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The sinoatrial node (SAN), the primary pacemaker of the heart, is responsible for the initiation and robust regulation of sinus rhythm. 3D mapping studies of the ex-vivo human heart suggested that the robust regulation of sinus rhythm relies on specialized fibrotically-insulated pacemaker compartments (head, center and tail) with heterogeneous expressions of key ion channels and receptors. They also revealed up to five sinoatrial conduction pathways (SACPs), which electrically connect the SAN with neighboring right atrium (RA). To elucidate the role of these structural-molecular factors in the functional robustness of human SAN, we developed comprehensive biophysical computer models of the SAN based on 3D structural, functional and molecular mapping of ex-vivo human hearts. Our key finding is that the electrical insulation of the SAN except SACPs, the heterogeneous expression of If, INa currents and adenosine A1 receptors (A1R) across SAN pacemaker-conduction compartments are required to experimentally reproduce observed SAN activation patterns and important phenomena such as shifts of the leading pacemaker and preferential SACP. In particular, we found that the insulating border between the SAN and RA, is required for robust SAN function and protection from SAN arrest during adenosine challenge. The heterogeneity in the expression of A1R within the human SAN compartments underlies the direction of pacemaker shift and preferential SACPs in the presence of adenosine. Alterations of INa current and fibrotic remodelling in SACPs can significantly modulate SAN conduction and shift the preferential SACP/exit from SAN. Finally, we show that disease-induced fibrotic remodeling, INa suppression or increased adenosine make the human SAN vulnerable to pacing-induced exit blocks and reentrant arrhythmia. In summary, our computer model recapitulates the structural and functional features of the human SAN and can be a valuable tool for investigating mechanisms of SAN automaticity and conduction as well as SAN arrhythmia mechanisms under different pathophysiological conditions. Author summary: The human heart is driven and modulated by the sinoatrial node (SAN), our body's natural pacemaker. Recent studies using explanted human hearts discovered that to regulate heart rhythm robustly, the SAN has three pacemaker compartments–SAN head, center and tail characterized by heterogeneous expression of key ion channels and receptors. In addition, the fibrotically-insulated SAN electrically connects with the right atrium (RA) through up to five sinoatrial conduction pathways (SACPs). Due to the complexities of the human 3D structure and limited functional data on SAN conduction, the specific role of the SAN insulation/border, distinct SACPs and intranodal pacemaker molecular heterogeneity in regulating sinus rhythm in health and diseased hearts remain debatable. The goals of this study were to define the key factors influencing human SAN pacemaking function and SAN dysfunction by developing and utilizing computer models of the human SAN. This study presents the first comprehensive biophysical computer model of the human SAN complex based on direct molecular, structural and functional studies in the ex-vivo human heart. Our data show that the computer models can closely replicate pacemaking, SAN activation patterns and exit sites/earliest atrial activation through preferential SACPs, as well as physiological changes including the shift of the leading pacemaker in the presence of adenosine reported in the human heart ex-vivo. More importantly, the novel computer modeling simulation results illustrate the crucial role of the structural and electrical heterogeneity of the human SAN in pacemaking and conduction. Our human-specific SAN computer model represents a valuable tool for investigating SAN automaticity, conduction and arrhythmia mechanisms under normal and various disease conditions. [ABSTRACT FROM AUTHOR]

The integration of Building Information Modelling (BIM) and geographic information systems (GIS) is a promising but challenging topic to solve problems in construction industry. However, loading and rendering rich BIM geometric data and large-scale GIS spatial information in a unified system is still technologically challenging. Current efforts mainly simplify the geometry in BIM models, or convert BIM geometric data to a lower level of detail (LOD). By noticing that only exterior features of BIM models are visible from outdoor observation points, culling BIM interior facilities can dramatically reduce the computational burden when visualizing BIM models in GIS. This study explores the outline detection problem and presents the OutDet algorithm, which selects representative observation points, transforms & projects the BIM geometric data into the same coordinate system, and detects the visible facilities. Empirical study results show that OutDet can cull a large portion of unnecessary features when rendering BIM models in GIS. The use of outlines of BIM models is not an alternative but rather a supplementary approach for current solutions. Jointly using LOD and outer surface can help improve the efficiency of integrated BIM-GIS visualization.Because OutDet retains BIM geometry and semantics, it can be applied to more BIM-GIS applications.. [ABSTRACT FROM AUTHOR]

Introduction Despite a century of extensive study on the human sinoatrial node (SAN), the structure-to-function features of specialized SAN conduction pathways (SACP) are still unknown and debated. We report a new method for direct analysis of the SAN microstructure in optically-mapped human hearts with and without clinical history of SAN dysfunction. Methods Two explanted donor human hearts were coronary-perfused and optically-mapped. Structural analyses of histological sections parallel to epicardium (∼13–21 μm intervals) were integrated with optical maps to create 3D computational reconstructions of the SAN complex. High-resolution fiber fields were obtained using 3D Eigen-analysis of the structure tensor, and used to analyze SACP microstructure with a fiber-tracking approach. Results Optical mapping revealed normal SAN activation of the atria through a lateral SACP proximal to the crista terminalis in Heart #1 but persistent SAN exit block in diseased Heart #2. 3D structural analysis displayed a functionally-observed SAN border composed of fibrosis, fat, and/or discontinuous fibers between SAN and atria, which was only crossed by several branching myofiber tracts in SACP regions. Computational 3D fiber-tracking revealed that myofiber tracts of SACPs created continuous connections between SAN #1 and atria, but in SAN #2, SACP region myofiber tracts were discontinuous due to fibrosis and fat. Conclusions We developed a new integrative functional, structural and computational approach that allowed for the resolution of the specialized 3D microstructure of human SACPs for the first time. Application of this integrated approach will shed new light on the role of the specialized SAN microanatomy in maintaining sinus rhythm. [ABSTRACT FROM AUTHOR]

Abstract: High order integro-differential equations (IDEs), especially nonlinear, are usually difficult to solve even numerically. In this chapter, we give a highly accurate compact finite difference method to efficiently solve integro-differential equations, including high order and nonlinear problems. By numerical experiments, we show that compact finite difference method for integro-differential equations is fast and can obtain a high accuracy. [Copyright &y& Elsevier]

Computer models provide a powerful platform for investigating mechanisms that underlie atrial rhythm disturbances. We have used novel techniques to build a structurally-detailed, image-based model of 3-D atrial anatomy. A volume image of the atria from a normal sheep heart was acquired using serial surface macroscopy, then smoothed and down-sampled to 50 \,\mum^3 resolution. Atrial surface geometry was identified and myofiber orientations were estimated throughout by eigen-analysis of the 3-D image structure tensor. Sinus node, crista terminalis, pectinate muscle, Bachman's bundle, and pulmonary veins were segmented on the basis of anatomic characteristics. Heterogeneous electrical properties were assigned to this structure and electrical activation was simulated on it at 100 \mum^3 resolution, using both biophysically-detailed and reduced-order cell activation models with spatially-varying membrane kinetics. We confirmed that the model reproduced key features of the normal spread of atrial activation. Furthermore, we demonstrate that vulnerability to rhythm disturbance caused by structural heterogeneity in the posterior left atrium is exacerbated by spatial variation of repolarization kinetics across this region. These results provide insight into mechanisms that may sustain paroxysmal atrial fibrillation. We conclude that image-based computer models that incorporate realistic descriptions of atrial myofiber architecture and electrophysiologic properties have the potential to analyse and identify complex substrates for atrial fibrillation. [ABSTRACT FROM PUBLISHER]

Introduction: Atrial fibrillation is prevalent in the elderly and contributes to mortality in congestive heart failure. Development of computer models of atrial electrical activation that incorporate realistic structures provides a means of investigating the mechanisms that initiate and maintain reentrant atrial arrhythmia. As a step toward this, we have developed a model of the right atrial appendage (RAA) including detailed geometry of the pectinate muscles (PM) and crista terminalis (CT) with high spatial resolution, as well as complete fiber architecture. Methods and Results: Detailed structural images of a pig RAA were acquired using a semiautomated extended-volume imaging system. The generally accepted anisotropic ratio of 10:1 was adopted in the computer model. To deal with the regional action potential duration heterogeneity in the RAA, a Courtemanche cell model and a Luo-Rudy cell model were used for the CT and PM, respectively. Activation through the CT and PM network was adequately reproduced with acceptable accuracy using reduced-order computer models. Using a train of reducing cycle length stimuli applied to a CT/PM junction, we observed functional block both parallel with and perpendicular to the axis of the CT. Conclusion: With stimulation from the CT at the junction of a PM, we conclude: (a) that conduction block within the CT is due to a reduced safety factor; and (b) that unidirectional block and reentry within the CT is due to its high anisotropy. Regional differences in effective refractive period do not explain the observed conduction block. [ABSTRACT FROM AUTHOR]

Abstract: A compact finite difference method is designed to obtain quick and accurate solutions to partial differential equation problems. The problem of pricing an American option can be cast as a partial differential equation. Using the compact finite difference method this problem can be recast as an ordinary differential equation initial value problem. The complicating factor for American options is the existence of an optimal exercise boundary which is jointly determined with the value of the option. In this article we develop three ways of combining compact finite difference methods for American option price on a single asset with methods for dealing with this optimal exercise boundary. Compact finite difference method one uses the implicit condition that solutions of the transformed partial differential equation be nonnegative to detect the optimal exercise value. This method is very fast and accurate even when the spatial step size h is large . Compact difference method two must solve an algebraic nonlinear equation obtained by Pantazopoulos (1998) at every time step. This method can obtain second order accuracy for space x and requires a moderate amount of time comparable with that required by the Crank Nicolson projected successive over relaxation method. Compact finite difference method three refines the free boundary value by a method developed by Barone-Adesi and Lugano [The saga of the American put, 2003], and this method can obtain high accuracy for space x. The last two of these three methods are convergent, moreover all the three methods work for both short term and long term options. Through comparison with existing popular methods by numerical experiments, our work shows that compact finite difference methods provide an exciting new tool for American option pricing. [Copyright &y& Elsevier]

Abstract: Finite difference method, and finite element method are widely used partly for their simplicity, though these methods can obtain first-order or second-order of accuracy. In this paper, we give two highly accurate (fourth-order and sixth-order of accuracy respectively), while still quite simple schemes for two point boundary value problems. We call them compact mixed methods, since they can obtain numerical solutions for unknown function and its first derivative simultaneously. To yield best numerical solutions, we combine our compact mixed schemes with a direct solver and an iterative solver. Then we employ Fourier method to analyze differencing errors shows that our compact mixed formulae are closer to the true wavenumber. Numerical experiments show compact mixed schemes are very efficient, and highly accurate techniques. [Copyright &y& Elsevier]

Abstract: A graft copolymerization of acrylamide with N,N′-methylenebisacrylamide on chitosan in aqueous medium was utilized in the synthesis of molecularly imprinted polymer (MIP) gels using bovine serum albumin (BSA) as a template. The effect of the amount of initiator and the molecular weight and amount of chitosan on BSA rebinding was investigated. It was found that the resultant MIP gels based on chitosan-g-polyacrylamide (CS-g-PAM) showed significantly higher imprinting efficiency than those only consisting of polyacrylamide (PAM), and also better than those composed of chitosan/PAM semi-interpenetrating polymer network (CS/PAM-s-IPN). The batchwise adsorption of BSA and some non-template proteins showed that the CS-g-PAM based MIP gels demonstrated a quite significant template binding capacity different from the non-imprinted polymer (NIP) gels, and an obvious binding specificity for BSA. The adsorption isotherms of BSA on the MIP gels were determined and well fitted by a Langmuir model with a maximum binding capacity of 39.49mg/g wet gels. The adsorption kinetics was analyzed by a linear driving force mass-transfer model. The MIP gels also showed much better stability in rebinding of the imprint molecules than those based on CS/PAM-s-IPN after three adsorption–regeneration cycles. [Copyright &y& Elsevier]

Abstract: In this paper, we give a fourth-order compact finite difference scheme for the general forms of two point boundary value problems and two-dimensional elliptic partial differential equations (PDE’s). By decomposing the coefficient matrix into a sum of several matrixes after we discretize the original problems, we can obtain a lower bound for the smallest eigenvalue of the coefficient matrix. Thus we prove the compact finite difference scheme converges with the fourth order of accuracy. To solve the discretized block tri-diagonal matrix equations of the two-dimensional elliptic PDE’s, we develop an efficient iterative method: Full Multigrid Method. In our numerical experiments, we compare the compact finite difference method with the finite element method and Crank–Nicolson finite difference method. The results show that the compact finite difference scheme is a highly efficient and accurate method. [Copyright &y& Elsevier]

Abstract: In this paper, we give sixth order compact finite difference formula for second order integro-differential equations (IDE) with different boundary conditions, and both of error estimates and numerical experiments confirm our compact finite difference method can get fifth order of accuracy. We also adjust compact finite difference method for first order IDE and a system of IDE and give numerical experiments for them. Our algorithm even can solve nonlinear IDE and unsplit kernel of IDE. The most advantages of compact finite difference method for IDE are that it obtains high order of accuracy, while the time complexity to solve the matrix equations after we use compact finite difference method on IDE is O(N), and it can solve very general case of IDE. [Copyright &y& Elsevier]

Building Information Model/Modeling (BIM) upgrades the digitization of buildings from 2D to 3D and has become a common paradigm in architecture, engineering, construction, operations, and facility management (AECO/FM) industry. However, embedding BIM in decision support systems is still a challenge because the BIM standard (Industry Foundation Classes, or IFC) is complex, and the geometries in BIM cannot be directly rendered in decision support systems, e.g., web and mobile-phone applications. Current efforts mainly focus on rendering BIM triangulation data, and limited studies investigate solutions solving quite long running time and enormously large memory usage in BIM triangulation process, especially in big BIM files. This study addresses this issue by introducing a parallel computing framework and providing an online geometry triangulation service. First, the reference relationships among the BIM objects were modeled as a graph according to the IFC specification. Second, the original large IFC file was split into several small independent IFC files in which all geometric objects that share the same shape representation were aggregated. Finally, the small separate IFC files were assigned to and triangulated in different computers in a parallel computing cluster. Experiments showed that the proposed online service could greatly reduce memory usage and time consumption when triangulating the geometry of BIM objects. Processability has become a critical issue for BIM in the era of construction Big Data. The proposed scheme can triangulate big BIM files efficiently using limited memory and thus can dramatically improve the processability of BIM Big Data. • The geometry description of IFC was systematically analyzed. • A novel IFC geometry splitting algorithm was proposed to split an IFC file into several independent small IFC files. • An online geometry triangulation service for BIM Big Data using parallel computing was presented. • Adoption of parallel computing can dramatically improve the processability of BIM Big Data. [ABSTRACT FROM AUTHOR]

Most of the current studies on social network (SN) mainly focused on a single SN platform. Integration of SNs can provide more sufficient user behaviour data and more complete network structure, and thus is rewarding to an ocean of studies on social computing. Recognizing the identical users across SNs, or user identification, naturally bridges the SNs through users and has attracted extensive attentions. Due to the fragmentation, inconsistency and disruption of the accessible information among SNs, user identification is still an intractable problem. Different from the efforts implemented on user profiles and users' content, many studies have noticed the accessibility and reliability of network structure in most of the SNs for addressing this issue. Although substantial achievements have been made, most of the current network structure-based solutions are supervised or semi-supervised and require some given identified users or seed users. In the scenarios where seed users are hard to obtain, it is laborious to label the seed users manually. In this study, we proposed an unsupervised scheme by employing the reliability and consistence of friend relationships in different SNs, termed Unsupervised Friend Relationship-based User Identification algorithm (UFRUI). The UFRUI first models the network structure and embeds the feature of each user into a vector using network embedding technique, and then converts the user identification problem into a nearest neighbour problem. Finally, the matching user is computed using the scalable nearest neighbour algorithm. Results of experiments demonstrated that UFRUI performs much better than current state-of-art network structure-based algorithm without seed users. [ABSTRACT FROM AUTHOR]

Online social networks have continued to attract increased attention since the introduction of this concept nearly three decades ago. Consequently, a study about the workings of online social networks may help in understanding the structure of human society and the characteristics of generic complex networks. Over the past few years, interest in neighboring nodes, which are the number of nodes between any two nodes, the number of neighbors and how many triangles are present in a social network have produced the concepts of a six-degree separation (Milgram, Psychol Today 2(1):60–67, 1967; Backstrom et al., Proceedings of the 4th annual ACM web science conference, p 33–42, 2012), a heavy tail in the degree distribution (Barabási, Albert, Science 286(5439):509–512, 1999) and a high clustering coefficient (Luce, Perry, Psychometrika 14(2):95–116, 1949; Watts, Strogatz, Nature 393(6684):440–442, 1998; Amaral et al., Proc Natl Acad Sci USA 97(21):11149–11152, 2000). In a similar manner, researchers have also been curious about how many polygons are present in a given online social network. Although much effort has been expended (Dantzig et al., International symposium on theory of graphs, p 77–83, 1967; Kamae, IEEE Trans Circuit Theory 14(2):166–171, 1967; Gotlieb, Corneil, Commun ACM 10(12):780–783, 1967; Welch, J ACM 13(2):205–210, 1966; Tiernan, Commun ACM 13(12):722–726, 1970; Tarjan, SIAM J Comput 2(3):211–216, 1973; Johnson, SIAM J Comput 4:77–84, 1975; Mateti, Deo, SIAM J Comput 5(5):90–99, 1976; Marinari et al., Europhys Lett 73(3):301–307, 2005), studying this subject, the inability to enumerate polygons has stymied an in depth understanding of the properties of polygons in an online social network. In the study described in this paper, the estimated number of polygons in an online social network is revealed. It was found that in the current widely used online social networks, e.g., Facebook, Twitter, the number of polygons increases drastically when the length of a polygon is below a set value and then it decreases rapidly. The average length of the network polygons was calculated and it was found that online social networks contain a relatively large average length of polygons. Based on this perspective, a massive labyrinth of polygons would make the online social networks appear to be very complicated. To further investigate this area, a generalized clustering coefficient was explored. Results showed that the generalized clustering coefficient appeared to descend exponentially with the length of polygon and expeditiously approached zero. This result suggested that the polygons with large lengths should be ignored in many scenarios. Since the polygons with lengths greater than five appeared to have little impact on the network, the online social networks appeared to be less complex than anticipated. The polygon is one of the fundamental problems in graph theory and complex networks, so that the work reported here may be beneficial for many disciplines, including transportation [7], engineering [8], computer science [9–16], physics (Birmelé et al., Proceedings of the 24th annual ACM–SIAM symposium on discrete algorithms, p 1884–1896, 2013), sociology (Motter, Albert, Phys Today 65:43, 2012), epidemiology (Feld, Am J Sociol 96(6):1464–1477, 1991; Cohen et al., Phys Rev Lett 91(24):12343, 2002), psychology (Sun et al., Sci Rep 4(6188):5099–5099, 2014), biology (Feiler, Kleinbaum, Psychol Sci, 2015), medicine (Kincaid, Pilette, Comput Appl Biosci Cabios 8:267–273, 1992), geography (Kim et al., Lancet 386(9989):145–153, 2015), etc. [ABSTRACT FROM AUTHOR]

Micro-anatomical reentry has been identified as a potential driver of atrial fibrillation (AF). In this paper, we introduce a novel computational method which aims to identify which atrial regions are most susceptible to micro-reentry. The approach, which considers the structural basis for micro-reentry only, is based on the premise that the accumulation of electrically insulating interstitial fibrosis can be modelled by simulating percolation-like phenomena on spatial networks. Our results suggest that at high coupling, where micro-reentry is rare, the micro-reentrant substrate is highly clustered in areas where the atrial walls are thin and have convex wall morphology, likely facilitating localised treatment via ablation. However, as transverse connections between fibres are removed, mimicking the accumulation of interstitial fibrosis, the substrate becomes less spatially clustered, and the bias to forming in thin, convex regions of the atria is reduced, possibly restricting the efficacy of localised ablation. Comparing our algorithm on image-based models with and without atrial fibre structure, we find that strong longitudinal fibre coupling can suppress the micro-reentrant substrate, whereas regions with disordered fibre orientations have an enhanced risk of micro-reentry. With further development, these methods may be useful for modelling the temporal development of the fibrotic substrate on an individualised basis. [ABSTRACT FROM AUTHOR]

Micro-computed tomography (micro-CT) has been widely used to generate high-resolution 3-D tissue images from small animals nondestructively, especially for mineralized skeletal tissues. However, its application to the analysis of soft cardiovascular tissues has been limited by poor inter-tissue contrast. Recent ex vivo studies have shown that contrast between muscular and connective tissue in micro-CT images can be enhanced by staining with iodine. In the present study, we apply this novel technique for imaging of cardiovascular structures in canine hearts. We optimize the method to obtain high-resolution X-ray micro-CT images of the canine atria and its distinctive regions—including the Bachmann's bundle, atrioventricular node, pulmonary arteries and veins—with clear inter-tissue contrast. The imaging results are used to reconstruct and segment the detailed 3-D geometry of the atria. Structure tensor analysis shows that the arrangement of atrial fibers can also be characterized using the enhanced micro-CT images, as iodine preferentially accumulates within the muscular fibers rather than in connective tissues. This novel technique can be particularly useful in nondestructive imaging of 3-D cardiac architectures from large animals and humans, due to the combination of relatively high speed (\sim 1 h/per scan of the large canine heart) and high voxel resolution (36 \mum) provided. In summary, contrast micro-CT facilitates fast and nondestructive imaging and segmenting of detailed 3-D cardiovascular geometries, as well as measuring fiber orientation, which are crucial in constructing biophysically detailed computational cardiac models. [ABSTRACT FROM PUBLISHER]

Poly(acrylic acid) (PAA)-grafted cellulose copolymer beads were synthesized and tested in vitro as an adsorbent for selective removal of low-density lipoprotein (LDL) from human plasma. The copolymers were prepared by graft copolymerization of acrylic acid (AA) onto porous cellulose beads using cerium ammonium nitrate (CAN) as an initiator. The effect of initiator concentration, monomer amount and reaction time on the grafting was examined, and it revealed that the extent of grafting could be controlled by setting the appropriate reaction conditions. In vitro batch-wise adsorption tests were conducted to evaluate the lipoprotein sorption properties of the resulted copolymer beads, and the effect of grafting conditions on the adsorption performance was investigated. It was shown that the binding capacities of the best adsorbent derived from the appropriate reaction conditions could reach 4.96 mg/g total cholesterol (TC) and 4.46 mg/g LDL cholesterol (LDL-C) from human plasma, respectively, without significantly affecting the contents of beneficial constitutes such as high-density lipoprotein (HDL) and total proteins (TP). The influences of plasma amount and adsorption period on the adsorption properties were also determined and analyzed. It appears that this kind of copolymer is worthy of being developed as an alternative LDL adsorbent. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) occurrence and maintenance is associated with progressive remodeling of electrophysiological (repolarization and conduction) and 3D structural (fibrosis, fiber orientations, and wall thickness) features of the human atria. Significant diversity in AF etiology leads to heterogeneous arrhythmogenic electrophysiological and structural substrates within the 3D structure of the human atria. Since current clinical methods have yet to fully resolve the patient-specific arrhythmogenic substrates, mechanism-based AF treatments remain underdeveloped. Here, we review current knowledge from in-vivo, ex-vivo, and in-vitro human heart studies, and discuss how these studies may provide new insights on the synergy of atrial electrophysiological and 3D structural features in AF maintenance. In-vitro studies on surgically acquired human atrial samples provide a great opportunity to study a wide spectrum of AF pathology, including functional changes in single-cell action potentials, ion channels, and gene/protein expression. However, limited size of the samples prevents evaluation of heterogeneous AF substrates and reentrant mechanisms. In contrast, coronary-perfused ex-vivo human hearts can be studied with state-of-the-art functional and structural technologies, such as high-resolution near-infrared optical mapping and contrast-enhanced MRI. These imaging modalities can resolve atrial arrhythmogenic substrates and their role in reentrant mechanisms maintaining AF and validate clinical approaches. Nonetheless, longitudinal studies are not feasible in explanted human hearts. As no approach is perfect, we suggest that combining the strengths of direct human atrial studies with high fidelity approaches available in the laboratory and in realistic patient-specific computer models would elucidate deeper knowledge of AF mechanisms. We propose that a comprehensive translational pipeline from ex-vivo human heart studies to longitudinal clinically relevant AF animal studies and finally to clinical trials is necessary to identify patient-specific arrhythmogenic substrates and develop novel AF treatments. Unlabelled Image • Electrical and structural bi-atrial remodeling form patient-specific AF substrates. • AF can be maintained by reentrant drivers within a fibrotic arrhythmogenic hub. • Number of AF drivers increases with the progression of remodeling. • AF treatment may depend on the AF progression and patient's comorbidities. • Ex-vivo human heart is an efficient platform to reveal human AF mechanisms. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is a major cause of stroke and morbidity. Recent genome-wide association studies have shown that paired-like homeodomain transcription factor 2 (Pitx2) to be strongly associated with AF. However, the mechanisms underlying Pitx2 modulated arrhythmogenesis and variable effectiveness of antiarrhythmic drugs (AADs) in patients in the presence or absence of impaired Pitx2 expression remain unclear. We have developed multi-scale computer models, ranging from a single cell to tissue level, to mimic control and Pitx2-knockout atria by incorporating recent experimental data on Pitx2-induced electrical and structural remodeling in humans, as well as the effects of AADs. The key findings of this study are twofold. We have demonstrated that shortened action potential duration, slow conduction and triggered activity occur due to electrical and structural remodelling under Pitx2 deficiency conditions. Notably, the elevated function of calcium transport ATPase increases sarcoplasmic reticulum Ca2+ concentration, thereby enhancing susceptibility to triggered activity. Furthermore, heterogeneity is further elevated due to Pitx2 deficiency: 1) Electrical heterogeneity between left and right atria increases; and 2) Increased fibrosis and decreased cell-cell coupling due to structural remodelling slow electrical propagation and provide obstacles to attract re-entry, facilitating the initiation of re-entrant circuits. Secondly, our study suggests that flecainide has antiarrhythmic effects on AF due to impaired Pitx2 by preventing spontaneous calcium release and increasing wavelength. Furthermore, our study suggests that Na+ channel effects alone are insufficient to explain the efficacy of flecainide. Our study may provide the mechanisms underlying Pitx2-induced AF and possible explanation behind the AAD effects of flecainide in patients with Pitx2 deficiency. Author summary: Atrial fibrillation (AF) is an abnormal heart rhythm that can lead to stroke and death. Recent studies have uncovered that AF-associated risk variants are adjacent to the Pitx2 locus, furthermore, the have demonstrated that AF patients with these variants respond better to certain antiarrhythmic drugs (AADs). However, the mechanisms underlying Pitx2 modulated arrhythmogenesis and variable effectiveness of AADs remain unclear. To untangle this issue, we have developed multi-scale computer models, ranging from single cell to tissue level, to mimic control and the Pitx2-knockout atria by incorporating experimental data on Pitx2-induced electrical and structural remodelling, as well as the effects of class I ADDs (flecainide). We discovered that removal of Pitx2 caused AF characterized by focal beats and re-entrant waves. It was found that these abnormalities can be attributed to triggered beats, action potential duration shortening and slow conduction arising from Pitx2-induced remodelling. Interestingly, these Pitx2-induced AF can be suppressed in the presence of class I AADs such as flecainide. Our simulations revealed that flecainide prevents triggered beats by blocking the function of ryanodine receptors and that flecainide can terminate re-entrant waves by prolonging action potential duration due to its actions on potassium channels. [ABSTRACT FROM AUTHOR]

Paths and cycles are the two pivotal elements in a network. Here, we demonstrate that paths, particularly the shortest ones, are incomplete in information network. However, based on such paths, many network centrality measures are designed. While extensive explorations on paths have been made, modest studies focus on the cycles on measuring network centrality. We study the relationship between the shortest cycle and the shortest path from extensive real-world networks. The results illustrate the incompleteness of the shortest paths on measuring network centrality. Noticing that the shortest cycle is much more robust than the shortest path, we propose two novel cycle-based network centrality measures to address the incompleteness of paths: the shortest cycle closeness centrality (SCC) and the all cycle betweenness centrality (ACC). Notwithstanding we focus on the network centrality problem, our findings on cycles can be applied to explain the incompleteness of paths in applications and could improve the applicability into more scenarios where the paths are employed in network science. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most prevalent form of cardiac arrhythmia. Current treatments for AF remain suboptimal due to a lack of understanding of the underlying atrial structures that directly sustain AF. Existing approaches for analyzing atrial structures in 3-D, especially from late gadolinium-enhanced (LGE) magnetic resonance imaging, rely heavily on manual segmentation methods that are extremely labor-intensive and prone to errors. As a result, a robust and automated method for analyzing atrial structures in 3-D is of high interest. We have, therefore, developed AtriaNet, a 16-layer convolutional neural network (CNN), on 154 3-D LGE-MRIs with a spatial resolution of 0.625 mm $\times0.625$ mm $\times1.25$ mm from patients with AF, to automatically segment the left atrial (LA) epicardium and endocardium. AtriaNet consists of a multi-scaled, dual-pathway architecture that captures both the local atrial tissue geometry and the global positional information of LA using 13 successive convolutions and three further convolutions for merging. By utilizing computationally efficient batch prediction, AtriaNet was able to successfully process each 3-D LGE-MRI within 1 min. Furthermore, benchmarking experiments have shown that AtriaNet has outperformed the state-of-the-art CNNs, with a DICE score of 0.940 and 0.942 for the LA epicardium and endocardium, respectively, and an inter-patient variance of <0.001. The estimated LA diameter and volume computed from the automatic segmentations were accurate to within 1.59 mm and 4.01 cm3 of the ground truths. Our proposed CNN was tested on the largest known data set for LA segmentation, and to the best of our knowledge, it is the most robust approach that has ever been developed for segmenting LGE-MRIs. The increased accuracy of atrial reconstruction and analysis could potentially improve the understanding and treatment of AF. [ABSTRACT FROM AUTHOR]

Identification of anonymous identical users of cross-platforms refers to the recognition of the accounts belonging to the same individual among multiple Social Network (SN) platforms. Evidently, cross-platform exploration may help solve many problems in social computing, in both theory and practice. However, it is still an intractable problem due to the fragmentation, inconsistency, and disruption of the accessible information among SNs. Different from the efforts implemented on user profiles and users’ content, many studies have noticed the accessibility and reliability of network structure in most of the SNs for addressing this issue. Although substantial achievements have been made, most of the current network structure-based solutions, requiring prior knowledge of some given identified users, are supervised or semi-supervised. It is laborious to label the prior knowledge manually in some scenarios where prior knowledge is hard to obtain. Noticing that friend relationships are reliable and consistent in different SNs, we proposed an unsupervised scheme, termed Friend Relationship-based User Identification algorithm without Prior knowledge (FRUI-P). The FRUI-P first extracts the friend feature of each user in an SN into friend feature vector, and then calculates the similarities of all the candidate identical users between two SNs. Finally, a one-to-one map scheme is developed to identify the users based on the similarities. Moreover, FRUI-P is proved to be efficient theoretically. Results of extensive experiments demonstrated that FRUI-P performs much better than current state-of-art network structure-based algorithm without prior knowledge. Due to its high precision, FRUI-P can additionally be utilized to generate prior knowledge for supervised and semi-supervised schemes. In applications, the unsupervised anonymous identical user identification method accommodates more scenarios where the seed users are unobtainable. [ABSTRACT FROM PUBLISHER]

Background The anatomical substrate for the mid-mural ventricular hyperechogenic zone remains uncertain, but it may represent no more than ultrasound reflected from cardiomyocytes orientated orthogonally to the ultrasonic beam. We sought to ascertain the relationship between the echogenic zone and the orientation of the cardiomyocytes. Methods We used 3D echocardiography, diffusion tensor imaging, and microcomputed tomography to analyze the location and orientation of cardiomyocytes within the echogenic zone. Results We demonstrated that visualization of the echogenic zone is dependent on the position of the transducer and is most clearly seen from the apical window. Diffusion tensor imaging and microcomputed tomography show that the echogenic zone seen from the apical window corresponds to the position of the circumferentially orientated cardiomyocytes. An oblique band seen in the parasternal view relates to cardiomyocytes orientated orthogonally to the ultrasonic beam. Conclusions The mid-mural ventricular hyperechogenic zone represents reflected ultrasound from cardiomyocytes aligned orthogonal to the ultrasonic beam. The echogenic zone does not represent a space, a connective tissue sheet, a boundary between ascending and descending limbs of a hypothetical helical ventricular myocardial band, nor an abrupt change in cardiomyocyte orientation. [ABSTRACT FROM AUTHOR]

Background: Adenosine provokes atrial fibrillation (AF) with a higher activation frequency in right atria (RA) versus left atria (LA) in patients, but the underlying molecular and functional substrates are unclear. We tested the hypothesis that adenosine-induced AF is driven by localized reentry in RA areas with highest expression of adenosine A1 receptor and its downstream GIRK (G protein-coupled inwardly rectifying potassium channels) channels (IK,Ado).Methods: We applied biatrial optical mapping and immunoblot mapping of various atrial regions to reveal the mechanism of adenosine-induced AF in explanted failing and nonfailing human hearts (n=37).Results: Optical mapping of coronary-perfused atria (n=24) revealed that adenosine perfusion (10-100 µmol/L) produced more significant shortening of action potential durations in RA (from 290±45 to 239±41 ms, 17.3±10.4%; P<0.01) than LA (from 307±24 to 286±23 ms, 6.7±6.6%; P<0.01). In 10 hearts, adenosine induced AF (317±116 s) that, when sustained (≥2 minutes), was primarily maintained by 1 to 2 localized reentrant drivers in lateral RA. Tertiapin (10-100 nmol/L), a selective GIRK channel blocker, counteracted adenosine-induced action potential duration shortening and prevented AF induction. Immunoblotting showed that the superior/middle lateral RA had significantly higher adenosine A1 receptor (2.7±1.7-fold; P<0.01) and GIRK4 (1.7±0.8-fold; P<0.05) protein expression than lateral/posterior LA.Conclusions: This study revealed a 3-fold RA-to-LA adenosine A1 receptor protein expression gradient in the human heart, leading to significantly greater RA versus LA repolarization sensitivity in response to adenosine. Sustained adenosine-induced AF is maintained by reentrant drivers localized in lateral RA regions with the highest adenosine A1 receptor/GIRK4 expression. Selective atrial GIRK channel blockade may effectively treat AF during conditions with increased endogenous adenosine. [ABSTRACT FROM AUTHOR]

Building Information Modeling (BIM) is a promising technology for the construction industry, and BIM models have become widely accepted as 3D construction models. Currently, BIM data are often organized by product level to support cross-platform parallel and real-time visualization. However, cross-platform visualization of BIM products with large volumes of geometric data still poses a challenge to both triangulation and rendering processes. Existing efforts have mainly used geometric simplification and geometric data streaming technologies. This study addresses this issue from a different perspective by partitioning original large-scale BIM products into small BIM sub-products. First, a novel heterogeneous geometric relationship model (HeGeo) is proposed to categorize BIM relationships into reference, decomposition, and association relationships according to Industry Foundation Classes. On top of the HeGeo, a strategy for partitioning the geometric data of the original BIM products is proposed. Empirical studies were conducted on nine BIM models with a BIM product embedding all the geometric data. The experimental results showed that the proposed scheme improved triangulation efficiency 3.05 ± 0.57 times with the same hardware resources and the same triangulation tool through a parallel computing framework and raised the triangular mesh loading efficiency 1.53 ± 0.29 times by processing requests concurrently. In addition, the proposed scheme improved the user experience of online BIM visualization tools through incremental rendering. The segmentation scheme was generalized to product-level and floor-level schemes by constraining the segmentation nodes to BIM products and floors respectively. Thus, the segmentation scheme could be applied to any BIM model and facilitate BIM adoption by all stakeholders during a building's life cycle. • Propose a heterogeneous geometric relationship model for BIM data according to IFC. • Develop a geometric data segmentation algorithm, which can applied to any BIM model. • Our scheme can improve the triangulation efficiency by 3.05 ± 0.57 times. • Our scheme can raise the loading efficiency by 1.53 ± 0.29 times by concurrent requests. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. Several major mechanisms cause AF in patients, including genetic predispositions to AF development. Genome-wide association studies have identified a number of genetic variants in association with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene for the homeobox transcription PITX2. Because of the inherent complexity of the human heart, experimental and basic research is insufficient for understanding the functional impacts of PITX2 variants on AF. Linking PITX2 properties to ion channels, cells, tissues, atriums and the whole heart, computational models provide a supplementary tool for achieving a quantitative understanding of the functional role of PITX2 in remodelling atrial structure and function to predispose to AF. It is hoped that computational approaches incorporating all we know about PITX2-related structural and electrical remodelling would provide better understanding into its proarrhythmic effects leading to development of improved anti-AF therapies. In the present review, we discuss advances in atrial modelling and focus on the mechanistic links between PITX2 and AF. Challenges in applying models for improving patient health are described, as well as a summary of future perspectives. [ABSTRACT FROM AUTHOR]

Electrical remodelling as a result of homeodomain transcription factor 2 (Pitx2)-dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with single nucleotide polymorphisms at chromosome 4q25 responded favorably to class I antiarrhythmic drugs (AADs). The possible reasons behind this remain elusive. The purpose of this study was to assess the efficacy of the AADs disopyramide, quinidine, and propafenone on human atrial arrhythmias mediated by Pitx2-induced remodelling, from a single cell to the tissue level, using drug binding models with multi-channel pharmacology. Experimentally calibrated populations of human atrial action po-tential (AP) models in both sinus rhythm (SR) and Pitx2-induced AF conditions were constructed by using two distinct models to represent morphological subtypes of AP. Multi-channel pharmaco-logical effects of disopyramide, quinidine, and propafenone on ionic currents were considered. Simulated results showed that Pitx2-induced remodelling increased maximum upstroke velocity (dVdtmax), and decreased AP duration (APD), conduction velocity (CV), and wavelength (WL). At the concentrations tested in this study, these AADs decreased dVdtmax and CV and prolonged APD in the setting of Pitx2-induced AF. Our findings of alterations in WL indicated that disopyramide may be more effective against Pitx2-induced AF than propafenone and quinidine by prolonging WL. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is an important risk factor for atrial fibrillation (AF) development. Sodium–glucose co-transporter-2 (SGLT-2) inhibitors are used for the treatment of type 2 diabetes mellitus (T2DM). Their cardioprotective effects have been reported but whether they prevent AF in T2DM patients are less well-explored. We tested the hypothesis that the SGLT-2 inhibitor, empagliflozin, can prevent atrial remodeling in a diabetic rat model. Methods: High-fat diet and low-dose streptozotocin (STZ) treatment were used to induce T2DM. A total of 96 rats were randomized into the following four groups: (i) control (ii) T2DM, (iii) low-dose empagliflozin (10 mg/kg/day)/T2DM; and (iv) high-dose empagliflozin (30 mg/kg/day)/T2DM by the intragastric route for 8 weeks. Results: Compared with the control group, left atrial diameter, interstitial fibrosis and the incidence of AF inducibility were significantly increased in the DM group. Moreover, atrial mitochondrial respiratory function, mitochondrial membrane potential, and mitochondrial biogenesis were impaired. Empagliflozin treatment significantly prevented the development of these abnormalities in DM rats, likely via the peroxisome proliferator-activated receptor-c coactivator 1α (PGC-1α)/nuclear respiratory factor-1 (NRF-1)/mitochondrial transcription factor A (Tfam) signaling pathway. Conclusions: Empagliflozin can ameliorate atrial structural and electrical remodeling as well as improve mitochondrial function and mitochondrial biogenesis in T2DM, hence may be potentially used in the prevention of T2DM-related atrial fibrillation. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, obesity and metabolic syndrome (MetS) have become more prevalent, owing to increased unhealthy habits and sedentary lifestyles becoming public health problems. Both conditions are linked with a higher prevalence of sudden cardiac death (SCD), but the exact mechanisms are not known. An autonomic nervous system imbalance can produce atrial and ventricular arrhythmias, which cause SCD, and this can be quantified by analyzing heart rate variability (HRV). We investigated HRV using time-domain, frequency-domain and nonlinear analyses during the development of MetS in rabbits and found HRV modifications that could be associated with the higher prevalence of SCD in this pathological condition. Metabolic syndrome (MetS) has been linked to a higher prevalence of sudden cardiac death (SCD), but the mechanisms are not well understood. One possible underlying mechanism may be an abnormal modulation of autonomic activity, which can be quantified by analyzing heart rate variability (HRV). Our aim was to investigate the modifications of short-term HRV in an experimental rabbit model during the time-course of MetS development. NZW rabbits were randomly assigned to a control (n = 10) or a MetS group (n = 13), fed 28 weeks with control or high-fat, high-sucrose diets. After anesthesia, a 15-min ECG recording was acquired before diet administration and at weeks 14 and 28. We analyzed short RR time series using time-domain, frequency-domain and nonlinear analyses. A mixed-model factorial ANOVA was used for statistical analysis. Time-domain analysis showed a 52.4% decrease in the standard deviation of heart rate in animals from the MetS group at week 28, but no changes in the rest of parameters. In the frequency domain, we found a 9.7% decrease in the very low frequency and a 380.0% increase of the low frequency bands in MetS animals at week 28, whereas high frequency remained unchanged. Nonlinear analyses showed increased complexity and irregularity of the RR time series in MetS animals. [ABSTRACT FROM AUTHOR]

Transcription factors TBX5 and PITX2 involve in the regulation of gene expression of ion channels and are closely associated with atrial fibrillation (AF), the most common cardiac arrhythmia in developed countries. The exact cellular and molecular mechanisms underlying the increased susceptibility to AF in patients with TBX5/PITX2 insufficiency remain unclear. In this study, we have developed and validated a novel human left atrial cellular model (TPA) based on the ten Tusscher-Panfilov ventricular cell model to systematically investigate how electrical remodeling induced by TBX5/PITX2 insufficiency leads to AF. Using our TPA model, we have demonstrated that spontaneous diastolic depolarization observed in atrial myocytes with TBX5-deletion can be explained by altered intracellular calcium handling and suppression of inward-rectifier potassium current (IK1). Additionally, our computer simulation results shed new light on the novel cellular mechanism underlying AF by indicating that the imbalance between suppressed outward current IK1 and increased inward sodium-calcium exchanger current (INCX) resulted from SR calcium leak leads to spontaneous depolarizations. Furthermore, our simulation results suggest that these arrhythmogenic triggers can be potentially suppressed by inhibiting sarcoplasmic reticulum (SR) calcium leak and reversing remodeled IK1. More importantly, this study has clinically significant implications on the drugs used for maintaining SR calcium homeostasis, whereby drugs such as dantrolene may confer significant improvement for the treatment of AF patients with TBX5/PITX2 insufficiency. [ABSTRACT FROM AUTHOR]