A Generic Communications Module for Cooperative 3D Visualization and Modelling over the Internet: the Collaborative API

Cooperative three-dimensional visualization and modeling applications allow a distributed group of users to work together with a model they share. To implement this kind of applications the underlying communications system must provide reliable and ordered multicast of users interactions. Due to the high complexity that characterizes the models, network bandwidth requirements have limited their use to intranets or in a few cases to very high-speed Internet connections. In this paper we present a communications module that solves this problem. The library exposed, which is called Collaborative API, supports the creation of very efficient cooperative 3D visualization and modeling applications by optimizing the use of the network resources. The Collaborative API, implements a new communications architecture: the dynamic client/server. The communications module presented in this paper is illustrated by two examples of applications that use it to provide cooperative 3D visualization over the Internet

L1CAM binds ErbB receptors through Ig-like domains coupling cell adhesion and neuregulin signalling.

During nervous system development different cell-to-cell communication mechanisms operate in parallel guiding migrating neurons and growing axons to generate complex arrays of neural circuits. How such a system works in coordination is not well understood. Cross-regulatory interactions between different signalling pathways and redundancy between them can increase precision and fidelity of guidance systems. Immunoglobulin superfamily proteins of the NCAM and L1 families couple specific substrate recognition and cell adhesion with the activation of receptor tyrosine kinases. Thus it has been shown that L1CAM-mediated cell adhesion promotes the activation of the EGFR (erbB1) from Drosophila to humans. Here we explore the specificity of the molecular interaction between L1CAM and the erbB receptor family. We show that L1CAM binds physically erbB receptors in both heterologous systems and the mammalian developing brain. Different Ig-like domains located in the extracellular part of L1CAM can support this interaction. Interestingly, binding of L1CAM to erbB enhances its response to neuregulins. During development this may synergize with the activation of erbB receptors through L1CAM homophilic interactions, conferring diffusible neuregulins specificity for cells or axons that interact with the substrate through L1CAM

GPER limits adverse changes to Ca2+ signalling and arrhythmogenic activity in ovariectomised guinea pig cardiomyocytes

Background: The increased risk of post-menopausal women developing abnormalities of heart function emphasises the requirement to understand the effect of declining oestrogen levels on cardiac electrophysiology and structure, and investigate possible therapeutic targets, namely the G protein-coupled oestrogen receptor 1 (GPER). Methods: Female guinea pigs underwent sham or ovariectomy (OVx) surgeries. Cardiomyocytes were isolated 150-days post-operatively. Membrane structure was assessed using di-8-ANEPPs staining and scanning ion conductance microscopy. Imunnohistochemistry (IHC) determined the localisation of oestrogen receptors. The effect of GPER activation on excitation-contraction coupling mechanisms were assessed using electrophysiological and fluorescence techniques. Downstream signalling proteins were investigated by western blot. Results: IHC staining confirmed the presence of nuclear oestrogen receptors and GPER, the latter prominently localised to the peri-nuclear region and having a clear striated pattern elsewhere in the cells. Following OVx, GPER expression increased and its activation reduced Ca2+ transient amplitude (by 40%) and sarcomere shortening (by 32%). In these cells, GPER activation reduced abnormal spontaneous Ca2+ activity, shortened action potential duration and limited drug-induced early after-depolarisation formation. Conclusion: In an animal species with comparable steroidogenesis and cardiac physiology to humans, we show the expression and localisation of all three oestrogen receptors in cardiac myocytes. We found that following oestrogen withdrawal, GPER expression increased and its activation limited arrhythmogenic behaviours in this low oestrogen state, indicating a potential cardioprotective role of this receptor in post-menopausal women

Étude de la corrosion du cuivre par microélectrochimie: Comparaison entre microélectrode et microcellule

Ce travail présente la comparaison de mesures électrochimiques réalisées à l'aide d'une microcellule et de microélectrodes conventionnelles. Des mesures de voltamétrie cyclique et d’impédances électrochimiques ont été réalisées sur des électrodes de cuivre pur, électrode classique couplée à des capillaires et microélectrodes, au potentiel de corrosion dans une solution NaCl 0,1 M, La comparaison entre ces deux types de mesure apporte des informations relatives à leurs sensibilités et limitations. En particulier, le domaine des basses fréquences du diagramme d’impédance est sensible à la géométrie de la microcellule ainsi qu'au positionnement relatif des électrodes

Microtubules regulate cardiomyocyte transversal Young's modulus.

The field of cardiomyocyte mechanobiology is gaining significant attention, due to accumulating evidence concerning the significant role of cellular mechanical effects on the integrated function of the heart. To date, the protein titin has been demonstrated as a major contributor to the cardiomyocytes Young's modulus (YM). The microtubular network represents another potential regulator of cardiac mechanics. However, the contribution of microtubules (MTs) to the membrane YM is still understudied and has not been interrogated in the context of myocardial infarction (MI) or mechanical loading and unloading. Using nanoscale mechanoscanning ion conductance microscopy, we demonstrate that MTs contribute to cardiomyocyte transverse YM in healthy and pathological states with different mechanical loading. Specifically, we show that posttranslational modifications of MTs have differing effects on cardiomyocyte YM: Acetylation provides flexibility, whereas detyrosination imparts rigidity. Further studies demonstrate that there is no correlation between the total protein amount of acetylated and detyrosinated MT. Yet, in the polymerized-only populations, an increased level of acetylation results in a decline of detyrosinated MTs in an MI model

Short-term angiotensin II treatment regulates cardiac nanomechanics: Via microtubule modifications

Mechanical properties of single myocytes contribute to the whole heart performance, but the measurement of mechanics in living cells at high resolution with minimal force interaction remains challenging. Angiotensin II (AngII) is a peptide hormone that regulates a number of physiological functions, including heart performance. It has also been shown to contribute to cell mechanics by inducing cell stiffening. Using non-contact high-resolution Scanning Ion Conductance Microscopy (SICM), we determine simultaneously cell topography and membrane transverse Young's modulus (YM) by a constant pressure application through a nanopipette. While applying pressure, the vertical position is recorded and a deformation map is generated from which YM can be calculated and corrected for the uneven geometry. High resolution of this method also allows studying specific membrane subdomains, such as Z-grooves and crests. We found that short-term AngII treatment reduces the transversal YM in isolated adult rat cardiomyocytes acting via an AT1 receptor. Blocking either a TGF-β1 receptor or Rho kinase abolishes this effect. Analysis of the cytoskeleton showed that AngII depletes microtubules by decreasing long-lived detyrosinated and acetylated microtubule populations. Interestingly, in the failing cardiomyocytes, which are stiffer than controls, the short-term AngII treatment also reduces the YM, thus normalizing the mechanical state of cells. This suggests that the short-term softening effect of AngII on cardiac cells is opposite to the well-characterized long-term hypertrophic effect. In conclusion, we generate a precise nanoscale indication map of location-specific transverse cortical YM within the cell and this can substantially advance our understanding of cellular mechanics in a physiological environment, for example in isolated cardiac myocytes

Experiences Developing Safe and Fault-Tolerant Tele-Operated Service Robots. A Case Study in Shipyards

Human operators use tele-operated service robots for performing more or less hazardous operations (manipulation of heavy and/or dangerous products) in more or less hostile environments (nuclear reactors, space missions, warehouses, etc). Anyway, independently of the operation, the robot has to interact with both the environment it is working on and with human operators. Therefore, it is essential that the design (which include both software and hardware) of the robot involves no risk, or at least an acceptable level of risk, neither for the operators, nor for the environment nor for the robot itself. Nevertheless, it is not always possible to make a system free of failures in its design or operation. Apart from the risk inherent to the use of the mechanisms themselves, these systems work in hazardous environments, where the probability of the risk is higher than normal. Should a failure happen, its consequences could even involve the loss of human lives. (Neumann, 1994) documents many cases of computer-related failures, such as the Therac-25 (a radiation-therapy device), the missiles shield in Saudi Arabia, etc. Nevertheless, safety aspects are seldom included in the early phases of the system design process from the beginning, even though they are a critic aspect. Generally, safety has to conform and adapt to the already designed system and not vice versa, when it is widely known that safety involves not only the design of the software but also the hardware. Even more, a simple hardware solution can eliminate a hazard or simplify the software design in many situations.This research has been funded by the Spanish CICYT project MEDWSA (TIN2006-15175- C05-02) and the Regional Government of Murcia Séneca Program (02998-PI-05)

Preference for oviposition of Spodoptera friegiperda (J.E. Smith) (Lepidoptera: Noctuidae) on corn, sorghum and cotton

Bajo condiciones de campo, se estudió la preferencia del Spodeoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) para ovipositar en cultivos de maíz, sorgo y algodón. Se registraron 10 veces más masas de huevos en maíz que en sorgo, y 15 veces más masas de huevos en maíz que en algodonero. Cuando las plantas de maíz tenían entre 25 y 40 días de edad, la mayoría de las posturas se encontraron en el haz de las hojas; antes y después de este período se hallaron en el envés. Se determinó una relación directa entre el número de huevos por masa y la altura de la planta de maíz.Preference by Spodoprerafrugiperda (J.E. Smith) (Lepidoptera: Noctuidae) for oviposition on plants of corn, sorghum and cotton, was studied under field conditions. There were ten times more egg clusters laid on corn than on sorghum, and fifteen times more egg clusters laid on corn than on cotton. The upper surface of the leaves of corn was prefered over the under surface for egg clusters deposition, when plants were between 25 and 40 days old. Before and after this period, the under surface was prefered over the upper surface. There was a direct relationship between eggs per cluster and the height of the corn plant.Algodón-Gossypium herbaceumMaíz-Zea maysSorgo-sorgos - Sorghum bicolo

Short-term angiotensin II treatment regulates cardiac nanomechanics via microtubule modifications.

Mechanical properties of single myocytes contribute to the whole heart performance, but the measurement of mechanics in living cells at high resolution with minimal force interaction remains challenging. Angiotensin II (AngII) is a peptide hormone that regulates a number of physiological functions, including heart performance. It has also been shown to contribute to cell mechanics by inducing cell stiffening. Using non-contact high-resolution Scanning Ion Conductance Microscopy (SICM), we determine simultaneously cell topography and membrane transverse Young's modulus (YM) by a constant pressure application through a nanopipette. While applying pressure, the vertical position is recorded and a deformation map is generated from which YM can be calculated and corrected for the uneven geometry. High resolution of this method also allows studying specific membrane subdomains, such as Z-grooves and crests. We found that short-term AngII treatment reduces the transversal YM in isolated adult rat cardiomyocytes acting via an AT1 receptor. Blocking either a TGF-β1 receptor or Rho kinase abolishes this effect. Analysis of the cytoskeleton showed that AngII depletes microtubules by decreasing long-lived detyrosinated and acetylated microtubule populations. Interestingly, in the failing cardiomyocytes, which are stiffer than controls, the short-term AngII treatment also reduces the YM, thus normalizing the mechanical state of cells. This suggests that the short-term softening effect of AngII on cardiac cells is opposite to the well-characterized long-term hypertrophic effect. In conclusion, we generate a precise nanoscale indication map of location-specific transverse cortical YM within the cell and this can substantially advance our understanding of cellular mechanics in a physiological environment, for example in isolated cardiac myocytes

Nanoscale regulation of L-type calcium channels differentiates between ischemic and dilated cardiomyopathies.

Background Subcellular localization and function of L-type calcium channels (LTCCs) play an important role in regulating contraction of cardiomyocytes. Understanding how this is affected by the disruption of transverse tubules during heart failure could lead to new insights into the disease. Methods Cardiomyocytes were isolated from healthy donor hearts, as well as from patients with cardiomyopathies and with left ventricular assist devices. Scanning ion conductance and confocal microscopy was used to study membrane structures in the cells. Super-resolution scanning patch-clamp was used to examine LTCC function in different microdomains. Computational modeling predicted the impact of these changes to arrhythmogenesis at the whole-heart level. Findings We showed that loss of structural organization in failing myocytes leads to re-distribution of functional LTCCs from the T-tubules to the sarcolemma. In ischemic cardiomyopathy, the increased LTCC open probability in the T-tubules depends on the phosphorylation by protein kinase A, whereas in dilated cardiomyopathy, the increased LTCC opening probability in the sarcolemma results from enhanced phosphorylation by calcium-calmodulin kinase II. LVAD implantation corrected LTCCs pathophysiological activity, although it did not improve their distribution. Using computational modeling in a 3D anatomically-realistic human ventricular model, we showed how LTCC location and activity can trigger heart rhythm disorders of different severity. Interpretation Our findings demonstrate that LTCC redistribution and function differentiate between disease aetiologies. The subcellular changes observed in specific microdomains could be the consequence of the action of distinct protein kinases. Funding This work was supported by NIH grant (ROI-HL 126802 to NT-JG) and British Heart Foundation (grant RG/17/13/33173 to JG, project grant PG/16/17/32069 to RAC). Funders had no role in study design, data collection, data analysis, interpretation, writing of the repor