3-D density structure and geological evolution of Stromboli volcano (Aeolian Islands, Italy) inferred from land-based and sea-surface gravity data

We present the first density model of Stromboli volcano (Aeolian Islands, Italy) obtained by simultaneously inverting land-based (543) and sea-surface (327) relative gravity data. Modern positioning technology, a 1 x 1 m digital elevation model, and a 15 x 15 m bathymetric model made it possible to obtain a detailed 3-D density model through an iteratively reweighted smoothness-constrained least-squares inversion that explained the land-based gravity data to 0.09 mGal and the sea-surface data to 5 mGal. Our inverse formulation avoids introducing any assumptions about density magnitudes. At 125 m depth from the land surface, the inferred mean density of the island is 2380 kg m(-3), with corresponding 2.5 and 97.5 percentiles of 2200 and 2530 kg m-3. This density range covers the rock densities of new and previously published samples of Paleostromboli I, Vancori, Neostromboli and San Bartolo lava flows. High-density anomalies in the central and southern part of the island can be related to two main degassing faults crossing the island (N41 and NM) that are interpreted as preferential regions of dyke intrusions. In addition, two low-density anomalies are found in the northeastern part and in the summit area of the island. These anomalies seem to be geographically related with past paroxysmal explosive phreato-magmatic events that have played important roles in the evolution of Stromboli Island by forming the Scari caldera and the Neostromboli crater, respectively. (C) 2014 Elsevier B.V. All rights reserved.

Exporting Contours to DICOM-RT Structure Set

This paper presents an ITK implementation for exportingthe contours of the automated segmentation results toDICOM-RT Structure Set format. The âeurooeradiotherapystructure setâeuro (RTSTRUCT) object of the DICOM standard isused for the transfer of patient structures and relateddata, between the devices found within and outside theradiotherapy department. It mainly contains theinformation of regions of interest (ROIs) and points ofinterest (E.g. dose reference points). In many cases,rather than manually drawing these ROIs on the CT images,one can indeed benefit from the automated segmentationalgorithms already implemented in ITK. But at present, itis not possible to export the ROIs obtained from ITK toRTSTRUCT format. In order to bridge this gap, we havedeveloped a framework for exporting contour data toRTSTRUCT. We provide here the complete implementation ofRTSTRUCT exporter and present the details of the pipelineused. Results on a 3-D CT image of the Head and Neck(H&N) region are presented.

Optimisation de la cryo microscopie électronique pour les études des minicercles d'ADN

RESUME : Bien que les propriétés physiques de la structure de l'ADN aient été intensivement étudiées pendant plus de 50 ans il y a encore beaucoup de questions importantes qui attendent des réponses. Par exemple, qu'arrive-t-il à la structure de la double hélice d'ADN nue (sans protéines liées) lorsqu'elle est fortement courbée, de la même manière que dans les nucléosomes? Cet ADN nu est-il facilement plié (il reste dans le régime élastique) ou réduit-il la contrainte de flexion en formant des sites hyperflexibles «kinks» (il sort du régime élastique en cassant l'empilement des paires de bases à certains endroits) ? La microscopie électronique peut fournir une réponse à cette question par visualisation directe des minicercles d'ADN de la longueur d'un tour de nucléosome (environ 90 paires de bases). Pour que la réponse soit scientifiquement valide, on doit observer les molécules d'ADN lorsqu'elles sont en suspension dans la solution d'intérêt et sans que des colorations, produits chimiques ou fixatifs n'aient été ajoutés, étant donné que ceux-ci peuvent changer les propriétés de l'ADN. La technique de la cryo-microscopie électronique (cryo-EM) développée par le groupe de Jacques Dubochet au début des années 80, permet la visualisation directe des molécules d'ADN suspendues dans des couche minces vitrifiées de solutions aqueuses. Toutefois, le faible contraste qui caractérise la cryo-EM combinée avec la très petite taille des minicercles d'ADN rendent nécessaire l'optimisation de plusieurs étapes, aussi bien dans la préparation des échantillons que dans le processus d'acquisition d'images afin d'obtenir deux clichés stéréo qui permettent la reconstruction 3-D des minicercles d'ADN. Dans la première partie de ma thèse, je décris l'optimisation de certains paramètres pour la cryoEM et des processus d'acquisition d'image utilisant comme objets de test des plasmides et d'autres molécules d'ADN. Dans la deuxième partie, je .décris comment j'ai construit les minicercles d'ADN de 94 bp et comment j'ai introduit des modifications structurelles comme des coupures ou des lacunes. Dans la troisième partie, je décris l'analyse des reconstructions des rninicercles d'ADN. Cette analyse, appuyée par des tests biochimiques, indique fortement que des molécules d'ADN sont capables de former de petites molécules circulaires de 94 bp sans dépasser les limites d'élasticité, indiquant que les minicercles adoptent une forme circulaire régulière où la flexion est redistribuée le long la molécule. ABSTRACT : Although physical properties of DNA structure have been intensively studied for over 50 years there are still many important questions that need to be answered. For example, what happens to protein-free double-stranded DNA when it is strongly bent, as in DNA forming nucleosomes? Is such protein-free DNA smoothly bent (i.e. it remains within elastic limits of DNA rigidity) or does it release its bending stress by forming sharp kinks (i.e. it exits the elastic regime and breaks the stacking between neighbouring base-pairs in localized regions)? Electron microscopy can provide an answer to this question by directly visualizing DNA minicircles that have the size of nucleosome gyres (ca 90 bp). For the answer to be scientifically valid, one needs to observe DNA molecules while they are still suspended in the solution of interest and no staining chemicals or fixatives have been added since these can change the properties of the DNA. CryoEM techniques developed by Jacques Dubochet's group beginning in the 1980's permit direct visualization of DNA molecules suspended in cryo-vitrified layers of aqueous solutions. However, a relatively weak contrast of cryo-EM preparations combined with the very small size of the DNA minicircles made it necessary to optimize many of the steps and parameters of the cryo-EM specimen preparation and image acquisition processes in order to obtain stereo-pairs of images that permit the 3-D reconstruction of the observed DNA minicircles. In the first part of my thesis I describe the optimization of the cryo-EM preparation and the image acquisition processes using plasmid size DNA molecules as a test object. In the second part, I describe how I formed the 94 by DNA minicircles and how I introduced structural modifications like nicks or gaps. In the third part, I describe the cryo-EM analysis of the constructed DNA minicircles. That analysis, supported by biochemical tests, strongly indicates that DNA minicircles as small as 94 by remain within the elastic limits of DNA structure, i.e. the minicircles adopt a regular circular shape where bending is redistributed along the molecules.

Role of hepatitis C virus genotype 3 in liver fibrosis progression : a systematic review and meta-analysis ; et, Impact of nurse vaccination program on hepatitis B immunity in a Swiss HIV clinic

Rôle du génotype 3 du virus de l'hépatite C dans la progression de la fibrose hépatique, une revue systématique avec méta-analyse. On estime à 170 millions le nombre de personnes atteintes d'hépatite C chronique dans le monde. La principale conséquence de cette maladie est la fibrose du foie, qui évolue plus ou moins rapidement, pour aboutir au développement d'une cirrhose et/ou d'un hépatocarcinome. Certains des facteurs accélérateurs de la fibrose, comme l'âge avancé au moment de l'infection, le sexe masculin, la consommation d'alcool, sont bien connus. On a longtemps considéré que les six différents génotypes viraux n'influençaient pas la progression de la fibrose. Des études récentes ont cependant suggéré que certains génotypes, en particulier ie génotype 3, pouvaient entraîner une fibrose plus rapide. Le but de ce travail de thèse était de déterminer à l'aide d'une méta-analyse le rôle du génotype viral dans la progression de la fibrose dans l'infection chronique au virus de l'hépatite C. Les études ont été sélectionnées dans la littérature médicale à partir d'une série de mots-clés. Le degré de fibrose a été estimé par biopsie, en utilisant le score Metavir. Deux types d'études ont décrits de manière différente la durée d'infection. Les premières ont calculé la progression de la fibrose depuis le moment estimée de l'infection (« études avec une biopsie »), les secondes ont exprimés cette durée comme étant l'intervalle entre deux biopsies (« études avec deux biopsies »). L'analyse a permis d'identifier 8 études avec une biopsie pour un collectif total de 3182 patients ainsi que 8 études avec deux biopsies pour un collectif de 896 patients. Dans une méta-analyse de type « random effect », le rapport de cote pour l'association du génotype 3 avec une fibrose accélérée est de 1.52 (95% IC 1.12-2.07, p=0.007) pour les études à une biopsie. Pour les études à deux biopsies, le rapport de cote pour cette association est de 1.37 (95% IC 0.87-2.17, P=0.17). Cette étude montre que les patients avec une hépatite C chronique due au génotype 3 ont une progression de fibrose plus rapide que ceux qui sont infectés par les autres génotypes. Alors que la méta-analyse des études avec une biopsie est clairement significative, celle des études avec deux biopsies est au-dessous du seuil de significativité. Les études à deux biopsies peuvent être limitées par plusieurs facteurs, comprenant un « biais d'indication » (seuls les patients évoluant rapidement vers la cirrhose ont plus de risque d'avoir une deuxième biopsie), une durée d'observation très courte (5 années comparée à 13 années pour les études à 2 biopsies), et un nombre de patient limité (896 pour le études à 2 biopsies comparé à 3182 pour les études à 1 biopsie). Impact d'un programme de vaccination sur l'immunité contre l'hépatite Β dans une clinique suisse du VIH Le virus de l'hépatite Β cause une infection aigûe dont la symptomatologie varie d'une présentation subclinique à une progression fulminante. Dans une minorité de cas, l'infection aigiie est suivie d'une infection chronique pouvant évoluer vers une cirrhose hépatique et/ou un hépatocarcinome. La prévalence de l'hépatite Β aiguë et chronique chez les personnes vivant avec le virus d'immunodéficience humaine (VIH) est supérieure à celle de la population générale. Par ailleurs la co-infection avec le virus du VIH entraine une progression plus rapide de l'hépatite B. Dès lors, l'immunité pour le virus de l'hépatite Β représente un facteur primordial de prévention dans la population infectée par le virus de l'HIV. Bien que l'administration d'un vaccin contre l'hépatite Β soit particulièrement recommandée chez tous les individus infectés par le VIH, la couverture vaccinale dans cette population est souvent insuffisante. Le but de cette étude était de déterminer l'état d'immunisation contre le virus de l'hépatite Β dans la population infectée par le VIH de la cohorte Suisse HIV et d'analyser l'efficacité d'un programme de vaccination administré par le personnel soignant. L'immunité avant et après intervention dans notre centre a été comparée aux autres centres de la cohorte HIV en Suisse. L'immunité pour le centre d'intervention a passé de 32% avant intervention à 76% après intervention alors que pour les autres centres, l'immunité n'a progressé que de 33% à 39% dans le même laps de temps (n=2712, P=0.001). Cette étude montre qu'un contrôle systématique de l'immunité par du personnel soignant augmente de manière significative l'immunité pour le vaccin de l'hépatite Β dans la population HIV.

Automated identification of minimal myocardial motion for improved image quality on MR angiography at 3 T

OBJECTIVE: Imaging during a period of minimal myocardial motion is of paramount importance for coronary MR angiography (MRA). The objective of our study was to evaluate the utility of FREEZE, a custom-built automated tool for the identification of the period of minimal myocardial motion, in both a moving phantom at 1.5 T and 10 healthy adults (nine men, one woman; mean age, 24.9 years; age range, 21-32 years) at 3 T. CONCLUSION: Quantitative analysis of the moving phantom showed that dimension measurements approached those obtained in the static phantom when using FREEZE. In vitro, vessel sharpness, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were significantly improved when coronary MRA was performed during the software-prescribed period of minimal myocardial motion (p < 0.05). Consistent with these objective findings, image quality assessments by consensus review also improved significantly when using the automated prescription of the period of minimal myocardial motion. The use of FREEZE improves image quality of coronary MRA. Simultaneously, operator dependence can be minimized while the ease of use is improved.

Pore space analysis of beech wood: The vessel network

Water transport in wood is vital for the survival of trees. With synchrotron radiation X-ray tomographic microscopy (SRXTM), it has become possible to characterize and quantify the three-dimensional (3D) network formed by vessels that are responsible for longitudinal transport. In the present study, the spatial size dependence of vessels and the organization inside single growth rings in terms of vessel-induced porosity was studied by SRXTM. Network characteristics, such as connectivity, were deduced by digital image analysis from the processed tomographic data and related to known complex network topologies.

Analysis of hepatitis C virus resistance to silibinin in vitro and in vivo points to a novel mechanism involving nonstructural protein 4B.

Intravenous silibinin (SIL) is an approved therapeutic that has recently been applied to patients with chronic hepatitis C, successfully clearing hepatitis C virus (HCV) infection in some patients even in monotherapy. Previous studies suggested multiple antiviral mechanisms of SIL; however, the dominant mode of action has not been determined. We first analyzed the impact of SIL on replication of subgenomic replicons from different HCV genotypes in vitro and found a strong inhibition of RNA replication for genotype 1a and genotype 1b. In contrast, RNA replication and infection of genotype 2a were minimally affected by SIL. To identify the viral target of SIL we analyzed resistance to SIL in vitro and in vivo. Selection for drug resistance in cell culture identified a mutation in HCV nonstructural protein (NS) 4B conferring partial resistance to SIL. This was corroborated by sequence analyses of HCV from a liver transplant recipient experiencing viral breakthrough under SIL monotherapy. Again, we identified distinct mutations affecting highly conserved amino acid residues within NS4B, which mediated phenotypic SIL resistance also in vitro. Analyses of chimeric viral genomes suggest that SIL might target an interaction between NS4B and NS3/4A. Ultrastructural studies revealed changes in the morphology of viral membrane alterations upon SIL treatment of a susceptible genotype 1b isolate, but not of a resistant NS4B mutant or genotype 2a, indicating that SIL might interfere with the formation of HCV replication sites. CONCLUSION: Mutations conferring partial resistance to SIL treatment in vivo and in cell culture argue for a mechanism involving NS4B. This novel mode of action renders SIL an attractive candidate for combination therapies with other directly acting antiviral drugs, particularly in difficult-to-treat patient cohorts.

Glucose and lactate are equally effective in energizing activity-dependent synaptic vesicle turnover in purified cortical neurons.

This study examines the role of glucose and lactate as energy substrates to sustain synaptic vesicle cycling. Synaptic vesicle turnover was assessed in a quantitative manner by fluorescence microscopy in primary cultures of mouse cortical neurons. An electrode-equipped perfusion chamber was used to stimulate cells both by electrical field and potassium depolarization during image acquisition. An image analysis procedure was elaborated to select in an unbiased manner synaptic boutons loaded with the fluorescent dye N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl)pyridinium dibromide (FM1-43). Whereas a minority of the sites fully released their dye content following electrical stimulation, others needed subsequent K(+) depolarization to achieve full release. This functional heterogeneity was not significantly altered by the nature of metabolic substrates. Repetitive stimulation sequences of FM1-43 uptake and release were then performed in the absence of any metabolic substrate and showed that the number of active sites dramatically decreased after the first cycle of loading/unloading. The presence of 1 mM glucose or lactate was sufficient to sustain synaptic vesicle cycling under these conditions. Moreover, both substrates were equivalent for recovery of function after a phase of decreased metabolic substrate availability. Thus, lactate appears to be equivalent to glucose for sustaining synaptic vesicle turnover in cultured cortical neurons during activity.

Pacing redistributes glycogen within the developing myocardium.

Electrical pacing at physiological rate induces myocardial remodeling associated with regional changes in workload, blood flow and oxygen consumption. However, to what extent energy-producing pathways are also modified within the paced heart remains to be investigated. Pacing could particularly affect glycogen metabolism since hypertrophy stimulates glycolysis and increased workload favors glucose over fat oxidation. In order to test this hypothesis, we used the embryonic chick heart model in which ventricular pacing rapidly resulted in thinning of the ventricle wall and thickening of the atrial wall. Hearts of stage 22HH chick embryos were submitted in ovo to asynchronous and intermittent ventricular pacing delivered at physiological rate during 24 h. The resulting alterations of glycogen content were determined in atrium, ventricle and conotruncus of paced and sham-operated hearts. Hemodynamic parameters of the paced and spontaneously beating hearts were derived from computerized image analysis of video recordings. With respect to sham, paced hearts showed a significant decrease in glycogen content (nmoles glucose units/microg protein; mean+/-S.D.) only in atrium (1.48+/-0.40 v 0.84+/-0.34, n=8) and conotruncus (0.75+/-0.28 v 0.42+/-0.23, n=8). Pacing decreased the end diastolic and stroke volumes by 34 and 44%, respectively. Thus, the rapid glycogen depletion in regions remote from the stimulation site appears to be associated with regional changes in workload and remodeling. These findings underscore the importance of the coupling mechanisms between metabolic pathways and myocardial remodeling in the ectopically paced heart.

Quantitative distribution of parvalbumin, calretinin, and calbindin D-28k immunoreactive neurons in the visual cortex of normal and Alzheimer cases.

The distribution of parvalbumin (PV), calretinin (CR), and calbindin (CB) immunoreactive neurons was studied with the help of an image analysis system (Vidas/Zeiss) in the primary visual area 17 and associative area 18 (Brodmann) of Alzheimer and control brains. In neither of these areas was there a significant difference between Alzheimer and control groups in the mean number of PV, CR, or CB immunoreactive neuronal profiles, counted in a cortical column going from pia to white matter. Significant differences in the mean densities (numbers per square millimeter of cortex) of PV, CR, and CB immunoreactive neuronal profiles were not observed either between groups or areas, but only between superficial, middle, and deep layers within areas 17 and 18. The optical density of the immunoreactive neuropil was also similar in Alzheimer and controls, correlating with the numerical density of immunoreactive profiles in superficial, middle, and deep layers. The frequency distribution of neuronal areas indicated significant differences between PV, CR, and CB immunoreactive neuronal profiles in both areas 17 and 18, with more large PV than CR and CB positive profiles. There were also significantly more small and less large PV and CR immunoreactive neuronal profiles in Alzheimer than in controls. Our data show that, although the brain pathology is moderate to severe, there is no prominent decrease of PV, CR and CB positive neurons in the visual cortex of Alzheimer brains, but only selective changes in neuronal perikarya.

Use of flow cytometric methods for single-cell analysis in environmental microbiology

Flow cytometry (FCM) is emerging as an important tool in environmental microbiology. Although flow cytometry applications have to date largely been restricted to certain specialized fields of microbiology, such as the bacterial cell cycle and marine phytoplankton communities, technical advances in instrumentation and methodology are leading to its increased popularity and extending its range of applications. Here we will focus on a number of recent flow cytometry developments important for addressing questions in environmental microbiology. These include (i) the study of microbial physiology under environmentally relevant conditions, (ii) new methods to identify active microbial populations and to isolate previously uncultured microorganisms, and (iii) the development of high-throughput autofluorescence bioreporter assays

Automatic classification of MR scans in Alzheimer's disease.

To be diagnostically useful, structural MRI must reliably distinguish Alzheimer's disease (AD) from normal aging in individual scans. Recent advances in statistical learning theory have led to the application of support vector machines to MRI for detection of a variety of disease states. The aims of this study were to assess how successfully support vector machines assigned individual diagnoses and to determine whether data-sets combined from multiple scanners and different centres could be used to obtain effective classification of scans. We used linear support vector machines to classify the grey matter segment of T1-weighted MR scans from pathologically proven AD patients and cognitively normal elderly individuals obtained from two centres with different scanning equipment. Because the clinical diagnosis of mild AD is difficult we also tested the ability of support vector machines to differentiate control scans from patients without post-mortem confirmation. Finally we sought to use these methods to differentiate scans between patients suffering from AD from those with frontotemporal lobar degeneration. Up to 96% of pathologically verified AD patients were correctly classified using whole brain images. Data from different centres were successfully combined achieving comparable results from the separate analyses. Importantly, data from one centre could be used to train a support vector machine to accurately differentiate AD and normal ageing scans obtained from another centre with different subjects and different scanner equipment. Patients with mild, clinically probable AD and age/sex matched controls were correctly separated in 89% of cases which is compatible with published diagnosis rates in the best clinical centres. This method correctly assigned 89% of patients with post-mortem confirmed diagnosis of either AD or frontotemporal lobar degeneration to their respective group. Our study leads to three conclusions: Firstly, support vector machines successfully separate patients with AD from healthy aging subjects. Secondly, they perform well in the differential diagnosis of two different forms of dementia. Thirdly, the method is robust and can be generalized across different centres. This suggests an important role for computer based diagnostic image analysis for clinical practice.

Functional analysis of human POT1 and RPA : insights into the role of single stranded DNA binding proteins at telomeres

Abstract Telomeres, the natural ends of chromosomes, need to be protected from chromosome end fusions, aberrant homologous recombination and degradation. In humans, chromosome ends are specified through arrays of tandemly repeated 5'-TTAGGG-3' hexamers, ending in a 3' overhang. A complex formed by the six proteins TRF1, TRF2, hRap1, TIN2, TPP1 and POT1 specifically assocìates with and protects telomeres. Telomeres are maintained by semiconservative DNA replication and by a specialized reverse transcriptase, telomerase, that carries an RNA subunit which templates new telomeric repeat synthesis. The telomeric single stranded (ss) DNA binding protein POT1 protects the telomeric 3' overhang and modulates telomerase-mediated telomere elongation. It is possible that POT1 also influences DNA synthesis during semiconservative DNA replication, which is initiated by the DNA polymerase alpha-primase complex. The heterotrimeric ss DNA-binding protein RPA plays essential roles during DNA replication. RPA binds to ss DNA with high affinity in order to stabilize ss DNA and facilitate nascent strand synthesis at the replication fork. Here we investigate how the two proteins RPA and POT1 contribute to telomere maintenance by regulating semi-conservative DNA replication and telomerase. Using chromatin immunoprecipitation experiments, we show that RPA associates with telomeres during S-phase. Analysis of telomere structure in cells shRNA-depleted for RPA and POT1 reveals that loss of RPA and POT1 causes exposure of single-stranded DNA at telomeres, suggestive of incomplete DNA replication. Biochemical experiments using purified recombinant POT1 and RPA show that saturating telomeric oligonucleotides with POT1 or RPA reduces the primase activity of the DNA polymerase alpha-primase complex and the overall activity of telomerase. POT1 and RPA also increase the primer extension by DNA polymerase alpha-primase complex and the processivity of telomerase under certain conditions, although POT1 increases the activities to a greater extent than RPA. We propose that POT1 is required for proper replication of the lagging strand of telomeres and that some phenotypes observed in POT1-depleted cells may stern from incomplete DNA replication rather than de-protection of the single-stranded overhang. Résumé Les télomères, les extrémités normales des chromosomes linéaires, doivent être protégés des fusions chromosomiques, d'événements de recombinaison homologue aberrants et de phénomènes de dégradation. Chez l'Homme, les extrémités des chromosomes sont constitués d'ADN double brin répétitif de séquence 5'-TTAGGG-3', d'une extension simple brin 3' sortante et d'un complexe protéique formé des six facteurs TRF1, TRF2, hRap1, TIN2, TPP1 et POT1 qui, s'associant à cette séquence, protègent l'ADN télomèrique. Les télomères sont maintenus par la télomérase, une transcriptase inverse capable d'allonger l'extension 3' sortante télomérique. POT1 lie l'ADN simple brin télomérique et module l'élongation des télomères par la télomérase. POT1 pourrait en théorie également influencer la réplication semi-conservative de l'ADN. L'ADN-polymérase Pal alpha-primase amorce et initie la synthèse d'ADN. Pendant la réplication, l'ADN simple brin est stabilisé par RPA, un complexe hétérotrimèrique qui lie l'ADN simple brin. RPA facilite la synthèse du brin naissant à la fourche de réplication. Ici nous avons étudié comment ces deux protéines qui lient l'ADN simple brin, RPA et POT1, régulent la réplication des télomères par la télomérase et la machinerie classique de réplication de l'ADN. Par immunoprécipitation de chromatine (ChIP), nous montrons que RPA est localisé aux télomères lors de la phase S du cycle cellulaire. De plus, l'analyse de la structure des télomeres indique que !a perte de RPA ou de POT1 conduit à l'apparition d'ADN simple brin télomérique, suggérant une réplication incomplète de l'ADN télomérique in vivo. Par une approche complémentaire biochimique utilisant les protéines POT1 et RPA recombinantes purifiées, nous montrons également que la liaison de POT1 ou de RPA à des oligonucléotides télomériques bloque l'activité primase du complexe polymérase alpha/primase et réduit l'activité télomérase sur ces substrats. En revanche, leur liaison augmente l'activité ADN-polymérase du complexe polymérase alpha/primase, ainsi que fa processivité de la télomérase dans certaines conditions, POT1 étant le plus efficace des deux facteurs. Nous proposons que POT1 est nécessaire à la réplication du brin retardé au niveau des télomères, ce qui suggère que certains phénotypes des cellules déplétés en POT1 puissent résulter d'une réplication incomplète de l'ADN télémétrique plutôt que d'une déprotection de l'extrémité sortante des télomères.

Heel and toe clearance estimation for gait analysis using wireless inertial sensors.

Tripping is considered a major cause of fall in older people. Therefore, foot clearance (i.e., height of the foot above ground during swing phase) could be a key factor to better understand the complex relationship between gait and falls. This paper presents a new method to estimate clearance using a foot-worn and wireless inertial sensor system. The method relies on the computation of foot orientation and trajectory from sensors signal data fusion, combined with the temporal detection of toe-off and heel-strike events. Based on a kinematic model that automatically estimates sensor position relative to the foot, heel and toe trajectories are estimated. 2-D and 3-D models are presented with different solving approaches, and validated against an optical motion capture system on 12 healthy adults performing short walking trials at self-selected, slow, and fast speed. Parameters corresponding to local minimum and maximum of heel and toe clearance were extracted and showed accuracy ± precision of 4.1 ± 2.3 cm for maximal heel clearance and 1.3 ± 0.9 cm for minimal toe clearance compared to the reference. The system is lightweight, wireless, easy to wear and to use, and provide a new and useful tool for routine clinical assessment of gait outside a dedicated laboratory.