Journal articles on the topic 'Oscillatory flow stimulation'
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1
Zhang, Xiao, Yan Gao, and Bo Huo. "Finite Element Analysis on Wall Fluid Shear Stress on Cells under Oscillatory Flow." Applied Sciences 11, no. 21 (October 26, 2021): 10021. http://dx.doi.org/10.3390/app112110021.
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During mechanical stimulation-induced bone remodeling, interstitial fluid around microcracks may produce a flow field with gradient fluid shear stress (FSS). Osteoclast precursors can sense this gradient FSS and migrate toward the low FSS region. However, the local distribution of wall FSS on bone cells under a flow field with globally gradient FSS remains unknown. In this study, finite element models of a modified plate flow chamber with cells were constructed. The effect of oscillatory flow with different FSS levels and cell spacings or frequencies on the distribution of local wall FSS around cells was simulated by using a fluid–solid coupling method. Results showed that the polarization of wall FSS distribution in a cell decreased with the increase in cell spacing. At a low FSS level, the frequency of oscillatory flow had a minimal effect on the wall FSS distribution. At a high FSS level, the increase in flow frequency enhanced the fluctuation of local wall FSS distribution on cells. These results provide a basis for future research on the flow-induced migration of osteoclast precursors and clarify the mechanism of mechanical stimulation-induced bone resorption.
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Gavriely, N., J. Solway, J. M. Drazen, A. S. Slutsky, R. Brown, S. H. Loring, and R. H. Ingram. "Radiographic visualization of airway wall movement during oscillatory flow in dogs." Journal of Applied Physiology 58, no. 2 (February 1, 1985): 645–52. http://dx.doi.org/10.1152/jappl.1985.58.2.645.
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It has been suggested that radial movement of the central airway walls during oscillatory flow might contribute to the increased frequency dependence of compliance seen in chronic obstructive pulmonary disease (COPD) (J. Appl. Physiol. 26: 670–677, 1969). Radial airway wall motion has also been invoked to explain the frequency-dependent decreases in the efficiency of gas exchange during low-volume high-frequency ventilation (HFV) in histamine-bronchoconstricted dogs and in patients with respiratory insufficiency. To test the possibility that airway wall motion increases with bronchoconstriction, we measured central airway diameters using cinebronchoradiography in anesthetized tracheostomized dogs during oscillatory HFV [50 and 100 ml tidal volume (VT) at frequencies (f) of 2, 6, and 12 Hz], under control conditions, during electrical stimulation of the vagi, and after exposure to histamine aerosol. Cineradiobronchograms from two dogs were evaluated quantitatively for tracheal diameter and for lengths and diameters of a number of major airways. Under control conditions, the diameter of the airways fluctuated 7–9% of the mean with VT of 50 ml and 9–18% with VT of 100 ml in the range of frequencies studied. Bronchoconstriction produced by aerosolized histamine increased radial airway wall movement to 10–47% with VT of 50 ml, and during vagal stimulation diameters changed 7–20% at VT of 50 ml. After histamine, the central airways displayed large diameter changes during HFV, whereas more peripheral airways were markedly constricted and did not change in diameter.
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Shivaram, Giridhar M., Chi Hyun Kim, Nikhil N. Batra, Wuchen Yang, Stephen E. Harris, and Christopher R. Jacobs. "Novel early response genes in osteoblasts exposed to dynamic fluid flow." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 368, no. 1912 (February 13, 2010): 605–16. http://dx.doi.org/10.1098/rsta.2009.0231.
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Cyclic mechanical loads applied to the skeleton from habitual physical activity result in increased bone formation. These loads lead to dynamic pressure gradients and oscillatory flow of bone interstitial fluid, which, in turn, exposes cells resident in the bony matrix to oscillatory fluid shear stress. Dynamic fluid flow has previously been shown to be a potent anabolic stimulus for cultured osteoblasts. In this study, we used cDNA microarrays to examine early phase, broad-spectrum gene expression in MC3T3-E1 osteoblasts in response to physical stimulation. RNA was harvested at 30 min and 1 h post-stimulation. RNA was used for microarray hybridization as well as subsequent reverse transcription polymerase chain reaction (RT-PCR) validation of expression levels for selected genes. Microarray results were analysed by both functional and expression profile clustering. We identified a small number of genes at both the 30 min and 1 h timepoints that were either upregulated or downregulated with flow compared to no-flow control by twofold or more. From the group of genes upregulated at 30 min, we selected nine for RT-PCR confirmation. All were found to be upregulated by at least twofold. We identify a novel set of early response genes potentially involved in mediating the anabolic response of MC3T3 osteoblasts to flow, and provide functional groupings of these genes that may shed light on the relevant mechanosensory pathways involved.
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Grudzińska, Ewa, Andrzej Lekstan, Ewelina Szliszka, and Zenon P. Czuba. "Cytokines Produced by Lymphocytes in the Incompetent Great Saphenous Vein." Mediators of Inflammation 2018 (June 14, 2018): 1–8. http://dx.doi.org/10.1155/2018/7161346.
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The pathogenesis of chronic venous disease (CVD) remains unclear, but lately inflammation is suggested to have an important role in its development. This study is aimed at assessing cytokines released by lymphocytes in patients with great saphenous vein (GSV) incompetence. In 34 patients exhibiting oscillatory flow (reflux) in GSV, blood was derived from the cubital vein and from the incompetent sapheno-femoral junction. In 12 healthy controls, blood was derived from the cubital vein. Lymphocyte culture with and without stimulation by phytohemagglutinin (PHA) was performed. Interleukins (IL) 1β, 2, 4, 10, 12 (p70), and 17A; interleukin 1 receptor α (IL-1ra); tumor necrosis factor-α (TNF-α); interferon-gamma (IFN-γ); and RANTES were assessed in culture supernatants by the Bio-Plex assay. In both stimulated and unstimulated samples, in the examined group, IL-1β and IFN-γ had higher concentrations and RANTES had lower concentrations when compared to those in the control group. In the examined group, IL-4 and IL-17A had higher concentrations without stimulation and TNF-α had higher concentrations with stimulation. The GSV samples had higher IL-2, IL-4, IL-12 (p70), and IFN-γ concentrations without stimulation and lower IL-2 and TNF-α concentrations with stimulation when compared to those of the upper limb in the examined group. These observations indicate that the oscillatory flow present in incompetent veins causes changes in the cytokine production by lymphocytes, promoting a proinflammatory profile. However, the relations between immunological cells, cytokines, and the endothelium require more insight.
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Xing, Yanghui, Liang Song, Yingying Zhang, Tengyu Zhang, Jian Li, and Chunjing Tao. "Purinergic Signaling Mediates PTH and Fluid Flow-Induced Osteoblast Proliferation." BioMed Research International 2021 (January 27, 2021): 1–8. http://dx.doi.org/10.1155/2021/6674570.
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Both parathyroid hormone (PTH) and mechanical signals are able to regulate bone growth and regeneration. They also can work synergistically to regulate osteoblast proliferation, but little is known about the mechanisms how PTH and mechanical signals interact with each other during this process. In this study, we investigated responses of MC3T3-E1 osteoblasts to PTH and oscillatory fluid flow. We found that osteoblasts are more sensitive to mechanical signals in the presence of PTH according to ERK1/2 phosphorylation, ATP release, CREB phosphorylation, and cell proliferation. PTH may also reduce the osteoblast refractory period after desensitization due to mechanical signals. We further found that the synergistic responses of osteoblasts to fluid flow or ATP with PTH had similar patterns, suggesting that synergy between fluid flow and PTH may be through the ATP pathway. After we inhibited ATP effects using apyrase in osteoblasts, their synergistic responses to mechanical stimulation and PTH were also inhibited. Additionally, knocking down P2Y2 purinergic receptors can significantly attenuate osteoblast synergistic responses to mechanical stimulation and PTH in terms of ERK1/2 phosphorylation, CREB phosphorylation, and cell proliferation. Thus, our results suggest that PTH enhances mechanosensitivity of osteoblasts via a mechanism involving ATP and P2Y2 purinergic receptors.
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Stauss, H. M., P. B. Persson, A. K. Johnson, and K. C. Kregel. "Frequency-response characteristics of autonomic nervous system function in conscious rats." American Journal of Physiology-Heart and Circulatory Physiology 273, no. 2 (August 1, 1997): H786—H795. http://dx.doi.org/10.1152/ajpheart.1997.273.2.h786.
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To characterize the efferent pathway from the hypothalamic paraventricular nucleus (PVN) to peripheral autonomic neurons and finally to selected effector organs, we stimulated the PVN in 10 conscious rats at frequencies ranging from 0.05 to 2.0 Hz. Simultaneously, blood pressure, heart rate, splanchnic sympathetic nerve activity, and mesenteric artery blood flow were measured. The sinus node of the heart responded to PVN stimulation via the parasympathetic pathway (during beta 1-adrenergic blockade) up to a stimulation frequency of 2.0 Hz, whereas the sympathetically mediated response (during muscarinic blockade) was limited to stimulation frequencies < 0.5 Hz. The splanchnic nerve responded to PVN stimulation with synchronous discharges up to stimulation frequencies of 2.0 Hz, whereas the oscillatory component of the vasoconstrictor response of the mesenteric artery was negligible beyond stimulation frequencies of 1.0 Hz. We conclude that sympathetic transmission to the heart is at least four times slower than parasympathetic transmission. In addition, the time-limiting step in sympathetic transmission from the hypothalamus to vascular smooth muscle contraction and pacemaker activity of the sinus node may be located at the site of synaptic transmission to the adrenergic receptors.
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Grudzińska, Ewa, Sławomir Grzegorczyn, and Zenon P. Czuba. "Chemokines and Growth Factors Produced by Lymphocytes in the Incompetent Great Saphenous Vein." Mediators of Inflammation 2019 (January 10, 2019): 1–10. http://dx.doi.org/10.1155/2019/7057303.
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The role of cytokines in the pathogenesis of chronic venous disease (CVD) remains obscure. It has been postulated that oscillatory flow present in incompetent veins causes proinflammatory changes. Our earlier study confirmed this hypothesis. This study is aimed at assessing chemokines and growth factors (GFs) released by lymphocytes in patients with great saphenous vein (GSV) incompetence. In 34 patients exhibiting reflux in GSV, blood was derived from the cubital vein and from the incompetent saphenofemoral junction. In 12 healthy controls, blood was derived from the cubital vein. Lymphocyte culture with and without stimulation by phytohemagglutinin (PHA) was performed. Eotaxin, interleukin 8 (IL-8), macrophage inflammatory protein 1 A and 1B (MIP-1A and MIP-1B), interferon gamma-induced protein (IP-10), monocyte chemoattractant protein-1 (MCP-1), interleukin 5 (IL-5), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor-BB (PDGF-BB), and vascular endothelial growth factor (VEGF) were assessed in culture supernatants by a Bio-Plex assay. Higher concentrations of eotaxin and G-CSF were revealed in the incompetent GSV, compared with the concentrations in the patients’ upper limbs. The concentrations of MIP-1A and MIP-1B were higher in the CVD group while the concentration of VEGF was lower. In the stimulated cultures, the concentration of G-CSF proved higher in the incompetent GSV, as compared with the patients’ upper limbs. Between the groups, the concentration of eotaxin was higher in the CVD group, while the IL-5 and MCP-1 concentrations were lower. IL-8, IP-10, FGF, GM-CSF, and PDGF-BB did not reveal any significant differences in concentrations between the samples. These observations suggest that the concentrations of chemokines and GFs are different in the blood of CVD patients. The oscillatory flow present in incompetent veins may play a role in these changes. However, the role of cytokines in CVD requires further study.
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Sherwood, Joseph M., W. Daniel Stamer, and Darryl R. Overby. "A model of the oscillatory mechanical forces in the conventional outflow pathway." Journal of The Royal Society Interface 16, no. 150 (January 2019): 20180652. http://dx.doi.org/10.1098/rsif.2018.0652.
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Intraocular pressure is regulated by mechanosensitive cells within the conventional outflow pathway, the primary route of aqueous humour drainage from the eye. However, the characteristics of the forces acting on those cells are poorly understood. We develop a model that describes flow through the conventional outflow pathway, including the trabecular meshwork (TM) and Schlemm’s canal (SC). Accounting for the ocular pulse, we estimate the time-varying shear stress on SC endothelium and strain on the TM. We consider a range of outflow resistances spanning normotensive to hypertensive conditions. Over this range, the SC shear stress increases significantly and becomes highly oscillatory. TM strain also increases, but with negligible oscillations. Interestingly, TM strain responds more to changes in outflow resistance around physiological values, while SC shear stress responds more to elevated levels of resistance. A modest increase in TM stiffness, as observed in glaucoma, suppresses TM strain and practically eliminates the influence of outflow resistance on SC shear stress. As SC and TM cells respond to mechanical stimulation by secreting factors that modulate outflow resistance, our model provides insight regarding the potential role of SC shear and TM strain as mechanosensory cues for homeostatic regulation of outflow resistance and hence intraocular pressure.
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Malcolm, Brenda R., John J. Foxe, John S. Butler, Sophie Molholm, and Pierfilippo De Sanctis. "Cognitive load reduces the effects of optic flow on gait and electrocortical dynamics during treadmill walking." Journal of Neurophysiology 120, no. 5 (November 1, 2018): 2246–59. http://dx.doi.org/10.1152/jn.00079.2018.
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During navigation of complex environments, the brain must continuously adapt to both external demands, such as fluctuating sensory inputs, and internal demands, such as engagement in a cognitively demanding task. Previous studies have demonstrated changes in behavior and gait with increased sensory and cognitive load, but the underlying cortical mechanisms remain largely unknown. In the present study, in a mobile brain/body imaging (MoBI) approach, 16 young adults walked on a treadmill with high-density EEG while 3-dimensional (3D) motion capture tracked kinematics of the head and feet. Visual load was manipulated with the presentation of optic flow with and without continuous mediolateral perturbations. The effects of cognitive load were assessed by the performance of a go/no-go task on half of the blocks. During increased sensory load, participants walked with shorter and wider strides, which may indicate a more restrained pattern of gait. Interestingly, cognitive task engagement attenuated these effects of sensory load on gait. Using an independent component analysis and dipole-fitting approach, we found that cautious gait was accompanied by neuro-oscillatory modulations localized to frontal (supplementary motor area, anterior cingulate cortex) and parietal (inferior parietal lobule, precuneus) areas. Our results show suppression in alpha/mu (8–12 Hz) and beta (13–30 Hz) rhythms, suggesting enhanced activation of these regions with unreliable sensory inputs. These findings provide insight into the neural correlates of gait adaptation and may be particularly relevant to older adults who are less able to adjust to ongoing cognitive and sensory demands while walking. NEW & NOTEWORTHY The neural underpinnings of gait adaptation in humans are poorly understood. To this end, we recorded high-density EEG combined with three-dimensional body motion tracking as participants walked on a treadmill while exposed to full-field optic flow stimulation. Perturbed visual input led to a more cautious gait pattern with neuro-oscillatory modulations localized to premotor and parietal regions. Our findings show a possible brain-behavior link that might further our understanding of gait and mobility impairments.
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Bril, Ekaterina V., Elena M. Belova, Aleksey S. Sedov, Anna A. Gamaleya, Anna A. Poddubskaya, Natalia V. Fedorova, and Аleksey A. Tomskiy. "Current understanding of neurostimulation for Parkinson's disease." Annals of Clinical and Experimental Neurology 16, no. 2 (June 30, 2022): 89–99. http://dx.doi.org/10.54101/acen.2022.2.10.
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Specific mechanisms underlying the therapeutic effects of neurostimulation in Parkinson's disease remain a topic of discussion and intense study. Understanding these mechanisms can serve as the foundation for developing and selecting more effective parameters to relieve the symptoms of Parkinson's disease, maximize the advantages, and reduce the adverse effects and need for surgical intervention. The article discusses existing models of motor control in the basal ganglia in healthy individuals and in PD from the point of view of neuromodulation (changes in the impulse flow model, oscillatory model), as well as the current understanding of the mechanisms of action of deep brain stimulation (DBS): the block depolarization hypothesis, neural interference hypothesis, synaptic depression hypothesis, synaptic modulation hypothesis, and the DBS astrocytes hypothesis. Factors such as DBS location and neurostimulation parameters, affecting the clinical outcome, are considered in detail. The neuroprotective effect of DBS is also touched on.
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Aires, Ana, António Andrade, Elsa Azevedo, Filipa Gomes, José Paulo Araújo, and Pedro Castro. "Neurovascular Coupling Impairment in Heart Failure with Reduction Ejection Fraction." Brain Sciences 10, no. 10 (October 7, 2020): 714. http://dx.doi.org/10.3390/brainsci10100714.
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The hemodynamic consequences of a persistent reduced ejection fraction and unknown cardiac output on the brain have not been thoroughly studied. We sought to explore the status of the mechanisms of cerebrovascular regulation in patients with heart failure with reduced (HFrEF) and recovered (HFrecEF) ejection fraction. We monitored cerebral blood flow velocity (CBFV) with transcranial Doppler and blood pressure. Cerebral autoregulation, assessed by transfer function from the spontaneous oscillations of blood pressure to CBFV and neurovascular coupling (NVC) with visual stimulation were compared between groups of HFrEF, HFrecEF and healthy controls. NVC was significantly impaired in HFrEF patients with reduced augmentation of CBFV during stimulation (overshoot systolic CBFV 19.11 ± 6.92 vs. 22.61 ± 7.78 vs. 27.92 ± 6.84, p = 0.04), slower upright of CBFV (rate time to overshoot: 1.19 ± 3.0 vs. 3.06 (4.30) vs. 2.90 ± 3.84, p = 0.02); p = 0.023) and reduced arterial oscillatory properties (natural frequency 0.17 ± 0.06 vs. 0.20 ± 0.09 vs. 0.24 ± 0.07, p = 0.03; attenuation 0.34 ± 0.24 vs. 0.48 ± 0.35 vs. 0.50 ± 0.23, p = 0.05). Cerebral autoregulation was preserved. The neurovascular unit of subjects with chronically reduced heart pumping capability is severely dysfunctional. Dynamic testing with transcranial Doppler could be useful in these patients, but whether it helps in predicting cognitive impairment must be addressed in future prospective studies.
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Cohen, Michael X., Nikolai Axmacher, Doris Lenartz, Christian E. Elger, Volker Sturm, and Thomas E. Schlaepfer. "Good Vibrations: Cross-frequency Coupling in the Human Nucleus Accumbens during Reward Processing." Journal of Cognitive Neuroscience 21, no. 5 (May 2009): 875–89. http://dx.doi.org/10.1162/jocn.2009.21062.
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The nucleus accumbens is critical for reward-guided learning and decision-making. It is thought to “gate” the flow of a diverse range of information (e.g., rewarding, aversive, and novel events) from limbic afferents to basal ganglia outputs. Gating and information encoding may be achieved via cross-frequency coupling, in which bursts of high-frequency activity occur preferentially during specific phases of slower oscillations. We examined whether the human nucleus accumbens engages such a mechanism by recording electrophysiological activity directly from the accumbens of human patients undergoing deep brain stimulation surgery. Oscillatory activity in the gamma (40–80 Hz) frequency range was synchronized with the phase of simultaneous alpha (8–12 Hz) waves. Further, losing and winning small amounts of money elicited relatively increased gamma oscillation power prior to and following alpha troughs, respectively. Gamma–alpha synchronization may reflect an electrophysiological gating mechanism in the human nucleus accumbens, and the phase differences in gamma–alpha coupling may reflect a reward information coding scheme similar to phase coding.
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Pastor, M. A., C. Vidaurre, M. A. Fernández-Seara, A. Villanueva, and K. J. Friston. "Frequency-Specific Coupling in the Cortico-Cerebellar Auditory System." Journal of Neurophysiology 100, no. 4 (October 2008): 1699–705. http://dx.doi.org/10.1152/jn.01156.2007.
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Induced oscillatory activity in the auditory cortex peaks at around 40 Hz in humans. Using regional cerebral blood flow and positron emission tomography we previously confirmed frequency-selective cortical responses to 40-Hz tones in auditory primary cortices and concomitant bilateral activation of the cerebellar hemispheres. In this study, using functional magnetic resonance imaging (fMRI) we estimated the influence of 40-Hz auditory stimulation on the coupling between auditory cortex and superior temporal sulcus (STS) and Crus II, using a dynamic causal model of the interactions between medial geniculate nuclei, auditory superior temporal gyrus (STG)/STS, and the cerebellar Crus II auditory region. Specifically, we tested the hypothesis that 40-Hz-selective responses in the cerebellar Crus II auditory region could be explained by frequency-specific enabling of interactions in the auditory cortico–cerebellar–thalamic loop. Our model comparison results suggest that input from auditory STG/STS to cerebellum is enhanced selectively at gamma-band frequencies around 40 Hz.
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Armengol, J., R. L. Jones, and E. G. King. "Collateral ventilation during high-frequency oscillation in dogs." Journal of Applied Physiology 58, no. 1 (January 1, 1985): 173–79. http://dx.doi.org/10.1152/jappl.1985.58.1.173.
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Mechanics of collateral channels during high-frequency oscillatory ventilation (HFOV) were assessed in eight anesthetized dogs, using a modification of Hilpert's technique. Base-line functional residual capacity was measured with a body plethysmograph, with inspiratory efforts induced by phrenic nerve stimulation. The resistance (Rcoll) and time constant (Tcoll) of collateral channels at five lung volumes were measured during HFOV and positive end-expiratory pressure (PEEP). Rcoll and Tcoll were significantly higher during HFOV (P less than 0.001); the differences did not correlate with resting lung volumes. The calculated static compliance of the wedged segment was similar during HFOV and PEEP (P greater than 0.005). Mean pressures measured in small airways during HFOV corresponded to the midline between the inflation and deflation limbs of the static pressure-volume curves, indicating similar pressure-volume characteristics of the respiratory system during HFOV and static conditions. We conclude that HFOV increases resistance to gas flow through collateral channels but that this pathway may still be important in gas exchange.
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Maki, L. W., and J. Keizer. "Analysis of possible mechanisms for in vitro oscillations of insulin secretion." American Journal of Physiology-Cell Physiology 268, no. 3 (March 1, 1995): C780—C791. http://dx.doi.org/10.1152/ajpcell.1995.268.3.c780.
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We explore possible kinetic mechanisms responsible for the oscillatory (pulsatile) secretion of insulin observed in vitro when pancreatic islets or islet-derived cells are perifused with glucose. Three primary processes are included: 1) glucose stimulation of insulin secretion, controlled by glucokinase; 2) uptake of glucose through GLUT transporters; and 3) glucose metabolism. Perifusion is approximated as a limiting case of a chemical flow reactor. Using experimentally determined rate laws for the three processes, we examine the effects of exogenous insulin as a phenomenological activator and inhibitor of secretion. The resulting differential equations support oscillations using either direct or indirect inhibition by insulin. The oscillations have many of the characteristics observed in vitro, although the indirect model is in better overall agreement with experiment. We conclude that the mechanisms explored here may help explain insulin oscillations for HIT cells, but not for islets, and predict that oscillations can be modulated by including insulin in the perifusion medium.
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Hanaguri, Junya, Harumasa Yokota, Akifumi Kushiyama, Sakura Kushiyama, Masahisa Watanabe, Satoru Yamagami, and Taiji Nagaoka. "The Effect of Sodium-Dependent Glucose Cotransporter 2 Inhibitor Tofogliflozin on Neurovascular Coupling in the Retina in Type 2 Diabetic Mice." International Journal of Molecular Sciences 23, no. 3 (January 25, 2022): 1362. http://dx.doi.org/10.3390/ijms23031362.
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We investigated the effect of tofogliflozin, a sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i), on retinal blood flow dysregulation, neural retinal dysfunction, and the impaired neurovascular coupling in type 2 diabetic mice. Tofogliflozin was added to mouse chow to deliver 5 mg/kg/day and 6-week-old mice were fed for 8 weeks. The longitudinal changes in the retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice that received tofogliflozin (n =6) or placebo (n = 6) from 8 to 14 weeks of age. We also evaluated glial activation and vascular endothelial growth factor (VEGF) expression by immunofluorescence. Tofogliflozin treatment caused a sustained decrease in blood glucose in db/db mice from 8 weeks of the treatment. In tofogliflozin-treated db/db mice, both responses improved from 8 to 14 weeks of age, compared with vehicle-treated diabetic mice. Subsequently, the electroretinography implicit time for the oscillatory potential was significantly improved in SGLT2i-treated db/db mice. The systemic tofogliflozin treatment prevented the activation of glial fibrillary acidic protein and VEGF protein expression, as detected by immunofluorescence. Our results suggest that glycemic control with tofogliflozin significantly improved the impaired retinal neurovascular coupling in type 2 diabetic mice with the inhibition of retinal glial activation.
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Theofilis, Panagiotis, Marios Sagris, Evangelos Oikonomou, Alexios S. Antonopoulos, Gerasimos Siasos, Costas Tsioufis, and Dimitris Tousoulis. "Inflammatory Mechanisms Contributing to Endothelial Dysfunction." Biomedicines 9, no. 7 (July 6, 2021): 781. http://dx.doi.org/10.3390/biomedicines9070781.
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Maintenance of endothelial cell integrity is an important component of human health and disease since the endothelium can perform various functions including regulation of vascular tone, control of hemostasis and thrombosis, cellular adhesion, smooth muscle cell proliferation, and vascular inflammation. Endothelial dysfunction is encompassed by complex pathophysiology that is based on endothelial nitric oxide synthase uncoupling and endothelial activation following stimulation from various inflammatory mediators (molecular patterns, oxidized lipoproteins, cytokines). The downstream signaling via nuclear factor-κB leads to overexpression of adhesion molecules, selectins, and chemokines that facilitate leukocyte adhesion, rolling, and transmigration to the subendothelial space. Moreover, oscillatory shear stress leads to pro-inflammatory endothelial activation with increased monocyte adhesion and endothelial cell apoptosis, an effect that is dependent on multiple pathways and flow-sensitive microRNA regulation. Moreover, the role of neutrophil extracellular traps and NLRP3 inflammasome as inflammatory mechanisms contributing to endothelial dysfunction has recently been unveiled and is under further investigation. Consequently, and following their activation, injured endothelial cells release inflammatory mediators and enter a pro-thrombotic state through activation of coagulation pathways, downregulation of thrombomodulin, and an increase in platelet adhesion and aggregation owing to the action of von-Willebrand factor, ultimately promoting atherosclerosis progression.
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DeFelice, Mialy M., Helen R. Clark, Jacob J. Hughey, Inbal Maayan, Takamasa Kudo, Miriam V. Gutschow, Markus W. Covert, and Sergi Regot. "NF-κB signaling dynamics is controlled by a dose-sensing autoregulatory loop." Science Signaling 12, no. 579 (April 30, 2019): eaau3568. http://dx.doi.org/10.1126/scisignal.aau3568.
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Over the last decade, multiple studies have shown that signaling proteins activated in different temporal patterns, such as oscillatory, transient, and sustained, can result in distinct gene expression patterns or cell fates. However, the molecular events that ensure appropriate stimulus- and dose-dependent dynamics are not often understood and are difficult to investigate. Here, we used single-cell analysis to dissect the mechanisms underlying the stimulus- and dose-encoding patterns in the innate immune signaling network. We found that Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling dynamics relied on a dose-dependent, autoinhibitory loop that rendered cells refractory to further stimulation. Using inducible gene expression and optogenetics to perturb the network at different levels, we identified IL-1R–associated kinase 1 (IRAK1) as the dose-sensing node responsible for limiting signal flow during the innate immune response. Although the kinase activity of IRAK1 was not required for signal propagation, it played a critical role in inhibiting the nucleocytoplasmic oscillations of the transcription factor NF-κB. Thus, protein activities that may be “dispensable” from a topological perspective can nevertheless be essential in shaping the dynamic response to the external environment.
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Jia, Mengping, Qinhan Li, Jieyu Guo, Weihao Shi, Lei Zhu, Yijun Huang, Yongbo Li, et al. "Deletion of BACH1 Attenuates Atherosclerosis by Reducing Endothelial Inflammation." Circulation Research 130, no. 7 (April 2022): 1038–55. http://dx.doi.org/10.1161/circresaha.121.319540.
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Background: The transcription factor BACH1 (BTB and CNC homology 1) suppressed endothelial cells (ECs) proliferation and migration and impaired angiogenesis in the ischemic hindlimbs of adult mice. However, the role and underlying mechanisms of BACH1 in atherosclerosis remain unclear. Methods: Mouse models of atherosclerosis in endothelial cell (EC)-specific-Bach1 knockout mice were used to study the role of BACH1 in the regulation of atherogenesis and the underlying mechanisms. Results: Genetic analyses revealed that coronary artery disease-associated risk variant rs2832227 was associated with BACH1 gene expression in carotid plaques from patients. BACH1 was upregulated in ECs of human and mouse atherosclerotic plaques. Endothelial Bach1 deficiency decreased turbulent blood flow- or western diet-induced atherosclerotic lesions, macrophage content in plaques, expression of endothelial adhesion molecules (ICAM1 [intercellular cell adhesion molecule-1] and VCAM1 [vascular cell adhesion molecule-1]), and reduced plasma TNF-α (tumor necrosis factor-α) and IL-1β levels in atherosclerotic mice. BACH1 deletion or knockdown inhibited monocyte–endothelial adhesion and reduced oscillatory shear stress or TNF-α-mediated induction of endothelial adhesion molecules and/or proinflammatory cytokines in mouse ECs, human umbilical vein ECs, and human aortic ECs. Mechanistic studies showed that upon oscillatory shear stress or TNF-α stimulation, BACH1 and YAP (yes-associated protein) were induced and translocated into the nucleus in ECs. BACH1 upregulated YAP expression by binding to the YAP promoter. BACH1 formed a complex with YAP inducing the transcription of adhesion molecules. YAP overexpression in ECs counteracted the antiatherosclerotic effect mediated by Bach1-deletion in mice. Rosuvastatin inhibited BACH1 expression by upregulating microRNA let-7a in ECs, and decreased Bach1 expression in the vascular endothelium of hyperlipidemic mice. BACH1 was colocalized with YAP, and the expression of BACH1 was positively correlated with YAP and proinflammatory genes, as well as adhesion molecules in human atherosclerotic plaques. Conclusions: These data identify BACH1 as a mechanosensor of hemodynamic stress and reveal that the BACH1-YAP transcriptional network is essential to vascular inflammation and atherogenesis. BACH1 shows potential as a novel therapeutic target in atherosclerosis.
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Price, N. S. C., and M. R. Ibbotson. "Pretectal Neurons Optimized for the Detection of Saccade-Like Movements of the Visual Image." Journal of Neurophysiology 85, no. 4 (April 1, 2001): 1512–21. http://dx.doi.org/10.1152/jn.2001.85.4.1512.
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The visual response properties of nondirectional wide-field sensitive neurons in the wallaby pretectum are described. These neurons are called scintillation detectors (SD-neurons) because they respond vigorously to rapid, high contrast visual changes in any part of their receptive fields. SD-neurons are most densely located within a 1- to 2-mm radius from the nucleus of the optic tract, interspersed with direction-selective retinal slip cells. Receptive fields are monocular and cover large areas of the contralateral visual field (30–120°). Response sizes are equal for motion in all directions, and spontaneous activities are similar for all orientations of static sine-wave gratings. Response magnitude increases near linearly with increasing stimulus diameter and contrast. The mean response latency for wide-field, high-contrast motion stimulation was 43.4 ± 9.4 ms (mean ± SD, n = 28). The optimum visual stimuli for SD-neurons are wide-field, low spatial frequency (<0.2 cpd) scenes moving at high velocities (75–500°/s). These properties match the visual input during saccades, indicating optimal sensitivity to rapid eye movements. Cells respond to brightness increments and decrements, suggesting inputs from on and off channels. Stimulation with high-speed, low spatial frequency gratings produces oscillatory responses at the input temporal frequency. Conversely, high spatial frequency gratings give oscillations predominantly at the second harmonic of the temporal frequency. Contrast reversing sine-wave gratings elicit transient, phase-independent responses. These responses match the properties of Y retinal ganglion cells, suggesting that they provide inputs to SD-neurons. We discuss the possible role of SD-neurons in suppressing ocular following during saccades and in the blink or saccade-locked modulation of lateral geniculate nucleus activity to control retino-cortical information flow.
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Stenner, Max-Philipp, Vladimir Litvak, Robb B. Rutledge, Tino Zaehle, Friedhelm C. Schmitt, Jürgen Voges, Hans-Jochen Heinze, and Raymond J. Dolan. "Cortical drive of low-frequency oscillations in the human nucleus accumbens during action selection." Journal of Neurophysiology 114, no. 1 (July 2015): 29–39. http://dx.doi.org/10.1152/jn.00988.2014.
Full textAbstract:
The nucleus accumbens is thought to contribute to action selection by integrating behaviorally relevant information from multiple regions, including prefrontal cortex. Studies in rodents suggest that information flow to the nucleus accumbens may be regulated via task-dependent oscillatory coupling between regions. During instrumental behavior, local field potentials (LFP) in the rat nucleus accumbens and prefrontal cortex are coupled at delta frequencies (Gruber AJ, Hussain RJ, O'Donnell P. PLoS One 4: e5062, 2009), possibly mediating suppression of afferent input from other areas and thereby supporting cortical control (Calhoon GG, O'Donnell P. Neuron 78: 181–190, 2013). In this report, we demonstrate low-frequency cortico-accumbens coupling in humans, both at rest and during a decision-making task. We recorded LFP from the nucleus accumbens in six epilepsy patients who underwent implantation of deep brain stimulation electrodes. All patients showed significant coherence and phase-synchronization between LFP and surface EEG at delta and low theta frequencies. Although the direction of this coupling as indexed by Granger causality varied between subjects in the resting-state data, all patients showed a cortical drive of the nucleus accumbens during action selection in a decision-making task. In three patients this was accompanied by a significant coherence increase over baseline. Our results suggest that low-frequency cortico-accumbens coupling represents a highly conserved regulatory mechanism for action selection.
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Neupane, Sujaya, Daniel Guitton, and Christopher C. Pack. "Coherent alpha oscillations link current and future receptive fields during saccades." Proceedings of the National Academy of Sciences 114, no. 29 (July 3, 2017): E5979—E5985. http://dx.doi.org/10.1073/pnas.1701672114.
Full textAbstract:
Oscillations are ubiquitous in the brain, and they can powerfully influence neural coding. In particular, when oscillations at distinct sites are coherent, they provide a means of gating the flow of neural signals between different cortical regions. Coherent oscillations also occur within individual brain regions, although the purpose of this coherence is not well understood. Here, we report that within a single brain region, coherent alpha oscillations link stimulus representations as they change in space and time. Specifically, in primate cortical area V4, alpha coherence links sites that encode the retinal location of a visual stimulus before and after a saccade. These coherence changes exhibit properties similar to those of receptive field remapping, a phenomenon in which individual neurons change their receptive fields according to the metrics of each saccade. In particular, alpha coherence, like remapping, is highly dependent on the saccade vector and the spatial arrangement of current and future receptive fields. Moreover, although visual stimulation plays a modulatory role, it is neither necessary nor sufficient to elicit alpha coherence. Indeed, a similar pattern of coherence is observed even when saccades are made in darkness. Together, these results show that the pattern of alpha coherence across the retinotopic map in V4 matches many of the properties of receptive field remapping. Thus, oscillatory coherence might play a role in constructing the stable representation of visual space that is an essential aspect of conscious perception.
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Yasin, Amina, Abdul Rehman Yasin, Muhammad Rizwan Azam, Ali Raza, Robina Nazir, and Ridab Adlan Elamin Abdalla. "Computational-Model-Based Biopharmaceutics for p53 Pathway Using Modern Control Techniques for Cancer Treatment." Applied Sciences 12, no. 11 (June 6, 2022): 5748. http://dx.doi.org/10.3390/app12115748.
Full textAbstract:
The p53 pathway has been the focus of many researchers in the last few decades owing to its pivotal role as a frontline cancer suppressant protein. It plays a vital role in maintaining cell cycle checkpoints and cell apoptosis in response to a broken DNA strand. This is why it is found in the mutated form in more than 50% of malignant tumors. To overcome this, various drugs have been proposed to revive the p53 pathway in cancer patients. Small-molecule-based drugs, such as Nutlin 3a, which are capable of performing this stimulation, are at the fore of advanced clinical trials. However, the calculation of their dosage is a challenge. In this work, a method to determine the dosage of Nutlin 3a is investigated. A control-systems-based model is developed to study the response of the wild-type p53 protein to this drug. The proposed strategy regulates the p53 protein along with negative and positive feedback loops mediated by the MDM2 and MDM2 mRNA, respectively, along with the reversible repression of MDM2 caused by Nutlin 3a. For a broader perspective, the reported PBK dynamics of Nutlin 3a are also incorporated. It has been reported that p53 responds to stresses in two ways in terms of concentration to this drug: either it is a sustained (constant) or an oscillatory response. The claimed dosage strategy turned out to be appropriate for sustained p53 response. However, for the induction of oscillations, inhibition of MDM2 is not enough; rather, anti-repression of the p53–MDM2 complex is also needed, which opens new horizons for a new drug design paradigm.
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Yasin, Amina, Abdul Rehman Yasin, Muhammad Rizwan Azam, Ali Raza, Robina Nazir, and Ridab Adlan Elamin Abdalla. "Computational-Model-Based Biopharmaceutics for p53 Pathway Using Modern Control Techniques for Cancer Treatment." Applied Sciences 12, no. 11 (June 6, 2022): 5748. http://dx.doi.org/10.3390/app12115748.
Full textAbstract:
The p53 pathway has been the focus of many researchers in the last few decades owing to its pivotal role as a frontline cancer suppressant protein. It plays a vital role in maintaining cell cycle checkpoints and cell apoptosis in response to a broken DNA strand. This is why it is found in the mutated form in more than 50% of malignant tumors. To overcome this, various drugs have been proposed to revive the p53 pathway in cancer patients. Small-molecule-based drugs, such as Nutlin 3a, which are capable of performing this stimulation, are at the fore of advanced clinical trials. However, the calculation of their dosage is a challenge. In this work, a method to determine the dosage of Nutlin 3a is investigated. A control-systems-based model is developed to study the response of the wild-type p53 protein to this drug. The proposed strategy regulates the p53 protein along with negative and positive feedback loops mediated by the MDM2 and MDM2 mRNA, respectively, along with the reversible repression of MDM2 caused by Nutlin 3a. For a broader perspective, the reported PBK dynamics of Nutlin 3a are also incorporated. It has been reported that p53 responds to stresses in two ways in terms of concentration to this drug: either it is a sustained (constant) or an oscillatory response. The claimed dosage strategy turned out to be appropriate for sustained p53 response. However, for the induction of oscillations, inhibition of MDM2 is not enough; rather, anti-repression of the p53–MDM2 complex is also needed, which opens new horizons for a new drug design paradigm.
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Pérez-Cervera, Alberto, and Jaroslav Hlinka. "Perturbations both trigger and delay seizures due to generic properties of slow-fast relaxation oscillators." PLOS Computational Biology 17, no. 3 (March 29, 2021): e1008521. http://dx.doi.org/10.1371/journal.pcbi.1008521.
Full textAbstract:
The mechanisms underlying the emergence of seizures are one of the most important unresolved issues in epilepsy research. In this paper, we study how perturbations, exogenous or endogenous, may promote or delay seizure emergence. To this aim, due to the increasingly adopted view of epileptic dynamics in terms of slow-fast systems, we perform a theoretical analysis of the phase response of a generic relaxation oscillator. As relaxation oscillators are effectively bistable systems at the fast time scale, it is intuitive that perturbations of the non-seizing state with a suitable direction and amplitude may cause an immediate transition to seizure. By contrast, and perhaps less intuitively, smaller amplitude perturbations have been found to delay the spontaneous seizure initiation. By studying the isochrons of relaxation oscillators, we show that this is a generic phenomenon, with the size of such delay depending on the slow flow component. Therefore, depending on perturbation amplitudes, frequency and timing, a train of perturbations causes an occurrence increase, decrease or complete suppression of seizures. This dependence lends itself to analysis and mechanistic understanding through methods outlined in this paper. We illustrate this methodology by computing the isochrons, phase response curves and the response to perturbations in several epileptic models possessing different slow vector fields. While our theoretical results are applicable to any planar relaxation oscillator, in the motivating context of epilepsy they elucidate mechanisms of triggering and abating seizures, thus suggesting stimulation strategies with effects ranging from mere delaying to full suppression of seizures.
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Iassonov, Pavel, and Igor Beresnev. "Mobilization of Entrapped Organic Fluids by Elastic Waves and Vibrations." SPE Journal 13, no. 04 (December 1, 2008): 465–73. http://dx.doi.org/10.2118/104315-pa.
Full textAbstract:
Summary The organic fluids entrapped in pore constrictions by capillary forces can be mobilized by the application of elastic-wave vibrations because of the nudging effect, which allows quantitative description. The model used for such calculations is a single-pore channel with converging/diverging geometry, in which the organic phase is entrapped as a continuous blob occupying several adjacent pores. The ganglion is released from the constriction when the wave-acceleration amplitude exceeds a threshold value that scales with the frequency as A/f= a constant. This means that the wave intensity is the only required criterion for the release. In an ensemble of ganglia, the percentage of them mobilized and, therefore, the flow rate increases with the amplitude and decreases with frequency. The vibrations are inefficient for mobilization if the frequency is sufficiently high. The typical vibratory amplitudes required to produce noticeable increases in the average flow rates are on the order of 10 m/s2 and much higher at the frequencies in excess of approximately 10 Hz. These estimates provide guidelines for the possible applications of elastic-wave stimulation of organic-fluid flow in porous environments. Introduction A great deal of attention in recent years has been devoted to the possibility of enhanced petroleum recovery using elastic waves and vibrations (Beresnev and Johnson 1994, Hilpert et al. 2000, Roberts et al. 2001 and 2003, Dobronravov 2002, Poesio et al. 2002). Nonetheless, the difficulty of the method has been insufficient understanding of the physical mechanism by which the low-frequency vibrations could mobilize the entrapped organic fluids. Hilpert et al. (2000) calculated the frequencies of pulsing pressure in an axisymmetric channel with a sinusoidal profile that maximized the volume of the displaced nonwetting phase; however, no explicit mobilization criteria were established. Several studies recently have proposed a specific oil-release mechanism showing how vibrations overcome capillary entrapment that holds the fluids in place (Graham and Higdon 2000, Iassonov and Beresnev 2003, Beresnev et al. 2005), which allowed explanation of miscellaneous observations of the enhancement in organic-phase flow by vibrations under field and laboratory conditions. This mobilization mechanism, as summarized by Beresnev et al. (2005), can be represented as follows. The conditions for the capillary entrapment of nonwetting fluids in pores of variable diameter (the so-called Jamin effect) of course have been understood since the 1930s (Taber 1969). The residual fluids are immobilized in the form of isolated blobs (ganglia) because of an excess capillary pressure (Pc+) building up on the inner side of the downstream meniscus as it enters a narrow pore constriction, relative to the upstream meniscus (Pc-) (water-wet porous media will be assumed) (Payatakes 1982). Referring to Fig. 1, the oil ganglion can move if the absolute pressure in the oil at the left meniscus (Pw+ + ?Pw + Pc-) is greater than that at the right meniscus (Pw+ + Pc+), where Pw is the pressure in the water phase and Pc± is the capillary pressure determined from the Laplace equation. Equating the two leads to ?P0w = Pc+ - Pc- as the threshold external pressure drop in the water above which the ganglion is mobile (Taber 1969). It follows that the external gradient in the surrounding water needs to exceed a certain unplugging threshold ?P0w to carry the ganglion through (Taber 1969, Melrose and Brandner 1974). This process is represented schematically on a flow-force diagram in Fig. 2. The solid line depicts the oil-phase flow for various values of the external static forcing. Under an external gradient ?Psw < ?P0w, the system resides in static equilibrium. The flow can commence only when ?Psw exceeds the unplugging threshold ?P0w. Suppose that the flow is plugged (?Psw < ?P0w). In a cylindrical channel, the application of longitudinal vibrations of the wall (without a loss of generality, we consider the motion parallel to the pore axis) is equivalent to the addition of an external (inertial) oscillatory body force Posc to the constant gradient,Posc = ??pa,............................................(1) where ??p is the density of the oil (petroleum) and a is an instantaneous amplitude of the acceleration of the wall (Biot 1956). One period of the oscillatory forcing adding to the gradient is shown in Fig. 2. When this forcing acts along the gradient and the total ?Psw + Posc exceeds ?P0w, instant unplugging occurs (total forcing in the flow zone in Fig. 2). During the unplugged period, if a ganglion's leading meniscus moves beyond the narrowest point in the constriction, the magnitude of the restraining capillary force starts to decrease progressively. As a result, the blob accelerates upon exiting the constriction (Beresnev et al. 2005). This explains why the application of the reversed polarity of vibrations, opposing the gradient, cannot return the blob to its original position. The minimum amplitude for the vibrations needed to mobilize the blob is set by the condition ?Psw + Posc > ?P0w. Because the leading meniscus must reach the throat of the constriction to become mobilized, the period of vibrations should be long enough (for a given amplitude) to allow sufficient time for this movement. Frequencies above a certain threshold value will fail to mobilize the blob. We infer that, in addition to the existence of the minimum-amplitude threshold for the onset of mobilization, there will also be a maximum-frequency threshold. This mechanism of residual-organic-phase mobilization by elastic waves and vibrations allows quantitative description of the flow-enhancement effect produced by seismic waves of particular amplitudes and frequencies, which would be of direct practical interest and has so far been lacking. Performing such calculations is the goal of this paper.
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Sarmah, Abhishek, Ahmed Farid Ibrahim, Hisham Nasr-El-Din, and Jennifer Jackson. "A New Cationic Polymer System That Improves Acid Diversion in Heterogeneous Carbonate Reservoirs." SPE Journal 25, no. 05 (April 24, 2020): 2281–95. http://dx.doi.org/10.2118/194647-pa.
Full textAbstract:
Summary In-situ gelled acids are used for acid diversion in heterogeneous carbonate reservoirs. However, most of the gelled systems are based on anionic polymers that are difficult to clean up after the acid treatments. Residual polymer deposition leads to formation damage by blocking pore throats in the matrix. This work evaluates a new cationic-polymer acid system with self-breaking ability for application as an acid diverter in carbonate reservoirs. Experimental studies have been conducted to examine the rheological properties of these polymer-based acid systems. The apparent viscosities of the live and the partially neutralized acids at pH from 0 to 5 were measured against the shear rate (0 to 1000 s−1). The effects of salinity and temperature (80 to 250°F) on the rheological properties of the acid system were also studied. The viscoelastic properties of the gelled acid system were evaluated using an oscillatory rheometer. Dynamic sweep tests were used to determine the elastic (G′) and viscous (G″) moduli of the system. Single-coreflood experiments were conducted on Indiana limestone cores to study the nature of diversion caused by the polymer-acid system. The effect of permeability contrast on the process of diversion was investigated by conducting dual-coreflood experiments on Indiana limestone cores that had permeability contrasts of 1.5 to 20. Computed tomography (CT) scans were conducted to study wormhole propagation after acid injection for both single and dual cores. The live acid system displayed a non-Newtonian shear-thinning behavior with the viscosity declining as temperature increased. For 5 wt% hydrochloric acid (HCl) and 20 gal/t polymer content at 10 s−1, the viscosity decreased from 230 to 40 cp as the temperature increased from 88 to 250°F. Acid-spending tests demonstrated that the acid generated a gel with improved viscosity of 260 cp (at 250°F and 10 s−1) after it reached a pH of 2. The highly viscous gel plugged the wormhole and forced the acid that followed to the next higher-permeability zone. The viscosity of the gel continued to increase until it broke down to 69 cp (at 250°F and 10 s−1) at a pH of 4.8, which indicates a self-breaking system and more thorough cleanup potential. Coreflood studies indicated that the wormhole and the diversion process are dependent on the temperature and the flow rate. There was no indication of any damage caused by the system. The injected acid pore volume to breakthrough (PVBT) decreased from 2.2 to 1.4 when the temperature increased from 150 to 250°F. The strong elastic nature of the gel (G′ = 3.976 Pa at 1 Hz) formed by the partially neutralized acid system proves its suitability as a candidate for use as a diverting agent. This new acid-polymer system has significant promise for use in acid diversion to improve stimulation of carbonate reservoirs.
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Antal, Andrea, and Christoph S. Herrmann. "Transcranial Alternating Current and Random Noise Stimulation: Possible Mechanisms." Neural Plasticity 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/3616807.
Full textAbstract:
Background. Transcranial alternating current stimulation (tACS) is a relatively recent method suited to noninvasively modulate brain oscillations. Technically the method is similar but not identical to transcranial direct current stimulation (tDCS). While decades of research in animals and humans has revealed the main physiological mechanisms of tDCS, less is known about the physiological mechanisms of tACS.Method. Here, we review recent interdisciplinary research that has furthered our understanding of how tACS affects brain oscillations and by what means transcranial random noise stimulation (tRNS) that is a special form of tACS can modulate cortical functions.Results. Animal experiments have demonstrated in what way neurons react to invasively and transcranially applied alternating currents. Such findings are further supported by neural network simulations and knowledge from physics on entraining physical oscillators in the human brain. As a result, fine-grained models of the human skull and brain allow the prediction of the exact pattern of current flow during tDCS and tACS. Finally, recent studies on human physiology and behavior complete the picture of noninvasive modulation of brain oscillations.Conclusion. In future, the methods may be applicable in therapy of neurological and psychiatric disorders that are due to malfunctioning brain oscillations.
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Watanabe, Yasunori, Jun Sakai, Yuta Mitobe, and Yasuo Niida. "BIOLUMINESCENCE IMAGING FOR MEASURING FLUID SHEAR DISTRUBUTIONS." Coastal Engineering Proceedings 1, no. 33 (December 15, 2012): 31. http://dx.doi.org/10.9753/icce.v33.waves.31.
Full textAbstract:
The dinoflagellate Pyrocystis lunula emits light in response to water motion. The statistical features of the bioluminescence, emitted by P. lunula, owing to shear stress in oscillatory boundary layer flows over ripped bed were studied in this paper with the aim to develop a new imaging technique for measuring fluid strain rate and shear using plankton that emit light in response to mechanical stimulation. The flash intensity has been found to correlate with fluid strain rate estimated from fluid velocity over ripples. Thus the instantaneous planar distribution of the fluid shear can be estimated from video images of the bioluminescence in a fluid region by using the empirical relation determined in this study.
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Zierhofer, M. C., and E. S. Hochmair. "Transcutaneous Transmission of Digital Data and Energy in a Cochlear Prosthesis System." International Journal of Artificial Organs 15, no. 6 (June 1992): 378–82. http://dx.doi.org/10.1177/039139889201500612.
Full textAbstract:
This paper describes the inductive power and data link employed in the CAP Cochlear Prosthesis System (CAP stands for Combined Analog and Pulsative Stimulation Strategy). The inductive link consisting of a parallel-tuned receiver resonant circuit weakly coupled to a series-tuned transmitter resonant circuit, is driven by a self-oscillating class-E-tuned power amplifier. The class-E concept allows coupling-insensitive high-efficency transcutaneous transmission of power. In the CAP implant, variations of the coil distance within a range of 0 to 9 mm result in changes of the implant supply voltage which are lower than 10%. Within this coil distance range, the mean overall efficiency is 49%. In view of the excellent switching properties of the class-E tuned power oscillator, a practical scheme for data transmission is ASK (Amplitude Shift Keying). To ensure constant energy flow and easy synchronization of the bitstream in the implant, a self-clocking bit format is employed.
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MD, Shamshuddin, Siva Reddy Sheri, and O. Anwar Bég. "Oscillatory dissipative conjugate heat and mass transfer in chemically reacting micropolar flow with wall couple stress: A finite element numerical study." Proceedings of the Institution of Mechanical Engineers, Part E: Journal of Process Mechanical Engineering 233, no. 1 (November 19, 2017): 48–64. http://dx.doi.org/10.1177/0954408917743372.
Full textAbstract:
High temperature non-Newtonian materials processing provides a stimulating area for process engineering simulation. Motivated by emerging applications in this area, the present article studies time-dependent free convective flow of a chemically reacting micropolar fluid from a vertical plate oscillating in its own plane adjacent to a porous medium. Thermal radiative, viscous dissipation and wall couple stress effects are included. The Rosseland diffusion approximation is used to model uni-directional radiative heat flux in energy equation. Darcy’s model is adopted to mimic porous medium drag force effect. The governing two-dimensional conservation equations are normalized with appropriate variables and transformed into a dimensionless, coupled, nonlinear system of partial differential equations under the assumption of low Reynolds number. The governing boundary value problem is then solved under physically viable boundary conditions numerically with a finite element method based on the weighted residual approach. Graphical illustrations for velocity, micro-rotation (angular velocity), temperature, and concentration are obtained as functions of the emerging physical parameters, i.e. thermal radiation, viscous dissipation, first-order chemical reaction parameter, etc. Furthermore, friction factor (skin friction), surface heat transfer and mass transfer rates have been tabulated quantitatively for selected thermo-physical parameters. A comparison with previously published article is made to check the validity and accuracy of the present finite element solutions under some limiting cases and excellent agreement is attained. Additionally, a mesh independence study is conducted. The model is relevant to reactive polymeric materials processing simulation.
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Brummermann, M., and E. J. Braun. "Effect of salt and water balance on colonic motility of white leghorn roosters." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 268, no. 3 (March 1, 1995): R690—R698. http://dx.doi.org/10.1152/ajpregu.1995.268.3.r690.
Full textAbstract:
The motility of the lower gastrointestinal (GI) tract of white leghorn roosters was observed by radiographic methods. Intracolonic pressure changes were recorded, and the mechanical activity of the colon was quantified using strain gauges that were attached to the serosa. Two types of retrograde contraction waves were observed: small fast peristaltic contractions (15 min-1) and large slow contractions. The small fast contractions are the actual vehicle of the retrograde movement, but they seemed to be linked to respiratory movements in the fashion of coupled oscillators during most of their activity time (94%). This makes them an unlikely target for regulation. The large slow waves (3 min-1) probably reflect contractions of the longitudinal musculature. They are retrograde and may permit or modulate the refluxing of urine. The effects of water deprivation, intravenous volume, and salt loads on colonic motility were analyzed. All manipulations that increased urine flow rates without changing urine osmolality resulted in increased propagation speed of the large contraction waves. All manipulations that increased urine osmolality resulted in decreases in activity time of the large-wave pattern. These results suggest a hydration state-related control of the retrograde colonic motility in birds. Direct stimulation of central osmoreceptors had no such effects, indicating that local volume and osmolality receptors of the cloaca are more important than central receptors for this adjustment of colonic motility.
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Yan, Xiaoyu, Sihem Ait-Oudhia, and Wojciech Krzyzanski. "Erythropoietin Induced Erythroid Precursor Pool Depletion Causes Erythropoietin Hyporesponsiveness." Blood 120, no. 21 (November 16, 2012): 5156. http://dx.doi.org/10.1182/blood.v120.21.5156.5156.
Full textAbstract:
Abstract Abstract 5156 Background: Erythropoietin (EPO) hyporesponsiveness is demonstrated by a persistence of anemia despite high dose of recombinant human erythropoietin (rHuEPO) or requirement of large doses to maintain the target hemoglobin concentration. The purpose of this study is to demonstrate that the bone marrow depletion induced by rHuEPO treatment may another contributing factor to hyporesponsiveness. Methods: Healthy Wistar rats were given single dose (SD) or multiple doses (MD) of rHuEPO. In MD study, animals were challenged with thrice-weekly (100 IU/kg) over two weeks and the pharamcodynamic biomarkers included reticulocyte (RET) and red blood cells (RBC) counts, and hemoglobin (HGB) concentrations. In SD study, in addition to the biomarkers in the peripheral blood, the erythropoietic responses in bone marrow and spleen were also quantified using a flow cytometric immunophenotyping technique. The total marrow and spleen cellularity was quantitatively assessed using flow cytometry. A mathematical approach involving measuring RET age distribution was developed to evaluate the RET loss due to neocytolysis. The pharmacokinetics of rHuEPO was assessed by measuring serum concentrations over time using ELISA. Result: In MD study, a slow and oscillatory decline of RET response was observed before the administration of the last dose on day 11. The RET kept decreasing below the baseline and reached a nadir on day 22, followed by a slow return to the baseline on day 28. These observations demonstrated the tolerance and rebound phenomena. In SD study, the RET decreased below the baseline after day 6. A depletion of the bone marrow erythroid precursor cells was also observed. Meanwhile, neocytolysis of RET was only observed from day 3–5 after rHuEPO injection. These results suggested that the reduced levels of RET after day 6 resulted from the depletion in the erythroid precursor cells in bone marrow induced by rHuEPO treatment. Conclusion: The EPO hyporesponsiveness is of clinical importance because it is associated with an increased risk of death or cardiovascular events. The findings in this study demonstrate that EPO-induced erythroid precursor depletion may contribute to the rHuEPO hyporesponsiveness. When the erythroid precursor cells are depleted, an increase of rHuEPO dose would not show much benefit, due to the smaller number of cells present to initiate the erythropoiesis. These findings provide additional justification for reducing the doses of erythropoietin stimulating agents in anemic patients demonstrating hyporesponsiveness. Disclosures: No relevant conflicts of interest to declare.
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Simeoni, Ricardo. "Chronic Fatigue Syndrome: A Quantum Mechanical Perspective." UNET JOSS: Journal of Science and Society 2, no. 1 (May 9, 2022): 20–46. http://dx.doi.org/10.52042/unetjoss020103.
Full textAbstract:
Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME) or systemic exertional intolerance disease (SEID), is an illness dominated by long-term fatigue persisting for more than six months, incapacitating to the point of sufferers being bedridden or housebound in some cases, and unexplained by some other underlying medical condition. CFS is also often characterised by unrefreshing sleep, post-exertional discomfort ranging from malaise to extreme exhaustion, orthostatic (upright posture) intolerance, muscle pain, cognitive impairment (including the commonly described symptom of "brain fog"), and deterioration in cellular bioenergetics [1-3]. Scientific estimates of the world-wide population percentage that suffer from CFS naturally vary, but a conservative estimate based on several studies is at least 0.4%, thereby equating to millions world-wide [1-4]. Thankfully, after decades of dismissal by some quarters, leading to despair and exasperation of sufferers, CFS is now widely accepted as a legitimate illness. However, while depreciating labels such as "yuppy flu" have subsequently been banished to recent history, this new-found acceptance provides comfort for sufferers only up to a certain point. Viz., CFS is still far from fully understood and is often described as a complex, multisystem illness with no clear pathological mechanisms or diagnostic biomarkers [1-3], from which treatment uncertainty ensues [1,2]. Sadly, due in no small part to this uncertainty and the illness characteristics of the opening paragraph, the suicide rate of CFS sufferers has been reported as approximately seven times that of their healthy counterparts [1,5]. The economic and other social impacts of CFS are difficult to determine because of the arbitrariness of case definitions, lack of evidence including prevalence data, diagnostic inability of some physicians due to factors such as disbelief and lack of understanding (one major survey [4] reveals that 62% of sufferers are not confident in their general physician’s understanding), and difficulty many sufferers have in explaining the symptoms of their illness (another survey [2] shows that a majority or substantial proportion, depending on factors such as country of origin, have difficulty explaining their illness to not only physicians but also family and friends). Societal impacts of CFS have nonetheless been assessed by various committees (e.g., associated with the United States’ Institute of Medicine) and working/action groups (e.g., associated with the European Union). As expected, the economic impact of CFS is formally declared to be significant, with the net income of a CFS household in Europe being substantially lower than general population households (i.e., individual productivity effect), and the total annual cost burden being tens of billions of dollars in the United States alone [1-4]. The World Health Organization generally classifies CFS as a neurological illness involving the central nervous system. Some notable and more specific examples of proposed CFS aetiology components are summarised below, with these examples reflecting the complex multisystem nature of CFS and not necessarily being mutually exclusive: • Recent studies suggest that CFS arises from functional changes in the brain, with spectroscopic and inflammatory brain changes (e.g., following repeated exercise) also demonstrated. However, uncertainty over the character, location and propensity of such changes remains and the need for further functional neuroimaging studies is recognised [2,3,6,7]. • A significant increase in red blood cell (RBC) stiffness is reported in CFS, suggesting that compromised RBC transport through microcapillaries may contribute to CFS aetiology and that this diminished deformability could form the basis of a first-pass diagnostic test [8]. Further to this point, the previously identified CFS characteristic of orthostatic intolerance (estimated to occur in up to 97% of cases) is linked to under-oxygenatation of the brain to which diminished RBC deformability is thought to be a contributing factor [9]. • Unusual RBC shape, leading to reduced blood flow and changes in molecular docking on the RBC surface, is reported in CFS [10]. The subsequent increase in the number of stomatocytes (RBCs that have lost their typical concave shape, due for example to membrane defect), adds to the previous point of diminished RBC deformability to support poor microcirculation as contributing to CFS aetiology. • Dysfunction of mitochondria (subcellular organelles within the cytoplasm of aerobic cells) is found in CFS, with the interference of adenosine triphosphate (ATP) production being one of several consequences within the explanatory pathological pathway [11] (ATP is fundamentally essential for cellular-level metabolic energy requirements as outlined in Section 3). • CFS is largely resolved as not being attributable to some ongoing infection, endocrine disorder, or psychiatric condition [3,6]. While some similarly do not assign an immunological disorder attribution, more often over-stimulation or over-reaction of the immune system (hyperimmune response), impaired immune system response, immuno-inflammatory, and oxidative damage to the immune system, are all utilised expressions associated with CFS [3,6,8,1113], which in several research circles is described as a neuroimmune disease [1,11,14]. This immunological quandary again highlights the complexity of the ongoing medical challenge at hand. One clear aspect of CFS is that underlying pathophysiology implicates a range of different acute infections as onset triggers in a significant minority of cases (i.e., infections like Epstein-Barr, Ross River and the 2003 outbreak variant of Severe Acute Respiratory Syndrome, or SARS, viruses). No other medical or psychological factors are definitively implicated in CFS [7]. For many observers such triggerings are mindful of, if not directly related to, the crippling fatigue that is widely reported within contemporary media and recent studies as a lasting symptom of COVID-19. Such COVID-19-triggred CFS has led to the coined phrases of COVID-19 "long-haulers" or "long COVID", and has returned CFS to the public awareness spotlight [12]. However, too familiarly the lack of definitive CFS biomarkers is again confirmed by long COVID research, and sadly the dismissive attitudes of some in the medical profession is also a point of exasperation for long COVID sufferers [12], contributing for example to the in-desperation-establishment of a "long COVID kids" Facebook site in the United Kingdom. Established treatments, such as cognitive behaviour therapy (CBT) and graded exercise therapy (GET), primarily aim to manage the symptoms and improve the overall function of sufferers. The confounding nature of CFS extends to these treatments, since there is wide ongoing debate over their effectiveness [1,15]. For example, while GET is shown to benefit some, for others it is essentially considered just "cruel". A host of alternative treatments, some of which may be described as holistic or naturopathic or similar, naturally also exist, such as cryogenic, floatation and oxygen therapies, to name just a few. It is not the intention or place of the present article to compare, critique or scientifically review such treatments. It will simply be stated that, at least anecdotally, some such treatments seem to bring relief to some individuals (which is a positive outcome for those lucky enough to find any relief), but certainly most do not consider these treatments to be CFS cures or long-term major alleviators for the majority. Contemporary scientific scrutiny into how COVID-19 can damage the brain [13,16,17], and suggesting that the virus’ fatigue and adverse neurological effects (such as loss of smell and taste, altered mental states that can lead to the development of psychoses, and brain shrinkage in regions essential for processing memory, cognition and emotion) are indeed due to some hyperimmune response with neuroinflammation, does however offer many CFS sufferers new hope. Viz., hope that as a result of such scrutiny highly effective treatments (e.g., neural rewiring therapies [16]) and eventual cure await, even with the caveat of caution around some uncertain degree of overlap between COVID and non-COVID CFS. The present article’s title with cartoon of a fatigued physicist upon first glance likely appears incongruous. However, while some delight was taken in choosing this "humorous-to-a-physicist" title, the article is journalistically serious and does not make light of CFS. Rather, in addition to the above CFS overview, the article reflects upon a presented clinical Case Study of a seemingly recovering CFS sufferer, to form a justified CFS hypothesis for future testing. The to-be-formed hypothesis follows from the unique neuro-perspectives of [18], which explore central nervous system impulse encoding revelations via a new approach to high-order electroencephalogram (EEG) phase analysis. Given that CFS has a neurological component, can these new perspectives be applied to the area of CFS, and in particular to the to-be-presented Case Study of recovery? While this tangent might seem a long bow to draw, perhaps a fresh CFS perspective is just what is currently needed. Despite the quantum mechanical aspects to come and references [18] and [19], the latter on a discrete oscillator phase noise effect applied within phase-shift keying radiofrequency (RF) digital signal modulation, being recommended prior readings for those with a biomedical engineering or similar background, no such specialist backgrounds are assumed for readers. In brief, the present article represents academic (science and medicine) journalism that is hopefully considered high-interest, and shares via Case Study the clinical/medical results, collated over several years, for a scientifically dependent individual. The eventually formed hypothesis is intended for testing within a future formalised study, and so presently may be countered by alternative explanatory hypotheses, such as placebo and simple recovery coincidence, which are also identified.
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Violante, Ines R., Lucia M. Li, David W. Carmichael, Romy Lorenz, Robert Leech, Adam Hampshire, John C. Rothwell, and David J. Sharp. "Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance." eLife 6 (March 14, 2017). http://dx.doi.org/10.7554/elife.22001.
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Cognitive functions such as working memory (WM) are emergent properties of large-scale network interactions. Synchronisation of oscillatory activity might contribute to WM by enabling the coordination of long-range processes. However, causal evidence for the way oscillatory activity shapes network dynamics and behavior in humans is limited. Here we applied transcranial alternating current stimulation (tACS) to exogenously modulate oscillatory activity in a right frontoparietal network that supports WM. Externally induced synchronization improved performance when cognitive demands were high. Simultaneously collected fMRI data reveals tACS effects dependent on the relative phase of the stimulation and the internal cognitive processing state. Specifically, synchronous tACS during the verbal WM task increased parietal activity, which correlated with behavioral performance. Furthermore, functional connectivity results indicate that the relative phase of frontoparietal stimulation influences information flow within the WM network. Overall, our findings demonstrate a link between behavioral performance in a demanding WM task and large-scale brain synchronization.
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Janssens, Shanice E. W., and Alexander T. Sack. "Spontaneous Fluctuations in Oscillatory Brain State Cause Differences in Transcranial Magnetic Stimulation Effects Within and Between Individuals." Frontiers in Human Neuroscience 15 (December 2, 2021). http://dx.doi.org/10.3389/fnhum.2021.802244.
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Transcranial magnetic stimulation (TMS) can cause measurable effects on neural activity and behavioral performance in healthy volunteers. In addition, TMS is increasingly used in clinical practice for treating various neuropsychiatric disorders. Unfortunately, TMS-induced effects show large intra- and inter-subject variability, hindering its reliability, and efficacy. One possible source of this variability may be the spontaneous fluctuations of neuronal oscillations. We present recent studies using multimodal TMS including TMS-EMG (electromyography), TMS-tACS (transcranial alternating current stimulation), and concurrent TMS-EEG-fMRI (electroencephalography, functional magnetic resonance imaging), to evaluate how individual oscillatory brain state affects TMS signal propagation within targeted networks. We demonstrate how the spontaneous oscillatory state at the time of TMS influences both immediate and longer-lasting TMS effects. These findings indicate that at least part of the variability in TMS efficacy may be attributable to the current practice of ignoring (spontaneous) oscillatory fluctuations during TMS. Ignoring this state-dependent spread of activity may cause great individual variability which so far is poorly understood and has proven impossible to control. We therefore also compare two technical solutions to directly account for oscillatory state during TMS, namely, to use (a) tACS to externally control these oscillatory states and then apply TMS at the optimal (controlled) brain state, or (b) oscillatory state-triggered TMS (closed-loop TMS). The described multimodal TMS approaches are paramount for establishing more robust TMS effects, and to allow enhanced control over the individual outcome of TMS interventions aimed at modulating information flow in the brain to achieve desirable changes in cognition, mood, and behavior.
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Pinheiro-de-Sousa, Iguaracy, Miriam H. Fonseca-Alaniz, Samantha K. Teixeira, Mariliza V. Rodrigues, and Jose E. Krieger. "Uncovering emergent phenotypes in endothelial cells by clustering of surrogates of cardiovascular risk factors." Scientific Reports 12, no. 1 (January 25, 2022). http://dx.doi.org/10.1038/s41598-022-05404-7.
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AbstractEndothelial dysfunction (ED) is a hallmark of atherosclerosis and is influenced by well-defined risk factors, including hypoxia, dyslipidemia, inflammation, and oscillatory flow. However, the individual and combined contributions to the molecular underpinnings of ED remain elusive. We used global gene expression in human coronary artery endothelial cells to identify gene pathways and cellular processes in response to chemical hypoxia, oxidized lipids, IL-1β induced inflammation, oscillatory flow, and these combined stimuli. We found that clustering of the surrogate risk factors differed from the sum of the individual insults that gave rise to emergent phenotypes such as cell proliferation. We validated these observations in samples of human coronary artery atherosclerotic plaques analyzed using single-cell RNA sequencing. Our findings suggest a hierarchical interaction between surrogates of CV risk factors and the advent of emergent phenotypes in response to combined stimulation in endothelial cells that may influence ED.
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Hanaguri, Junya, Harumasa Yokota, Masahisa Watanabe, Satoru Yamagami, Akifumi Kushiyama, Lih Kuo, and Taiji Nagaoka. "Retinal blood flow dysregulation precedes neural retinal dysfunction in type 2 diabetic mice." Scientific Reports 11, no. 1 (September 15, 2021). http://dx.doi.org/10.1038/s41598-021-97651-3.
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AbstractWe investigated and compared the susceptibility of retinal blood flow regulation and neural function in mice developing type 2 diabetes. The longitudinal changes in retinal neuronal function and blood flow responses to a 10-min systemic hyperoxia and a 3-min flicker stimulation were evaluated every 2 weeks in diabetic db/db mice and nondiabetic controls (db/m) from age 8 to 20 weeks. The retinal blood flow and neural activity were assessed using laser speckle flowgraphy and electroretinography (ERG), respectively. The db/db mice had significantly higher blood glucose levels and body weight. The resting retinal blood flow was steady and comparable between two groups throughout the study. Hyperoxia elicited a consistent decrease, and flicker light an increase, in retinal blood flow in db/m mice independent of age. However, these flow responses were significantly diminished in db/db mice at 8 weeks old and then the mice became unresponsive to stimulations at 12 weeks. Subsequently, the ERG implicit time for oscillatory potential was significantly increased at 14 weeks of age while the a-wave and b-wave amplitudes and implicit times remained unchanged. The deficiencies of flow regulation and neurovascular coupling in the retina appear to precede neural dysfunction in the mouse with type 2 diabetes.
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Mowbray, Amy, Sang Won Kang, Sue Goo Rhee, and Hanjoong Jo. "Abstract 927: The Role Of Peroxiredoxins As Mechanosensitive Antioxidants In Endothelial Cells." Circulation 116, suppl_16 (October 16, 2007). http://dx.doi.org/10.1161/circ.116.suppl_16.ii_182-c.
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Atherosclerosis is an inflammatory disease occurring primarily in curved or branching regions of the arterial tree where disturbed flow patterns, such as oscillation, exist. We have previously shown that oscillatory shear stress (OS) increases reactive oxygen species (ROS) levels in endothelial cells, while laminar shear stress (LS) reduces ROS compared to static controls. OS stimulation of ROS has been shown to occur in an NADPH oxidase-dependent manner. However, the mechanism by which LS removes ROS remains unclear. Peroxiredoxins (PRX) are a family of antioxidant proteins that have been linked to the prevention of oxidative stress and inflammation, but their role in atherosclerosis is unknown. Here, we hypothesize that shear stress regulates ROS levels in endothelial cells by controlling antioxidant peroxiredoxins. To test this hypothesis, bovine aortic endothelial cells (BAEC) were subjected to static, laminar, and oscillatory fluid flow conditions via cone-and-plate viscometer. Western blot analysis and immunofluorescent staining were used to evaluate the expression and subcellular localization of six known mammalian peroxiredoxins (PRX I-VI). Immunoblots indicated that BAEC express all six isoforms of peroxiredoxin proteins and that LS upregulated PRX I levels significantly compared to static controls and OS. Immunofluorescence also showed a distinct subcellular localization of each PRX: PRX I, II, IV, V and VI in the cytoplasm, PRX I, IV and V in the Golgi, PRX III in the mitochondria, and PRX I in the nucleus. These results indicate that peroxiredoxins are mechanosensitive antioxidants, removing ROS in a subcellular-specific manner. Based on these data, we suggest that peroxiredoxin antioxidants are likely involved in the molecular mechanisms that control shear stress-dependent atherosclerotic plaque development.
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Araujo, Gustavo S. M., Thiago O. C. Silva, Grazia M. Guerra, João E. Izaias, Helena M. N. Rocha, Diego Faria, Natalia G. Rocha, et al. "Effects of Postprandial Lipemia Combined With Disturbed Blood Flow on the Flow-Mediated Dilation, Oxidative Stress, and Endothelial Microvesicles in Healthy Subjects." Frontiers in Physiology 13 (February 24, 2022). http://dx.doi.org/10.3389/fphys.2022.812942.
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AimsBoth postprandial lipemia (PPL) and disturbed blood flow (DBF) induce endothelial dysfunction. However, the interactive effect of these stimuli on endothelial function is currently unknown. In the present study, we tested whether PPL plus DBF causes a greater reduction in flow-mediated dilation (FMD) than PPL and if this response is associated with elevations in oxidative stress and endothelial microvesicles (EMVs).MethodsEighteen individuals (aged 28 ± 1yrs, 3 females, and BMI 24.43 ± 0.8kg/m2) randomly underwent two experimental sessions: PPL and PPL plus DBF. FMD and venous blood samples were obtained at baseline and 30, 70, and 110 min after stimulation. PPL was induced by fat overload via mozzarella pizza ingestion and DBF by forearm cuff inflation to 75 mm Hg per 30 min. Lipidic profile, oxidative stress (thiobarbituric acid reactive substances, TBARS; ferric reducing/antioxidant power, FRAP; hydrogen peroxide, H2O2) and EMVs were measured in blood samples.ResultsHypertriglyceridemia was observed in both sessions. Retrograde shear rate and oscillatory index responses were significantly higher in the PPL plus DBF compared with PPL. PPL plus DBF evoked a greater reduction in FMD than did PPL and EMVs, NADPH oxidase, and H2O2 similarly increased in both sessions, but TBARS and FRAP did not change.ConclusionThese data indicate that the association of PPL plus DBF additively impairs endothelium-dependent function in 110 min after stimulus in healthy individuals, despite a similar increase in oxidative stress and EMVs. Further studies are needed to understand the mechanisms associated with the induced-endothelial dysfunction by association of PPL and DBF.
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Chung, Jihwa, Ga-Young Lee, Kyoung Hwa Kim, Yoon Pyo Lee, Seok Cheol Lee, Shung Hyun An, and Kihwan Kwon. "Abstract 18936: Fluid Shear Stress Regulates Expression of Coxsackievirus-adenovirus Receptor Through Mechanosensory Complex in Endothelial Cells." Circulation 132, suppl_3 (November 10, 2015). http://dx.doi.org/10.1161/circ.132.suppl_3.18936.
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Backgrounds: Vascular endothelial cells, which form the innermost layer of blood vessels, are exposed to fluid shear stress that modulates endothelial function and vascular pathophysiology. The coxsackie- and adenovirus receptor (CAR) is a transmembrane protein belonging to the immunoglobulin superfamily. However, the function of CAR as a virus receptor has been extensively studied, while its physiological role and expression pattern in endothelial cells under fluid shear stress have remained less clear. Methods and Results: We demonstrated that mechanisms involved in CAR expression and underlying molecular mechanism by comparing the laminar and oscillatory fluid shear stresses in endothelial cells. Confluent HUVECs were exposed to a unidirectional steady flow (shear stress of 25 dyne/cm2) for laminar shear stress (LSS), and a bidirectional disturbed flow (shear stress of ± 5 dyne/cm2) for oscillatory shear stress (OSS), under various time periods. Additionally, we used a model of atherosclerosis induced by disturbed flow in mice by partial carotid artery ligation. Western blot and RT-PCR analyses in HUVECs showed that OSS has upregulated CAR expression in both protein and mRNA levels; on the other hand, LSS has downregulated them. In enface staining of mice with partial carotid artery ligation, ligated left carotid artery (LCA) with OSS showed significantly increased CAR expression compared to expression from normal right carotid artery (RCA). In knockdown of CAR in HUVECs with siRNA encoding CAR, suppression in phosphorylation of Akt and eNOS by OSS was improved, whereas LSS-induced phosphorylation of Akt and eNOS was much activated. Moreover, transfection of HUVECs with siRNA encoding VEGFR2, PECAM-1 and VE-cadherin blocked OSS-induced CAR expression. Conclusions: Our results indicate that fluid shear stress can regulate CAR expression in endothelial cells and its regulation is mediated through the mechanosensory complex. Furthermore, it suggests that inhibition of CAR expression may lead to protective effects in endothelial cells via improving stimulation in signaling of mechanosensor under fluid shear stress. (Acknowledgements: NRF-2011-0019695)
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Tian, Shuai, Wei Pan, Junping Peng, Hui Wang, Bin Deng, Yi Liang, Xinghua Li, et al. "Hemodynamic Responses in Carotid Bifurcation Induced by Enhanced External Counterpulsation Stimulation in Healthy Controls and Patients With Neurological Disorders." Frontiers in Physiology 12 (August 31, 2021). http://dx.doi.org/10.3389/fphys.2021.717080.
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Enhanced external counterpulsation is a Food and Drug Administration–approved, non-invasive, assisted circulation therapy for ischemic cardiovascular and cerebrovascular diseases. Previous studies have confirmed that EECP stimulation induces largely different cerebral hemodynamic responses in patients with ischemic stroke and healthy controls. However, the underlying mechanisms remain uncertain. We hypothesize that different blood redistributions at the carotid bifurcation may play a key role. Ten subjects were enrolled in this study, namely, five patients with neurological disorders and five young healthy volunteers as controls. Magnetic resonance angiography (MRA) was performed on the carotid artery. All the subjects received a single session of EECP treatment, with external cuff pressures ranging from 20 to 40 kPa. Vascular ultrasound measurements were taken in the common carotid artery (CCA), external carotid artery (ECA) and internal carotid artery (ICA). Three-dimensional patient-specific numerical models were developed to calculate the WSS-derived hemodynamic factors. The results indicated that EECP increased CCA and ECA blood flow in both groups. The ICA blood flow in the patient group exhibited a mean increase of 6.67% during EECP treatment compared with the pre-EECP condition; a mean decrease of 9.2% was observed in the healthy control group. EECP increased the averaged wall shear stress (AWSS) throughout the carotid bifurcation in the patient group; the ICA AWSS of the healthy group decreased during EECP. In both groups, the oscillatory shear index (OSI) in the ICA increased proportionally with external cuff pressure. In addition, the relative resident time (RRT) was constant or slightly decreased in the CCA and ECA in both groups but increased in the ICA. We suggest that the benefits of EECP to patients with neurological disorders may partly result from blood flow promotion in the ICA and increase in WSS at the carotid bifurcation. In the healthy subjects, the ICA blood flow remained constant during EECP, although the CCA blood flow increased significantly. A relatively low external cuff pressure (20 kPa) is recommended as the optimal treatment pressure for better hemodynamic effects. This study may play an important role in the translation of physiological benefits of EECP treatment in populations with or without neurological disorders.
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Li, Chunyan, Kevin A. Shah, Keren Powell, Yi-Chen Wu, Wayne Chaung, Anup N. Sonti, Timothy G. White, et al. "CBF oscillations induced by trigeminal nerve stimulation protect the pericontusional penumbra in traumatic brain injury complicated by hemorrhagic shock." Scientific Reports 11, no. 1 (October 4, 2021). http://dx.doi.org/10.1038/s41598-021-99234-8.
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AbstractTraumatic peri-contusional penumbra represents crucial targets for therapeutic interventions after traumatic brain injury (TBI). Current resuscitative approaches may not adequately alleviate impaired cerebral microcirculation and, hence, compromise oxygen delivery to peri-contusional areas. Low-frequency oscillations in cerebral blood flow (CBF) may improve cerebral oxygenation in the setting of oxygen deprivation. However, no method has been reported to induce controllable oscillations in CBF and it hasn’t been applied as a therapeutic strategy. Electrical stimulation of the trigeminal nerve (TNS) plays a pivotal role in modulating cerebrovascular tone and cerebral perfusion. We hypothesized that TNS can modulate CBF at the targeted frequency band via the trigemino-cerebrovascular network, and TNS-induced CBF oscillations would improve cerebral oxygenation in peri-contusional areas. In a rat model of TBI complicated by hemorrhagic shock, TNS-induced CBF oscillations conferred significant preservation of peri-contusional tissues leading to reduced lesion volume, attenuated hypoxic injury and neuroinflammation, increased eNOS expression, improved neurological recovery and better 10-day survival rate, despite not significantly increasing CBF as compared with those in immediate and delayed resuscitation animals. Our findings indicate that low-frequency CBF oscillations enhance cerebral oxygenation in peri-contusional areas, and play a more significant protective role than improvements in non-oscillatory cerebral perfusion or volume expansion alone.
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Qureshi, A., M. Balmus, G. Y. H. Lip, S. Williams, D. A. Nordsletten, O. Aslanidi, and A. De Vecchi. "Mechanistic modelling of Virchows triad to assess thrombogenicity and stroke risk in atrial fibrillation patients." European Heart Journal 43, Supplement_2 (October 1, 2022). http://dx.doi.org/10.1093/eurheartj/ehac544.2788.
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Abstract Background Atrial fibrillation (AF) is responsible for almost one third of all strokes, with the left atrial appendage (LAA) being the primary thromboembolic source due to localised stimulation of prothrombotic mechanisms; blood stasis, hypercoagulability and endothelial damage, known as Virchow's triad. Aim We propose an in-silico modelling pipeline that leverages clinical imaging data to mechanistically assess patient thrombogenicity for all aspects of Virchow's triad to improve the prediction and prevention of AF-related stroke. Methods Two AF patients undergoing Cine magnetic resonance imaging (sinus rhythm (SR) N=1 or AF N=1 during imaging) were selected for 3D left atrial (LA) modelling with patient-specific myocardial deformation prescribed from image-derived wall motion. Blood stasis was quantified by computational fluid dynamics (CFD) simulations of 5 cardiac cycles [1]. Generation of three key coagulation proteins; thrombin, fibrinogen and fibrin, were modelled to represent thrombus growth and hypercoagulability [2]. Regions prone to thrombogenesis by endothelial damage were identified by the oscillatory shear index (OSI), time averaged wall shear stress (TAWSS) and endothelial cell activation potential (ECAP) metrics in the LAA [3]. Results Patient-specific LA simulations enabled the assessment of differences between SR and AF conditions, quantified as numerical characteristics of each aspect of Virchow's triad. In SR, blood flow velocities were in the range 0–2.6 m/s with mean of 0.85 m/s in the LA cavity, while AF had a range between 0–1.6 m/s with mean of 0.55 m/s. The peak and mean LAA velocities in SR were 0.85 m/s and 0.14 m/s, while AF had a peak LAA velocity of 0.32 m/s and mean of 0.09 m/s, showing a 38% decrease during AF. The thrombin concentration reached its steady state at 1.26 mmol/m3 in the AF case after 4.7 seconds, while thrombin was washed away from the initial injury site in SR. After 5 cardiac cycles of thrombus growth dynamics, the peak fibrin concentration in the LAA was 1.3 mmol/m3 in SR and 3.8 mmol/m3 in AF, with the thrombus area in AF being 40% larger. Fibrinogen concentration decreased at a rate equal to fibrin generation in both SR and AF solely in the area of thrombus formation. ECAP in the LAA had peak values of 2.9 in SR and 3.7 in AF, with the location at highest risk of thrombogenesis above the LAA entrance. LAA OSI had an average value of 0.45 in AF versus 0.36 in SR, showing a 26% increase. Similarly, the TAWSS was 3.5x10–3 Pa on average over the LAA in AF compared to 1.4x10–3 Pa in SR. Conclusions Patient-specific LA models combining these three quantitative characteristics can be used to predict the higher thrombogenic risk in AF. After further validation, this novel approach for quantitative assessment of AF patient thrombogenicity based on modelling all factors in Virchow's triad can personalise and improve management of AF patients with a risk of stroke. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK Engineering and Physical Sciences Research Council
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Qureshi, A., M. Balmus, G. Y. H. Lip, S. Williams, D. A. Nordsletten, O. Aslanidi, and A. De Vecchi. "Mechanistic modelling of Virchows triad to assess thrombogenicity and stroke risk in atrial fibrillation patients." European Heart Journal - Digital Health 3, no. 4 (December 22, 2022). http://dx.doi.org/10.1093/ehjdh/ztac076.2788.
Full textAbstract:
Abstract Background Atrial fibrillation (AF) is responsible for almost one third of all strokes, with the left atrial appendage (LAA) being the primary thromboembolic source due to localised stimulation of prothrombotic mechanisms; blood stasis, hypercoagulability and endothelial damage, known as Virchow's triad. Aim We propose an in-silico modelling pipeline that leverages clinical imaging data to mechanistically assess patient thrombogenicity for all aspects of Virchow's triad to improve the prediction and prevention of AF-related stroke. Methods Two AF patients undergoing Cine magnetic resonance imaging (sinus rhythm (SR) N=1 or AF N=1 during imaging) were selected for 3D left atrial (LA) modelling with patient-specific myocardial deformation prescribed from image-derived wall motion. Blood stasis was quantified by computational fluid dynamics (CFD) simulations of 5 cardiac cycles [1]. Generation of three key coagulation proteins; thrombin, fibrinogen and fibrin, were modelled to represent thrombus growth and hypercoagulability [2]. Regions prone to thrombogenesis by endothelial damage were identified by the oscillatory shear index (OSI), time averaged wall shear stress (TAWSS) and endothelial cell activation potential (ECAP) metrics in the LAA [3]. Results Patient-specific LA simulations enabled the assessment of differences between SR and AF conditions, quantified as numerical characteristics of each aspect of Virchow's triad. In SR, blood flow velocities were in the range 0–2.6 m/s with mean of 0.85 m/s in the LA cavity, while AF had a range between 0–1.6 m/s with mean of 0.55 m/s. The peak and mean LAA velocities in SR were 0.85 m/s and 0.14 m/s, while AF had a peak LAA velocity of 0.32 m/s and mean of 0.09 m/s, showing a 38% decrease during AF. The thrombin concentration reached its steady state at 1.26 mmol/m3 in the AF case after 4.7 seconds, while thrombin was washed away from the initial injury site in SR. After 5 cardiac cycles of thrombus growth dynamics, the peak fibrin concentration in the LAA was 1.3 mmol/m3 in SR and 3.8 mmol/m3 in AF, with the thrombus area in AF being 40% larger. Fibrinogen concentration decreased at a rate equal to fibrin generation in both SR and AF solely in the area of thrombus formation. ECAP in the LAA had peak values of 2.9 in SR and 3.7 in AF, with the location at highest risk of thrombogenesis above the LAA entrance. LAA OSI had an average value of 0.45 in AF versus 0.36 in SR, showing a 26% increase. Similarly, the TAWSS was 3.5x10–3 Pa on average over the LAA in AF compared to 1.4x10–3 Pa in SR. Conclusions Patient-specific LA models combining these three quantitative characteristics can be used to predict the higher thrombogenic risk in AF. After further validation, this novel approach for quantitative assessment of AF patient thrombogenicity based on modelling all factors in Virchow's triad can personalise and improve management of AF patients with a risk of stroke. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK Engineering and Physical Sciences Research Council
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Moradkhani, Mehdi, Bahman Vahidi, and Bahram Ahmadian. "Finite element study of stem cells under fluid flow for mechanoregulation toward osteochondral cells." Journal of Materials Science: Materials in Medicine 32, no. 7 (July 2021). http://dx.doi.org/10.1007/s10856-021-06545-3.
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AbstractInvestigating the effects of mechanical stimuli on stem cells under in vitro and in vivo conditions is a very important issue to reach better control on cellular responses like growth, proliferation, and differentiation. In this regard, studying the effects of scaffold geometry, steady, and transient fluid flow, as well as influence of different locations of the cells lodged on the scaffold on effective mechanical stimulations of the stem cells are of the main goals of this study. For this purpose, collagen-based scaffolds and implicit surfaces of the pore architecture was used. In this study, computational fluid dynamics and fluid-structure interaction method was used for the computational simulation. The results showed that the scaffold microstructure and the pore architecture had an essential effect on accessibility of the fluid to different portions of the scaffold. This leads to the optimization of shear stress and hydrodynamic pressure in different surfaces of the scaffold for better transportation of oxygen and growth factors as well as for optimized mechanoregulative responses of cell–scaffold interactions. Furthermore, the results indicated that the HP scaffold provides more optimizer surfaces to culture stem cells rather than Gyroid and IWP scaffolds. The results of exerting oscillatory fluid flow into the HP scaffold showed that the whole surface of the HP scaffold expose to the shear stress between 0.1 and 40 mPa and hydrodynamics factors on the scaffold was uniform. The results of this study could be used as an aid for experimentalists to choose optimist fluid flow conditions and suitable situation for cell culture.
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Kavlock, Katherine D., and Aaron S. Goldstein. "Effect of Pulse Frequency on the Osteogenic Differentiation of Mesenchymal Stem Cells in a Pulsatile Perfusion Bioreactor." Journal of Biomechanical Engineering 133, no. 9 (September 1, 2011). http://dx.doi.org/10.1115/1.4004919.
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Perfusion bioreactors are a promising in vitro strategy to engineer bone tissue because they supply needed oxygen and nutrients and apply an osteoinductive mechanical stimulus to osteoblasts within large porous three-dimensional scaffolds. Model two-dimensional studies have shown that dynamic flow conditions (e.g., pulsatile oscillatory waveforms) elicit an enhanced mechanotransductive response and elevated expression of osteoblastic proteins relative to steady flow. However, dynamic perfusion of three-dimensional scaffolds has been primarily examined in short term cultures to probe for early markers of mechanotransduction. Therefore, the objective of this study was to investigate the effect of extended dynamic perfusion culture on osteoblastic differentiation of primary mesenchymal stem cells (MSCs). To accomplish this, rat bone marrow-derived MSCs were seeded into porous foam scaffolds and cultured for 15 days in osteogenic medium under pulsatile regimens of 0.083, 0.050, and 0.017 Hz. Concurrently, MSCs seeded in scaffolds were also maintained under static conditions or cultured under steady perfusion. Analysis of the cells after 15 days of culture indicated that alkaline phosphatase (ALP) activity, mRNA expression of osteopontin (OPN), and accumulation of OPN and prostaglandin E2 were enhanced for all four perfusion conditions relative to static culture. ALP activity, OPN and OC mRNA, and OPN protein accumulation were slightly higher for the intermediate frequency (0.05 Hz) as compared with the other flow conditions, but the differences were not statistically significant. Nevertheless, these results demonstrate that dynamic perfusion of MSCs may be a useful strategy for stimulating osteoblastic differentiation in vitro.