location of these interaction effects. This review addresses current evidence regarding how the spatio-temporal brain dynamics of auditory information processing likely curtails the information content of multisensory interactions observable in humans at a given latency and within a given brain region. First, we consider the time course of signal propagation as a limitation on when auditory information (of any kind) can impact the responsiveness of a given brain region. Next, we overview the dual pathway model for the treatment of auditory spatial and object information ranging from rudimentary to complex environmental stimuli. These dual pathways are considered an intrinsic feature of auditory information processing, which are not only partially distinct in their associated brain networks, but also (and perhaps more importantly) manifest only after several tens of milliseconds of cortical signal processing. This architecture of auditory functioning would thus pose a constraint on when and in which brain regions specific spatial and object information are available for multisensory interactions. We then separately consider evidence regarding mechanisms and dynamics of spatial and object processing with a particular emphasis on when discriminations along either dimension are likely performed by specific brain regions. We conclude by discussing open issues and directions for future research.

Late Cretaceous to Eocene geology of the South Central American forearc area (southern Costa Rica and western Panama) : initiation and evolution of an intra-oceanic convergent margin

Résumé : L'arc volcanique du sud de l'Amérique Centrale se situe sur la marge SW de la Plaque Caraïbe, au-dessus des plaques subduites de Cocos et Nazca. Il s'agit de l'un des arcs intra-océaniques les plus étudiés au monde, qui est généralement considéré comme s'étant développé à la fin du Crétacé le long d'un plateau océanique (le Plateau Caraïbe ou CLIP) et se trouvant actuellement dans un régime de subduction érosive. Au cours des dernières décennies, des efforts particuliers ont été faits pour comprendre les processus liés à la subduction sur la base d'études géophysiques et géochimiques. Au sud du Costa Rica et à l'ouest du Panama, des complexes d'accrétions et structures à la base de l'arc volcanique ont été exposés grâce à la subduction de rides asismiques et de failles transformantes. Des affleurements, situés jusqu'à seulement 15 km de la fosse, offrent une possibilité unique de mieux comprendre quelques uns des processus ayant lieu le long de la zone de subduction. Nous présentons de nouvelles contraintes sur l'origine de ces affleurements en alliant une étude de terrain poussée, de nouvelles données géochimiques, sédimentaires et paléontologiques, ainsi que des observations structurales effectuées en télédétection. Une nouvelle stratigraphie tectonique entre le Campanien et l'Éocène est définie pour la région d'avant-arc située entre la Péninsule d'Osa (Costa Rica) et la Péninsule d'Azuero (Panama). Nos résultats montrent que la partie externe de la marge est composée d'un arrangement complexe de roches ignées et de séquences sédimentaires de recouvrement qui comprennent principalement le socle de l'arc, des roches d'arc primitif, des fragments de monts sous-marins accrétés et des mélanges d'accrétion. Des preuves sont données pour le développement de l'arc volcanique du sud de l'Amérique Centrale sur un plateau océanique. Le début de la subduction le long de la marge SW de la Plaque Caraïbe a eu lieu au Campanien et a généré des roches d'arc primitif caractérisées par des affinités géochimiques particulières, globalement intermédiaires entre des affinités de plateau et d'arc insulaire. L'arc était mature au Maastrichtien et formait un isthme essentiellement continu entre l'Amérique du Nord et l'Amérique du Sud. Ceci a permis la migration de faunes terrestres entre les Amériques et pourrait avoir contribué à la crise fin Crétacé -Tertiaire en réduisant les courants océaniques subéquatoriaux entre le Pacifique et l'Atlantique. Plusieurs unités composées de fragments de monts sous-marins accrétés sont définies. La nature et l'arrangement structural de ces unités définissent de nouvelles contraintes sur les modes d'accrétion des monts sous-marins/îles océaniques et sur l'évolution de la marge depuis la formation de la zone de subduction. Entre la fin du Crétacé et l'Éocène moyen, la marge a enregistré plusieurs épisodes ponctuels d'accrétion de monts sous-marins alternant avec de la subduction érosive. A l'Éocène moyen, un événement tectonique régional pourrait avoir causé un fort couplage entre les plaques supérieure et inférieure, menant à des taux plus important d'accrétion de monts sous-marins. Durant cette période, la situation le long de la marge était très semblable à la situation actuelle et caractérisée par la présence de monts sous-marins subductants et l'absence d'accrétion de sédiments. L'enregistrement géologique montre qu'il n'est pas possible d'attribuer une nature érosive ou accrétionnaire à la marge dans le passé ou -par analogie- aujourd'hui, parce que (1) les processus d'accrétion et érosifs varient fortement spatialement et temporellement et (2) il est impossible d'évaluer la quantité exacte de matériel tectoniquement enlevé à la marge depuis le début de la subduction. Au sud du Costa Rica, certains fragments de monts sous-marins accrétés sont représentatifs d'une interaction entre une ride et un point chaud dans le Pacifique au Crétacé terminal/Paléocène. L'existence de ces fragments de monts sous-marins et la morphologie du fond de l'Océan Pacifique indiquent que la formation de la ride de Cocos-Nazca s'est formée au moins ~40 Ma avant l'âge proposé par les modèles tectoniques actuels. Au Panama, nous avons identifié une île océanique d'âge début Éocène qui a été accrétée à l'Éocène moyen. L'accrétion a eu lieu à très faible profondeur par détachement de l'île dans la fosse, et a mené à une exceptionnelle préservation des structures volcaniques. Des affleurement comprenant aussi bien des parties basses et hautes de l'édifice volcanique on été étudiées, depuis la phase sous-marine bouclier jusqu'à la phase subaérienne post-bouclier. La stratigraphie nous a permis de différencier les laves de la phase sous-marine de celles de la phase subaérienne. La composition des laves indique une diminution progressive de l'intensité de la fusion partielle de la source et une diminution de la température des laves produites durant les derniers stades de l'activité volcanique. Nous interprétons ces changements comme étant liés à l'éloignement progressif de l'île océanique de la zone de fusion ou point chaud. Abstract The southern Central American volcanic front lies on the SW edge of the Caribbean Plate, inboard of the subducting Cocos and Nazca Plates. It is one of the most studied intra-oceanic convergent margins around the world, which is generally interpreted to have developed in the late Cretaceous along an oceanic plateau (the Caribbean Large Igneous Province or CLIP) and to be currently undergoing a regime of subduction erosion. In the last decades a particular effort has been made to understand subduction-related processes on the basis of geophysical and geochemical studies. In southern Costa Rica and western Panama accretionary complexes and structures at the base of the volcanic front have been exposed in response to subduction of aseismic ridges and transforms. Onland exposures are located as close as to 15 km from the trench and provide a unique opportunity to better understand some of the processes occurring along the subduction zone. We provide new constraints on the origins of these exposures by integrating a comprehensive field work, new geochemical, sedimentary and paleontological data, as well as structural observations based on remote imaging. A new Campanian to Eocene tectonostratigraphy is defined for the forearc area located between the Osa Peninsula (Costa Rica) and the Azuero Peninsula (Panama). Our results show that the outer margin is composed of a complicated arrangement of igneous complexes and overlapping sedimentary sequences that essentially comprise an arc basement, primitive island-arc rocks, accreted seamount fragments and accretionary mélanges. Evidences are provided for the development of the southern Central American arc on the top an oceanic plateau. The subduction initiation along the SW edge of the Caribbean Plate occurred in the Campanian and led to formation of primitive island-arc rocks characterized by unusual geochemical affinities broadly intermediate between plateau and arc affinities. The arc was mature in the Maastrichtian and was forming a predominantly continuous landbridge between the North and South Americas. This allowed migration of terrestrial fauna between the Americas and may have contributed to the Cretaceous-Tertiary crisis by limiting trans-equatorial oceanic currents between the Pacific and the Atlantic. Several units composed of accreted seamount fragments are defined. The nature of the units and their structural arrangement provide new constraints on the modes of accretion of seamounts/oceanic islands and on the evolution of the margin since subduction initiation. Between the late Cretaceous and the middle Eocene, the margin recorded several local episodes of seamount accretion alternating with tectonic erosion. In the middle Eocene a regional tectonic event may have triggered strong coupling between the overriding and subducting plates, leading to higher rates of seamount accretion. During this period the situation along the margin was very similar to the present and characterized by subducting seamounts and absence of sediment accretion. The geological record shows that it is not possible to ascribe an overall erosive or accretionary nature to the margin in the past and, by analogy, today, because (1) accretionary and erosive processes exhibit significant lateral and temporal variations and (2) it is impossible to estimate the exact amount of material tectonically eroded from the margin since subduction initiation. In southern Costa Rica, accreted seamount fragments point toward a plume-ridge interaction in the Pacific in the late Cretaceous/Paleocene. This occurrence of accreted seamount fragments and morphology of the Pacific Ocean floor is indicative of the formation of the Cocos-Nazca spreading system at least ~40 Ma prior to the age proposed in current tectonic models. In Panama, we identified a remarkably-well preserved early Eocene oceanic island that accreted in the middle Eocene. The accretion probably occurred at very shallow depth by detachment of the island in the trench and led to an exceptional preservation of the volcanic structures. Exposures of both deep and superficial parts of the volcanic edifice have been studied, from the submarine-shield to subaerial-postshield stages. The stratigraphy allowed us to distinguish lavas produced during the submarine and subaerial stages. The lava compositions likely define a progressive diminution of source melting and a decrease in the temperature of erupted melts in the latest stages of volcanic activity. We interpret these changes to primarily reflect the progressive migration of the oceanic island out of the melting region or hotspot.

Indexing strategies for rapid searches of short words in genome sequences.

Searching for matches between large collections of short (14-30 nucleotides) words and sequence databases comprising full genomes or transcriptomes is a common task in biological sequence analysis. We investigated the performance of simple indexing strategies for handling such tasks and developed two programs, fetchGWI and tagger, that index either the database or the query set. Either strategy outperforms megablast for searches with more than 10,000 probes. FetchGWI is shown to be a versatile tool for rapidly searching multiple genomes, whose performance is limited in most cases by the speed of access to the filesystem. We have made publicly available a Web interface for searching the human, mouse, and several other genomes and transcriptomes with oligonucleotide queries.

Spatial and temporal regulation of " cdc16p " in the fission yeast " Schizosaccharomyces pombe "

Abstract: The fission yeast Schizosaccharomyces pombe has proven to be an excellent model system for the study of eukaryotic cell cycle control. S. pombe cells are rod-shaped and grow mainly by elongation at their tips. They divide by the means of a centrallyplaced division septum which provides two daughter cells of equal size. S. pombe cytokinesis begins at mitotic entry, when the division site is defined by formation of the contractile acto-myosin ring (CAR). Formation of the division septum is triggered at the end of mitosis by the spindle pole body (SPB) associated septation initiation network (SIN) proteins. SIN signalling requires activation of the GTPase spg1p, whose nucleotide status is regulated by the bipartite GAP byr4pcdc16p. Removal of cdc16p from the SPB during early mitosis is thought to allow priming of the SIN by association of cdc7p with both SPBs. During anaphase cdc7p is retained on the new SPB, which also recruits the kinase sid1 p and cdc14p, while the old SP8 reassembles the byr4-cdc16p GAP and is presumed not to signal; SPB asymmetry persists throughout anaphase. The trigger for inactivation of SIN signalling at the new SPB is unknown. This study has concentrated upon cdc16p. We have undertaken the analysis of the localisation of cdc16p using time-lapse microscopy. We have observed that the localisation of cdc16p is regulated at different transitions. We have shown that cdc16p is removed from the SPB prior to the onset of spindle formation and that it reappears asymmetrically at the beginning of anaphase B. We have also demonstrated that the resetting of the SIN at the new SPB is linked to completion of CAR contraction and septum formation. We propose the existence of a mechanism that monitors cytokinesis and that couples the activity of the SI N with the presence of the CAR. During the biochemical characterization of cdc16p, We have found that it is an unstable protein and that it is subjected to polyubiquitination by the SCF and proteasomal degradation. Together, these observations help to shed new light upon the mechanisms by which cytokinesis is regulated in S. pombe. Résumé: La levure Schizosaccharomyces pombe est un excellent organisme modèle pour l'étude du cycle cellulaire eucaryote. Les cellules S. pombe ont la forme de bâtonnets et croissent par l'allongement de leurs extrémités. Elles se divisent en formant, en leur milieu une paroi cellulaire, appelé septum, permettant ainsi l'obtention de deux cellules filles de même taille. Chez S. pombe, la cytokinèse commence en début de mitose lorsque le site de division est déterminé par la formation d'un anneau d'acto-myosine. Le septum, lui, est formé uniquement en fin de mitose par la contraction de l'anneau d'actomyosine. Cette contraction est sous le contrôle d'un réseau de signalisation cellulaire appelé le «réseau d'initiation de synthèse du septum » ou « septation initiation network » (SIN), qui se situe sur les pôles du fuseau mitotique. L'activation du SIN dépend d'une GTPase appelé spg1p dont le statut nucléotidique dépend des protéines cdclóp et byr4p qui forment un complexe qui favorise l'hydrolyse du GTP en GDP. En début de mitose, cdc16p ne se situe plus sur les poles du fuseau mitotique. La GTPase spg1p se retrouve donc principalement sous sa forme couplée au GTP, ce quí va permettre son interaction avec la kinase cdc7p. Cette protéine ainsi que deux autres kinases sid2p (avec mob1p) et sid1p (avec cdc14p) permettent la transmission du signal d'initiation de la contraction de l'anneau d'acto-myosine en fin d'anaphase. Pendant l'anaphase, cdc7p, sid1 p et cdc14p localisent sur un des deux pôles du fuseau mitotique. Il en est de même pour cdc1p et by14p et le pôle contenant cdc16p et byr4p est toujours différent de celui ou les régulateurs positifs du SIN se situent. En fin de cytokinèse, cdc16 et byr4p se retrouvent à nouveau sur chaque pôle des deux cellules filles. Dans cette étude, nous nous sommes concentrés sur l'analyse de la localisation de cdc16p pendant la mitose en utilisant une technique de microscopie en temps réel. Nous avons été en mesure de déterminer que le départ de cdc16p du pole s'effectue juste avant la formation du fuseau mitotique. Nous avons aussi découvert que la localisation asymétrique des composants du SIN dépend fortement de l'entrée en anaphase B. Finalement, Nous avons montré que distribution asymétrique des composants du SIN sur les pôles du fuseau mitotique dépendait aussi fortement de !a présence de l'anneau d'acto-myosine. Ceci nous permet donc de proposer l'existence d'un mécanisme cellulaire qui permet de s'assurer que la cytokinèse est achevée avant de diminuer la signalisation du SIN. Par ailleurs, des études biochimiques nous ont permis de montrer que cdc16p est dégradé par le proteosome. Ces travaux ont permis la découverte de nouveaux modes de régulation du SIN.

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07).

BACKGROUND: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T]. PATIENTS AND METHODS: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models. RESULTS: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements. Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < -2.5 standard deviation). CONCLUSIONS: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherapy.

Temporal variation in glucocorticoid levels during the resting phase is associated in opposite way with maternal and paternal melanic coloration.

Sex-dependent selection can help maintain sexual dimorphism. When the magnitude of selection exerted on a heritable sex trait differs between the sexes, it may prevent each sex to reach its phenotypic optimum. As a consequence, the benefit of expressing a sex trait to a given value may differ between males and females favouring sex-specific adaptations associated with different values of a sex trait. The level of metabolites regulated by genes that are under sex-dependent selection may therefore covary with the degree of ornamentation differently in the two sexes. We investigated this prediction in the barn owl, a species in which females display on average larger black spots on the plumage than males, a heritable ornament. This melanin-based colour trait is strongly selected in females and weakly counter-selected in males indicating sex-dependent selection. In nestling barn owls, we found that daily variation in baseline corticosterone levels, a key hormone that mediates life history trade-offs, covaries with spot diameter displayed by their biological parents. When their mother displayed larger spots, nestlings had lower corticosterone levels in the morning and higher levels in the evening, whereas the opposite pattern was found with the size of paternal spots. Our study suggests a link between daily regulation of glucocorticoids and sex-dependent selection exerted on sexually dimorphic melanin-based ornaments.

Comparison of 3D segmented gradient-echo and steady-state free precession coronary MRI sequences in patients with coronary artery disease.

OBJECTIVE: Our objective was to compare two state-of-the-art coronary MRI (CMRI) sequences with regard to image quality and diagnostic accuracy for the detection of coronary artery disease (CAD). SUBJECTS AND METHODS: Twenty patients with known CAD were examined with a navigator-gated and corrected free-breathing 3D segmented gradient-echo (turbo field-echo) CMRI sequence and a steady-state free precession sequence (balanced turbo field-echo). CMRI was performed in a transverse plane for the left coronary artery and a double-oblique plane for the right coronary artery system. Subjective image quality (1- to 4-point scale, with 1 indicating excellent quality) and objective image quality parameters were independently determined for both sequences. Sensitivity, specificity, and accuracy for the detection of significant (> or = 50% diameter) coronary artery stenoses were determined as defined in invasive catheter X-ray coronary angiography. RESULTS: Subjective image quality was superior for the balanced turbo field-echo approach (1.8 +/- 0.9 vs 2.3 +/- 1.0 for turbo field-echo; p < 0.001). Vessel sharpness, signal-to-noise ratio, and contrast-to-noise ratio were all superior for the balanced turbo field-echo approach (p < 0.01 for signal-to-noise ratio and contrast-to-noise ratio). Of the 103 segments, 18% of turbo field-echo segments and 9% of balanced turbo field-echo segments had to be excluded from disease evaluation because of insufficient image quality. Sensitivity, specificity, and accuracy for the detection of significant coronary artery stenoses in the evaluated segments were 92%, 67%, 85%, respectively, for turbo field-echo and 82%, 82%, 81%, respectively, for balanced turbo field-echo. CONCLUSION: Balanced turbo field-echo offers improved image quality with significantly fewer nondiagnostic segments when compared with turbo field-echo. For the detection of CAD, both sequences showed comparable accuracy for the visualized segments.

Spatio-temporal sequence of cross-regulatory events in root meristem growth.

A central question in developmental biology is how multicellular organisms coordinate cell division and differentiation to determine organ size. In Arabidopsis roots, this balance is controlled by cytokinin-induced expression of SHORT HYPOCOTYL 2 (SHY2) in the so-called transition zone of the meristem, where SHY2 negatively regulates auxin response factors (ARFs) by protein-protein interaction. The resulting down-regulation of PIN-FORMED (PIN) auxin efflux carriers is considered the key event in promoting differentiation of meristematic cells. Here we show that this regulation involves additional, intermediary factors and is spatio-temporally constrained. We found that the described cytokinin-auxin crosstalk antagonizes BREVIS RADIX (BRX) activity in the developing protophloem. BRX is an auxin-responsive target of the prototypical ARF MONOPTEROS (MP), a key promoter of vascular development, and transiently enhances PIN3 expression to promote meristem growth in young roots. At later stages, cytokinin induction of SHY2 in the vascular transition zone restricts BRX expression to down-regulate PIN3 and thus limit meristem growth. Interestingly, proper SHY2 expression requires BRX, which could reflect feedback on the auxin responsiveness of SHY2 because BRX protein can directly interact with MP, likely acting as a cofactor. Thus, cross-regulatory antagonism between BRX and SHY2 could determine ARF activity in the protophloem. Our data suggest a model in which the regulatory interactions favor BRX expression in the early proximal meristem and SHY2 prevails because of supplementary cytokinin induction in the later distal meristem. The complex equilibrium of this regulatory module might represent a universal switch in the transition toward differentiation in various developmental contexts.

Temporal evolution of MR perfusion in neonatal hypoxic-ischemic encephalopathy

PURPOSE: To illustrate the evolution of brain perfusion-weighted magnetic resonance imaging (PWI-MRI) in severe neonatal hypoxic-ischemic (HI) encephalopathy, and its possible relation to further neurodevelopmental outcome. MATERIALS AND METHODS: Two term neonates with HI encephalopathy underwent an early and a late MRI, including PWI. They were followed until eight months of age. A total of three "normal controls" were also included. Perfusion maps were obtained, and relative cerebral blood flow (rCBF) and cerebral blood volume (rCBV) values were measured. RESULTS: Compared to normal neonates, a hyperperfusion (increased rCBF and rCBV) was present on early scans in the whole brain. On late scans, hyperperfusion persisted in cortical gray matter (normalization of rCBF and rCBV ratios in white matter and basal ganglia, but not in cortical gray matter). Diffusion-weighted imaging (DWI) was normalized, and extensive lesions became visible on T2-weighted images. Both patients displayed very abnormal outcome: Patient 2 with the more abnormal early and late hyperperfusion being the worst. CONCLUSION: PWI in HI encephalopathy did not have the same temporal evolution as DWI, and remained abnormal for more than one week after injury. This could be a marker of an ongoing mechanism underlying severe neonatal HI encephalopathy. Evolution of PWI might help to predict further neurodevelopmental outcome.