scholarly journals Macro-scale phenomena of arterial coupled cells: a massively parallel simulation

2011 ◽  
Vol 9 (70) ◽  
pp. 972-987 ◽  
Author(s):  
Mohsin Ahmed Shaikh ◽  
David J. N. Wall ◽  
Tim David

Impaired mass transfer characteristics of blood-borne vasoactive species such as adenosine triphosphate in regions such as an arterial bifurcation have been hypothesized as a prospective mechanism in the aetiology of atherosclerotic lesions. Arterial endothelial cells (ECs) and smooth muscle cells (SMCs) respond differentially to altered local haemodynamics and produce coordinated macro-scale responses via intercellular communication. Using a computationally designed arterial segment comprising large populations of mathematically modelled coupled ECs and SMCs, we investigate their response to spatial gradients of blood-borne agonist concentrations and the effect of micro-scale-driven perturbation on the macro-scale. Altering homocellular (between same cell type) and heterocellular (between different cell types) intercellular coupling, we simulated four cases of normal and pathological arterial segments experiencing an identical gradient in the concentration of the agonist. Results show that the heterocellular calcium (Ca 2+ ) coupling between ECs and SMCs is important in eliciting a rapid response when the vessel segment is stimulated by the agonist gradient. In the absence of heterocellular coupling, homocellular Ca 2+  coupling between SMCs is necessary for propagation of Ca 2+  waves from downstream to upstream cells axially. Desynchronized intracellular Ca 2+  oscillations in coupled SMCs are mandatory for this propagation. Upon decoupling the heterocellular membrane potential, the arterial segment looses the inhibitory effect of ECs on the Ca 2+  dynamics of the underlying SMCs. The full system comprises hundreds of thousands of coupled nonlinear ordinary differential equations simulated on the massively parallel Blue Gene architecture. The use of massively parallel computational architectures shows the capability of this approach to address macro-scale phenomena driven by elementary micro-scale components of the system.

Author(s):  
William G. Zhao ◽  
Gary L. Solbrekken ◽  
Steven F. Mullen ◽  
James D. Benson ◽  
Xu Han ◽  
...  

Cryopreservation is an effective way to store biological materials for an extended period of time. The process of freezing biological materials is rather traumatic, however, due to the water phase change that takes place. Successful cooling procedures have been developed for a limited number of cell types primarily through a large amount of experimentation. Fundamental cryobiological studies of cellular heat and mass transfer are currently under way in an attempt to develop an accurate model that will reduce the need for many costly experiments. The purpose of this paper is to describe the development of a tool that will allow more accurate measurements of the phase change temperature for a single cell (∼100 μm diameter) as it freezes. The resulting data will be used to improve the fundamental cryopreservation model. A proof-of-concept micro-scale DSC (μDSC) is designed and built using 250 μm × 250 μm × 500 μm thermoelectric elements. The elements are connected electrically in series to one another with metal electrodes that double as the sample and reference pans. The advantage of this configuration is that Peltier heating and cooling of the sample each have the same time constant, in contrast with macro-scale DSC machines. Thermocouples with 25 μm beads are attached to the pans providing the local temperature of the sample used for feedback control. The feedback temperature is used as the control signal for the power supply which supplies electric current to the thermoelectric structure described above. Initial experiments on the prototype μDSC indicate that the phase change of a single swine oocyte with a diameter of about 100 μm can be detected.


Author(s):  
Feng Li ◽  
Gulnigar Ablat ◽  
Siqi Zhou ◽  
Yixin Liu ◽  
Yufeng Bi ◽  
...  

AbstractIn ice and snow weather, the surface texture characteristics of asphalt pavement change, which will significantly affect the skid resistance performance of asphalt pavement. In this study, five asphalt mixture types of AC-5, AC-13, AC-16, SMA-13, SMA-16 were prepared under three conditions of the original state, ice and snow. In this paper, a 2D-wavelet transform approach is proposed to characterize the micro and macro texture of pavement. The Normalized Energy (NE) is proposed to describe the pavement texture quantitatively. Compared with the mean texture depth (MTD), NE has the advantages of full coverage, full automation and wide analytical scale. The results show that snow increases the micro-scale texture because of its fluffiness, while the formation of the ice sheets on the surface reduces the micro-scale texture. The filling effect of snow and ice reduces the macro-scale texture of the pavement surface. In a follow-up study, the 2D-wavelet transform approach can be applied to improve the intelligent driving braking system, which can provide pavement texture information for the safe braking strategy of driverless vehicles.


1993 ◽  
Vol 296 (2) ◽  
pp. 309-312 ◽  
Author(s):  
M F Rossier ◽  
C P Python ◽  
M M Burnay ◽  
W Schlegel ◽  
M B Vallotton ◽  
...  

Thapsigargin, an inhibitor of the microsomal Ca2+ pumps, has been extensively used to study the intracellular Ca2+ pool participating in the generation of the agonist-induced Ca2+ signal in various cell types. A dual effect of this agent was observed in bovine adrenal zona glomerulosa cells. At nanomolar concentrations, thapsigargin stimulated a sustained Ca2+ influx, probably resulting from Ca(2+)-store depletion. In contrast, when added at micromolar concentrations, thapsigargin prevented the rise in cytosolic free Ca2+ concentration ([Ca2+]c) induced by K+. This inhibitory effect of thapsigargin on voltage-activated Ca2+ channels was confirmed by measuring Ba2+ currents by the patch-clamp technique. Both low-threshold (T-type) and high-threshold (L-type) Ca2+ channels were affected by micromolar concentrations of thapsigargin. Analysis of the current-voltage relationship for T-type channels revealed that thapsigargin did not modify the sensitivity of these channels to the voltage, but decreased the maximal current flowing through the channels. In conclusion, thapsigargin appears to exert a dual effect on adrenal glomerulosa cells. At lower concentrations, this agent induces a sustained Ca2+ entry, whereas at higher concentrations it decreases [Ca2+]c by blocking voltage-activated Ca2+ channels.


2006 ◽  
Vol 12 (4) ◽  
pp. 461-485 ◽  
Author(s):  
Keisuke Suzuki ◽  
Takashi Ikegami

We study a system of self-replicating loops in which interaction rules between individuals allow competition that leads to the formation of a hypercycle-like network. The main feature of the model is the multiple layers of interaction between loops, which lead to both global spatial patterns and local replication. The network of loops manifests itself as a spiral structure from which new kinds of self-replicating loops emerge at the boundaries between different species. In these regions, larger and more complex self-replicating loops live for longer periods of time, managing to self-replicate in spite of their slower replication. Of particular interest is how micro-scale interactions between replicators lead to macro-scale spatial pattern formation, and how these macro-scale patterns in turn perturb the micro-scale replication dynamics.


1989 ◽  
Vol 262 (1) ◽  
pp. 83-89 ◽  
Author(s):  
K J Föhr ◽  
J Scott ◽  
G Ahnert-Hilger ◽  
M Gratzl

The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ compartment of endocrine cells was studied with alpha-toxin- and digitonin-permeabilized rat insulinoma (RINA2) and rat pheochromocytoma (PC12) cells. The Ca2+ uptake was ATP-dependent, and submicromolar concentrations of IP3 specifically released the stored Ca2+. Half-maximal Ca2+ release was observed with 0.25-0.5 mumol of IP3/l, and the amount of Ca2+ released due to IP3 could be enhanced by additional loading of the Ca2+ compartment. Consecutive additions of the same concentration of IP3 for 1-2 h always released the same amount of Ca2+ without desensitization, providing an ideal basis to further characterize the IP3-induced Ca2+ release. Here we describe for the first time a reversible inhibitory effect of decavanadate on the IP3-induced Ca2+ release. Among the vanadium species tested (decavanadate, oligovanadate and monovanadate), only decavanadate was inhibitory, with a half-maximal effect at 5 mumol/l in both cell types. The effect of decavanadate could be overcome by increasing the amount of sequestered Ca2+ or added IP3. Decavanadate did not affect the ATP-driven Ca2+ uptake but oligovanadate was inhibitory on Ca2+ uptake. p-Hydroxymercuribenzoate (pHMB) at concentrations between 10 and 30 mumol/l also inhibited the Ca2+ release due to IP3. Thiol compounds such as dithiothreitol (DTT; 1 mmol/l) added before pHMB removed all its inhibitory effect on the IP3-induced Ca2+ release, whereas the inhibition caused by decavanadate was unaffected by DTT. Thus, the decavanadate-dependent inhibition functions by a distinctly different mechanism than pHMB and could serve as a specific tool to analyse various aspects of the IP3-induced Ca2+ release within endocrine cells.


2008 ◽  
Vol 294 (4) ◽  
pp. C966-C976 ◽  
Author(s):  
Sunwoo Lee ◽  
Joon-Chul Kim ◽  
Yuhua Li ◽  
Min-Jeong Son ◽  
Sun-Hee Woo

This study examines whether fluid pressure (FP) modulates the L-type Ca2+ channel in cardiomyocytes and investigates the underlying cellular mechanism(s) involved. A flow of pressurized (∼16 dyn/cm2) fluid, identical to that bathing the myocytes, was applied onto single rat ventricular myocytes using a microperfusion method. The Ca2+ current ( ICa) and cytosolic Ca2+ signals were measured using a whole cell patch-clamp and confocal imaging, respectively. It was found that the FP reversibly suppressed ICa (by 25%) without altering the current-voltage relationships, and it accelerated the inactivation of ICa. The level of ICa suppression by FP depended on the level and duration of pressure. The Ba2+ current through the Ca2+ channel was only slightly decreased by the FP (5%), suggesting an indirect inhibition of the Ca2+ channel during FP stimulation. The cytosolic Ca2+ transients and the basal Ca2+ in field-stimulated ventricular myocytes were significantly increased by the FP. The effects of the FP on the ICa and on the Ca2+ transient were resistant to the stretch-activated channel inhibitors, GsMTx-4 and streptomycin. Dialysis of myocytes with high concentrations of BAPTA, the Ca2+ buffer, eliminated the FP-induced acceleration of ICa inactivation and reduced the inhibitory effect of the FP on ICa by ≈80%. Ryanodine and thapsigargin, abolishing sarcoplasmic reticulum Ca2+ release, eliminated the accelerating effect of FP on the ICa inactivation, and they reduced the inhibitory effect of FP on the ICa. These results suggest that the fluid pressure indirectly suppresses the Ca2+ channel by enhancing the Ca2+-induced intracellular Ca2+ release in rat ventricular myocytes.


2018 ◽  
Vol 115 (4) ◽  
pp. 413
Author(s):  
Nida Naveed

This study, on a micro-scale, of the WEDM cut surfaces of specimens to which the contour method of residual stress measurement is being applied provides detailed information about the effects of the cutting process on the surface quality. This is defined by a combination of several parameters: variation in surface contour profile, sub-surface damage and surface texture. Measurements were taken at the start, the middle and at the end of the cut. This study shows that during WEDM cutting, a thin layer, extending to a depth of a few micrometres below the surface of the cut, is transformed. This layer is known as the recast layer. Using controlled-depth etching and X-ray diffraction, it is shown that this induces an additional tensile residual stress, parallel to the plane of the cut surface. The WEDM cut surface and sub-surface characteristics are also shown to vary along the length of the cut. Moreover, these micro-scale changes were compared with macro-scale residual stress results and provides an indication of the point at which the changes occurred by cutting process can be significantly relative to the macro-scale residual stress in a specimen.


1999 ◽  
Vol 1 (1) ◽  
pp. 11-19 ◽  
Author(s):  
B. Z. XUE ◽  
W. O. WILKISON ◽  
R. L. MYNATT ◽  
N. MOUSTAID ◽  
M. GOLDMAN ◽  
...  

Xue, B. Z., W. O. Wilkison, R. L. Mynatt, N. Moustaid, M. Goldman, and M. B. Zemel. The agouti gene product stimulates pancreatic β-cell Ca2+ signaling and insulin release. Physiol. Genomics 1: 11-19, 1999.—Ubiquitous expression of the mouse agouti gene results in obesity and hyperinsulinemia. Human agouti is expressed in adipose tissue, and we found recombinant agouti protein to stimulate lipogenesis in adipocytes in a Ca2+-dependent fashion. However, adipocyte-specific agouti transgenic mice only became obese in the presence of hyperinsulinemia. Because intracellular Ca2+ concentration ([Ca2+]i) is a primary signal for insulin release, and we have shown agouti protein to increase [Ca2+]i in several cell types, we examined the effects of agouti on [Ca2+]i and insulin release. We demonstrated the expression of agouti in human pancreas and generated recombinant agouti to study its effects on Ca2+ signaling and insulin release. Agouti (100 nM) stimulated Ca2+ influx, [Ca2+]i increase, and a marked stimulation of insulin release in two β-cell lines (RIN-5F and HIT-T15; P < 0.05). Agouti exerted comparable effects in isolated human pancreatic islets and β-cells, with a 5-fold increase in Ca2+ influx ( P < 0.001) and a 2.2-fold increase in insulin release ( P < 0.01). These data suggest a potential role for agouti in the development of hyperinsulinemia in humans.


2013 ◽  
Vol 114 (5) ◽  
pp. 665-674
Author(s):  
Chengju Tian ◽  
Caronda J. Moore ◽  
Puttappa Dodmane ◽  
Chun Hong Shao ◽  
Debra J. Romberger ◽  
...  

Individuals working in commercial hog confinement facilities have elevated incidences of headaches, depression, nausea, skeletal muscle weakness, fatigue, gastrointestinal disorders, and cardiovascular diseases, and the molecular mechanisms for these nonrespiratory ailments remain incompletely undefined. A common element underlying these diverse pathophysiologies is perturbation of intracellular Ca2+ homeostasis. This study assessed whether the dust generated inside hog confinement facilities contains compounds that alter Ca2+ mobilization via ryanodine receptors (RyRs), key intracellular channels responsible for mobilizing Ca2+ from internal stores to elicit an array of physiologic functions. Hog barn dust (HBD) was extracted with phosphate-buffered saline, sterile-filtered (0.22 μm), and size-separated using Sephadex G-100 resin. Fractions (F) 1 through 9 (Mw >10,000 Da) had no measurable effects on RyR isoforms. However, F10 through F17, which contained compounds of Mw ≤2,000 Da, modulated the [3H]ryanodine binding to RyR1, RyR2, and RyR3 in a biphasic (Gaussian) manner. The Ki values for F13, the most potent fraction, were 3.8 ± 0.2 μg/ml for RyR1, 0.2 ± 0.01 μg/ml and 19.1 ± 2.8 μg/ml for RyR2 (two binding sites), and 44.9 ± 2.8 μg/ml and 501.6 ± 9.2 μg/ml for RyR3 (two binding sites). In lipid bilayer assays, F13 dose-dependently decreased the open probabilities of RyR1, RyR2, and RyR3. Pretreating differentiated mouse skeletal myotubes (C2C12 cells) with F13 blunted the amplitudes of ryanodine- and K+-induced Ca2+ transients. Because RyRs are present in many cell types, impairment in Ca2+ mobilization from internal stores via these channels is a possible mechanism by which HBD may trigger these seemingly unrelated pathophysiologies.


Lubricants ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 78 ◽  
Author(s):  
Gregory de Boer ◽  
Andreas Almqvist

A two-scale method for modelling the Elastohydrodynamic Lubrication (EHL) of tilted-pad bearings is derived and a range of solutions are presented. The method is developed from previous publications and is based on the Heterogeneous Multiscale Methods (HMM). It facilitates, by means of homogenization, incorporating the effects of surface topography in the analysis of tilted-pad bearings. New to this article is the investigation of three-dimensional bearings, including the effects of both ideal and real surface topographies, micro-cavitation, and the metamodeling procedure used in coupling the problem scales. Solutions for smooth bearing surfaces, and under pure hydrodynamic operating conditions, obtained with the present two-scale EHL model, demonstrate equivalence to those obtained from well-established homogenization methods. Solutions obtained for elastohydrodynamic operating conditions, show a dependency of the solution to the pad thickness and load capacity of the bearing. More precisely, the response for the real surface topography was found to be stiffer in comparison to the ideal. Micro-scale results demonstrate periodicity of the flow and surface topography and this is consistent with the requirements of the HMM. The means of selecting micro-scale simulations based on intermediate macro-scale solutions, in the metamodeling approach, was developed for larger dimensionality and subsequent calibration. An analysis of the present metamodeling approach indicates improved performance in comparison to previous studies.


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