Areas Of High Curvature Research Articles

Subduction Zone Geometry Modulates the Megathrust Earthquake Cycle: Magnitude, Recurrence, and Variability

AbstractMegathrust geometric properties exhibit some of the strongest correlations with maximum earthquake magnitude in global surveys of large subduction zone earthquakes, but the mechanisms through which fault geometry influences subduction earthquake cycle dynamics remain unresolved. Here, we develop 39 models of sequences of earthquakes and aseismic slip (SEAS) on variably‐dipping planar and variably‐curved nonplanar megathrusts using the volumetric, high‐order accurate code tandem to account for fault curvature. We vary the dip, downdip curvature and width of the seismogenic zone to examine how slab geometry mechanically influences megathrust seismic cycles, including the size, variability, and interevent timing of earthquakes. Dip and curvature control characteristic slip styles primarily through their influence on seismogenic zone width: wider seismogenic zones allow shallowly‐dipping megathrusts to host larger earthquakes than steeply‐dipping ones. Under elevated pore pressure and less strongly velocity‐weakening friction, all modeled fault geometries host uniform periodic ruptures. In contrast, shallowly‐dipping and sharply‐curved megathrusts host multi‐period supercycles of slow‐to‐fast, small‐to‐large slip events under higher effective stresses and more strongly velocity‐weakening friction. We discuss how subduction zones' maximum earthquake magnitudes may be primarily controlled by the dip and dimensions of the seismogenic zone, while second‐order effects from structurally‐derived mechanical heterogeneity modulate the recurrence frequency and timing of these events. Our results suggest that enhanced co‐ and interseismic strength and stress variability along the megathrust, such as induced near areas of high or heterogeneous fault curvature, limits how frequently large ruptures occur and may explain curved faults' tendency to host more frequent, smaller earthquakes than flat faults.

Wavefront curvature analysis derived from preprocedural imaging can identify the critical isthmus in patients with postinfarcted ventricular tachycardia

BackgroundWhere activation wavefront curvature is convexly shaped, functional conduction block can occur. ObjectiveThe purpose of this study was to determine whether left ventricular (LV) wall thickness determined from contrast-enhanced computed tomography (CT) is useful in localizing such areas in clinical postinfarction reentrant ventricular tachycardia (VT). MethodsWe evaluated data from 6 patients who underwent catheter ablation for postinfarction VT. CT imaging with inHEART processing was conducted 1–3 days before electrophysiological (EP) study to determine LV wall thickness (T). Activation wavefront curvature was approximated as ΔT/T, where ΔT represents wall thickness change. During EP study, bipolar LV VT electrograms were acquired using a high-density mapping catheter, and activation times were determined. Maps of T, ΔT/T, and VT activation were subsequently compared using statistical analyses. ResultsTwo of 6 cases exhibited dual circuit morphologies, resulting in a total of 8 VT morphologies analyzed. The LV wall near the VT isthmus location tended to be thin, on the order of a few hundred micrometers. Regions of largest ΔT/T partially coincided with the lateral isthmus boundaries where electrical conduction block occurred during VT. ΔT/T at the boundaries, measured from imaging, was significantly larger compared to values at the isthmus midline and to the global LV mean value (P <.001). ConclusionWavefront curvature measured by ΔT/T and caused by source–sink mismatch is dependent on ventricular wall thickness. Areas of high wavefront curvature partly coincide with and may be helpful in locating the VT isthmus in infarct border zones using preprocedural imaging analysis.

Relaxing Wrinkles in Jammed Interfacial Assemblies

AbstractDynamic covalent bonding has emerged as a mean by which stresses in a network can be relaxed. Here, the strength of the bonding of ligands to nanoparticles at the interface between two immiscible liquids affect the same results in jammed assemblies of nanoparticle surfactants. Beyond a critical degree of overcrowding induced by the compression of jammed interfacial assemblies, the bonding of ligands to nanoparticles (NPs) can be broken, resulting in a desorption of the NPs from the interface. This reduces the areal density of nanoparticle surfactants at the interface, allowing the assemblies to relax, not to a fluid state but rather another jammed state. The relaxation of the wrinkles caused by the compression reflects the tendency of these assemblies to eliminate areas of high curvature, favoring a more planar geometry. This enabled the generation of giant vesicular and multivesicular structures from these assemblies.

Relaxing Wrinkles in Jammed Interfacial Assemblies.

Dynamic covalent bonding has emerged as a mean by which stresses in a network can be relaxed. Here, the strength of the bonding of ligands to nanoparticles at the interface between two immiscible liquids affect the same results in jammed assemblies of nanoparticle surfactants. Beyond a critical degree of overcrowding induced by the compression of jammed interfacial assemblies, the bonding of ligands to nanoparticles (NPs) can be broken, resulting in a desorption of the NPs from the interface. This reduces the areal density of nanoparticle surfactants at the interface, allowing the assemblies to relax, not to a fluid state but rather another jammed state. The relaxation of the wrinkles caused by the compression reflects the tendency of these assemblies to eliminate areas of high curvature, favoring a more planar geometry. This enabled the generation of giant vesicular and multivesicular structures from these assemblies.

PATTERN RELATED ISSUES IN THE MODELLING OF DEFORMED OVER SURFACE WARP KNITTED STRUCTURES WITH LONGER UNDERLAPS

The yarn level modelling of warp knitted structures is a complex process. For structures placed on the plane, it is well investigated and there are a few software solutions and papers reported. This paper considers the simulation of warp knitted structure, deformed in the 3D space. Especially the modelling of the areas of high curvature are detailed observed. Underlaps with longer lengths makes an unreal visualization for simulation results. Different pattern with different length of the underlaps are modelled with original algorithm developed by the authors. Modelling and visualization problems in the areas with long underlaps are discussed and possible solutions are proposed.

WPMAVM: Weighted plus-and-minus allowance variance minimization algorithm for solving matching distortion

• A weighted plus-and-minus allowance variance minimization (WPMAVM) algorithm is proposed. • WPMAVM takes the plus-and-minus allowance in the objective function of VMM into account. • The distance function is introduced to suppress the distortion caused by the abnormal allowance. • WPMAVM has better robustness to minus allowance and abnormal point clouds compared to ICP and VMM. • The proposed algorithm is suitable for calibration and measurement of complex curved surfaces. Point cloud matching is widely used in the calibration and measurement of complex curved surfaces, and the matching accuracy affects both the subsequently machined surface quality and measurement results. In the actual application, the existing iterative closest point (ICP) algorithm is prone to matching distortion when the measurement point clouds have inherent defects such as unclosed shape, uneven density and Gaussian noise . Despite this problem can be solved by the variance-minimization matching (VMM) algorithm, but the point clouds match distortedly both for ICP and VMM particularly when the workpieces behave with complex and unknown allowance distribution. For examples, the car bodywork is characterized by remarkable flexibility with local deformation, resulting in abnormal allowance, while the machined engine blade shows over- and less-cutting induced minus and abnormal allowances in high and low curvature areas, respectively. In this paper, a weighted plus-and-minus allowance variance minimization (WPMAVM) algorithm is proposed to overcome these problems. Specifically, the plus-and-minus allowance in the objective function of VMM algorithm is subdivided into the sum of plus-and-minus allowance variance minimization to suppress the distortion caused by the plus-and-minus allowance. The weighted term w , defined as the distance function from the point to the weighted plus-and-minus mean, is introduced to suppress the distortion caused by the abnormal allowance. The simulation and experimental comparisons on three typical workpieces show that the proposed algorithm has better robustness to minus allowance and abnormal point clouds compared to the existing ICP and VMM algorithms.

Turbulent flow simulation near fixed drone propeller using immersed boundary method

Current paper investigates the possibility of modeling the flow near the drone propeller on a simply connected mesh using the immersed boundary method and calculating its aerodynamic characteristics. An important part of the technique is the moving mesh adaptation to the surface of a streamlined body that retains its topology. The position and shape of the body are given by an interpolation grid, which stores the function of the distance to the body surface, as well as a number of geometry parameters. The method described in this paper is usually used to simulate flow near moving bodies, but here a stationary formulation is considered to assess the possibilities of using the proposed method for modeling flow near bodies of complex shapes where there are areas of high curvature and thin edges. For the proposed formulation of the problem, the results of the calculation carried out by the classical method on a body-fitted mesh and the results of modeling obtained using the method of immersed boundaries on a simply connected mesh are presented. The paper compares the results of these approaches, evaluates the possibility of using the immersed boundary method in combination with mesh adaptation to simulate the flow around bodies of complex shapes, and identifies the weaknesses of the proposed approach.

A clustering-based simplification of massive automobile-bodies point cloud for lightweight design

Adaptive simplification for massive and large-scale automobile-bodies point cloud obtained by 3D laser-scanning has been proven to be an effective technology to conduct lightweight design. This paper introduces a point-based algorithm to simplify laser-scanning point cloud without any support of fitted surface. The intrinsic characteristic of laser-scanning data is investigated to produce a topological connectivity for adjacent points in scanlines. We explore an automatic normal-vector estimation framework through the relationship between normal-vector and its adjacent geometric elements. To retain more points in high-curvature areas and fewer points in planar regions efficiently, the local normal-vector variance is adopted to determine subdivision-decision condition. The boundary points are detected and then preserved before non-uniform subdivision. A relevant simplification system based on our algorithm is developed. Many simplification cases are implemented to validate the effectiveness of our method and demonstrate the feasibility for automobile-bodies point cloud. The comparison with other point-based methods is also performed to illustrate the superiority of our method.

Back-propagating rupture evolution within a curved slab during the 2019 Mw 8.0 Peru intraslab earthquake

SUMMARY The 26 May 2019 MW 8.0 Peru intraslab earthquake ruptured the subducting Nazca Plate where the dip angle of the slab increases sharply and the strike angle rotates clockwise from the epicentre to north. To obtain a detailed seismic source model of the 2019 Peru earthquake, including not only the rupture evolution but also the spatiotemporal distribution of focal mechanisms, we performed comprehensive seismic waveform analyses using both a newly developed flexible finite-fault teleseismic waveform inversion method and a back-projection method. The source model revealed a complex rupture process involving a back-propagating rupture. The initial rupture propagated downdip from the hypocentre, then unilaterally northward along the strike of the slab. Following a large slip occurring ∼50–100 km north of the hypocentre, the rupture propagated bilaterally both further northward and back southward. The spatial distribution of focal mechanisms shows that the direction of T-axis azimuth gradually rotated clockwise from the epicentre northward, corresponding to the clockwise rotation of the strike of the subducting Nazca Plate, and the large-slip area corresponds to the high-curvature area of the slab iso-depth lines. Our results show that the complex rupture process, including the focal-mechanism transition, of the Peru earthquake was related to the slab geometry of the subducting Nazca Plate.

OPACITY-BASED EDGE HIGHLIGHTING FOR TRANSPARENT VISUALIZATION OF 3D SCANNED POINT CLOUDS

Abstract. The recent development of 3D scanning technologies has made it possible to quickly and accurately record various 3D objects in the real world. The 3D scanned data take the form of large-scale point clouds, which describe complex 3D structures of the target objects and the surrounding scenes. The complexity becomes significant in cases that a scanned object has internal 3D structures, and the acquired point cloud is created by merging the scanning results of both the interior and surface shapes. To observe the whole 3D structure of such complex point-based objects, the point-based transparent visualization, which we recently proposed, is useful because we can observe the internal 3D structures as well as the surface shapes based on high-quality see-through 3D images. However, transparent visualization sometimes shows us too much information so that the generated images become confusing. To address this problem, in this paper, we propose to combine “edge highlighting” with transparent visualization. This combination makes the created see-through images quite understandable because we can highlight the 3D edges of visualized shapes as high-curvature areas. In addition, to make the combination more effective, we propose a new edge highlighting method applicable to 3D scanned point clouds. We call the method “opacity-based edge highlighting,” which appropriately utilizes the effect of transparency to make the 3D edge regions look clearer. The proposed method works well for both sharp (high-curvature) and soft (low-curvature) 3D edges. We show several experiments that demonstrate our method’s effectiveness by using real 3D scanned point clouds.

The influence of shape and charge on protein corona composition in common gold nanostructures.

With increasing importance of gold nanoparticles (AuNPs) in the medical field, the understanding of their interactions in biological environments is essential. It is known that the exposure to biological fluids of particles in the nanometric range leads to accumulation of proteins on the particle surface proximity, generating the so-called protein corona. This fact can completely change the properties of AuNPs, thus drastically influencing the characteristics and intended purpose of the particles. Therefore, deep insight on the formation and composition of this protein corona is of extreme importance. Between the different factors that can alter the corona formation, our study focuses on the influence of the shape and particle surface charge. In detail, four different shapes of nanometrical scale (spheres, rods, stars and cages) of comparable size were used, all of them stabilized with three different heterofunctionalized poly(ethylene glycol) thiol (R-PEG-SH) linkers (R=OCH3, COOH or NH2) to check the effect of charge as well. After incubation with human serum, abundant proteins were identified via liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC ESI MS/MS) and compared in terms of their relative abundance. On the basis of statistical evaluations, the shape of our AuNPs showed a greater influence than the surface charge. Especially, cage-shaped AuNPs showed a lower amount of total corona proteins. This shape showed differences in the abundances of individual proteins like albumin, vitronectin and members of the complement system. These results indicate that nanocages could present an improved biocompatibility compared with the other shapes due to the high curvature areas and dense ligation on the flat surfaces that could hinder opsonisation and fast removal by the immune system.

A novel centerline extraction algorithm for a laser stripe applied for turbine blade inspection

Line-laser 3D scanning is a novel and promising automation technique for turbine blade inspection. One key task encountered in line-laser 3D scanning is centerline extraction of the laser stripes. In some regions, there is asymmetry of the line profiles caused by high curvature, such as the leading and trailing edges of a blade. According to the asymmetric Gaussian distribution line profile, this paper presents a new algorithm to extract the centerline of a laser stripe based on sub-pixel boundary extraction and medial axis transformation. The candidate boundary points of the laser stripe are extracted by zero crossing. Based on Taylor expansion and interpolation, the gray gradient distribution of the boundary can be estimated accurately. Following this, the accurate boundary points are extracted by extreme values of the gray gradient, and the centerline is calculated by medial axis transformation of the accurate boundary points. The proposed method can effectively reduce errors caused by the asymmetry of line profiles in areas of high curvature. The effectiveness of this method is verified using simulation and measuring experiments. The experiment results show that the extraction error of the asymmetric Gaussian line profile is within ± 0.15 pixels, and the root mean square error in measurement accuracy experiments does not exceed 0.015 mm.

A Novel A\u03b240 Assembly at Physiological Concentration

Aggregates of amyloid-β (Aβ) are characteristic of Alzheimer’s disease, but there is no consensus as to either the nature of the toxic molecular complex or the mechanism by which toxic aggregates are produced. We report on a novel feature of amyloid-lipid interactions where discontinuities in the lipid continuum can serve as catalytic centers for a previously unseen microscale aggregation phenomenon. We show that specific lipid membrane conditions rapidly produce long contours of lipid-bound peptide, even at sub-physiological concentrations of Aβ. Using single molecule fluorescence, time-lapse TIRF microscopy and AFM imaging we characterize this phenomenon and identify some exceptional properties of the aggregation pathway which make it a likely contributor to early oligomer and fibril formation, and thus a potential critical mechanism in the etiology of AD. We infer that these amyloidogenic events occur only at areas of high membrane curvature, which suggests a range of possible mechanisms by which accumulated physiological changes may lead to their inception. The speed of the formation is in hours to days, even at 1 nM peptide concentrations. Lipid features of this type may act like an assembly line for monomeric and small oligomeric subunits of Aβ to increase their aggregation states. We conclude that under lipid environmental conditions, where catalytic centers of the observed type are common, key pathological features of AD may arise on a very short timescale under physiological concentration.

Measurement of Scars Using Structured-Light 3D Scanning in Forensic Practice.

Objective To validate the accuracy and reliability of structured-light three-dimensional （SL-3D） scanning in measuring the length and area of the regular and irregular scars on body surface and discuss its value in forensic practice. Methods The lengths of 30 cases of simulated linear scars and 50 cases of linear scars after injury were measured using soft ruler, vernier caliper + thin line method, and SL-3D scanning. The areas of 35 cases of simulated patchy scars and 15 cases of patchy scars after injury were measured using length × width, film tracing with coordinate paper method, pixel method, and SL-3D scanning, and then statistically analyzed. Results The differences between the length of the simulated linear scars measured by SL-3D scanning and standard length had no statistical significance. When simulated patchy scars and patchy scars after injury were measured with high surface curvature and large irregular areas, the differences between the results of SL-3D scanning measurement and the standard area had no statistical significance. When the length of 50 cases of linear scars after injury were measured using SL-3D scanning, the correlation coefficient between the measurement results of two different investigators was 0.998, and the correlation coefficient between the two measurement results by the same investigator was 1.000. The correlation coefficient between the results of SL-3D scanning and that of vernier caliper + thin line method was 0.996. Conclusion The three-dimensional information of the scars on the body surface can be acquired using SL-3D scanning. The measurement of the length and area of the scars is not influenced by the location of scars, curvature of surface, and human factors. The measurement results are accurate, reliable and has unique advantages.

Numerical simulation of binary fluid–surfactant phase field model coupled with geometric curvature on the curved surface

In this paper, we consider the numerical simulation of the binary fluid–surfactant phase field model coupled with geometric curvature on the curved surface. By taking account of the effect of the curvature, we firstly modify the free energy of the fluid–surfactant system, which results a new phase field model on the curved surface. Then, based on the scalar auxiliary variable method, we study the numerical schemes, which consist of a surface finite element method for the spatial discretization, and first- and second-order implicit schemes for the temporal discretization. The unconditional energy stability of the first-order one is also strictly proved. Finally, some numerical examples are shown to verify the theoretical prediction. Furthermore, two important features of the system are observed: one is that the curvature can cause one of the two fluids to favor or avoid areas of high curvature on the curved surface; the other one is that the higher the coupling intensity is, the faster the energy reaches stability.

Development of a Scalable Two-Additive Electrodeposition System for Bottom-up Copper Filling of Sub-Millimeter through Silicon Vias

A two-additive electrodeposition system for Cu feature filling of sub-millimeter scale through silicon vias (TSVs) is discussed. This 1.0 mol/L CuSO4 – 0.5 mol/L H2SO4 acid sulfate electrolyte contains a polyether surfactant and halide additive which together promote a bottom-up Cu growth profile through positive feedback between localized disruption of the adsorbed polyether-halide layer and metal deposition.1 The functionality of this system relies on a tightly controlled additive concentration gradient down the length of the feature at the onset of metal deposition to allow bottom-up Cu growth to propagate. Careful consideration of convective contributions is also made to ensure an appropriate boundary layer thickness is maintained for non-linear bottom-up filling, where localized active and passive zone bifurcation of rapid electrodeposition is present. Initial experiments demonstrate the efficacy of potentiostatic control in determining the applied current window by which galvanostatic control can ultimately be achieved for a sub-millimeter feature geometry. Nominally void-free bottom-up deposition of multiple recessed feature geometries is presented.One advantage of the two-additive bottom-up electrodeposition system is that it has been demonstrated across multiple length scales and with multiple materials,2-9 making it suitable for heterogeneous integration (HI) of a wide array of devices which can require unique feature geometries and interconnect materials. Depending on the application, the two-additive bottom-up electrodeposition system can replace the more traditional three or four-additive system in damascene processing10 which can yield superconformal deposition profiles in TSVs as explained by the curvature enhanced adsorbate coverage (CEAC) mechanism.11 The CEAC mechanism relies upon high curvature areas and is thus most appropriate for micro and nanoscale features which exhibit proximity of locally high curvature areas as deposition proceeds due to area change affects. Void-free superconformal deposition is more difficult to repeatably achieve on larger, mesoscale features. Thus, a bottom-up deposition technique that relies upon the non-curvature dependent S-shaped negative differential resistance (S-NDR) between just two constituent additives to fill conductively seeded features is desirable.The issue of scalability is of significant interest after developing an electrodeposition process at the die level. While this two-additive system has been successfully implemented using potentiostatic control, industrial full wafer plating tools rely exclusively on galvanostatic control as they are not equipped with reference electrodes. In addition, they combine wafer rotation and forced fluid flow to maintain a controlled convective contribution across the wafer. So, to demonstrate scalability of this two-additive chemistry, the effect of the field surface area, feature geometry, and sample rotation rate on the deposition profile at a given applied potential or current is investigated. Altering the feature quantity and field area for a given deposition experiment can provide a means to estimate the effective current density required to fill features at the same rate across different sample sizes. By altering the sample rotation rate in the otherwise quiescent electrolyte, the impact of the transport phenomena of the constituent surfactant and halide additives are assessed. Cross-sectional images along with computed tomography (CT) produced images are produced to obtain Cu fill profiles across features arrays to demonstrate TSV uniformity. 1. P. Moffat and D. Josell, J. Electrochem. Soc., 159, D208 (2012).2. A. Menk et al., J. Electrochem. Soc. 166, D3066-D3071 (2018).3. Josell, M. E. Williams, S. Ambrozik, C. Zhang, T. P. Moffat, J. Electrochem. Soc. 166, D487-D495 (2019).4. Josell, M. Silva, T. P. Moffat, ECS Trans. 75, 25-30 (2016).5. Josell, T. P. Moffat, J. Electrochem. Soc. 166, D3022-D3034 (2018).6. Josell, T. P. Moffat, ECS Trans. 75, 19-24 (2016).7. Josell, T. P. Moffat, J. Electrochem. Soc. 162, D129-D135 (2015).8. Josell, T. P. Moffat, J. Electrochem. Soc. 160, D3035-D3039 (2013).9. Josell, L. A. Menk, A. E. Hollowell, M. Blain, T. P. Moffat, J. Electrochem. Soc. 166, D3254-D3258 (2019).10. C. Andricacos, C. Uzoh, J. O. Dukovic, J. Horkans, and H. Deligianni, IBM J. Res. Dev., 42, 567 (1998).11. P. Moffat, D. Wheeler, M. Edelstein, and D. Josell, IBM J. Res. Dev., 49, 19 (2005). Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA-0003525.

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Red blood cells (RBC) have been shown to exhibit stable submicrometric lipid domains enriched in cholesterol (chol), sphingomyelin (SM), phosphatidylcholine (PC) or ganglioside GM1, which represent the four main lipid classes of their outer plasma membrane leaflet. However, whether those lipid domains co-exist at the RBC surface or are spatially related and whether and how they are subjected to reorganization upon RBC deformation are not known. Using fluorescence and/or confocal microscopy and well-validated probes, we compared these four lipid-enriched domains for their abundance, curvature association, lipid order, temperature dependence, spatial dissociation and sensitivity to RBC mechanical stimulation. Our data suggest that three populations of lipid domains with decreasing abundance coexist at the RBC surface: (i) chol-enriched ones, associated with RBC high curvature areas; (ii) GM1/PC/chol-enriched ones, present in low curvature areas; and (iii) SM/PC/chol-enriched ones, also found in low curvature areas. Whereas chol-enriched domains gather in increased curvature areas upon RBC deformation, low curvature-associated lipid domains increase in abundance either upon calcium influx during RBC deformation (GM1/PC/chol-enriched domains) or upon secondary calcium efflux during RBC shape restoration (SM/PC/chol-enriched domains). Hence, abrogation of these two domain populations is accompanied by a strong impairment of the intracellular calcium balance. Lipid domains could contribute to calcium influx and efflux by controlling the membrane distribution and/or the activity of the mechano-activated ion channel Piezo1 and the calcium pump PMCA. We currently investigate whether this contribution results from lipid domain biophysical properties.

An Adaptive Moving Mesh Method for Forced Curve Shortening Flow.

We propose a novel adaptive moving mesh method for the numerical solution of a forced curve shortening geometric evolution equation. Control of the mesh quality is obtained using a tangential mesh velocity derived from a mesh equidistribution principle, where a positive adaptivity measure or monitor function is approximately equidistributed along the evolving curve. Central finite differences are used to discretize in space the governing evolution equation for the position vector, and a second-order implicit scheme is used for the temporal integration. Simulations are presented indicating the generation of meshes which resolve areas of high curvature and are of second-order accuracy. Furthermore, the new method delivers improved solution accuracy compared to the use of uniform arc-length meshes.

Characterization of Endothelial Cilia Distribution During Cerebral-Vascular Development in Zebrafish ( Danio rerio).

Objective- Endothelial cells (ECs) sense and respond to flow-induced mechanical stress, in part, via microtubule-based projections called primary cilia. However, many critical steps during vascular morphogenesis occur independent of flow. The involvement of cilia in regulating these stages of cranial vascular morphogenesis is poorly understood because cilia have not been visualized in primary head vessels. The objective of this study was to investigate involvement of cilia in regulating the early stages of cranial vascular morphogenesis. Approach and Results- Using high-resolution imaging of the Tg(kdrl:mCherry-CAAX) y171 ;(bactin::Arl13b:GFP) zebrafish line, we showed that cilia are enriched in the earliest formed cranial vessels that assemble via vasculogenesis and in angiogenic hindbrain capillaries. Cilia were more prevalent around the boundaries of putative intravascular spaces in primary and angiogenic vessels. Loss of cardiac contractility and blood flow, because of knockdown of cardiac troponin T type 2a ( tnnt2a) expression, did not affect the distribution of cilia in primary head vasculature. In later stages of development, cilia were detected in retinal vasculature, areas of high curvature, vessel bifurcation points, and during vessel anastomosis. Loss of genes crucial for cilia biogenesis ( ift172 and ift81) induced intracerebral hemorrhages in an EC-autonomous manner. Exposure to high shear stress induced premature cilia disassembly in brain ECs and was associated with intracerebral hemorrhages. Conclusions- Our study suggests a functional role for cilia in brain ECs, which is associated with the emergence and remodeling of the primary cranial vasculature. This cilia function is flow-independent, and cilia in ECs are required for cerebral-vascular stability.

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Background/Aims: Red blood cells (RBC) have been shown to exhibit stable submicrometric lipid domains enriched in cholesterol (chol), sphingomyelin (SM), phosphatidylcholine (PC) or ganglioside GM1, which represent the four main lipid classes of their outer plasma membrane leaflet. However, whether those lipid domains co-exist at the RBC surface or are spatially related and whether and how they are subjected to reorganization upon RBC deformation are not known. Methods: Using fluorescence and/or confocal microscopy and well-validated probes, we compared these four lipid-enriched domains for their abundance, curvature association, lipid order, temperature dependence, spatial dissociation and sensitivity to RBC mechanical stimulation. Results: Our data suggest that three populations of lipid domains with decreasing abundance coexist at the RBC surface: (i) chol-enriched ones, associated with RBC high curvature areas; (ii) GM1/PC/chol-enriched ones, present in low curvature areas; and (iii) SM/PC/chol-enriched ones, also found in low curvature areas. Whereas chol-enriched domains gather in increased curvature areas upon RBC deformation, low curvature-associated lipid domains increase in abundance either upon calcium influx during RBC deformation (GM1/PC/chol-enriched domains) or upon secondary calcium efflux during RBC shape restoration (SM/PC/chol-enriched domains). Hence, abrogation of these two domain populations is accompanied by a strong impairment of the intracellular calcium balance. Conclusion: Lipid domains could contribute to calcium influx and efflux by controlling the membrane distribution and/or the activity of the mechano-activated ion channel Piezo1 and the calcium pump PMCA. Whether this results from lipid domain biophysical properties, the strength of their anchorage to the underlying cytoskeleton and/or their correspondence with inner plasma membrane leaflet lipids remains to be demonstrated.