Topographical and mechanical characterization of living eukaryotic cells on opaque substrates: development of a general procedure and its application to the study of non-adherent lymphocytes

The mechanical behavior of living murine T-lymphocytes was assessed by atomic force microscopy (AFM). A robust experimental procedure was developed to overcome some features of lymphocytes, in particular their spherical shape and non-adherent character. The procedure included the immobilization of the lymphocytes on amine-functionalized substrates, the use of hydrodynamic effects on the deflection of the AFM cantilever to monitor the approaching, and the use of the jumping mode for obtaining the images. Indentation curves were analyzed according to Hertz's model for contact mechanics. The calculated values of the elastic modulus are consistent both when considering the results obtained from a single lymphocyte and when comparing the curves recorded from cells of different specimens

A clustering technique for partial discharge and noise sources identification in power cables by means of waveform parameters

On-line partial discharge (PD) measurements have become a common technique for assessing the insulation condition of installed high voltage (HV) insulated cables. When on-line tests are performed in noisy environments, or when more than one source of pulse-shaped signals are present in a cable system, it is difficult to perform accurate diagnoses. In these cases, an adequate selection of the non-conventional measuring technique and the implementation of effective signal processing tools are essential for a correct evaluation of the insulation degradation. Once a specific noise rejection filter is applied, many signals can be identified as potential PD pulses, therefore, a classification tool to discriminate the PD sources involved is required. This paper proposes an efficient method for the classification of PD signals and pulse-type noise interferences measured in power cables with HFCT sensors. By using a signal feature generation algorithm, representative parameters associated to the waveform of each pulse acquired are calculated so that they can be separated in different clusters. The efficiency of the clustering technique proposed is demonstrated through an example with three different PD sources and several pulse-shaped interferences measured simultaneously in a cable system with a high frequency current transformer (HFCT).

Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a

Current evidence indicates that methylation of cytosine in mammalian DNA is restricted to both strands of the symmetrical sequence CpG, although there have been sporadic reports that sequences other than CpG may also be methylated. We have used a dual-labeling nearest neighbor technique and bisulphite genomic sequencing methods to investigate the nearest neighbors of 5-methylcytosine residues in mammalian DNA. We find that embryonic stem cells, but not somatic tissues, have significant cytosine-5 methylation at CpA and, to a lesser extent, at CpT. As the expression of the de novo methyltransferase Dnmt3a correlates well with the presence of non-CpG methylation, we asked whether Dnmt3a might be responsible for this modification. Analysis of genomic methylation in transgenic Drosophila expressing Dnmt3a reveals that Dnmt3a is predominantly a CpG methylase but also is able to induce methylation at CpA and at CpT.

Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody

Inflammatory destruction of insulin-producing β cells in the pancreatic islets is the hallmark of insulin-dependent diabetes mellitus, a spontaneous autoimmune disease of non-obese diabetic mice resembling human juvenile (type I) diabetes. Histochemical analysis of diabetic pancreata revealed that mononuclear cells infiltrating the islets and causing autoimmune insulitis, as well as local islet cells, express the CD44 receptor; hyaluronic acid, the principal ligand of CD44, is detected in the islet periphery and islet endothelium. Injection of anti-CD44 mAb 1 hr before cell transfer of diabetogenic splenocytes and subsequently on alternate days for 4 weeks induced considerable resistance to diabetes in recipient mice, reflected by reduced insulitis. Contact sensitivity to oxazolone was not influenced by this treatment. A similar antidiabetic effect was observed even when the anti-CD44 mAb administration was initiated at the time of disease onset: i.e., 4–7 weeks after cell transfer. Administration of the enzyme hyaluronidase also induced appreciable resistance to insulin-dependent diabetes mellitus, suggesting that the CD44–hyaluronic acid interaction is involved in the development of the disease. These findings demonstrate that CD44-positive inflammatory cells may be a potential therapeutic target in insulin-dependent diabetes.

High speed imaging and algorithms for non invasive vibrations measurement

Comunicación presentada en EVACES 2011, 4th International Conference on Experimental Vibration Analysis for Civil Engineering Structures, Varenna (Lecco), Italy, October 3-5, 2011.

Selective SWIFT-R. A Flexible Software-Based Technique for Soft Error Mitigation in Low-Cost Embedded Systems

Commercial off-the-shelf microprocessors are the core of low-cost embedded systems due to their programmability and cost-effectiveness. Recent advances in electronic technologies have allowed remarkable improvements in their performance. However, they have also made microprocessors more susceptible to transient faults induced by radiation. These non-destructive events (soft errors), may cause a microprocessor to produce a wrong computation result or lose control of a system with catastrophic consequences. Therefore, soft error mitigation has become a compulsory requirement for an increasing number of applications, which operate from the space to the ground level. In this context, this paper uses the concept of selective hardening, which is aimed to design reduced-overhead and flexible mitigation techniques. Following this concept, a novel flexible version of the software-based fault recovery technique known as SWIFT-R is proposed. Our approach makes possible to select different registers subsets from the microprocessor register file to be protected on software. Thus, design space is enriched with a wide spectrum of new partially protected versions, which offer more flexibility to designers. This permits to find the best trade-offs between performance, code size, and fault coverage. Three case studies have been developed to show the applicability and flexibility of the proposal.

3D Visual Data-Driven Spatiotemporal Deformations for Non-Rigid Object Grasping Using Robot Hands

Sensing techniques are important for solving problems of uncertainty inherent to intelligent grasping tasks. The main goal here is to present a visual sensing system based on range imaging technology for robot manipulation of non-rigid objects. Our proposal provides a suitable visual perception system of complex grasping tasks to support a robot controller when other sensor systems, such as tactile and force, are not able to obtain useful data relevant to the grasping manipulation task. In particular, a new visual approach based on RGBD data was implemented to help a robot controller carry out intelligent manipulation tasks with flexible objects. The proposed method supervises the interaction between the grasped object and the robot hand in order to avoid poor contact between the fingertips and an object when there is neither force nor pressure data. This new approach is also used to measure changes to the shape of an object’s surfaces and so allows us to find deformations caused by inappropriate pressure being applied by the hand’s fingers. Test was carried out for grasping tasks involving several flexible household objects with a multi-fingered robot hand working in real time. Our approach generates pulses from the deformation detection method and sends an event message to the robot controller when surface deformation is detected. In comparison with other methods, the obtained results reveal that our visual pipeline does not use deformations models of objects and materials, as well as the approach works well both planar and 3D household objects in real time. In addition, our method does not depend on the pose of the robot hand because the location of the reference system is computed from a recognition process of a pattern located place at the robot forearm. The presented experiments demonstrate that the proposed method accomplishes a good monitoring of grasping task with several objects and different grasping configurations in indoor environments.

Rowing Biomechanics: Technique Changes with an Increase of Power Demand

The sport of rowing has become more popular in the past decade. While it is a relatively low impact sport, injuries can occur, specifically to the ribs (Karlson K. A., 1998) and more often in female athletes (Hickey, Fricker, & McDonald , 1997). It has been proposed that as the athlete rows, applying a cyclical load to the body, the mid trapezius fatigues and is unable to resist the force produced during the drive phase (Warden S. J., Gutschlag, Wajswelner, & Crossley, 2002). Once this happens, the scapulae are then pulled anterio-laterally which increases the compression force on the ribs, increasing the risk of injury. The rowing motion of 12 female varsity and club rowers was tracked as they completed a fatiguing rowing test on a rowing ergometer. Results showed that the curvature of thoracic spine changed throughout the rowing cycle but did not change with increasing power level. The transverse shoulder angle decreased (the upper back was less straight) as power level increased (R2=-0.69±19), suggesting that the scapula moved anterio-laterally. This may be that as it tired, the mid-trapezius was unable to hold the scapulae in position. The decreasing transverse shoulder angle when the power level is increased indirectly supports the fatiguing of the retractor muscles as a mechanism of injury. It would be valuable to understand the limitations of each athlete and to be able to prescribe the optimal training zone to reduce the risk of injury.

Traitement du cancer pulmonaire non à petites cellules par radiothérapie stéréotaxique d’ablation

Les néoplasies pulmonaires demeurent la première cause de décès par cancer au Québec représentant près de 6000 décès par année. Au cours des dernières années, la radiothérapie stéréotaxique d’ablation (SABR) s’est imposée comme un traitement alternatif à la résection anatomique pour les patients inopérables atteints d’un cancer pulmonaire non à petites cellules de stade précoce. Il s’agit d’une modalité de traitement qui permet d’administrer des doses élevées, typiquement 30-60 Gy en 1-8 fractions, dans le but de cibler précisément le volume de traitement tout en épargnant les tissus sains. Le Centre Hospitalier de l’Université de Montréal s’est muni en 2009 d’un appareil de SABR de fine pointe, le CyberKnife™ (CK), un accélérateur linéaire produisant un faisceau de photons de 6 MV dirigé par un bras robotisé, permettant d’administrer des traitements non-coplanaires avec une précision infra-millimétrique. Ce mémoire est dédié à la caractérisation de certains enjeux cliniques et physiques associés au traitement par CK. Il s’articule autour de deux articles scientifiques revus par les pairs. D’une part, une étude prospective clinique présentant les avantages de la SABR pulmonaire, une technique qui offre un excellent contrôle tumoral à long terme et aide au maintien de la qualité de vie et de la fonction pulmonaire. D’autre part, une étude de physique médicale illustrant les limites de l’acquisition d’images tomodensitométriques en auto-rétention respiratoire lors de la planification de traitement par CK.

Sensitive Questions in Online Surveys: Experimental Results for the Randomized Response Technique (RRT) and the Unmatched Count Technique (UCT)

Gaining valid answers to so-called sensitive questions is an age-old problem in survey research. Various techniques have been developed to guarantee anonymity and minimize the respondent's feelings of jeopardy. Two such techniques are the randomized response technique (RRT) and the unmatched count technique (UCT). In this study we evaluate the effectiveness of different implementations of the RRT (using a forced-response design) in a computer-assisted setting and also compare the use of the RRT to that of the UCT. The techniques are evaluated according to various quality criteria, such as the prevalence estimates they provide, the ease of their use, and respondent trust in the techniques. Our results indicate that the RRTs are problematic with respect to several domains, such as the limited trust they inspire and non-response, and that the RRT estimates are unreliable due to a strong false "no" bias, especially for the more sensitive questions. The UCT, however, performed well compared to the RRTs on all the evaluated measures. The UCT estimates also had more face validity than the RRT estimates. We conclude that the UCT is a promising alternative to RRT in self-administered surveys and that future research should be directed towards evaluating and improving the technique.

Développement d’une lentille cornéenne médicamentée

L’utilisation de lentilles cornéennes peut servir à améliorer le profil d’administration d’un principe actif dans les yeux. Avec une efficacité d’administration de 5% par l’utilisation de gouttes, on comprend rapidement que l’administration oculaire doit être améliorée. Cette faible administration a donné naissance à plusieurs tentatives visant à fabriquer des lentilles cornéennes médicamentées. Cependant, à cause de multiples raisons, aucune de ces tentatives n’a actuellement été mise sur le marché. Nous proposons dans cette étude, une possible amélioration des systèmes établis par le développement d’une lentille cornéenne à base de 2-(hydroxyéthyle)méthacrylate (HEMA), dans laquelle des microgels, à base de poly N-isopropylacrylamide (pNIPAM) thermosensible encapsulant un principe actif, seront incorporé. Nous avons donc débuté par développer une méthode analytique sensible par HPCL-MS/MS capable de quantifier plusieurs molécules à la fois. La méthode résultante a été validée selon les différents critères de la FDA et l’ICH en démontrant des limites de quantifications et de détections suffisamment basses, autant dans des fluides simulés que dans les tissus d’yeux de lapins. La méthode a été validée pour sept médicaments ophtalmiques : Pilocarpine, lidocaïne, proparacaïne, atropine, acétonide de triamcinolone, timolol et prednisolone. Nous avons ensuite fait la synthèse des microgels chargés négativement à base de NIPAM et d’acide méthacrylique (MAA). Nous avons encapsulé une molécule modèle dans des particules ayant une taille entre 200 et 600 nm dépendant de la composition ainsi qu’un potentiel zêta variant en fonction de la température. L’encapsulation de la rhodamine 6G (R6G) dans les microgels a été possible jusqu’à un chargement (DL%) de 38%. L’utilisation des isothermes de Langmuir a permis de montrer que l’encapsulation était principalement le résultat d’interactions électrostatiques entre les MAA et la R6G. Des cinétiques de libérations ont été effectuées à partir d’hydrogels d’acrylamide chargés en microgels encapsulant la R6G. Il a été trouvé que la libération des hydrogels chargés en microgels s’effectuait majoritairement selon l’affinité au microgel et sur une période d’environ 4-24 heures. La libération à partir de ces systèmes a été comparée à des formules d’hydrogels contenant des liposomes ou des nanogels de chitosan. Ces trois derniers (liposomes, microgels et nanogels) ont présenté des résultats prometteurs pour différentes applications avec différents profils de libérations. Enfin, nous avons transposé le modèle développé avec les gels d’acrylamide pour fabriquer des lentilles de contact de 260 à 340 µm d’épaisseur à base de pHEMA contenant les microgels avec une molécule encapsulée devant être administrée dans les yeux. Nous avons modifié la composition de l’hydrogel en incorporant un polymère linéaire, la polyvinylpyrrolidone (PVP). L’obtention d’hydrogels partiellement interpénétrés améliore la rétention d’eau dans les lentilles cornéennes. L’encapsulation dans les microgels chargés négativement a donné de meilleurs rendements avec la lidocaïne et cette dernière a été libérée de la lentille de pHEMA en totalité en approximativement 2 heures qu’elle soit ou non encapsulée dans des microgels. Ainsi dans cette étude pilote, l’impact des microgels n’a pas pu être déterminé et, de ce fait, nécessitera des études approfondies sur la structure et les propriétés de la lentille qui a été développée. En utilisant des modèles de libération plus représentatifs de la physiologie de l’œil, nous pourrions conclure avec plus de certitude concernant l’efficacité d’un tel système d’administration et s’il est possible de l’optimiser.

Global database of surface ocean particulate organic carbon export fluxes diagnosed from the 234Th technique

Through the processes of the biological pump, carbon is exported to the deep ocean in the form of dissolved and particulate organic matter. There are several ways by which downward export fluxes can be estimated. The great attraction of the 234Th technique is that its fundamental operation allows a downward flux rate to be determined from a single water column profile of thorium coupled to an estimate of POC/234Th ratio in sinking matter. We present a database of 723 estimates of organic carbon export from the surface ocean derived from the 234Th technique. Data were collected from tables in papers published between 1985 and 2013 only. We also present sampling dates, publication dates and sampling areas. Most of the open ocean Longhurst provinces are represented by several measurements. However, the Western Pacific, the Atlantic Arctic, South Pacific and the South Indian Ocean are not well represented. There is a variety of integration depths ranging from surface to 220m. Globally the fluxes ranged from -22 to 125 mmol of C/m**2/d. We believe that this database is important for providing new global estimate of the magnitude of the biological carbon pump.