Effect of Calcium-Channel Blockade on the Aldosterone Response to Sodium Depletion and Potassium Loading in Man

Angiotensin II (Ang II) and potassium (K+) increase aldosterone (Aldo) production in vitro via Ca2+-dependent mechanisms. To determine the effects of Ca2+ antagonism in vivo, we examined the influence of nifedipine on the Aldo response to Na+ depletion and K+ loading in 11 healthy subjects. On the fifth day of a low-Na+/high-K+ diet (10 mmol Na+/100 mmol K+) the subjects were randomly given either nifedipine 30 mg po or placebo, and on the sixth day they received the alternative drug. KCl in 5% glucose was infused on days 5 and 6 from 10:00 to 12:00 AM(0.6 mmol/kg over 2 hours). Dexamethasone was given to suppress adrenal corticotrophic hormone. Plasma renin activity (PRA) and plasma Aldo were determined every 20 minutes. Nifedipine induced a rise in heart rate at 60 minutes but did not change blood pressure. During KCl/glucose infusions, plasma glucose increased significantly, but plasma K+ remained stable. PRA, but not baseline plasma Aldo, was stimulated by nifedipine. KCl provoked a significant and similar Aldo rise (P < .01) under placebo and nifedipine. Baseline Aldo/PRA ratio was reduced under nifedipine when compared to placebo (P < .01), whereas during KCl infusions this ratio was similarly elevated under placebo and nifedipine. We conclude that acute inhibition of slow Ca2+ channels does not interfere with K+-induced Aldo secretion in man, suggesting that adaptive mechanisms operate in vivo. Am J Hypertens 1988;1:245-24

A biologically inspired meta-control navigation system for the Psikharpax rat robot

A biologically inspired navigation system for the mobile rat-like robot named Psikharpax is presented, allowing for self-localization and autonomous navigation in an initially unknown environment. The ability of parts of the model (e. g. the strategy selection mechanism) to reproduce rat behavioral data in various maze tasks has been validated before in simulations. But the capacity of the model to work on a real robot platform had not been tested. This paper presents our work on the implementation on the Psikharpax robot of two independent navigation strategies (a place-based planning strategy and a cue-guided taxon strategy) and a strategy selection meta-controller. We show how our robot can memorize which was the optimal strategy in each situation, by means of a reinforcement learning algorithm. Moreover, a context detector enables the controller to quickly adapt to changes in the environment-recognized as new contexts-and to restore previously acquired strategy preferences when a previously experienced context is recognized. This produces adaptivity closer to rat behavioral performance and constitutes a computational proposition of the role of the rat prefrontal cortex in strategy shifting. Moreover, such a brain-inspired meta-controller may provide an advancement for learning architectures in robotics

Tolerance synthesis using bond graph inversion and fuzzy logic

International audienceIn the context of mechatronic systems design, this paper addresses a parameter tolerance synthesis with respect to specifications including output epistemic uncertainties. The methodology proposed here concerns uncertainties modelled with fuzzy logic. The procedure relies on output uncertainties propagation through an inverse model. Design parameter tolerance is then synthesized. The results are validated injecting designed parameters in the direct model. The methodology is illustrated on a linear model with specifications including combined uncertainties

Methodology of tolerance synthesis using bond graph

International audienceThis paper presents a methodology of parametric tolerance synthesis with respect to output aleatory uncertainty specifications. It relies on density function propagation through the inverse model. The resulting parameter density function is then used to synthesize a confidence interval suitable for sizing purpose. As an illustration, parametric tolerance synthesis on a DC motor rotating a load is processed

Bond Graph Representation of Standard Interconnection Model

International audienceThe study of the robustness of a system's parametric uncertainties is based on state representations which separate the nominal part of the system from the uncertain part. The most used form is the standard interconnection model. Recent works have been formulated so as to find this representation graphically by the bond graph approach. A new procedure is proposed in this paper to determine an uncertain model adapted to the study of robustness and for robust control. The advantage of this procedure is in simplifying the resulting graphical model

A novel bioinformatics pipeline to discover genes related to arbuscular mycorrhizal symbiosis based on their evolutionary conservation pattern among higher plants

Genes involved in arbuscular mycorrhizal (AM) symbiosis have been identified primarily by mutant screens, followed by identification of the mutated genes (forward genetics). In addition, a number of AM-related genes has been identified by their AM-related expression patterns, and their function has subsequently been elucidated by knock-down or knock-out approaches (reverse genetics). However, genes that are members of functionally redundant gene families, or genes that have a vital function and therefore result in lethal mutant phenotypes, are difficult to identify. If such genes are constitutively expressed and therefore escape differential expression analyses, they remain elusive. The goal of this study was to systematically search for AM-related genes with a bioinformatics strategy that is insensitive to these problems. The central element of our approach is based on the fact that many AM-related genes are conserved only among AM-competent species.Results: Our approach involves genome-wide comparisons at the proteome level of AM-competent host species with non-mycorrhizal species. Using a clustering method we first established orthologous/paralogous relationships and subsequently identified protein clusters that contain members only of the AM-competent species. Proteins of these clusters were then analyzed in an extended set of 16 plant species and ranked based on their relatedness among AM-competent monocot and dicot species, relative to non-mycorrhizal species. In addition, we combined the information on the protein-coding sequence with gene expression data and with promoter analysis. As a result we present a list of yet uncharacterized proteins that show a strongly AM-related pattern of sequence conservation, indicating that the respective genes may have been under selection for a function in AM. Among the top candidates are three genes that encode a small family of similar receptor-like kinases that are related to the S-locus receptor kinases involved in sporophytic self-incompatibility.Conclusions: We present a new systematic strategy of gene discovery based on conservation of the protein-coding sequence that complements classical forward and reverse genetics. This strategy can be applied to diverse other biological phenomena if species with established genome sequences fall into distinguished groups that differ in a defined functional trait of interest

Local tetragonal distortion in La_{0.7}Sr_{0.3}MnO_3 strained thin films probed by x-ray absorption spectroscopy

We report on an angular resolved X-ray Absorption Spectroscopy study of $La_{0.7}Sr_{0.3}MnO_{3}$ thin films epitaxially grown by pulsed laser deposition on slightly mismatched substrates which induce tensile or compressive strains. XANES spectra give evidence of tetragonal distortion within the $MnO_{6}$ octahedra, with opposite directions for tensile and compressive strains. Quantitative analysis has been done and a model of tetragonal distortion reflecting the strain has been established. EXAFS data collected in plane for tensile substrate confirm the change in the $Mn-O$ average bond distance and the increase of $Mn-Mn$ length matching with the enlargement of the cell parameter. From these results we conclude that there is no significant change in the $Mn-O-Mn$ angle. Our observations conflict with the scenarios which this angle is the main driving parameter in the sensitivity of manganite films properties to external strains and suggest that the distortion within the octahedra plays a key role in the modification of the transport and magnetic properties.Comment: 8 pages, 6 figure

Structural analysis by bond graph approach: Duality between causal and bicausal procedure

Postprint version.International audienceThe infinite structure of linear time-invariant systems has been principally used to solve control problems. Nevertheless, this system characterization appears interesting in the design and sizing of mechatronic systems as well. Indeed, based on the bond graph language and inverse modelling, a methodology has already been developed for sizing mechatronic systems according to energy and dynamic criteria. One of the novelties of this methodology is its structural analysis step. This step enables structural properties to be deduced and helps in the formulation of the specifications. The aim of this paper is to add new graphical procedures to the structural analysis step to determine some structural properties (infinite pole orders and relative orders) from the inverse model (bicausal bond graph model). The structural analysis of the inverse model remains interesting since the essential orders are immediately obtained on the bicausal model. A discussion is carried out regarding the duality between the causal and bicausal procedures

Use and comparison of different internal ribosomal entry sites (IRES) in tricistronic retroviral vectors

BACKGROUND: Polycistronic retroviral vectors that contain several therapeutic genes linked via internal ribosome entry sites (IRES), provide new and effective tools for the co-expression of exogenous cDNAs in clinical gene therapy protocols. For example, tricistronic retroviral vectors could be used to genetically modify antigen presenting cells, enabling them to express different co-stimulatory molecules known to enhance tumor cell immunogenicity. RESULTS: We have constructed and compared different retroviral vectors containing two co-stimulatory molecules (CD70, CD80) and selectable marker genes linked to different IRES sequences (IRES from EMCV, c-myc, FGF-2 and HTLV-1). The tricistronic recombinant amphotropic viruses containing the IRES from EMCV, FGF-2 or HTLV-1 were equally efficient in inducing the expression of an exogenous gene in the transduced murine or human cells, without displaying any cell type specificity. The simultaneous presence of several IRESes on the same mRNA, however, can induce the differential expression of the various cistrons. Here we show that the IRESes of HTLV-1 and EMCV interfere with the translation induced by other IRESes in mouse melanoma cells. The IRES from FGF-2 did however induce the expression of exogenous cDNA in human melanoma cells without any positive or negative regulation from the other IRESs present within the vectors. Tumor cells that were genetically modified with the tricistronic retroviral vectors, were able to induce an in vivo anti-tumor immune response in murine models. CONCLUSION: Translation of the exogenous gene is directed by the IRES and its high level of expression not only depends on the type of cell that is transduced but also on the presence of other genetic elements within the vector

Finite Element Analysis of the Mechanical Performances of 8 Marketed Aortic Stent-Grafts

International audiencePurpose: To assess numerically the flexibility and mechanical stresses undergone by stents and fabric of currently manufactured stent-grafts. Methods: Eight marketed stent-graft limbs (Aorfix, Anaconda, Endurant, Excluder, Talent, Zenith Flex, Zenith LP, and Zenith Spiral-Z) were modeled using finite element analysis. A numerical benchmark combining bending up to 180° and pressurization at 150 mmHg of the stent-grafts was performed. Stent-graft flexibility, assessed by the calculation of the luminal reduction rate, maximal stresses in stents, and maximal strains in fabric were assessed. Results: The luminal reduction rate at 90° was ‹<20% except for the Talent stent-graft. The rate at 180° was higher for Z-stented models (Talent, Endurant, Zenith, and Zenith LP; range 39%-78%) than spiral (Aorfix, Excluder, and Zenith Spiral-Z) or circular-stented (Anaconda) devices (range 14%-26%). At 180°, maximal stress was higher for Z-stented stent-grafts (range 370-622 MPa) than spiral or circular-stented endografts (range 177-368 MPa). At 90° and 180°, strains in fabric were low and did not differ significantly among the polyester stent-grafts (range 0.5%-7%), while the expanded polytetrafluoroethylene fabric of the Excluder stent-graft underwent higher strains (range 11%-18%). Conclusion: Stent design strongly influences mechanical performances of aortic stentgrafts. Spiral and circular stents provide greater flexibility, as well as lower stress values than Z-stents, and thus better durability