Evaluation of Ablation Patterns Using a Biophysical Model of Atrial Fibrillation

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Surgical/Radiofrequency (RF) ablation is a therapeutic procedure that consists of creating lines of conduction block to interrupt AF. The present study evaluated 13 different ablation patterns by means of a biophysical model of the human atria. In this model, ablation lines were abruptly applied transmurally during simulated sustained AF, and success rate, time to AF termination and average beat-to-beat interval were documented. The gold standard Cox's Maze III procedure was taken as reference. The effectiveness of twelve less invasive patterns was compared to it. In some of these incomplete lines (entailing a gap) were simulated. Finally, the computer simulations were compared to clinical data. The results show that the model reproduces observations made in vivo: (1) the Maze III is the most efficient ablation procedure; (2) less invasive patterns should include lines in both right and left atrium; (3) incomplete ablation lines between the pulmonary veins and the mitral valve annulus lead to uncommon flutter; (4) computer simulations of incomplete lines are consistent with clinical results of non-transumural RF ablation. Biophysical modeling may therefore be considered as a useful tool for understanding the mechanisms underlying AF therapie

CO2 streams containing associated components—A review of the thermodynamic and geochemical properties and assessment of some reactive transport codes

AbstractModelling of the impact on storage of “ CO2-associated components” has rarely been addressed so far. This review, performed within the European research project CO2ReMoVe, exposes a selection of CO2 streams compositions coming from thermal power plants emissions and those injected in pilot sites part of the CO2ReMoVe project. It highlights the lack of data coming from laboratory experiments to describe properly the physical properties of some relevant gas mixtures. The geochemical impact of only 2 components (SO2 and H2S) is evidenced by some geochemical studies. Concerning the numerical modelling, four reactive transport codes (PHREEQC, SCALE2000, TOUGHREACT and COORES) were assessed. Actual limitations lie mainly in the capacity of calculating the physical properties of the whole set of gases (CO2–O2–SO2–N2–Ar–NOx–H2S–COS–CO–H2–HCl–NH3–CH4–C2H6–H2O). The new data acquired within on-going French projects will complete the knowledge of such complex gas mixtures behaviour

The SARAF-LINAC Project for SARAF-PHASE 2

THPF005International audienceSNRC and CEA collaborate to the upgrade of theSARAF accelerator to 5 mA CW 40 MeV deuteron andproton beams (Phase 2). This paper presents the referencedesign of the SARAF-LINAC Project including a fourvane176 MHz RFQ, a MEBT and a superconducting linacmade of four five-meter cryomodules housing 26superconducting HWR cavities and 20 superconductingsolenoids. The first two identical cryomodules house lowbeta($\beta$opt = 0.091), 280 mm long (flange to flange), 176MHz HWR cavities, the two identical last cryomoduleshouse high-beta ($\beta$opt = 0.181), 410 mm long, 176 MHz,HWR cavities. The beam is focused with superconductingsolenoids located between cavities housing steering coils.A BPM is placed upstream each solenoid

On commensurable hyperbolic Coxeter groups

For Coxeter groups acting non-cocompactly but with finite covolume on real hyperbolic space Hn, new methods are presented to distinguish them up to (wide) commensurability. We exploit these ideas and determine the commensurability classes of all hyperbolic Coxeter groups whose fundamental polyhedra are pyramids over a product of two simplices of positive dimensions

AMPK negatively regulates tensin-dependent integrin activity

Tight regulation of integrin activity is paramount for dynamic cellular functions such as cell matrix adhesion and mechanotransduction. Integrin activation is achieved through intracellular interactions at the integrin cytoplasmic tails and through integrin-ligand binding. In this study, we identify the metabolic sensor AMP-activated protein kinase (AMPK) as a beta 1-integrin inhibitor in fibroblasts. Loss of AMPK promotes beta 1-integrin activity, the formation of centrally located active beta 1-integrin- and tensin-rich mature fibrillar adhesions, and cell spreading. Moreover, in the absence of AMPK, cells generate more mechanical stress and increase fibronectin fibrillogenesis. Mechanistically, we show that AMPK negatively regulates the expression of the integrin-binding proteins tensin1 and tensin3. Transient expression of tensins increases beta 1-integrin activity, whereas tensin silencing reduces integrin activity in fibroblasts lacking AMPK. Accordingly, tensin silencing in AMPK-depleted fibroblasts impedes enhanced cell spreading, traction stress, and fibronectin fiber formation. Collectively, we show that the loss of AMPK up-regulates tensins, which bind beta 1-integrins, supporting their activity and promoting fibrillar adhesion formation and integrin-dependent processes.Peer reviewe

Effects of Electrical and Structural Remodeling on Atrial Fibrillation Maintenance: A Simulation Study

Atrial fibrillation, a common cardiac arrhythmia, often progresses unfavourably: in patients with long-term atrial fibrillation, fibrillatory episodes are typically of increased duration and frequency of occurrence relative to healthy controls. This is due to electrical, structural, and contractile remodeling processes. We investigated mechanisms of how electrical and structural remodeling contribute to perpetuation of simulated atrial fibrillation, using a mathematical model of the human atrial action potential incorporated into an anatomically realistic three-dimensional structural model of the human atria. Electrical and structural remodeling both shortened the atrial wavelength - electrical remodeling primarily through a decrease in action potential duration, while structural remodeling primarily slowed conduction. The decrease in wavelength correlates with an increase in the average duration of atrial fibrillation/flutter episodes. The dependence of reentry duration on wavelength was the same for electrical vs. structural remodeling. However, the dynamics during atrial reentry varied between electrical, structural, and combined electrical and structural remodeling in several ways, including: (i) with structural remodeling there were more occurrences of fragmented wavefronts and hence more filaments than during electrical remodeling; (ii) dominant waves anchored around different anatomical obstacles in electrical vs. structural remodeling; (iii) dominant waves were often not anchored in combined electrical and structural remodeling. We conclude that, in simulated atrial fibrillation, the wavelength dependence of reentry duration is similar for electrical and structural remodeling, despite major differences in overall dynamics, including maximal number of filaments, wave fragmentation, restitution properties, and whether dominant waves are anchored to anatomical obstacles or spiralling freely

Proteome Based Construction of the Lymphocyte Function-Associated Antigen 1 (LFA-1) Interactome in Human Dendritic Cells.

The β2-integrin lymphocyte function-associated antigen 1 (LFA-1) plays an important role in the migration, adhesion and intercellular communication of dendritic cells (DCs). During the differentiation of human DCs from monocyte precursors, LFA-1 ligand binding capacity is completely lost, even though its expression levels were remained constant. Yet LFA-1-mediated adhesive capacity on DCs can be regained by exposing DCs to the chemokine CCL21, suggesting a high degree of regulation of LFA-1 activity during the course of DC differentiation. The molecular mechanisms underlying this regulation of LFA-1 function in DCs, however, remain elusive. To get more insight we attempted to identify specific LFA-1 binding partners that may play a role in regulating LFA-1 activity in DCs. We used highly sensitive label free quantitative mass-spectrometry to identify proteins co-immunoprecipitated (co-IP) with LFA-1 from ex vivo generated DCs. Among the potential binding partners we identified not only established components of integrin signalling pathways and cytoskeletal proteins, but also several novel LFA-1 binding partners including CD13, galectin-3, thrombospondin-1 and CD44. Further comparison to the LFA-1 interaction partners in monocytes indicated that DC differentiation was accompanied by an overall increase in LFA-1 associated proteins, in particular cytoskeletal, signalling and plasma membrane (PM) proteins. The here presented LFA-1 interactome composed of 78 proteins thus represents a valuable resource of potential regulators of LFA-1 function during the DC lifecycle

Cargo-specific recruitment in clathrin and dynamin-independent endocytosis

Spatially controlled, cargo-specific endocytosis is essential for development, tissue homeostasis, and cancer invasion and is often hijacked by viral infections. Unlike clathrin-mediated endocytosis, which exploits cargo-specific adaptors for selective protein internalization, the clathrin and dynamin-independent endocytic pathway (CLIC-GEEC, CG-pathway) has until now been considered a bulk internalization route for the fluid phase, glycosylated membrane proteins and lipids. Although the core molecular players of CG endocytosis have been recently defined, no cargo-specific adaptors are known and evidence of selective protein uptake into the pathway is lacking. Here, we identify the first cargo-specific adaptor for CG-endocytosis and demonstrate its clinical relevance in breast cancer progression. By combining unbiased molecular characterization and super-resolution imaging, we identified the actin-binding protein swiprosin-1 (EFHD2) as a cargo-specific adaptor regulating integrin internalization via the CG-pathway. Swiprosin-1 couples active Rab21-associated integrins with key components of the CG-endocytic machinery, IRSp53 and actin. Swiprosin-1 is critical for integrin endocytosis, but not for other CG-cargo and supports integrin-dependent cancer cell migration and invasion, with clinically relevant implications for breast cancer. Our results demonstrate a previously unknown cargo selectivity for the CG-pathway and opens the possibility to discover more adaptors regulating it