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Sample records for human detrusor smooth

  1. Cultured smooth muscle cells of the human vesical sphincter are more sensitive to histamine than are detrusor smooth muscle cells.

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    Neuhaus, Jochen; Oberbach, Andreas; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe

    2006-05-01

    To compare histamine receptor expression in cultured smooth muscle cells from the human detrusor and internal sphincter using receptor-specific agonists. Smooth muscle cells from the bladder dome and internal sphincter were cultured from 5 male patients undergoing cystectomy for bladder cancer therapy. Calcium transients in cells stimulated with carbachol, histamine, histamine receptor 1 (H1R)-specific heptanecarboxamide (HTMT), dimaprit (H2R), and R-(alpha)-methylhistamine (H3R) were measured by calcium imaging. Histamine receptor proteins were detected by Western blot analysis and immunocytochemistry. H1R, H2R, and H3R expression was found in tissue and cultured cells. Carbachol stimulated equal numbers of detrusor and sphincter cells (60% and 51%, respectively). Histamine stimulated significantly more cells than carbachol in detrusor (100%) and sphincter (99.34%) cells. Calcium responses to carbachol in detrusor and sphincter cells were comparable and did not differ from those to histamine in detrusor cells. However, histamine and specific agonists stimulated more sphincter cells than did carbachol (P <0.001), and the calcium increase was greater in sphincter cells than in detrusor cells. Single cell analysis revealed comparable H2R responses in detrusor and sphincter cells, but H1R and H3R-mediated calcium reactions were significantly greater in sphincter cells. Histamine very effectively induces calcium release in smooth muscle cells. In sphincter cells, histamine is even more effective than carbachol regarding the number of reacting cells and the intracellular calcium increase. Some of the variability in the outcome of antihistaminic interstitial cystitis therapies might be caused by the ineffectiveness of the chosen antihistaminic or unintentional weakening of sphincteric function.

  2. Deletion of Dicer in smooth muscle affects voiding pattern and reduces detrusor contractility and neuroeffector transmission.

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    Mardjaneh Karbalaei Sadegh

    Full Text Available MicroRNAs have emerged as important regulators of smooth muscle phenotype and may play important roles in pathogenesis of various smooth muscle related disease states. The aim of this study was to investigate the role of miRNAs for urinary bladder function. We used an inducible and smooth muscle specific Dicer knockout (KO mouse which resulted in significantly reduced levels of miRNAs, including miR-145, miR-143, miR-22, miR125b-5p and miR-27a, from detrusor preparations without mucosa. Deletion of Dicer resulted in a disturbed micturition pattern in vivo and reduced depolarization-induced pressure development in the isolated detrusor. Furthermore, electrical field stimulation revealed a decreased cholinergic but maintained purinergic component of neurogenic activation in Dicer KO bladder strips. The ultrastructure of detrusor smooth muscle cells was well maintained, and the density of nerve terminals was similar. Western blotting demonstrated reduced contents of calponin and desmin. Smooth muscle α-actin, SM22α and myocardin were unchanged. Activation of strips with exogenous agonists showed that depolarization-induced contraction was preferentially reduced; ATP- and calyculin A-induced contractions were unchanged. Quantitative real time PCR and western blotting demonstrated reduced expression of Cav1.2 (Cacna1c. It is concluded that smooth muscle miRNAs play an important role for detrusor contractility and voiding pattern of unrestrained mice. This is mediated in part via effects on expression of smooth muscle differentiation markers and L-type Ca(2+ channels in the detrusor.

  3. TGF-beta1 inhibits Cx43 expression and formation of functional syncytia in cultured smooth muscle cells from human detrusor.

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    Neuhaus, Jochen; Heinrich, Marco; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe

    2009-02-01

    Human detrusor smooth muscle cells (hBSMCs) are coupled by connexin 43 (Cx43)-positive gap junctions to form functional syncytia. Gap junctional communication likely is necessary for synchronised detrusor contractions and is supposed to be altered in voiding disturbances. Other authors have shown that the pleiotropic cytokine TGF-beta1 upregulates Cx43 expression in human aortic smooth muscle cells. In this study, we examined the TGF-beta1 effects on Cx43 expression in cultured hBSMCs. hBSMC cultures, established from patients undergoing cystectomy, were treated with recombinant human TGF-beta1. Cx43 expression was then examined by Western blotting, real-time PCR, and immunocytochemistry. Dye-injection experiments were used to study the size of functional syncytia. Dye-coupling experiments revealed stable formation of functional syncytia in passaged cell cultures (P1-P4). Stimulation with TGF-beta1 led to significant reduction of Cx43 immunoreactivity and coupling. Cx43 protein expression was significantly downregulated and Cx43 mRNA was only 30% of the control level. Interestingly, low phosphorylation species of Cx43 were particularly affected. Our experiments demonstrated a significant down regulation of connexin 43 by TGF-beta1 in cultured hBSMCs. These findings support the view that TGF-beta1 is involved in the pathophysiology of urinary bladder dysfunction.

  4. Low amplitude rhythmic contraction frequency in human detrusor strips correlates with phasic intravesical pressure waves.

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    Colhoun, Andrew F; Speich, John E; Cooley, Lauren F; Bell, Eugene D; Barbee, R Wayne; Guruli, Georgi; Ratz, Paul H; Klausner, Adam P

    2017-08-01

    Low amplitude rhythmic contractions (LARC) occur in detrusor smooth muscle and may play a role in storage disorders such as overactive bladder and detrusor overactivity. The purpose of this study was to determine whether LARC frequencies identified in vitro from strips of human urinary bladder tissue correlate with in vivo LARC frequencies, visualized as phasic intravesical pressure (p ves ) waves during urodynamics (UD). After IRB approval, fresh strips of human urinary bladder were obtained from patients. LARC was recorded with tissue strips at low tension (rhythmic frequency similar to the in vitro LARC frequency quantified in human urinary bladder tissue strips. Further refinements of this technique may help identify subsets of individuals with LARC-mediated storage disorders.

  5. Histamine receptors in human detrusor smooth muscle cells: physiological properties and immunohistochemical representation of subtypes.

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    Neuhaus, Jochen; Weimann, Annett; Stolzenburg, Jens-Uwe; Dawood, Waled; Schwalenberg, Thilo; Dorschner, Wolfgang

    2006-06-01

    The potent inflammatory mediator histamine is released from activated mast cells in interstitial cystitis (IC). Here, we report on the histamine receptor subtypes involved in the intracellular calcium response of cultured smooth muscle cells (cSMC). Fura-2 was used to monitor the calcium response in cSMC, cultured from human detrusor biopsies. The distribution of histamine receptor subtypes was addressed by immunocytochemistry in situ and in vitro. Histamine stimulated a maximum of 92% of the cells (n=335), being more effective than carbachol (70%, n=920). HTMT (H1R-agonist), dimaprit (H2R) and MTH (H3R) lead to significant lower numbers of reacting cells (60, 48 and 54%). Histamine receptor immunoreactivity (H1R, H2R, H3R, H4R) was found in situ and in vitro. Histamine-induced calcium increase is mediated by distinct histamine receptors. Thus, pre-therapeutic evaluation of histamine receptor expression in IC patients may help to optimize therapy by using a patient-specific cocktail of subtype-specific histamine receptor antagonists.

  6. Enhancement of S1P-induced contractile response in detrusor smooth muscle of rats having cystitis.

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    Anjum, Irfan; Denizalti, Merve; Kandilci, Hilmi Burak; Durlu-Kandilci, Nezahat Tugba; Sahin-Erdemli, Inci

    2017-11-05

    Interstitial cystitis is a chronic disease characterized by lower abdominal pain and some nonspecific symptoms including an increase in urinary frequency and urgency. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that controls smooth muscle tone via G-protein coupled receptors (S1P 1-3 receptors). S1P production is known to take place both in physiological states and some pathological situations, such as in overactive bladder syndrome. The intracellular mechanism of S1P-induced contractile response was investigated in β-escin permeabilized detrusor smooth muscle of rats having cyclophosphamide-induced cystitis. The bladder was isolated from rats and detrusor smooth muscle strips were permeabilized with β-escin. S1P (50µM)-induced contraction and calcium sensitization response were significantly increased in cystitis. S1P-induced augmented contractile response was inhibited by S1P 2 receptor antagonist JTE-013 and S1P 3 receptor antagonist suramin. S1P 2 receptor protein expressions were increased in cystitis, where no change was observed in S1P 3 expressions between control and cystitis groups. S1P-induced contraction was reduced by Rho kinase (ROCK) inhibitor Y-27632 and protein kinase C (PKC) inhibitor GF-109203X in both control and cystitis group. S1P-induced increased calcium sensitization response was decreased by ROCK inhibitor and PKC inhibitor in cystitis. Our findings provide the first evidence that interstitial cystitis triggers S1P-induced increase in intracellular calcium in permeabilized detrusor smooth muscle of female rats. Both S1P 2 and S1P 3 receptors are involved in S1P mediated enhanced contractile response. The augmentation in S1P-induced contraction in interstitial cystitis involves both PKC and ROCK pathways of calcium sensitization. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia

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    Tomonori Yamanishi

    2015-06-01

    Full Text Available The aim of this study was to compare the effect of antimuscarinic antagonists on carbachol-induced contraction of normal human bladder and detrusor overactivity associated with benign prostatic hyperplasia (DO/BPH. Samples of human bladder muscle were obtained from patients undergoing total cystectomy for bladder cancer (normal bladder, and those undergoing retropubic prostatectomy for BPH. All of the patients with DO/BPH had detrusor overactivity according to urodynamic studies. Detrusor muscle strips were mounted in 10-ml organ baths containing Krebs solution, and concentration–response curves for carbachol were obtained in the presence of antimuscarinic antagonists (4-DAMP, methoctramine, pirenzepine, tolterodine, solifenacin, trospium, propiverine, oxybutynin, and imidafenacin or vehicle. All antagonists competitively antagonized concentration–response curves to carbachol with high affinities in normal bladder. The rank order of mean pA2 values was as follows: trospium (10.1 > 4-DAMP (9.87, imidafenacin (9.3 > solifenacin (8.8 > tolterodine (8.6 > oxybutynin (8.3 > propiverine (7.7 > pirenzepine (7.4 > methoctramine (6.6. The effects of these antimuscarinic antagonists did not change when tested with DO/BPH bladder, suggesting that each antimuscarinic antagonist has a similar effect in this condition. Schild plots showed a slope corresponding to unity, except for propiverine with DO/BPH detrusor. In conclusion, M3-receptors mainly mediate contractions in human bladder strips with normal state and DO/BPH.

  8. Monitoring Detrusor Oxygenation and Hemodynamics Noninvasively during Dysfunctional Voiding

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    Macnab, Andrew J.; Stothers, Lynn S.; Shadgan, Babak

    2012-01-01

    The current literature indicates that lower urinary tract symptoms (LUTSs) related to benign prostatic hyperplasia (BPH) have a heterogeneous pathophysiology. Pressure flow studies (UDSs) remain the gold standard evaluation methodology for such patients. However, as the function of the detrusor muscle depends on its vasculature and perfusion, the underlying causes of LUTS likely include abnormalities of detrusor oxygenation and hemodynamics, and available treatment options include agents thought to act on the detrusor smooth muscle and/or vasculature. Hence, near infrared spectroscopy (NIRS), an established optical methodology for monitoring changes in tissue oxygenation and hemodynamics, has relevance as a means of expanding knowledge related to the pathophysiology of BPH and potential treatment options. This methodological report describes how to conduct simultaneous NIRS monitoring of detrusor oxygenation and hemodynamics during UDS, outlines the clinical implications and practical applications of NIRS, explains the principles of physiologic interpretation of NIRS voiding data, and proposes an exploratory hypothesis that the pathophysiological causes underlying LUTS include detrusor dysfunction due to an abnormal hemodynamic response or the onset of oxygen debt during voiding. PMID:23019422

  9. Monitoring Detrusor Oxygenation and Hemodynamics Noninvasively during Dysfunctional Voiding

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    Andrew J. Macnab

    2012-01-01

    Full Text Available The current literature indicates that lower urinary tract symptoms (LUTSs related to benign prostatic hyperplasia (BPH have a heterogeneous pathophysiology. Pressure flow studies (UDSs remain the gold standard evaluation methodology for such patients. However, as the function of the detrusor muscle depends on its vasculature and perfusion, the underlying causes of LUTS likely include abnormalities of detrusor oxygenation and hemodynamics, and available treatment options include agents thought to act on the detrusor smooth muscle and/or vasculature. Hence, near infrared spectroscopy (NIRS, an established optical methodology for monitoring changes in tissue oxygenation and hemodynamics, has relevance as a means of expanding knowledge related to the pathophysiology of BPH and potential treatment options. This methodological report describes how to conduct simultaneous NIRS monitoring of detrusor oxygenation and hemodynamics during UDS, outlines the clinical implications and practical applications of NIRS, explains the principles of physiologic interpretation of NIRS voiding data, and proposes an exploratory hypothesis that the pathophysiological causes underlying LUTS include detrusor dysfunction due to an abnormal hemodynamic response or the onset of oxygen debt during voiding.

  10. CD34-positive interstitial cells of the human detrusor

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    Rasmussen, Helle; Hansen, Alastair; Smedts, Frank

    2007-01-01

    using a panel of antibodies directed against CD117/c-kit, CD34, CD31, S100, tryptase, neurofilament, NSE, Factor-VIII and GFAP. A striking finding was an interstitial type of cell which is CD34 immunoreactive (CD34-ir) but CD117/c-kit negative. The cells have a tentacular morphology, enveloping...... flattened processes, ramifying primarily in a bipolar fashion. Using immunoelectron microscopy (I-TEM) it was possible to view CD34 gold labelling of cells corresponding to interstitial cells. Although similar CD34-positive cells have been demonstrated in the bowel wall, they have never been described...... in the detrusor. The ontogeny and function of CD34-ir, a kit-negative cell, is unknown, but it may be involved in smooth muscle contraction....

  11. Effect of a Carbohydrate-Rich Diet on Rat Detrusor Smooth Muscle Contractility: An Experimental Study

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    Mustafa Suat Bolat

    2017-01-01

    Full Text Available Objectives. We aimed to investigate the effect of a carbohydrate-rich diet on detrusor contractility in rats. Materials and Methods. Sprague-Dawley rats were randomized into two groups. The control group received regular food and water. The study group received carbohydrate-rich diet for six weeks. The rats’ detrusor muscle was isolated for pharmacological and histopathological examinations. Results. In the control and study groups, mean body weights were 431.5 ± 27.6 g and 528.0 ± 36.2 g, respectively (p < 0.001. Electrical stimulation of the detrusor strips of the control group resulted in gradual contraction. A decreased contractile response was shown in the study group. Acetylcholine in 10-7-10-3 molar concentration produced a decreased contractile response in the study group, compared to the control group (p < 0.01. The study group showed marked subepithelial and intermuscular fibrosis in the bladder. Conclusion. Carbohydrate-rich diet causes marked subepithelial and extracellular fibrosis and changes in contractility in the detrusor within a six-week period. Changes have higher costs in therapeutic choices and correction of these changes remains difficult. Putting an end to carbohydrate-rich diet would seem to be more cost-effective than dealing with the effects of consuming it in high proportions which should be the national policy worldwide.

  12. NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels

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    Parajuli, Shankar P; Hristov, Kiril L; Soder, Rupal P; Kellett, Whitney F; Petkov, Georgi V

    2013-01-01

    Background and Purpose Overactive bladder (OAB) is often associated with abnormally increased detrusor smooth muscle (DSM) contractions. We used NS309, a selective and potent opener of the small or intermediate conductance Ca2+-activated K+ (SK or IK, respectively) channels, to evaluate how SK/IK channel activation modulates DSM function. Experimental Approach We employed single-cell RT-PCR, immunocytochemistry, whole cell patch-clamp in freshly isolated rat DSM cells and isometric tension recordings of isolated DSM strips to explore how the pharmacological activation of SK/IK channels with NS309 modulates DSM function. Key Results We detected SK3 but not SK1, SK2 or IK channels expression at both mRNA and protein levels by RT-PCR and immunocytochemistry in DSM single cells. NS309 (10 μM) significantly increased the whole cell SK currents and hyperpolarized DSM cell resting membrane potential. The NS309 hyperpolarizing effect was blocked by apamin, a selective SK channel inhibitor. NS309 inhibited the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated DSM strips in a concentration-dependent manner. The inhibitory effect of NS309 on spontaneous phasic contractions was blocked by apamin but not by TRAM-34, indicating no functional role of the IK channels in rat DSM. NS309 also significantly inhibited the pharmacologically and electrical field stimulation-induced DSM contractions. Conclusions and Implications Our data reveal that SK3 channel is the main SK/IK subtype in rat DSM. Pharmacological activation of SK3 channels with NS309 decreases rat DSM cell excitability and contractility, suggesting that SK3 channels might be potential therapeutic targets to control OAB associated with detrusor overactivity. PMID:23145946

  13. Muscarinic receptor subtypes in porcine detrusor: comparison with humans and regulation by bladder augmentation

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    Goepel, M.; Gronewald, A.; Krege, S.; Michel, M. C.

    1998-01-01

    The properties of muscarinic acetylcholine receptors of porcine and human bladder detrusor were compared in radioligand binding studies using [3H]quinuclidinylbenzylate as the radioligand. The receptor affinity for the radioligand and the density of muscarinic receptors was similar in male and

  14. The cholinergic and purinergic components of detrusor contractility in a whole rabbit bladder model.

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    Chancellor, M B; Kaplan, S A; Blaivas, J G

    1992-09-01

    Whole rabbit bladders were suspended in a bath chamber and stimulated with ATP, bethanechol, electrical field stimulation, and bethanechol + ATP. Detrusor pressure and fluid expelled by the bladder were recorded, synchronized, and digitized. Detrusor work and power were calculated with a computer program. Maximum work was 61.4 +/- 28.7, 83.3 +/- 17.0, 85.0 +/- 15.0, 90.8 +/- 13.1 cm. H2O, ml. for ATP, bethanechol, electrical and bethanechol + ATP, respectively. Maximum power generated by ATP was 4.8 +/- 3.0 cm. H2O, ml./sec and was approximately 66% of that generated by bethanechol, and 50% of that generated by electrical stimulation, and bethanechol + ATP. ATP cannot empty the bladder with moderate outlet resistance while bethanechol and electrical stimulation can. Our results suggest that ATP is able to generate detrusor power and achieve work in bladder emptying. However, ATP generated power and work is considerably less than that of electrical stimulation or bethanechol alone. ATP mediated contraction is not inhibited by atropine or tetrodotoxin but is inhibited by P2 purinoceptor desensitization, suggesting a functional role of purine receptors on detrusor smooth muscle. Since ATP generated pressure is more rapid than with bethanechol alone, we support the hypothesis that ATP may be important in the initiation of micturition.

  15. The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa

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    Dyer David W

    2006-01-01

    Full Text Available Abstract Background An organ such as the bladder consists of complex, interacting set of tissues and cells. Inflammation has been implicated in every major disease of the bladder, including cancer, interstitial cystitis, and infection. However, scanty is the information about individual detrusor and urothelium transcriptomes in response to inflammation. Here, we used suppression subtractive hybridizations (SSH to determine bladder tissue- and disease-specific genes and transcriptional regulatory elements (TREs. Unique TREs and genes were assembled into putative networks. Results It was found that the control bladder mucosa presented regulatory elements driving genes such as myosin light chain phosphatase and calponin 1 that influence the smooth muscle phenotype. In the control detrusor network the Pax-3 TRE was significantly over-represented. During development, the Pax-3 transcription factor (TF maintains progenitor cells in an undifferentiated state whereas, during inflammation, Pax-3 was suppressed and genes involved in neuronal development (synapsin I were up-regulated. Therefore, during inflammation, an increased maturation of neural progenitor cells in the muscle may underlie detrusor instability. NF-κB was specifically over-represented in the inflamed mucosa regulatory network. When the inflamed detrusor was compared to control, two major pathways were found, one encoding synapsin I, a neuron-specific phosphoprotein, and the other an important apoptotic protein, siva. In response to LPS-induced inflammation, the liver X receptor was over-represented in both mucosa and detrusor regulatory networks confirming a role for this nuclear receptor in LPS-induced gene expression. Conclusion A new approach for understanding bladder muscle-urothelium interaction was developed by assembling SSH, real time PCR, and TRE analysis results into regulatory networks. Interestingly, some of the TREs and their downstream transcripts originally involved in

  16. Functional investigation of β-adrenoceptors in human isolated detrusor focusing on the novel selective β3-adrenoceptor agonist KUC-7322

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    Igawa, Yasuhiko; Schneider, Tim; Yamazaki, Yoshinobu; Tatemichi, Satoshi; Homma, Yukio; Nishizawa, Osamu; Michel, Martin C.

    2012-01-01

    This study aimed to characterize the β-adrenoceptor (β-AR) subtype mediating relaxation of isolated human bladder strips and to explore relaxation by the novel β3-AR-selective agonist KUC-7322 for its relaxant effect on the human isolated detrusor and for its effect on the carbachol (CCh)-induced

  17. Highly specific detection of muscarinic M3 receptor, G protein interaction and intracellular trafficking in human detrusor using Proximity Ligation Assay (PLA).

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    Berndt-Paetz, Mandy; Herbst, Luise; Weimann, Annett; Gonsior, Andreas; Stolzenburg, Jens-Uwe; Neuhaus, Jochen

    2018-05-01

    -subtype coupling patterns. Detection of M3 interactions with endocytic trafficking proteins by PLA resulted in object sizes correlating with well-documented vesicle sizes of the endocytosis pathway. PLA enabled highly specific detection of M3 receptor expression, demonstration of M3/GP differential coupling and intracellular M3 trafficking in human detrusor smooth muscle cells. This new approach minimized background fluorescence and antibody cross-reactions resulting from single antibody application, and enhanced specificity due to the use of two primary antibodies. Use of subcellular markers allowed visualization of subcellular receptor location. PLA/CLSM allows analyses of muscarinic "receptor - G protein - promiscuity" and intracellular trafficking even in bladder paraffin sections and may give new insights into the etiology and pathology of BPS/IC. Copyright © 2018 Elsevier GmbH. All rights reserved.

  18. Bladder contractility is modulated by Kv7 channels in pig detrusor

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    Svalø, Julie; Bille, Michala; Parameswaran Theepakaran, Neeraja

    2013-01-01

    Kv7 channels are involved in smooth muscle relaxation, and accordingly we believe that they constitute potential targets for the treatment of overactive bladder syndrome. We have therefore used myography to examine the function of Kv7 channels in detrusor, i.e. pig bladder, with a view...... relaxation, suggesting that Kv7.2 and/or Kv7.4 channels constitute the subtypes that are relevant to bladder contractility. The effects of retigabine and ML213 were attenuated by pre-incubation with 10µM XE991 (Kv7.1-7.5 channel blocker) (P...

  19. Urinary Bladder Detrusor Dysfunction Symptoms in Lyme Disease

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    Basant K. Puri

    2013-09-01

    Full Text Available Purpose Symptoms of urinary bladder detrusor dysfunction have been rarely reported in Lyme disease. The aim was to carry out the first systematic study to compare the prevalence of such symptoms in a group of Lyme disease patients and a group of matched controls. Methods A questionnaire relating to detrusor function was administered to 17 serologically positive Lyme disease patients and to 18 control subjects. Results The two groups were matched in respect of age, sex, body mass, and mean arterial blood pressure. None of the 35 subjects was taking medication which might affect urinary function and none had undergone a previous operative procedure on the lower urinary tract. Six of the Lyme patients (35% and none of the controls (0% had symptoms of detrusor dysfunction (P<0.01. Conclusions This first systematic controlled study confirms that Lyme disease is associated with urinary bladder detrusor dysfunction. Further evaluation of detrusor function is warranted in this disease.

  20. Radiologic signs of detrusor instability in children

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    Hidalgo Teran, D.G.; Podesta, M.; Mendel, R.

    2004-01-01

    Purpose: To revalue radiologic signs of detrusor instability in children. Material and Methods: Retrospective analysis of videourodynamic studies performed in 85 children consulting for urinary incontinence and/or infection. Patients were free from neuropathic diseases, alterations of the urinary tract, previous surgery or anticholinergic treatment. Images of the bladder coinciding to the peaks of unstable detrusor contractions in patients with unstable bladders, and those at the end of filling in stable bladders were analyzed. Results: Bladder outlets were open in 38 patients and close in 47. Detrusor instability was found in 97 % of those with an open bladder outlet and in 36 % when close. Bladder outlets were open in all cases with contractions stronger than 60 cm.water. All 'spinning-top' urethras were associated to contractions stronger than 70 cm.water. Most false negatives (close bladder outlet in unstable bladders) corresponded to contractions lower than 30 cm.water. Different shapes of the bladder were found irrespective of detrusor instability. Conclusions: 1) An open bladder outlet observed during bladder filling is a reliable sign of significant detrusor instability in children without neuropathy; 2) It is highly specific of instability; 3) Most false negatives coincide with low amplitude contractions; 4) 'Spinning-top' images indicate strong contractions. (author)

  1. Evaluation of flurbiprofen in detrusor instability.

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    Cardozo, L D; Stanton, S L; Robinson, H; Hole, D

    1980-01-01

    Thirty women with detrusor instability (27 cases idiopathic, and three secondary to multiple sclerosis) completed a double-blind, cross-over trial of the prostaglandin synthetase inhibitor flurbiprofen and a placebo, results being evaluated by questionnaire and cystometry. Frequency, urgency, and urge incontinence were all significantly reduced with flurbiprofen (P less than 0.001, P less than 0.025, and P less than 0.025 respectively), as was the detrusor-pressure rise during bladder filling...

  2. Neuromodulation of detrusor hyper-reflexia by functional magnetic stimulation of the sacral roots.

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    Sheriff, M K; Shah, P J; Fowler, C; Mundy, A R; Craggs, M D

    1996-07-01

    To investigate the acute effects of functional magnetic stimulation (FMS) on detrusor hyper-reflexia using a multi-pulse magnetic stimulator. Seven male patients with established and intractable detrusor hyper-reflexia following spinal cord injury were studied. No patient was on medication and none had had previous surgery for detrusor hyper-reflexia. After optimization of magnetic stimulation of S2-S4 sacral anterior roots by recording toe flexor electromyograms, unstable detrusor activity was provoked during cystometry by rapid infusion of fluid into the bladder. The provocation test produced consistent and predictable detrusor hyper-reflexia. On some provocations, supramaximal FMS at 20 pulses/s for 5 s was applied at detrusor pressures which were > 15 cmH2O. Following FMS there was an obvious acute suppression of detrusor hyper-reflexia. There was a profound reduction in detrusor contraction, as assessed by the area under the curves of detrusor pressure with time. Functional magnetic stimulation applied over the sacrum can profoundly suppress detrusor hyper-reflexia in man. It may provide a non-invasive method of assessing patients for implantable electrical neuromodulation devices and as a therapeutic option in its own right.

  3. Detrusor Arreflexia as an End Stage of Neurogenic Bladder in HAM/TSP?

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    Matheus Tannus

    2011-01-01

    Full Text Available The HTLV-1 virus is a known agent involved in the development of HAM/TSP. Past studies have typically observed patients with autonomic dysfunction consisting of detrusor overactivity and detrusor-sphincter dyssynergia, with the occasional observation of underactive detrusor or detrusor arreflexia. However, studies have not yet evaluated the progression of neurogenic bladder over time. In this paper, we describe a HAM/TSP patient with the initial development of overactive detrusor, and subsequent development of detrusor arreflexia. Given a paucity of studies characterizing the effects of HTLV-1 on the autonomic nervous system, particularly aspects controlling continence, this patient's clinical course may represent one type of end point for patients with HAM/TSP and neurogenic bladder. Further cohort or case-series studies, with particular emphasis on the progression of neurogenic bladder, are needed to evaluate the significance of this described case in relation to typical disease progression patterns.

  4. Detrusor Acontractility after Acute Spinal Cord Injury-Myth or Reality?

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    Bywater, Mirjam; Tornic, Jure; Mehnert, Ulrich; Kessler, Thomas M

    2018-01-17

    We assessed urodynamic parameters within the first 40 days after spinal cord injury to investigate whether the detrusor is acontractile during the acute phase of spinal cord injury. We performed a prospective cohort study in 54 patients with neurogenic lower urinary tract dysfunction due to acute spinal cord injury who underwent urodynamic investigation within the first 40 days after injury at a single university spinal cord injury center. Urodynamic investigation revealed an acontractile detrusor in only 20 of the 54 patients (37%) but unfavorable urodynamic parameters in 34 (63%). We found detrusor overactivity in 32 patients, detrusor-sphincter dyssynergia in 25, maximum storage detrusor pressure greater than 40 cm H 2 O in 17, vesicoureteral reflux in 3 and low bladder compliance (less than 20 ml/cm H 2 O) in 1. More than 1 unfavorable urodynamic parameter per patient was possible. In contrast to the common notion of an acontractile detrusor during acute spinal cord injury, almost two-thirds of our patients showed unfavorable urodynamic parameters within the first 40 days after spinal cord injury. Considering that early treatment of neurogenic lower urinary tract dysfunction in patients with acute spinal cord injury might improve the long-term urological outcome, urodynamic investigation should be performed timely to optimize patient tailored therapy. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. Neuromodulation: urodynamic effects of sacral (S3) spinal nerve stimulation in patients with detrusor instability or detrusor hyperflexia.

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    Bosch, J L; Groen, J

    1998-05-01

    The aim of this study was to determine the urodynamic effects of sacral (S3) nerve stimulation in patients with urge incontinence due to detrusor overactivity which has been refractory to conservative treatment. A total of 24 patients with idiopathic detrusor instability and five with neurogenic hyperreflexia were studied urodynamically before and 6 months after a permanent S3 foramen electrode implant. The urodynamic studies at follow-up were done with the stimulus on. Clinically, the average voiding frequency, the number of leakage episodes and pad use per 24 h decreased significantly. Improvement in several urodynamic parameters was noted. In the idiopathic as well as in the neurogenic group, the correlation between symptomatic and urodynamic improvement was incomplete. Neuromodulation leads to improvement of several urodynamic parameters in patients with urge incontinence due to detrusor overactivity which has been refractory to conservative treatment and appears to be a valuable treatment option in these patients.

  6. Novel role for the transient potential receptor melastatin 4 channel in guinea pig detrusor smooth muscle physiology

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    Smith, Amy C.; Hristov, Kiril L.; Cheng, Qiuping; Xin, Wenkuan; Parajuli, Shankar P.; Earley, Scott; Malysz, John

    2013-01-01

    Members of the transient receptor potential (TRP) channel superfamily, including the Ca2+-activated monovalent cation-selective TRP melastatin 4 (TRPM4) channel, have been recently identified in the urinary bladder. However, their expression and function at the level of detrusor smooth muscle (DSM) remain largely unexplored. In this study, for the first time we investigated the role of TRPM4 channels in guinea pig DSM excitation-contraction coupling using a multidisciplinary approach encompassing protein detection, electrophysiology, live-cell Ca2+ imaging, DSM contractility, and 9-phenanthrol, a recently characterized selective inhibitor of the TRPM4 channel. Western blot and immunocytochemistry experiments demonstrated the expression of the TRPM4 channel in whole DSM tissue and freshly isolated DSM cells with specific localization on the plasma membrane. Perforated whole cell patch-clamp recordings and real-time Ca2+ imaging experiments with fura 2-AM, both using freshly isolated DSM cells, revealed that 9-phenanthrol (30 μM) significantly reduced the cation current and decreased intracellular Ca2+ levels. 9-Phenanthrol (0.1–30 μM) significantly inhibited spontaneous, 0.1 μM carbachol-induced, 20 mM KCl-induced, and nerve-evoked contractions in guinea pig DSM-isolated strips with IC50 values of 1–7 μM and 70–80% maximum inhibition. 9-Phenanthrol also reduced nerve-evoked contraction amplitude induced by continuous repetitive electrical field stimulation of 10-Hz frequency and shifted the frequency-response curve (0.5–50 Hz) relative to the control. Collectively, our data demonstrate the novel finding that TRPM4 channels are expressed in guinea pig DSM and reveal their critical role in the regulation of guinea pig DSM excitation-contraction coupling. PMID:23302778

  7. Do β3-adrenergic receptors play a role in guinea pig detrusor smooth muscle excitability and contractility?

    Science.gov (United States)

    Afeli, Serge A. Y.; Hristov, Kiril L.

    2012-01-01

    In many species, β3-adrenergic receptors (β3-ARs) have been reported to play a primary role in pharmacologically induced detrusor smooth muscle (DSM) relaxation. However, their role in guinea pig DSM remains controversial. The aim of this study was to investigate whether β3-ARs are expressed in guinea pig DSM and to evaluate how BRL37344 and L-755,507, two selective β3-AR agonists, modulate guinea pig DSM excitability and contractility. We used a combined experimental approach including RT-PCR, patch-clamp electrophysiology, and isometric DSM tension recordings. β3-AR mRNA message was detected in freshly isolated guinea pig DSM single cells. BRL37344 but not L-755,507 caused a slight decrease in DSM spontaneous phasic contraction amplitude and frequency in a concentration-dependent manner. In the presence of atropine (1 μM), only the spontaneous phasic contractions frequency was inhibited by BRL37344 at higher concentrations. Both BRL37344 and L-755,507 significantly decreased DSM carbachol-induced phasic and tonic contractions in a concentration-dependent manner. However, only BRL37344 inhibitory effect was partially antagonized by SR59230A (10 μM), a β3-AR antagonist. In the presence of atropine, BRL37344 and L-755,507 had no inhibitory effect on electrical field stimulation-induced contractions. Patch-clamp experiments showed that BRL37344 (100 μM) did not affect the DSM cell resting membrane potential and K+ conductance. Although β3-ARs are expressed at the mRNA level, they play a minor to no role in guinea pig DSM spontaneous contractility without affecting cell excitability. However, BRL37344 and L-755,507 have pronounced inhibitory effects on guinea pig DSM carbachol-induced contractions. The study outlines important DSM β3-ARs species differences. PMID:21993887

  8. Detrusor after-contraction: a new insight

    Directory of Open Access Journals (Sweden)

    Françoise A. Valentini

    2015-06-01

    Full Text Available ABSTRACTAims:Detrusor after-contractions (DAC are non-common in adults. Both definition (nothing in ICS reports and significance (artefact, link with detrusor overactivity (DO or bladder outlet obstruction (BOO remain discussed. Our purpose was to carry out an analysis of the urodynamic parameters during voidings with DAC and, using the VBN model, to simulate pathophysiological conditions able to explain both voiding phase and DAC.Materials and Methods:From large urodynamic database of patients referred for evaluation of lower urinary tract dysfunction, DAC were observed in 60 patients (5.7%. Criteria for DAC were post-void residual 10cmH2O. VBN model was used for analysis of both pressure and flow curves, and simulations of pathophysiological conditions.Results:Onset of DAC (ODAC occurred when Q=7.3±5.7mL/s and bladder volume=17.9±15.4mL. Urgency-frequency syndrome and urodynamic diagnosis of DO were the more frequent scenarios associated with DAC. ODAC was associated to an inversion of the slope of detrusor pressure curve without any perturbation in flow curve. Among tested pathophysiological hypothesis (great, abnormal, detrusor force, sphincter contraction, none allowed restoring all recorded curves (flow rate, voiding pressure and DAC.Conclusion:No urodynamic characteristic of the first part of voiding is an index of occurrence of DAC. ODAC is a significant phenomenon linked with the bladder collapse. DAC is not associated with BOO but more probably with DO and appears as the result of local conditions in an almost empty bladder (concentration of stresses around a transducer; thus DAC seems of weak clinical significance.

  9. Botulinum Toxin in Neurogenic Detrusor Overactivity

    Directory of Open Access Journals (Sweden)

    Carlos Arturo Levi D'Ancona

    2012-09-01

    Full Text Available Purpose To evaluate the effects of botulinum toxin on urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity. Methods Thirty four adult patients with spinal cord injury and detrusor overactivity were selected. The patients received 300 units of botulinum toxin type A. The endpoints evaluated with the episodes of urinary incontinence and measured the maximum cystometric capacity, maximum amplitude of detrusor pressure and bladder compliance at the beginning and end of the study (24 weeks and evaluated the quality of life by applying the Qualiveen questionnaire. Results A significant decrease in the episodes of urinary incontinence was observed. All urodynamic parameters presented a significant improvement. The same was observed in the quality of life index and the specific impact of urinary problems scores from the Qualiveen questionnaire. Six patients did not complete the study, two due to incomplete follow-up, and four violated protocol and were excluded from the analyses. No systemic adverse events of botulinum toxin type A were reported. Conclusions A botulinum toxin type A showed a significantly improved response in urodynamics parameters and specific and general quality of life.

  10. Effects of electroacupuncture at BL33 on detrusor smooth muscle activity in a rat model of urinary retention.

    Science.gov (United States)

    Liu, Xiaoxu; Liu, Kun; Zhi, Mujun; Mo, Qian; Gao, Xinyan; Liu, Zhishun

    2017-12-01

    Detrusor smooth muscle (DSM) underactivity may lead to urinary retention (UR). Electroacupuncture (EA) at BL33 may be effective in improving DSM contractions. This study aimed to investigate: (1) the effect of EA at BL33; and (2) the effect of different manipulation methods at BL33 on the modulation of DSM contractions in UR rats. 30 male Sprague-Dawley rats were anaesthetised with urethane and modelled by urethral outlet obstruction. First, 2 Hz EA at BL33, SP6 and LI4 wasrandomly applied to the UR rats for 5 min to observe the immediate effects (n=10); second, manual acupuncture (MA) (n=10) and 100 Hz EA (n=10) were applied with the same programme. DSM electromyography (EMG) and cystometrogram data were evaluated. (1) 2 Hz EA at BL33 and SP6 significantly increased DSM discharging frequency (0.80±0.10 Hz, P0.05). Compared with SP6, EA at BL33 had greater positive effects on DSM discharging frequency, duration of discharging, and duration of voiding (all P<0.05). (2) No statistically significant differences were shown between MA, 2 Hz EA and 100 Hz EA interventions when stimulating at BL33, SP6 or LI4. EA at BL33 improved DSM contractions to a greater degree than EA at SP6 or LI4. There were no differences in effect when stimulating using 2 Hz EA, 100 Hz EA and MA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Renal deterioration after spinal cord injury is associated with length of detrusor contractions during cystometry

    DEFF Research Database (Denmark)

    Elmelund, Marlene; Klarskov, Niels; Bagi, Per

    2017-01-01

    AIMS: To investigate which urodynamic parameters are associated with renal deterioration over a median of 41 years follow-up after traumatic spinal cord injury. METHODS: Medical records of patients with a traumatic spinal cord injury sustained 1944-1975 were reviewed from time of injury until 2012....... Patients who attended regular renography and/or renal clearance examinations and had minimum one cystometry and pressure-flow study were included. Renal deterioration was diagnosed as split renal function ≤30% in one kidney or relative glomerular filtration rate ≤51% of expected according to age and gender....... Detrusor function, presence of detrusor sphincter dyssynergia, maximum detrusor pressure, post-void residual volume, and cystometric bladder capacity were obtained. In patients with detrusor overactivity, a detrusor overactivity/cystometry ratio was calculated using duration of detrusor contraction...

  12. Relation between flexor spasms, uninhibited detrusor contractions and anal sphincter activity

    DEFF Research Database (Denmark)

    Pedersen, E; Petersen, T; Schrøder, H D

    1986-01-01

    The time relation between flexor spasms, detrusor contractions and anal sphincter activity was recorded in a consecutive series of 111 patients with hyperreflexic bladder and flexor spasms. In 76 of the patients flexor spasms were preceded by detrusor contractions. The opposite pattern, namely de...

  13. Is Detrusor Contraction during Rapid Bladder Filling Caused by Cold or Warm Water? A Randomized, Controlled, Double-Blind Trial.

    Science.gov (United States)

    Kozomara, Marko; Mehnert, Ulrich; Seifert, Burkhardt; Kessler, Thomas M

    2018-01-01

    We investigated whether detrusor contraction during rapid bladder filling is provoked by cold or warm water. Patients with neurogenic lower urinary tract dysfunction were included in this randomized, controlled, double-blind trial. At the end of a standard urodynamic investigation patients underwent 2 bladder fillings using a 4C ice water test or a 36C warm water test saline solution at a filling speed of 100 ml per minute. The order was randomly selected, and patients and investigators were blinded to the order. The primary outcome measure was detrusor overactivity, maximum detrusor pressure and maximum bladder filling volume during the ice and warm water tests. Nine women and 31 men were the subject of data analysis. Neurogenic lower urinary tract dysfunction was caused by spinal cord injury in 33 patients and by another neurological disorder in 7. Irrespective of test order detrusor overactivity occurred significantly more often during the ice water test than during the warm water test (30 of 40 patients or 75% vs 25 of 40 or 63%, p = 0.02). When comparing the ice water test to the warm water test, maximum detrusor pressure was significantly higher and maximum bladder filling volume was significantly lower during the ice water test (each p warm water first) had no effect on the parameters. Our findings imply that the more frequent detrusor overactivity, higher maximum detrusor pressure and lower bladder filling volume during the ice water test compared to the warm water test were caused by cold water. This underlies the theory of a C-fiber mediated bladder cooling reflex in humans. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  14. Detrusor overactivity in diabetic and non-diabetic patients: is there a difference?

    LENUS (Irish Health Repository)

    Golabek, Tomasz

    2013-07-22

    To compare urodynamic characteristics in patients with idiopathic detrusor overactivity (IDO) with those of an age matched cohort with diabetes mellitus (DM) and detrusor overactivity (DO). Secondly, to determine whether urodynamic features could help distinguish these two groups of patients.

  15. Interleukin-4 and 13 induce the expression and release of monocyte chemoattractant protein 1, interleukin-6 and stem cell factor from human detrusor smooth muscle cells: synergy with interleukin-1beta and tumor necrosis factor-alpha

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Andresen, Lars; Alvarez, Susana

    2006-01-01

    Interstitial cystitis is characterized by an increased number of activated MCs in the detrusor muscle. However, to our knowledge the factors that influence the anatomical relationship between MCs and HDSMCs are unknown. MCP-1, IL-6 and SCF have a critical role in the regulation of MC development,......, signaling and function. We investigated whether HDSMCs are capable of expressing and releasing MCP-1, IL-6 and SCF in response to IL-4, IL-13, IL-1beta and tumor necrosis factor-alpha.......Interstitial cystitis is characterized by an increased number of activated MCs in the detrusor muscle. However, to our knowledge the factors that influence the anatomical relationship between MCs and HDSMCs are unknown. MCP-1, IL-6 and SCF have a critical role in the regulation of MC development...

  16. Blebbistain, a myosin II inhibitor, as a novel strategy to regulate detrusor contractility in a rat model of partial bladder outlet obstruction.

    Directory of Open Access Journals (Sweden)

    Xinhua Zhang

    Full Text Available Partial bladder outlet obstruction (PBOO, a common urologic pathology mostly caused by benign prostatic hyperplasia, can coexist in 40-45% of patients with overactive bladder (OAB and is associated with detrusor overactivity (DO. PBOO that induces DO results in alteration in bladder myosin II type and isoform composition. Blebbistatin (BLEB is a myosin II inhibitor we recently demonstrated potently relaxed normal detrusor smooth muscle (SM and reports suggest varied BLEB efficacy for different SM myosin (SMM isoforms and/or SMM vs nonmuscle myosin (NMM. We hypothesize BLEB inhibition of myosin II as a novel contraction protein targeted strategy to regulate DO. Using a surgically-induced male rat PBOO model, organ bath contractility, competitive and Real-Time-RT-PCR were performed. It was found that obstructed-bladder weight significantly increased 2.74-fold while in vitro contractility of detrusor to various stimuli was impaired ∼50% along with decreased shortening velocity. Obstruction also altered detrusor spontaneous activities with significantly increased amplitude but depressed frequency. PBOO switched bladder from a phasic-type to a more tonic-type SM. Expression of 5' myosin heavy chain (MHC alternatively spliced isoform SM-A (associated with tonic-type SM increased 3-fold while 3' MHC SM1 and essential light chain isoform MLC(17b also exhibited increased relative expression. Total SMMHC expression was decreased by 25% while the expression of NMM IIB (SMemb was greatly increased by 4.5-fold. BLEB was found to completely relax detrusor strips from both sham-operated and PBOO rats pre-contracted with KCl, carbachol or electrical field stimulation although sensitivity was slightly decreased (20% only at lower doses for PBOO. Thus we provide the first thorough characterization of the response of rat bladder myosin to PBOO and demonstrate complete BLEB-induced PBOO bladder SM relaxation. Furthermore, the present study provides valuable

  17. Idiopathic detrusor sphincter dyssynergia in neurologically normal patients with voiding abnormalities

    DEFF Research Database (Denmark)

    Jørgensen, T M; Djurhuus, J C; Schrøder, H D

    1982-01-01

    Symptomatology and clinical manifestations of detrusor sphincter dyssynergia are described in 23 patients without neurological disease. Their cardinal symptoms were recurrent cystitis, enuresis, frequent voiding, back pain during voiding and anal discomfort. The major objective finding was vesico......Symptomatology and clinical manifestations of detrusor sphincter dyssynergia are described in 23 patients without neurological disease. Their cardinal symptoms were recurrent cystitis, enuresis, frequent voiding, back pain during voiding and anal discomfort. The major objective finding...... was vesicoureteral reflux in 11 cases with kidney scarring in 10. Bladder trabeculation was found in 13 patients, bladder hyperreflexia in 8, and significant residual urine in 16 patients. The etiology of detrusor sphincter dyssynergia in non-neurological patients is discussed. By means of exclusion it is most...

  18. The novel β3-adrenoceptor agonist mirabegron reduces carbachol-induced contractile activity in detrusor tissue from patients with bladder outflow obstruction with or without detrusor overactivity

    DEFF Research Database (Denmark)

    Svalø, Julie; Nordling, Jørgen; Bouchelouche, Kirsten

    2013-01-01

    preparations from patients with bladder outflow obstruction (BOO) with and without detrusor overactivity (DO), and from patients with normal bladder function. We compared the effects to those of isoprenaline, a non-selective β-adrenoceptor agonist. Detrusor specimens were obtained from patients with benign...... carbachol-induced tone in tissues from all groups. Isoprenaline decreased tension with higher potency than mirabegron in normal, BOO and BOO+DO detrusor strips with pIC(50) values of 7.49 ± 0.16 vs. 6.23 ± 0.26 (P=0.0002), 6.89 ± 0.34 vs. 6.04 ± 0.31 (P=0.01), and 6.57 ± 0.20 vs. 5.41 ± 0.08 (P...), respectively. The maximal relaxant effect of isoprenaline and mirabegron in the normal, BOO and BOO+DO detrusor was 37.7 ± 14.4% and 36.1 ± 23.3%, 14.4 ± 12.2% vs. 33.4 ± 21.0% and 18.3 ± 10.0% vs. 28.3 ± 12.2% (n=4, P>0.05), respectively. Mirabegron and isoprenaline reduced carbachol-induced tone in both...

  19. A urodynamic study of surface neuromodulation versus sham in detrusor instability and sensory urgency.

    Science.gov (United States)

    Bower, W F; Moore, K H; Adams, R D; Shepherd, R

    1998-12-01

    We studied the effect of surface neuromodulation on cystometric pressure and volume parameters in women with detrusor instability or sensory urgency. Electrical current was delivered to the suprapubic region and third sacral foramina via a transcutaneous electrical nerve stimulator with sham neuromodulation control. A consecutive series of women with proved detrusor instability or sensory urgency were randomized to 3 surface neuromodulation groups. Volume and pressure parameters were the main outcomes of transcutaneous electrical nerve stimulation applied during second cystometric fill. Sham transcutaneous electrical nerve stimulation did not alter the outcome measures. However, neuromodulation delivered across the suprapubic and sacral skin effected a reduction in mean maximum height of detrusor contraction. A current which inhibits motor activity was not superior to that which inhibits sensory perception in reducing detrusor pressure. Response in sensory urgency was poor. Results from our sham controlled study suggest that short-term surface neuromodulation via transcutaneous electrical nerve stimulation may have a role in the treatment of detrusor instability. Future studies must examine the clinical effect of long-term surface neuromodulation.

  20. Expression and function of K(V)2-containing channels in human urinary bladder smooth muscle.

    Science.gov (United States)

    Hristov, Kiril L; Chen, Muyan; Afeli, Serge A Y; Cheng, Qiuping; Rovner, Eric S; Petkov, Georgi V

    2012-06-01

    The functional role of the voltage-gated K(+) (K(V)) channels in human detrusor smooth muscle (DSM) is largely unexplored. Here, we provide molecular, electrophysiological, and functional evidence for the expression of K(V)2.1, K(V)2.2, and the electrically silent K(V)9.3 subunits in human DSM. Stromatoxin-1 (ScTx1), a selective inhibitor of K(V)2.1, K(V)2.2, and K(V)4.2 homotetrameric channels and of K(V)2.1/9.3 heterotetrameric channels, was used to examine the role of these channels in human DSM function. Human DSM tissues were obtained during open bladder surgeries from patients without a history of overactive bladder. Freshly isolated human DSM cells were studied using RT-PCR, immunocytochemistry, live-cell Ca(2+) imaging, and the perforated whole cell patch-clamp technique. Isometric DSM tension recordings of human DSM isolated strips were conducted using tissue baths. RT-PCR experiments showed mRNA expression of K(V)2.1, K(V)2.2, and K(V)9.3 (but not K(V)4.2) channel subunits in human isolated DSM cells. K(V)2.1 and K(V)2.2 protein expression was confirmed by Western blot analysis and immunocytochemistry. Perforated whole cell patch-clamp experiments revealed that ScTx1 (100 nM) inhibited the amplitude of the voltage step-induced K(V) current in freshly isolated human DSM cells. ScTx1 (100 nM) significantly increased the intracellular Ca(2+) level in DSM cells. In human DSM isolated strips, ScTx1 (100 nM) increased the spontaneous phasic contraction amplitude and muscle force, and enhanced the amplitude of the electrical field stimulation-induced contractions within the range of 3.5-30 Hz stimulation frequencies. These findings reveal that ScTx1-sensitive K(V)2-containing channels are key regulators of human DSM excitability and contractility and may represent new targets for pharmacological or genetic intervention for bladder dysfunction.

  1. Chronic treatment with fluoxetine and sertraline prevents forced swimming test-induced hypercontractility of rat detrusor muscle.

    Science.gov (United States)

    Bilge, Sirri; Bozkurt, Ayhan; Bas, Duygu B; Aksoz, Elif; Savli, Evren; Ilkaya, Fatih; Kesim, Yuksel

    2008-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors represent important targets for the development of new treatments for detrusor overactivity and urinary incontinence. The present study was undertaken to investigate the effects of the forced swimming test (FST) on the contractile response of isolated rat detrusor muscle and to examine the effects of in vivo treatments of fluoxetine and sertraline on altered detrusor muscle contractility. Fluoxetine (20 mg/kg ip) and sertraline (10 mg/kg ip) were administered once a day for 14 days. Rats were exposed to the FST on the 15th day. After the test, detrusor muscles were removed and placed in organ baths, and the contraction responses induced by carbachol, potassium chloride (KCl) and electrical field stimulation (EFS) were recorded. The contractile responses of detrusor muscle strips to carbachol and electrical field stimulation were found to be increased at all carbachol doses and frequencies, respectively. FST also increased the contractile responses to KCl, which is used to test the differences in postreceptor-mediated contractions. The hypercontractile responses of detrusor strips to carbachol, EFS and KCl were abolished by treatment with both fluoxetine and sertraline. These treatments also decreased the immobility duration in the FST consistent with an antidepressant-like effect in this test. The results of this study provide the first evidence that FST increases contractility of the rat detrusor muscle, and this hypercontractility was abolished by chronic treatments of fluoxetine and sertraline at antidepressant doses by decreasing the postreceptor-mediated events.

  2. Detrusor instability in children with recurrent urinary tract infection and/or enuresis. I

    DEFF Research Database (Denmark)

    Qvist, N; Kristensen, E S; Nielsen, K K

    1986-01-01

    Forty-one children, aged 5-15 years, were referred because of recurrent urinary infections and/or enuresis. They were examined prospectively by means of cystometry. CO2 cystometry revealed detrusor instability in 18 children (44%), but if complete reproducibility were to be requested in repeated ...... tests, only 7 children (17%) would have presented instability. Detrusor instability was not significantly related to definite pathological changes in the urinary tract or to irritative bladder symptoms.......Forty-one children, aged 5-15 years, were referred because of recurrent urinary infections and/or enuresis. They were examined prospectively by means of cystometry. CO2 cystometry revealed detrusor instability in 18 children (44%), but if complete reproducibility were to be requested in repeated...

  3. Failure of botulinum toxin injection for neurogenic detrusor overactivity: Switch of toxin versus second injection of the same toxin.

    Science.gov (United States)

    Peyronnet, Benoit; Castel-Lacanal, Evelyne; Manunta, Andréa; Roumiguié, Mathieu; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

    2015-12-01

    To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs. 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs. 50%, P = 0.88). After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results. © 2015 The Japanese Urological Association.

  4. Muscarinic receptors mediate cold stress-induced detrusor overactivity in type 2 diabetes mellitus rats.

    Science.gov (United States)

    Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Gautam, Sudha Silwal; Nishizawa, Osamu

    2014-10-01

    This study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type 2 diabetes mellitus rats. Ten-week-old female Goto-Kakizaki diabetic rats (n = 12) and Wister Kyoto non-diabetic rats (n = 12) were maintained on a high-fat diet for 4 weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (27 ± 2°C) for 20 min. They were intravenously administered imidafenacin (0.3 mg/kg, n = 6) or vehicle (n = 6). After 5 min, the rats were transferred to a low temperature (4 ± 2°C) for 40 min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M3 and M2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. In non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M3 to M2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats. Imidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M3 receptors partially mediate cold stress-induced detrusor overactivity. © 2014 The Japanese Urological Association.

  5. Neurogenic detrusor overactivity is associated with decreased expression and function of the large conductance voltage- and Ca(2+-activated K(+ channels.

    Directory of Open Access Journals (Sweden)

    Kiril L Hristov

    Full Text Available Patients suffering from a variety of neurological diseases such as spinal cord injury, Parkinson's disease, and multiple sclerosis often develop neurogenic detrusor overactivity (NDO, which currently lacks a universally effective therapy. Here, we tested the hypothesis that NDO is associated with changes in detrusor smooth muscle (DSM large conductance Ca(2+-activated K(+ (BK channel expression and function. DSM tissue samples from 33 patients were obtained during open bladder surgeries. NDO patients were clinically characterized preoperatively with pressure-flow urodynamics demonstrating detrusor overactivity, in the setting of a clinically relevant neurological condition. Control patients did not have overactive bladder and did not have a clinically relevant neurological disease. We conducted quantitative polymerase chain reactions (qPCR, perforated patch-clamp electrophysiology on freshly-isolated DSM cells, and functional studies on DSM contractility. qPCR experiments revealed that DSM samples from NDO patients showed decreased BK channel mRNA expression in comparison to controls. Patch-clamp experiments demonstrated reduced whole cell and transient BK currents (TBKCs in freshly-isolated DSM cells from NDO patients. Functional studies on DSM contractility showed that spontaneous phasic contractions had a decreased sensitivity to iberiotoxin, a selective BK channel inhibitor, in DSM strips isolated from NDO patients. These results reveal the novel finding that NDO is associated with decreased DSM BK channel expression and function leading to increased DSM excitability and contractility. BK channel openers or BK channel gene transfer could be an alternative strategy to control NDO. Future clinical trials are needed to evaluate the value of BK channel opening drugs or gene therapies for NDO treatment and to identify any possible adverse effects.

  6. Detrusor wall thickness compared to other non-invasivemethods in ...

    African Journals Online (AJOL)

    Introduction: The current study aims to compare the diagnostic accuracy of detrusor wall thickness to othernoninvasive, tools, using pressure flow studies as a reference, in the assessment of bladder outlet, obstructionamong men presenting with lower urinary tract symptoms. Patients and Methods: Men aged 50 or older ...

  7. [Structure and function of suburothelial myofibroblasts in the human urinary bladder under normal and pathological conditions].

    Science.gov (United States)

    Neuhaus, J; Heinrich, M; Schlichting, N; Oberbach, A; Fitzl, G; Schwalenberg, T; Horn, L-C; Stolzenburg, J-U

    2007-09-01

    Myofibroblasts play a pivotal role in numerous pathological alterations. Clarification of the structure and function and of the cellular plasticity of this cell type in the bladder may lead to new insights into the pathogenesis of lower urinary tract disorders. Bladder biopsies from patients with bladder carcinoma and interstitial cystitis were used to analyse the morphology and receptor expression using confocal immunofluorescence and electron microscopy. Cytokine effects and coupling behavior were tested in cultured myofibroblasts and detrusor smooth muscle cells. Myofibroblasts are in close contact with the suburothelial capillary network. They express Cx43 and form functional syncytia. The expression of muscarinic and purinergic receptors is highly variable. Dye coupling experiments showed differences to detrusor myocytes. Upregulation of smooth muscle cell alpha-actin and/or transdifferentiation into smooth muscle cells may contribute to the etiology of urge incontinence. A multi-step model is presented as a working hypothesis.

  8. Characterization of muscarinic and P2X receptors in the urothelium and detrusor muscle of the rat bladder

    Directory of Open Access Journals (Sweden)

    Masaki Ogoda

    2016-05-01

    Full Text Available Muscarinic and purinergic (P2X receptors play critical roles in bladder urothelium under physiological and pathological conditions. Aim of present study was to characterize these receptors in rat bladder urothelium and detrusor muscle using selective radioligands of [N-methyl-3H]scopolamine methyl chloride ([3H]NMS and αβ-methylene ATP [2,8-3H]tetrasodium salt ([3H]αβ-MeATP. Similar binding parameters for each radioligand were observed in urothelium and detrusor muscle. Pretreatment with N-(2-chloroethyl-4-piperidinyl diphenylacetate (4-DAMP mustard mustard revealed co-existence of M2 and M3 receptors, with the number of M2 receptors being larger in the urothelium and detrusor muscle. Intravesical administration of imidafenacin and Dpr-P-4 (N → O (active metabolite of propiverine displayed significant binding of muscarinic receptors in the urothelium and detrusor muscle. The treatment with cyclophosphamide (CYP or resiniferatoxin (RTX resulted in a significant decrease in maximal number of binding sites (Bmax for [3H]NMS and/or [3H]αβ-MeATP in the urothelium and detrusor muscle. These results demonstrated that 1 pharmacological characteristics of muscarinic and P2X receptors in rat bladder urothelium were similar to those in the detrusor muscle, 2 that densities of these receptors were significantly altered by pretreatments with CYP and RTX, and 3 that these receptors may be pharmacologically affected by imidafenacin and Dpr-P-4 (N → O which are excreted in the urine.

  9. Beta adrenoreceptors in the rabbit bladder detrusor muscle

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, G.F.; Marks, B.H.

    1984-02-01

    This study examines the beta adrenergic receptors of the rabbit detrusor smooth muscle, employing (/sup 125/I)iodocyanopindolol (ICYP) as a ligand for the binding of beta adrenergic receptors. Saturation binding experiments on the isolated membrane fraction yielded a KD for ICYP of 14.7 pM and a maximum binding of 147.6 fmol/mg of protein. Displacement of labeled ICYP by a series of beta adrenergic agents yielded the following KD values for the combined high and low affinity binding sites: I-propranolol, 0.76 nM; ICI 118,551, 1.7 nM; zinterol, 38.0 nM; metoprolol, 3.5 microM; and practolol, 61.4 microM. When these displacement experimental results were compared to KD values from other reported binding studies with ICYP for beta adrenoreceptors, both the order of potency and the KD values indicated primarily beta-2 adrenergic receptor subtypes. Computer program Scatfit analysis of the displacement curves indicated a single slope and affinity constant for all five beta adrenergic agents. Hofstee plots for zinterol, ICI 118,551 and metoprolol, however, were not linear and indicated that minor populations of beta-1 adrenoreceptors were also present as both high and low affinity binding sites could be defined. It is concluded that the primary receptor population is beta-2 and that this tissue is heterogenous with a small population of beta-1 adrenoreceptors representing approximately 13 to 23% of the total beta adrenoreceptor population.

  10. Beta adrenoreceptors in the rabbit bladder detrusor muscle

    International Nuclear Information System (INIS)

    Anderson, G.F.; Marks, B.H.

    1984-01-01

    This study examines the beta adrenergic receptors of the rabbit detrusor smooth muscle, employing [ 125 I]iodocyanopindolol (ICYP) as a ligand for the binding of beta adrenergic receptors. Saturation binding experiments on the isolated membrane fraction yielded a KD for ICYP of 14.7 pM and a maximum binding of 147.6 fmol/mg of protein. Displacement of labeled ICYP by a series of beta adrenergic agents yielded the following KD values for the combined high and low affinity binding sites: I-propranolol, 0.76 nM; ICI 118,551, 1.7 nM; zinterol, 38.0 nM; metoprolol, 3.5 microM; and practolol, 61.4 microM. When these displacement experimental results were compared to KD values from other reported binding studies with ICYP for beta adrenoreceptors, both the order of potency and the KD values indicated primarily beta-2 adrenergic receptor subtypes. Computer program Scatfit analysis of the displacement curves indicated a single slope and affinity constant for all five beta adrenergic agents. Hofstee plots for zinterol, ICI 118,551 and metoprolol, however, were not linear and indicated that minor populations of beta-1 adrenoreceptors were also present as both high and low affinity binding sites could be defined. It is concluded that the primary receptor population is beta-2 and that this tissue is heterogenous with a small population of beta-1 adrenoreceptors representing approximately 13 to 23% of the total beta adrenoreceptor population

  11. Botulinum toxin A for treatment of neurogenic detrusor overactivity and incontinence in patients with spinal cord lesions

    DEFF Research Database (Denmark)

    Bagi, Per; Biering-Sørensen, Fin

    2004-01-01

    To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs).......To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs)....

  12. [Definition of botulinum toxin failure in neurogenic detrusor overactivity: Preliminary results of the DETOX survey].

    Science.gov (United States)

    Peyronnet, B; Sanson, S; Amarenco, G; Castel-Lacanal, E; Chartier-Kastler, E; Charvier, K; Damphousse, M; Denys, P; de Seze, M; Egon, G; Even, A; Forin, V; Karsenty, G; Kerdraon, J; le Normand, L; Loche, C-M; Manunta, A; Mouracade, P; Phe, V; Previnaire, J-G; Ruffion, A; Saussine, C; Schurch, B; Game, X

    2015-12-01

    There is currently no guideline regarding the management of neurogenic detrusor overactivity (NDO) refractory to intra-detrusor botulinum toxin injections. The primary objective of the present study was to find a consensus definition of failure of botulinum toxin intra-detrusor injections for NDO. The secondary objective was to report current trends in the managment of NDO refractory to botulinum toxin. A survey was created, based on data drawn from current literature, and sent via e-mail to all the experts form the Group for research in neurourology in french language (GENULF) and from the comittee of neurourology of the French urological association (AFU). The experts who did not answer to the first e-mail were contacted again twice. Main results from the survey are presented and expressed as numbers and proportions. Out of the 42 experts contacted, 21 responded to the survey. Nineteen participants considered that the definition of failure should be a combination of clinical and urodynamics criteria. Among the urodynamics criteria, the persistence of a maximum detrusor pressure>40 cm H2O was the most supported by the experts (18/21, 85%). According to the vast majority of participants (19/21, 90.5%), the impact of injections on urinary incontinence should be included in the definition of failure. Regarding the management, most experts considered that the first line treatment in case of failure of a first intra-detrusor injection of Botox(®) 200 U should be a repeat injection of Botox(®) at a higher dosage (300 U) (15/20, 75%), regardless of the presence or not of urodynamics risk factors of upper tract damage (16/20, 80%). This work has provided a first overview of the definition of failure of intra-detrusor injections of botulinum toxin in the management of NDO. For 90.5% of the experts involved, the definition of failure should be clinical and urodynamic and most participants (75%) considered that, in case of failure of a first injection of Botox(®) 200 U

  13. Pathways Involving Beta-3 Adrenergic Receptors Modulate Cold Stress-Induced Detrusor Overactivity in Conscious Rats.

    Science.gov (United States)

    Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Nishizawa, Osamu

    2015-01-01

    To investigate pathways involving beta-3 adrenergic receptors (ARs) in detrusor overactivity induced by cold stress, we determined if the beta-3 AR agonist CL316243 could modulate the cold stress-induced detrusor overactivity in normal rats. Two days prior to cystometric investigations, the bladders of 10-week-old female Sprague-Dawley rats were cannulated. Cystometric measurements of the unanesthetized, unrestricted rats were taken to estimate baseline values at room temperature (RT, 27 ± 2 °C) for 20 min. They were then intravenously administered vehicle, 0.1, or 1.0 mg/kg CL316243 (n = 6 in each group). Five minutes after the treatments, they were gently and quickly transferred to the low temperature (LT, 4 ± 2 °C) room for 40 min where the cystometric measurements were again made. Afterward, the rats were returned to RT for final cystometric measurements. The cystometric effects of CL316243 were also measured at RT (n = 6 in each group). At RT, both low and high dose of CL316243 decreased basal and micturition pressure while the high dose (1.0 mg/kg) significantly increased voiding interval and bladder capacity. During LT exposure, the high dose of CL316243 partially reduced cold stress-induced detrusor overactivity characterized by increased basal pressure and urinary frequency. The high drug dose also significantly inhibited the decreases of both voiding interval and bladder capacity compared to the vehicle- and low dose (0.1 mg/kg)-treated rats. A high dose of the beta-3 agonist CL316243 could modulate cold stress-induced detrusor overactivity. Therefore, one of the mechanisms in cold stress-induced detrusor overactivity includes a pathway involving beta-3 ARs. © 2014 Wiley Publishing Asia Pty Ltd.

  14. Nuclear fusion-independent smooth muscle differentiation of human adipose-derived stem cells induced by a smooth muscle environment.

    Science.gov (United States)

    Zhang, Rong; Jack, Gregory S; Rao, Nagesh; Zuk, Patricia; Ignarro, Louis J; Wu, Benjamin; Rodríguez, Larissa V

    2012-03-01

    Human adipose-derived stem cells hASC have been isolated and were shown to have multilineage differentiation capacity. Although both plasticity and cell fusion have been suggested as mechanisms for cell differentiation in vivo, the effect of the local in vivo environment on the differentiation of adipose-derived stem cells has not been evaluated. We previously reported the in vitro capacity of smooth muscle differentiation of these cells. In this study, we evaluate the effect of an in vivo smooth muscle environment in the differentiation of hASC. We studied this by two experimental designs: (a) in vivo evaluation of smooth muscle differentiation of hASC injected into a smooth muscle environment and (b) in vitro evaluation of smooth muscle differentiation capacity of hASC exposed to bladder smooth muscle cells. Our results indicate a time-dependent differentiation of hASC into mature smooth muscle cells when these cells are injected into the smooth musculature of the urinary bladder. Similar findings were seen when the cells were cocultured in vitro with primary bladder smooth muscle cells. Chromosomal analysis demonstrated that microenvironment cues rather than nuclear fusion are responsible for this differentiation. We conclude that cell plasticity is present in hASCs, and their differentiation is accomplished in the absence of nuclear fusion. Copyright © 2011 AlphaMed Press.

  15. Can we predict detrusor overactivity in women with lower urinary tract symptoms? The King's Detrusor Overactivity Score (KiDOS)

    OpenAIRE

    Giarenis, Ilias; Musonda, Patrick; Mastoroudes, Heleni; Robinson, Dudley; Cardozo, Linda

    2016-01-01

    Objective Traditionally, urodynamic studies (UDS) have been used to assess lower urinary tract symptoms (LUTS), but their routine use is now discouraged. While urodynamic stress incontinence is strongly associated with the symptom of stress urinary incontinence (SUI) and a positive cough test, there is a weak relationship between symptoms of overactive bladder and detrusor overactivity (DO). The aim of our study was to develop a model to predict DO in women with LUTS. Study Design This prospe...

  16. The effect of intravesical oxybutynin on the ice water test and on electrical perception thresholds in patients with neurogenic detrusor overactivity.

    Science.gov (United States)

    Van Meel, Tom David; De Wachter, Stefan; Wyndaele, Jean Jacques

    2010-03-01

    The C-fiber-mediated bladder-cooling reflex and the determination of the current perception thresholds (CPTs) permit to investigate afferent LUT pathways. They have both been proposed to detect and differentiate neurologic bladder dysfunction. This study evaluates, prospectively, the effect of oxybutynin, an antimuscarinic with direct antispasmodic effect on smooth muscle, on repeated ice water test (IWT) and CPTs in patients with a known incomplete neurogenic bladder. Patients with a known incomplete lesion of the bladder innervation, detrusor overactivity during cystometric bladder filling and a continuous positive response to repeated IWT were included. After the initial tests, 30 mg intravesical oxybutynin (1 mg/ml) was instilled and left in the bladder for 15 min. Afterwards CPTs and IWT were re-assessed. After the drug application, the bladder-cooling reflex could not be initiated, even after three instillations, in 16/17 patients. The bladder CPT increased from 29.7 +/- 11.3 to 39.1 +/- 15.7 mA after oxybutynin (P = 0.001). No difference was found in CPT of the left forearm (P = 0.208). Intravesical oxybutynin blocks the bladder-cooling reflex and increases but does not block CPT sensation in the bladder in most patients with incomplete neurogenic lesion and detrusor overactivity. These results help explain the clinical effect of intravesical oxybutynin in neurogenic patients. They also indicate that a pharmacological local influence on C-fiber-related activity can give different clinical effects. (c) 2009 Wiley-Liss, Inc.

  17. Botulinum toxin A for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    S. Deffontaines-Rufin

    2011-10-01

    Full Text Available PURPOSE: Neurogenic detrusor overactivity (NDO is common in patients who suffer from multiple sclerosis (MS. When the usual pharmacological treatment fails, botulinum toxin type A (BTX-A injections can be proposed. The safety and efficacy of this treatment are already well known, but only a few studies focus on its use in patients with MS. MATERIALS AND METHODS: Seventy-one patients with MS underwent their first BTX-A injection for refractory NDO. They had clinical and urodynamic cystometry assessment before and three months after injection. The patients were divided in three groups according to treatment efficacy: full success (total urinary continence, no overactive detrusor, improvement, or total failure (urge incontinence and overactive detrusor. RESULTS: 77% of the patients had clinical improvement or full success of the treatment with a reduction of their urgency and incontinence. Significant urodynamic improvement after treatment was shown on different parameters: volume at first involuntary bladder contraction (p = 0.0000001, maximum cystometric capacity (p = 0.0035, maximum detrusor pressure (p = 0.0000001. 46% of the patients were in the "full success" group. 31% of the patients had a partial improvement. 23% of the patients had no efficacy of the treatment. Duration of MS was a predictive factor of treatment failure (p = 0.015. CONCLUSIONS: Despite that a full success was obtained in 46% of the cases, BTX-A injection therapy failed to treat refractory NDO in 23% of patients suffering from MS. Duration of the disease was a predictive factor for an inefficient treatment. The injection therapy should be considered as soon as oral anticholinergic drugs fail to reduce NDO.

  18. The telocytes/myofibroblasts 3-D network forms a stretch receptor in the human bladder mucosa. Is this structure involved in the detrusor overactive diseases?

    Science.gov (United States)

    Vannucchi, Maria-Giuliana; Traini, Chiara

    2018-04-11

    Several connective tissue cells are present in the human bladder wall; among them, the myofibroblasts (MyF) and the so-called interstitial cells (IC) are a matter of investigation either by basic researchers or clinicians. The interest derives from the possibility that these two cell types could regulate the organ function forming a special sensory system in the bladder mucosa. Whereas attention for the myofibroblasts was mainly focused on understanding their role, the so-called IC are debatable starting from their nomenclature. Indeed, the IC should correspond to the previously called fibroblasts-like cells/interstitial Cajal-like cells (ICLC)/interstitial cells of Cajal (ICC) or PDGFRα positive cells, or CD34 positive cells. Recently a proper name was proposed to give them an identity, i.e. telocyte (TC). To date, this nomenclature is a better term than IC that is quite vague and can be used for all the cells that reside in the connective tissue. Noteworthy, in the bladder mucosa, TC and MyF form a hetero-cellular 3-D network. The detrusor overactivity/overactive bladder (DO/OAB) are pathological conditions characterized by hypersensitivity to filling. It has been hypothesized that erroneous afferent inputs generated in the mucosa affect the efferent pathways and, consequently, the detrusor response. Presently, we review the literature regarding the presence and the potential role of TC and MyF in control conditions and in DO/OAB. On the possibility that the 3D-network made up by these two cell types might play a major role in the genesis of anomalous afferent stimuli will be given attention. Copyright © 2018 Elsevier GmbH. All rights reserved.

  19. Mediators on human airway smooth muscle.

    Science.gov (United States)

    Armour, C; Johnson, P; Anticevich, S; Ammit, A; McKay, K; Hughes, M; Black, J

    1997-01-01

    1. Bronchial hyperresponsiveness in asthma may be due to several abnormalities, but must include alterations in the airway smooth muscle responsiveness and/or volume. 2. Increased responsiveness of airway smooth muscle in vitro can be induced by certain inflammatory cell products and by induction of sensitization (atopy). 3. Increased airway smooth muscle growth can also be induced by inflammatory cell products and atopic serum. 4. Mast cell numbers are increased in the airways of asthmatics and, in our studies, in airway smooth muscle that is sensitized and hyperresponsive. 5. We propose that there is a relationship between mast cells and airway smooth muscle cells which, once an allergic process has been initiated, results in the development of critical features in the lungs in asthma.

  20. Urodynamic and molecular characteristics of detrusor underactivity in a rat cryoinjury model and effects of low energy shock wave therapy.

    Science.gov (United States)

    Chuang, Yao-Chi; Tyagi, Pradeep; Wang, Hung-Jen; Huang, Chao-Cheng; Lin, Chih-Chieh; Chancellor, Michael B

    2018-02-01

    Low energy shock wave (LESW) has been shown to facilitate tissue regeneration and reduce inflammation. We investigated the effects of LESW in an underactive (DU) model induced by cryoinjury of rat detrusor. Forty-six female Sprague-Dawley rats were divided into sham, cryoinjury with or without LESW (0.12 mJ/mm 2 ; 200 pulses). Under halothane anesthesia, a low midline incision was made and a cryoinjury of detrusor was induced by placing an aluminum rod (chilled with dry ice) for 30 s on the serosal side of the bladder filled with 1 mL sterile saline bilaterally. Awake cystometrogram (CMG), molecular and histopathology studies were performed on Day 8 or 15 after cryoinjury. Significant urodynamic, histological, and molecular changes induced by cryoinjury of rat detrusor were detected on Day 8 and decrease in the contraction amplitude (54.3%), a significant increase in wet bladder weight (64.1%), edematous changes, muscle thinning and downregulation of α-SMA, IL-6, and upregulation of COX-2. LESW reversed the cryoinjury induced histological and COX-2 expression to cause a 49.0% increase in the contraction amplitude (P < 0.05). LESW induced cell proliferation was revealed by increased CD31 and Ki67 immunostaining. The effect of cryoinjury on urodynamic and histological changes was maintained till Day 15. The cryoinjury of rat detrusor models myogenic DU, which is partially reversed by LESW. LESW may afford a simple, non-invasive modality to facilitate tissue regeneration and improve voiding function in myogenic detrusor underactivity. © 2017 Wiley Periodicals, Inc.

  1. Selective detrusor activation by electrical sacral nerve root stimulation in spinal cord injury

    NARCIS (Netherlands)

    Rijkhoff, N. J.; Wijkstra, H.; van Kerrebroeck, P. E.; Debruyne, F. M.

    1997-01-01

    Electrical sacral nerve root stimulation can be used in spinal cord injury patients to induce urinary bladder contraction. However, existing stimulation methods activate simultaneously both the detrusor muscle and the urethral sphincter. Urine evacuation is therefore only possible using poststimulus

  2. β-adrenoceptor agonist effects in experimental models of bladder dysfunction

    NARCIS (Netherlands)

    Michel, Martin C.; Ochodnicky, Peter; Homma, Yukio; Igawa, Yasuhiko

    2011-01-01

    β-adrenoceptor stimulation can enhance the storage function of the urinary bladder by acting on detrusor smooth muscle tone, mediator release from the urothelium and/or afferent nerve activity. In humans this may occur predominantly if not exclusively via the β₃-subtype. The effects of

  3. Testosterone Modifies Alterations to Detrusor Muscle after Partial Bladder Outlet Obstruction in Juvenile Mice

    Directory of Open Access Journals (Sweden)

    Andrew S. Flum

    2017-06-01

    Full Text Available Lower urinary tract symptoms secondary to posterior urethral valves (PUV arise in boys during adolescence. The reasons for this have previously been attributed to increased urine output as boys experience increased growth. Additionally, there are few choices for clinicians to effectively treat these complications. We formed the new hypothesis that increased androgen levels at this time of childhood development could play a role at the cellular level in obstructed bladders. To test this hypothesis, we investigated the role of testosterone on bladder detrusor muscle following injury from partial bladder outlet obstruction (PO in mice. A PO model was surgically created in juvenile male mice. A group of mice were castrated by bilateral orchiectomy at time of obstruction (CPO. Testosterone cypionate was administered to a group of castrated, obstructed mice (CPOT. Bladder function was assessed by voiding stain on paper (VSOP. Bladders were analyzed at 7 and 28 days by weight and histology. Detrusor collagen to smooth muscle ratio (Col/SM was calculated using Masson’s trichrome stain. All obstructed groups had lower max voided volumes (MVV than sham mice at 1 day. Hormonally intact mice (PO continued to have lower MVV at 7 and 28 days while CPO mice improved to sham levels at both time points. In accordance, PO mice had higher bladder-to-body weight ratios than CPO and sham mice demonstrating greater bladder hypertrophy. Histologically, Col/SM was lower in sham and CPO mice. When testosterone was restored in CPOT mice, MVV remained low at 7 and 28 days compared to CPO and bladder-to-body weight ratios were also greater than CPO. Histologic changes were also seen in CPOT mice with higher Col/SM than sham and CPO mice. In conclusion, our findings support a role for testosterone in the fibrotic changes that occur after obstruction in male mice. This suggests that while other changes may occur in adolescent boys that cause complication in boys

  4. [Distribution and significance of α1-adrenoceptor subtypes in patients with chronic prostatitis in prostate, bladder detrusor and posterior urethral tissue].

    Science.gov (United States)

    Yang, Yu; Xie, Hui; Zheng, Jian-jian; Chen, Bi-cheng; He, Qiu-xiang; Shen, Ji-hong

    2010-12-14

    To study the distribution of alpha1-adrenoceptor (α1-AR) subtype in prostate, posterior urethra and bladder detrusor of patients with chronic prostatitis (CP). The prostate specimens were collected at autopsy from 30 organ donors (aged 20-35 years old) dying of non-prostatic diseases. The pathological specimens of prostate peripheral zone were examined. The method of real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) was employed for quantification of α1a-AR and α1b-AR subtype expression in prostate transition zone and its surrounding zone, posterior urethra and bladder detrusor tissue. Among all donors, there were 24 cases with pathological inflammation in prostatic peripheral zone and 6 with pathological non-inflammation. The mRNA expression of α1-AR subtypes in bladder detrusor and posterior urethra was significantly higher in the inflammation group than in the control group (Pposterior urethra was significantly lower in the inflammation group than in the control group (Pposterior urethra may explain various urodynamic changes in CP and lead to the occurrence and development of CP in prostate, posterior urethra and bladder detrusor.

  5. Luminal DMSO: Effects on Detrusor and Urothelial/Lamina Propria Function

    Directory of Open Access Journals (Sweden)

    Katrina J. Smith

    2014-01-01

    Full Text Available DMSO is used as a treatment for interstitial cystitis and this study examined the effects of luminal DMSO treatment on bladder function and histology. Porcine bladder was incubated without (controls or with DMSO (50% applied to the luminal surface and the release of ATP, acetylcholine, and LDH assessed during incubation and in tissues strips after DMSO incubation. Luminally applied DMSO caused ATP, Ach, and LDH release from the urothelial surface during treatment, with loss of urothelial layers also evident histologically. In strips of urothelium/lamina propria from DMSO pretreated bladders the release of both ATP and Ach was depressed, while contractile responses to carbachol were enhanced. Detrusor muscle contractile responses to carbachol were not affected by DMSO pretreatment, but neurogenic responses to electrical field stimulation were enhanced. The presence of an intact urothelium/lamina propria inhibited detrusor contraction to carbachol by 53% and this inhibition was significantly reduced in DMSO pretreated tissues. Detection of LDH in the treatment medium suggests that DMSO permeabilised urothelial membranes causing leakage of cytosolic contents including ATP and Ach rather than enhancing release of these mediators. The increase in contractile response and high levels of ATP are consistent with initial flare up in IC/PBS symptoms after DMSO treatment.

  6. Characterization of prejunctional serotonin receptors modulating [3H]acetylcholine release in the human detrusor.

    Science.gov (United States)

    D'Agostino, Gianluigi; Condino, Anna M; Gallinari, Paola; Franceschetti, Gian P; Tonini, Marcello

    2006-01-01

    Bladder overactivity (OAB) is a chronic and debilitating lower urinary tract (LUT) disorder that affects millions of individuals worldwide. LUT symptoms associated with OAB, such as urgency and urinary incontinence, cause a hygienic and social concern to patients, but their current pharmacological treatment is largely inadequate due to the lack of uroselectivity. Although OAB etiology remains multifactorial and poorly understood, increasing evidence indicates that serotonin [5-hydroxytryptamine (5-HT)] is an endogenous substance involved in the control of micturition at central and peripheral sites. In this study, we demonstrated the presence of three distinct 5-HT receptors localized at parasympathetic nerve terminals of the human bladder by measuring electrically evoked tritiated acetylcholine release in isolated detrusor strips. These prejunctional receptors, involved in both positive and negative feedback mechanisms regulating cholinergic transmission, have been characterized by means of three highly selective 5-HT antagonists for 5-HT(4), 5-HT(7), and 5-HT(1A) receptors, namely GR113808A ([1-[2-[(-methylsulphonyl) amino] ethyl]4-piperinidyl]methyl1-methyl-1H-indole-3-carboxylate succinate), SB269970 [(R)-3-(2-(2-(4-methylpiperidin-1-yl)ethyl)pyrrolidine-1-sulfonyl)phenol hydrochloride], and WAY100635 [N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl)-cyclohexane-carboxamide trichloride]. Under these conditions, we confirmed the facilitatory role of 5-HT(4) heteroreceptors on acetylcholine release and revealed for the first time the occurrence of 5-HT(7) and 5-HT(1A) heteroreceptors with a facilitatory and an inhibitory action, respectively. Our findings strengthen the novel concept for the use of recently patented selective 5-HT agonists and antagonists for the control of OAB dysfunctions associated with inflammatory conditions, although their therapeutic efficacy needs to be explored in the clinical setting.

  7. Brain SPECT study of detrusor overactivity and healthy men in urine withholding

    International Nuclear Information System (INIS)

    Yin Yafu; Li Xuena; Li Yaming; Noriyuki Shuke; Atsutaka Okizaki; Junichi Sato; Tamio Aburano

    2009-01-01

    The aim of the study is to identify the brain areas, which control the bladder storage by 99 Tc m -HMPAO SPECT with Neurological Statistical Image Analysis Software (NEUROSTAT). SPECT were performed on twenty-five patients with some storage symptoms of lower urinary tract, among which nineteen patients were with detrusor overactivity (DO) (Group II) and six patients were with normal detrusor function (Group III), and fifteen healthy volunteers (Group I). All the subjects were male and right-handed, and were scanned twice under two conditions: resting state and urine withholding state. NEUROSTAT was adopted to analyze the difference in rCBF between groups and states. The results were displayed on Z-score images at a significance threshold of P<0.05 with correction for multiple comparisons. No region reached significant threshold in comparison of Group II and III in resting state. There were significant increases in tracer activity in bilateral inferior frontal gyri and the right middle temporal gyrus in urine withholding state as compared with resting state in Group I and III (P<0.05 with correction for multiple comparisons, the corresponding Z value was more than 4.476 for Group I, more than 4.414 for Group III). Among the regions,the right inferior frontal gyrus was distinctly prominent at both Z-score and the extent. In Group II, only the left middle temporal gyrus and middle frontal gyrus were activated significantly in urine withholding state as compared with resting (P<0.05 with correction for multiple comparisons, the corresponding Z value was more than 4.35). The results indicated that bilateral inferior frontal gyri and the right middle temporal gyrus associated with the control of bladder storage.Especially, the right inferior frontal gyrus played a more important role in cerebral control of bladder storage, inhibiting the contraction of detrusor in urine storage. (authors)

  8. SMOOTH MYOCYTES AND COLLAGENOUS FIBERS OF THE URINARY BLADDER OF RATS IN DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Nadiya Tokaruk

    2015-12-01

    Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine   Key words: diabetes mellitus; smooth myocytes; collagenous fibers.   Introduction. Diabetes mellitus (DM causes diabetic cystopathy, which is associated with detrusor dysfunction and the content of collagenous fibers. The results of the performed studies are ambiguous and often contradictory, requiring objective data which could be obtained on the basis of the simultaneous determination of relative areas of smooth myocytes and collagenous fibers and their ultrastructural study. Objective: To determine the peculiarities of the structural and metric organization of smooth myocytes and collagenous fibers of the urinary bladder (UB of rats during different stages of DM. Materials and methods. DM was modeled by streptozotocin in Wistar rats. Relative areas of the studied structures were defined on digital images of histological sections of UB stained by Mason using the original automatic way. Smooth myocytes were studied ultrastructurally. Results. During the 14th-28th day of DM development the percent of collagenous fibers area decreases and the percentage of smooth myocytes area of UB wall increases. The expanding of intercellular spaces and the development of vacuolar degeneration of myocytes are observed. During the 42nd-56th days the percentage of collagenous fibers area increases and the percentage of the area of smooth myocytes decreases. Ultrastructurally subsiding of vacuolar dystrophy, short-term baloon dystrophy, the appearance of dark myocytes, moderate karyorrhexis were observed. During the 70th day of the experiment the percentage of collagenous fibers and smooth myocytes areas does not change significantly, most dark myocytes are involutive, there are local fibrosis and myocyte sequestration areas. Conclusions. Ultrastructural changes are characterized by a pronounced polymorphism and have a chronological relationship. Author’s worked out original method of determination of the

  9. Ultrastructure of Cajal-like interstitial cells in the human detrusor

    DEFF Research Database (Denmark)

    Rasmussen, Helle; Rumessen, Jüri J; Hansen, Alastair

    2009-01-01

    reticulum and Golgi apparatus were observed in the cell somata and cytoplasmic processes. Intermediate filaments were abundant but no thick filaments were found. ICC-L were interconnected by close appositions, gap junctions and peg-and-socket junctions (PSJ) but no specialised contacts to smooth muscle...

  10. Directional asymmetries in human smooth pursuit eye movements.

    Science.gov (United States)

    Ke, Sally R; Lam, Jessica; Pai, Dinesh K; Spering, Miriam

    2013-06-27

    Humans make smooth pursuit eye movements to bring the image of a moving object onto the fovea. Although pursuit accuracy is critical to prevent motion blur, the eye often falls behind the target. Previous studies suggest that pursuit accuracy differs between motion directions. Here, we systematically assess asymmetries in smooth pursuit. In experiment 1, binocular eye movements were recorded while observers (n = 20) tracked a small spot of light moving along one of four cardinal or diagonal axes across a featureless background. We analyzed pursuit latency, acceleration, peak velocity, gain, and catch-up saccade latency, number, and amplitude. In experiment 2 (n = 22), we examined the effects of spatial location and constrained stimulus motion within the upper or lower visual field. Pursuit was significantly faster (higher acceleration, peak velocity, and gain) and smoother (fewer and later catch-up saccades) in response to downward versus upward motion in both the upper and the lower visual fields. Pursuit was also more accurate and smoother in response to horizontal versus vertical motion. CONCLUSIONS. Our study is the first to report a consistent up-down asymmetry in human adults, regardless of visual field. Our findings suggest that pursuit asymmetries are adaptive responses to the requirements of the visual context: preferred motion directions (horizontal and downward) are more critical to our survival than nonpreferred ones.

  11. Randomized controlled trial of foot reflexology for patients with symptomatic idiopathic detrusor overactivity.

    Science.gov (United States)

    Mak, Ho-Leung Jimmy; Cheon, Willy Cecilia; Wong, To; Liu, Yu Sun John; Tong, Wai Mei Anny

    2007-06-01

    The aim of this study was to examine whether foot reflexology has beneficial effects on patients with idiopathic detrusor overactivity. One hundred and nine women with symptomatic idiopathic detrusor overactivity were randomized into either foot reflexology treatment group or nonspecific foot massage control group. The primary outcome measure was the change in the diurnal micturition frequency. There was significant change in the number of daytime frequency in the reflexology group when compared with the massage group (-1.90 vs -0.55, p = 0.029). There was also a decrease in the 24-h micturition frequency in both groups, but the change was not statistically significant (-2.80 vs -1.04 p = 0.055). In the reflexology group, more patients believed to have received "true" reflexology (88.9 vs 67.4%, p = 0.012). This reflects the difficulty of blinding in trials of reflexology. Larger scale studies with a better-designed control group and an improved blinding are required to examine if reflexology is effective in improving patients' overall outcome.

  12. Phasic or terminal detrusor overactivity in women: age, urodynamic findings and sphincter behavior relationships

    Directory of Open Access Journals (Sweden)

    Françoise A. Valentini

    2011-12-01

    Full Text Available OBJECTIVES: To search for relationships between phasic (P and terminal (T DO with age, urodynamic findings and sphincter behavior during involuntary detrusor contraction in woman. MATERIALS AND METHODS: Urodynamic studies (triple lumen catheter 7F, seated position of 164 successive women referred for LUTS with diagnosis of DO were reviewed. Patients were stratified in 4 sub-groups: pre- (18-44y, peri- (45-54 y, post-menopause (55-74 y and oldest old (≥ 75 y. The urethral sensor was positioned at the level of the maximum urethral closure pressure for sphincter behavior analysis. A variation of at least 5 cmH2O in pressure (detrusor or urethra was chosen to assert DO or sphincter response. Sphincter response was classified as relaxation (re before or during DO, or steady (st. RESULTS: Occurrence of P and TDO was similar: 77 P and 87 T. The PDO group was significantly younger (p = 0.0003. TDO was more frequent in patients with a history of neurological disease. The percentage of PDO remained almost constant in age groups, while that of TDO increased with age from 6.7% to 23.2% (p = 0.0013. Uninhibited contraction occurred at a smaller bladder volume in the P group: 149 ± 95 vs. 221 ± 113 mL (p < 0.0001. Steady sphincter predominated in the TDO subgroup: 45.9% vs. 32.1% and increased significantly in each DO sub-group of ³ 75y. CONCLUSION: Steady sphincter during both P and TDO, and occurrence of TDO appear as specific of aging. The last result could be related to structural changes in the detrusor muscle with aging.

  13. Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells.

    Science.gov (United States)

    Eoh, Joon H; Shen, Nian; Burke, Jacqueline A; Hinderer, Svenja; Xia, Zhiyong; Schenke-Layland, Katja; Gerecht, Sharon

    2017-04-01

    Obtaining vascular smooth muscle tissue with mature, functional elastic fibers is a key obstacle in tissue-engineered blood vessels. Poor elastin secretion and organization leads to a loss of specialization in contractile smooth muscle cells, resulting in over proliferation and graft failure. In this study, human induced-pluripotent stem cells (hiPSCs) were differentiated into early smooth muscle cells, seeded onto a hybrid poly(ethylene glycol) dimethacrylate/poly (l-lactide) (PEGdma-PLA) scaffold and cultured in a bioreactor while exposed to pulsatile flow, towards maturation into contractile smooth muscle tissue. We evaluated the effects of pulsatile flow on cellular organization as well as elastin expression and assembly in the engineered tissue compared to a static control through immunohistochemistry, gene expression and functionality assays. We show that culturing under pulsatile flow resulted in organized and functional hiPSC derived smooth muscle tissue. Immunohistochemistry analysis revealed hiPSC-smooth muscle tissue with robust, well-organized cells and elastic fibers and the supporting microfibril proteins necessary for elastic fiber assembly. Through qRT-PCR analysis, we found significantly increased expression of elastin, fibronectin, and collagen I, indicating the synthesis of necessary extracellular matrix components. Functionality assays revealed that hiPSC-smooth muscle tissue cultured in the bioreactor had an increased calcium signaling and contraction in response to a cholinergic agonist, significantly higher mature elastin content and improved mechanical properties in comparison to the static control. The findings presented here detail an effective approach to engineering elastic human vascular smooth muscle tissue with the functionality necessary for tissue engineering and regenerative medicine applications. Obtaining robust, mature elastic fibers is a key obstacle in tissue-engineered blood vessels. Human induced-pluripotent stem cells have

  14. Role of PKC and CaV1.2 in detrusor overactivity in a model of obesity associated with insulin resistance in mice.

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    Luiz O Leiria

    Full Text Available Obesity/metabolic syndrome are common risk factors for overactive bladder. This study aimed to investigate the functional and molecular changes of detrusor smooth muscle (DSM in high-fat insulin resistant obese mice, focusing on the role of protein kinase C (PKC and Ca(v1.2 in causing bladder dysfunction. Male C57BL/6 mice were fed with high-fat diet for 10 weeks. In vitro functional responses and cystometry, as well as PKC and Ca(v1.2 expression in bladder were evaluated. Obese mice exhibited higher body weight, epididymal fat mass, fasting glucose and insulin resistance. Carbachol (0.001-100 µM, α,β-methylene ATP (1-10 µM, KCl (1-300 mM, extracellular Ca(2+ (0.01-100 mM and phorbol-12,13-dibutyrate (PDBu; 0.001-3 µM all produced greater DSM contractions in obese mice, which were fully reversed by the Ca(v1.2 blocker amlodipine. Cystometry evidenced augmented frequency, non-void contractions and post-void pressure in obese mice that were also prevented by amlodipine. Metformin treatment improved the insulin sensitivity, and normalized the in vitro bladder hypercontractility and cystometric dysfunction in obese mice. The PKC inhibitor GF109203X (1 µM also reduced the carbachol induced contractions. PKC protein expression was markedly higher in bladder tissues from obese mice, which was normalized by metformin treatment. The Ca(v1.2 channel protein expression was not modified in any experimental group. Our findings show that Ca(v1.2 blockade and improvement of insulin sensitization restores the enhanced PKC protein expression in bladder tissues and normalizes the overactive detrusor. It is likely that insulin resistance importantly contributes for the pathophysiology of this urological disorder in obese mice.

  15. Experimental model of human corpus cavernosum smooth muscle relaxation

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    Rommel P. Regadas

    2010-08-01

    Full Text Available PURPOSE: To describe a technique for en bloc harvesting of the corpus cavernosum, cavernous artery and urethra from transplant organ donors and contraction-relaxation experiments with corpus cavernosum smooth muscle. MATERIALS AND METHODS: The corpus cavernosum was dissected to the point of attachment with the crus penis. A 3 cm segment (corpus cavernosum and urethra was isolated and placed in ice-cold sterile transportation buffer. Under magnification, the cavernous artery was dissected. Thus, 2 cm fragments of cavernous artery and corpus cavernosum were obtained. Strips measuring 3 x 3 x 8 mm3 were then mounted vertically in an isolated organ bath device. Contractions were measured isometrically with a Narco-Biosystems force displacement transducer (model F-60, Narco-Biosystems, Houston, TX, USA and recorded on a 4-channel Narco-Biosystems desk model polygraph. RESULTS: Phenylephrine (1µM was used to induce tonic contractions in the corpus cavernosum (3 - 5 g tension and cavernous artery (0.5 - 1g tension until reaching a plateau. After precontraction, smooth muscle relaxants were used to produce relaxation-response curves (10-12M to 10-4 M. Sodium nitroprusside was used as a relaxation control. CONCLUSION: The harvesting technique and the smooth muscle contraction-relaxation model described in this study were shown to be useful instruments in the search for new drugs for the treatment of human erectile dysfunction.

  16. Neurophysiology and Neuroanatomy of Smooth Pursuit in Humans

    Science.gov (United States)

    Lencer, Rebekka; Trillenberg, Peter

    2008-01-01

    Smooth pursuit eye movements enable us to focus our eyes on moving objects by utilizing well-established mechanisms of visual motion processing, sensorimotor transformation and cognition. Novel smooth pursuit tasks and quantitative measurement techniques can help unravel the different smooth pursuit components and complex neural systems involved…

  17. A pilot study of acotiamide hydrochloride hydrate in patients with detrusor underactivity

    Directory of Open Access Journals (Sweden)

    Sugimoto K

    2015-05-01

    Full Text Available Koichi Sugimoto,1 Takahiro Akiyama,2 Nobutaka Shimizu,3 Naoki Matsumura,1 Taiji Hayashi,1 Tsukasa Nishioka,1 Hirotsugu Uemura3 1Department of Urology, Sakai Hospital, Kinki University Faculty of Medicine, Sakai, Osaka, Japan; 2Department of Urology, Sakai-Onshinkai Hospital, Sakai, Osaka, Japan; 3Department of Urology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan Aim: To investigate the clinical efficacy of acotiamide hydrochloride hydrate in patients with detrusor underactivity. Methods: We measured the post-void residual urinary volume in 19 patients with underactive bladders. All these patients had been under treatment with distigmine bromide and were prescribed acotiamide hydrochloride hydrate at a dose of 100 mg three times daily for 2 weeks. Results: Compared with the post-void residual urinary volume value at baseline (161.4±90.0 mL a statistically significant reduction was observed at the end of treatment (116.3±63.1 mL (P=0.006. The drug was generally well tolerated by the majority of patients. Conclusion: Maybe, acotiamide hydrochloride hydrate showed clinical efficacy in patients with underactive bladders and may, therefore, be used alternatively in patients who do not respond sufficiently to distigmine bromide. Keywords: acotiamide hydrochloride hydrate, distigmine bromide, underactive bladder, detrusor underactive

  18. Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    Epidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38\\/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta

  19. Human lung mast cells modulate the functions of airway smooth muscle cells in asthma.

    Science.gov (United States)

    Alkhouri, H; Hollins, F; Moir, L M; Brightling, C E; Armour, C L; Hughes, J M

    2011-09-01

    Activated mast cell densities are increased on the airway smooth muscle in asthma where they may modulate muscle functions and thus contribute to airway inflammation, remodelling and airflow obstruction. To determine the effects of human lung mast cells on the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Freshly isolated human lung mast cells were stimulated with IgE/anti-IgE. Culture supernatants were collected after 2 and 24 h and the mast cells lysed. The supernatants/lysates were added to serum-deprived, subconfluent airway smooth muscle cells for up to 48 h. Released chemokines and extracellular matrix were measured by ELISA, proliferation was quantified by [(3) H]-thymidine incorporation and cell counting, and intracellular signalling by phospho-arrays. Mast cell 2-h supernatants reduced CCL11 and increased CXCL8 and fibronectin production from both asthmatic and nonasthmatic muscle cells. Leupeptin reversed these effects. Mast cell 24-h supernatants and lysates reduced CCL11 release from both muscle cell types but increased CXCL8 release by nonasthmatic cells. The 24-h supernatants also reduced asthmatic, but not nonasthmatic, muscle cell DNA synthesis and asthmatic cell numbers over 5 days through inhibiting extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI3)-kinase pathways. However, prostaglandins, thromboxanes, IL-4 and IL-13 were not involved in reducing the proliferation. Mast cell proteases and newly synthesized products differentially modulated the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Thus, mast cells may modulate their own recruitment and airway smooth muscle functions locally in asthma. © 2011 John Wiley & Sons A/S.

  20. Physiotherapy Management of Idiopathic Detrusor Instability in elderly women is effective for continence rehabilitation

    International Nuclear Information System (INIS)

    Al-Gazzar, Samir A.

    2006-01-01

    The aim of this work was to give an overview of the conservative treatment of idiopathic detrusor instability (IDI) in elderly women, describe the clinical and urodynamic features of the over-active bladder and the role of physiotherapy as well as the various physiotherapeutic techniques in the management of this condition. A prospective, uncontrolled clinical trial was designed. Twenty elderly women aged 55-75 were participated for 8 weeks in this study. Therapeutic modalities including biofeedback training, bladder retraining, pelvic floor exercise and electrical stimulation were applied for all subjects. Each of 1st desire to void, maximum capacity, flow rate and voiding intervals were increased in its mean at the end of the study (p<0.0001), while the means of residual volume and frequency of micturation had significantly decreased at the end of the study (p<0.0001). The study showed that correctly taught pelvic floor exercise, biofeed back combined with bladder retaining, electrical stimulation and restriction of fluids intake are an effective treatment for the idiopathic detrusor instability in elderly women and should be considered effective approach for continence rehabilitation. (author)

  1. Bioenergetic profile of human coronary artery smooth muscle cells and effect of metabolic intervention.

    Directory of Open Access Journals (Sweden)

    Mingming Yang

    Full Text Available Bioenergetics of artery smooth muscle cells is critical in cardiovascular health and disease. An acute rise in metabolic demand causes vasodilation in systemic circulation while a chronic shift in bioenergetic profile may lead to vascular diseases. A decrease in intracellular ATP level may trigger physiological responses while dedifferentiation of contractile smooth muscle cells to a proliferative and migratory phenotype is often observed during pathological processes. Although it is now possible to dissect multiple building blocks of bioenergetic components quantitatively, detailed cellular bioenergetics of artery smooth muscle cells is still largely unknown. Thus, we profiled cellular bioenergetics of human coronary artery smooth muscle cells and effects of metabolic intervention. Mitochondria and glycolysis stress tests utilizing Seahorse technology revealed that mitochondrial oxidative phosphorylation accounted for 54.5% of ATP production at rest with the remaining 45.5% due to glycolysis. Stress tests also showed that oxidative phosphorylation and glycolysis can increase to a maximum of 3.5 fold and 1.25 fold, respectively, indicating that the former has a high reserve capacity. Analysis of bioenergetic profile indicated that aging cells have lower resting oxidative phosphorylation and reduced reserve capacity. Intracellular ATP level of a single cell was estimated to be over 1.1 mM. Application of metabolic modulators caused significant changes in mitochondria membrane potential, intracellular ATP level and ATP:ADP ratio. The detailed breakdown of cellular bioenergetics showed that proliferating human coronary artery smooth muscle cells rely more or less equally on oxidative phosphorylation and glycolysis at rest. These cells have high respiratory reserve capacity and low glycolysis reserve capacity. Metabolic intervention influences both intracellular ATP concentration and ATP:ADP ratio, where subtler changes may be detected by the latter.

  2. Human eosinophil–airway smooth muscle cell interactions

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    J. Margaret Hughes

    2000-01-01

    Full Text Available Eosinophils are present throughout the airway wall of asthmatics. The nature of the interaction between human airway smooth muscle cells (ASMC and eosinophils was investigated in this study. We demonstrated, using light microscopy, that freshly isolated eosinophils from healthy donors rapidly attach to ASMC in vitro. Numbers of attached eosinophils were highest at 2 h, falling to 50% of maximum by 20 h. Eosinophil attachment at 2 h was reduced to 72% of control by anti-VCAM-1, and to 74% at 20 h by anti-ICAM-1. Pre-treatment of ASMC for 24 h with TNF-α, 10 nM, significantly increased eosinophil adhesion to 149 and 157% of control after 2 and 20 h. These results provide evidence that eosinophil interactions with ASMC involve VCAM-1 and ICAM-1 and are modulated by TNF-α.

  3. Calcification of human vascular smooth muscle cells: associations with osteoprotegerin expression and acceleration by high-dose insulin

    DEFF Research Database (Denmark)

    Olesen, Ping; Knudsen, Kirsten Quyen Nguyen; Wogensen, Lise

    2007-01-01

    Arterial medial calcifications occur often in diabetic individuals as part of the diabetic macroangiopathy. The pathogenesis is unknown, but the presence of calcifications predicts risk of cardiovascular events. We examined the effects of insulin on calcifying smooth muscle cells in vitro...... and measured the expression of the bone-related molecule osteoprotegerin (OPG). Human vascular smooth muscle cells (VSMCs) were grown from aorta from kidney donors. Induction of calcification was performed with beta-glycerophosphate. The influence of insulin (200 microU/ml or 1,000 microU/ml) on calcification...... calcification in human smooth muscle cells from a series of donors after variable time in culture. Decreased OPG amounts were observed from the cells during the accelerated calcification phase. High dose of insulin (1,000 microU/ml) accelerated the calcification, whereas lower concentrations (200 microU/ml) did...

  4. Human induced pluripotent stem cell-derived vascular smooth muscle cells

    DEFF Research Database (Denmark)

    Ayoubi, Sohrab; Sheikh, Søren P; Eskildsen, Tilde V

    2017-01-01

    . To this end, human induced pluripotent stem cells (hiPSCs) have generated great enthusiasm, and have been a driving force for development of novel strategies in drug discovery and regenerative cell-therapy for the last decade. Hence, investigating the mechanisms underlying the differentiation of hi......PSCs into specialized cell types such as cardiomyocytes, endothelial cells, and vascular smooth muscle cells (VSMCs) may lead to a better understanding of developmental cardiovascular processes and potentiate progress of safe autologous regenerative therapies in pathological conditions. In this review, we summarize...

  5. Prospective randomised controlled trial comparing trigone-sparing versus trigone-including intradetrusor injection of abobotulinumtoxinA for refractory idiopathic detrusor overactivity.

    LENUS (Irish Health Repository)

    Manecksha, Rustom P

    2012-05-01

    Botulinum toxin A is effective for treatment of idiopathic detrusor overactivity (IDO). The trigone is generally spared because of the theoretical risk of vesicoureteric reflux (VUR), although studies assessing injection sites are lacking.

  6. Cerebral control of bladder storage in patients with detrusor overactivity: An activation study using SPECT with NEUROSTAT

    International Nuclear Information System (INIS)

    Yafu, Y.; Li, X.; Li, Y.

    2007-01-01

    Full text: The aim of this study was to identify the brain areas which control the bladder storage in the patients with detrusor overactivity (DO) and those without DO by 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) SPECT with Neurological Statistical Image Analysis Software (NEUROSTAT). Methods: SPECT scans were performed on fifteen healthy volunteers (Group I) and twenty-five patients with some storage symptoms of lower urinary tract, among whom nineteen patients were with DO (Group II) and six patients were with normal detrusor function (Group III). All the subjects were male and right-handed. Each subject was scanned twice without movement in a supine position. 444MBq and 555MBq 99mTc- HMPAO were separately injected intravenously under the following two conditions: resting state with empty bladder and urine withholding state with full bladder. The final image during urine withholding was obtained by subtracting the first scan data from the second. NEUROSTAT was adopted to analyze the difference in rCBF between groups in resting state and to analyze the change in rCBF between urine withholding and resting states in each group. The results were displayed on Z-score images at a significance threshold of P < 0.05 with correction for multiple comparisons. Results: No region reached significant threshold in comparison of Group II and Group III in resting state, although Group II and III , as compared with Group I, showed decreases in tracer activity in superior temporal gyrus, medial frontal gyrus, inferior frontal gyrus, anterior cingulate and cingulate gyrus. There were significant increases in tracer activity in bilateral inferior frontal gyri and the right middle temporal gyrus in urine withholding state as compared with resting state in Group III. Among the regions, the right inferior frontal gyrus was distinctly prominent at both Z-score and the extent. In Group II, the regions that were activated significantly in Group III did not reach significant

  7. A new paradigm for the role of smooth muscle cells in the human cervix.

    Science.gov (United States)

    Vink, Joy Y; Qin, Sisi; Brock, Clifton O; Zork, Noelia M; Feltovich, Helen M; Chen, Xiaowei; Urie, Paul; Myers, Kristin M; Hall, Timothy J; Wapner, Ronald; Kitajewski, Jan K; Shawber, Carrie J; Gallos, George

    2016-10-01

    Premature cervical remodeling resulting in spontaneous preterm birth may begin with premature failure or relaxation at the internal os (termed "funneling"). To date, we do not understand why the internal os fails or why funneling occurs in some cases of premature cervical remodeling. Although the human cervix is thought to be mostly collagen with minimal cellular content, cervical smooth muscle cells are present in the cervix and can cause cervical tissue contractility. To understand why the internal os relaxes or why funneling occurs in some cases of premature cervical remodeling, we sought to evaluate cervical smooth muscle cell content and distribution throughout human cervix and correlate if cervical smooth muscle organization influences regional cervical tissue contractility. Using institutional review board-approved protocols, nonpregnant women cervix, whole cervical slices were obtained from the internal os, midcervix, and external os and immunostained with smooth muscle actin. To correlate tissue structure with function, whole slices from the internal and external os were stimulated to contract with 1 μmol/L of oxytocin in organ baths. In separate samples, we tested if the cervix responds to a common tocolytic, nifedipine. Cervical slices from the internal os were treated with oxytocin alone or oxytocin + increasing doses of nifedipine to generate a dose response and half maximal inhibitory concentration. Student t test was used where appropriate. Cervical tissue was collected from 41 women. Immunohistochemistry showed cervical smooth muscle cells at the internal and external os expressed mature smooth muscle cell markers and contraction-associated proteins. The cervix exhibited a gradient of cervical smooth muscle cells. The area of the internal os contained 50-60% cervical smooth muscle cells that were circumferentially organized in the periphery of the stroma, which may resemble a sphincter-like pattern. The external os contained approximately 10

  8. Overexpression of functional TrkA receptors after internalisation in human airway smooth muscle cells.

    Science.gov (United States)

    Freund-Michel, Véronique; Frossard, Nelly

    2008-10-01

    Trafficking of the TrkA receptor after stimulation by NGF is of emerging importance in structural cells in the context of airway inflammatory diseases. We have recently reported the expression of functional TrkA receptors in human airway smooth muscle cells (HASMC). We have here studied the TrkA trafficking mechanisms in these cells. TrkA disappearance from the cell membrane was induced within 5 min of NGF (3pM) stimulation. Co-immunoprecipitation of clathrin-TrkA was revealed, and TrkA internalisation inhibited either by clathrin inhibitors or by siRNA inducing downregulation of endogenous clathrin. TrkA internalised receptors were totally degraded in lysosomes, with no recycling phenomenon. Newly synthesized TrkA receptors were thereafter re-expressed at the cell membrane within 10 h. TrkA re-synthesis was inhibited by blockade of clathrin-dependent internalisation, but not of TrkA receptors lysosomal degradation. Finally, we observed that NGF multiple stimulations progressively increased TrkA expression in HASMC, which was associated with an increase in NGF/TrkA-dependent proliferation. In conclusion, we show here the occurrence of clathrin-dependent TrkA internalisation and lysosomal degradation in the airway smooth muscle, followed by upregulated re-synthesis of functional TrkA receptors and increased proliferative effect in the human airway smooth muscle. This may have pathophysiological consequences in airway inflammatory diseases.

  9. Differential gene expression profiling of human adipose stem cells differentiating into smooth muscle-like cells by TGFβ1/BMP4

    Energy Technology Data Exchange (ETDEWEB)

    Elçin, Ayşe Eser; Parmaksiz, Mahmut; Dogan, Arin; Seker, Sukran; Durkut, Serap; Dalva, Klara; Elçin, Yaşar Murat, E-mail: elcinmurat@gmail.com

    2017-03-15

    Regenerative repair of the vascular system is challenging from the perspectives of translational medicine and tissue engineering. There are fundamental hurdles in front of creating bioartificial arteries, which involve recaputilation of the three-layered structure under laboratory settings. Obtaining and maintaining smooth muscle characteristics is an important limitation, as the transdifferentiated cells fail to display mature phenotype. This study aims to shed light on the smooth muscle differentiation of human adipose stem cells (hASCs). To this end, we first acquired hASCs from lipoaspirate samples. Upon characterization, the cells were induced to differentiate into smooth muscle (SM)-like cells using a variety of inducer combinations. Among all, TGFβ1/BMP4 combination had the highest differentiation efficiency, based on immunohistochemical analyses. hSM-like cell samples were compared to hASCs and to the positive control, human coronary artery-smooth muscle cells (hCA-SMCs) through gene transcription profiling. Microarray findings revealed the activation of gene groups that function in smooth muscle differentiation, signaling pathways, extracellular modeling and cell proliferation. Our results underline the effectiveness of the growth factors and suggest some potential variables for detecting the SM-like cell characteristics. Evidence in transcriptome level was used to evaluate the TGFβ1/BMP4 combination as a previously unexplored effector for the smooth muscle differentiation of adipose stem cells. - Highlights: • Human adipose stem cells (hASCs) were isolated, characterized and cultured. • Growth factor combinations were evaluated for their effectiveness in differentiation using IHC. • hASCs were differentiated into smooth muscle (SM)-like cells using TGF-β1 and BMP4 combination. • Microarray analysis was performed for hASCs, SM-like cells and coronary artery-SMCs. • Microarray data was used to perform hierarchical clustering and interpretation

  10. LC/MS/MS data analysis of the human uterine smooth muscle S-nitrosoproteome fingerprint in pregnancy, labor, and preterm labor

    Directory of Open Access Journals (Sweden)

    Craig C. Ulrich

    2015-09-01

    Full Text Available The data described in this article is the subject of an article in the American Journal of Physiology: Cell Physiology, titled “The Human Uterine Smooth Muscle S-nitrosoproteome Fingerprint in Pregnancy, Labor, and Preterm Labor” (doi:10.1152/ajpcell.00198.2013 (Ulrich et al., 2013 [1]. The data described is a large scale mass spectrometry data set that defines the human uterine smooth muscle S-nitrosoproteome differences among laboring, non-laboring, preterm laboring tissue after treatment with S-nitrosoglutathione.

  11. Role of Nicotinic Acetylcholine Receptor α3 and α7 Subunits in Detrusor Overactivity Induced by Partial Bladder Outlet Obstruction in Rats

    Directory of Open Access Journals (Sweden)

    Hyo Sin Kim

    2015-03-01

    Full Text Available Purpose: To investigate the role of α3 and α7 nicotinic acetylcholine receptor subunits (nAChRs in the bladder, using a rat model with detrusor overactivity induced by partial bladder outlet obstruction (BOO. Methods: Forty Sprague-Dawley rats were used: 10 were sham-operated (control group and 30 were observed for 3 weeks after partial BOO. BOO-induced rats were further divided into 3 groups: Two groups of 10 rats each received intravesicular infusions with hexamethonium (HM group; n=10 or methyllycaconitine (MLC group; n=10, which are antagonists for α3 and α7 nAChRs, respectively. The remaining BOO-induced rats received only saline infusion (BOO group; n=10. Based on the contraction interval measurements using cystometrogram, the contraction pressure and nonvoiding bladder contractions were compared between the control and the three BOO-induced groups. Immunofluorescent staining and Western blotting were used to analyze α3 and α7 nAChRs levels. Results: The contraction interval of the MLC group was higher than that of the BOO group (P<0.05. Nonvoiding bladder contraction almost disappeared in the HM and MLC groups. Contraction pressure increased in the BOO group (P<0.05 compared with the control group and decreased in the HM and MLC groups compared with the BOO group (P<0.05. Immunofluorescence staining showed that the α3 nAChR signals increased in the urothelium, and the α7 nAChR signals increased in the urothelium and detrusor muscle of the BOO group compared with the control group. Western blot analysis showed that both α3 and α7 nAChR levels increased in the BOO group (P<0.05. Conclusions: Alpha3 and α7 nAChRs are associated with detrusor overactivity induced by BOO. Furthermore, nAChR antagonists could help in clinically improving detrusor overactivity.

  12. Inhibition effect of Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis and their related products on human colonic smooth muscle in vitro.

    Directory of Open Access Journals (Sweden)

    Jing Gong

    Full Text Available To investigate the effects of four strains, generally used in clinic, including Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis, and their related products on human colonic smooth muscle in vitro.Human colonic circular muscle strips obtained from disease-free margins of resected segments from 25 patients with colorectal cancer were isometrically examined in a constant-temperature organ bath and exposed to different concentrations of living bacteria, sonicated cell fractions and cell-free supernatant (CFS. The area under the curve (AUC representing the contractility of smooth muscle strips was calculated.(1 The four living probiotics inhibited the contractility of human colonic muscle strips only at high concentration (1010 CFUs/mL, all P0.05.Four common probiotics related products, including the sonicated cell fractions and the CFS, obviously inhibited human colonic smooth muscles strips contraction in a dose-dependent manner. Only high concentration living probiotics (1010 CFUs/mL can inhibit the colonic smooth muscles strips contraction. The NO pathway may be partly involved in the inhibitory effect of CFS from Streptococcus thermophilus and Enterococcus faecalis.

  13. Transcutaneous electrical nerve stimulation and temporary S3 neuromodulation in idiopathic detrusor instability.

    Science.gov (United States)

    Hasan, S T; Robson, W A; Pridie, A K; Neal, D E

    1996-06-01

    We studied the effects of electrical stimulation on idiopathic detrusor instability. Between January 1993 and December 1994, 30 men and 41 women (mean age plus or minus standard deviation 48 +/- 16 years) underwent transcutaneous electrical nerve stimulation (TENS) of the S2-S3 dermatomes, and 13 men and 22 women (mean age 48 +/- 12 years) underwent S3 neuromodulation. Subjective assessment was performed using a diary and symptom score of 0 to 14. Objective outcome was analyzed with urodynamic studies. Mean duration of TENS was 3 +/- 1 weeks (range 2 to 4). Although there were no major complications 31% of the patients reported local skin irritation. The overall urinary symptom scores improved from 10 +/- 2 (range 5 to 14) before the study to 7 +/- 3 (range 1 to 14) during stimulation. Urodynamic analysis revealed significant (p neuromodulation was 6 +/- 1 days (range 4 to 8 days). Four procedures failed due to electrode displacement in 3 cases and procedure intolerance in 1. Hemorrhage from the puncture site occurred in 1 patient. Overall urinary symptom scores were 10 +/- 3 (range 5 to 14) before the study and 5 +/- 2 (range 2 to 10) during stimulation. Although symptomatic relief was more pronounced with S3 neuromodulation, no statistically significant differences were found regarding urinary symptoms compared to TENS. In patients with severe detrusor instability refractory to conservative treatments the use of TENS and S3 neuromodulation produced significant changes in urodynamic parameters and presenting symptoms. Our results appear to justify evaluation with neuromodulatory techniques before definitive surgical intervention in these patients.

  14. Differentiation of Human Adipose Derived Stem Cells into Smooth Muscle Cells Is Modulated by CaMKIIγ

    Directory of Open Access Journals (Sweden)

    Kaisaier Aji

    2016-01-01

    Full Text Available The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII is known to participate in maintenance and switches of smooth muscle cell (SMC phenotypes. However, which isoform of CaMKII is involved in differentiation of adult mesenchymal stem cells into contractile SMCs remains unclear. In the present study, we detected γ isoform of CaMKII in differentiation of human adipose derived stem cells (hASCs into SMCs that resulted from treatment with TGF-β1 and BMP4 in combination for 7 days. The results showed that CaMKIIγ increased gradually during differentiation of hASCs as determined by real-time PCR and western blot analysis. The siRNA-mediated knockdown of CaMKIIγ decreased the protein levels and transcriptional levels of smooth muscle contractile markers (a-SMA, SM22a, calponin, and SM-MHC, while CaMKIIγ overexpression increases the transcriptional and protein levels of smooth muscle contractile markers. These results suggested that γ isoform of CaMKII plays a significant role in smooth muscle differentiation of hASCs.

  15. CD16(+) monocytes with smooth muscle cell characteristics are reduced in human renal chronic transplant dysfunction

    NARCIS (Netherlands)

    Boersema, M.; van den Born, Joost; van Ark, J.; Harms, Geertruida; Seelen, M. A.; van Dijk, M. C. R. F.; van Goor, H.; Navis, G. J.; Popa, E. R.; Hillebrands, J. L.

    In chronic transplant dysfunction (CTD), persistent (allo)immune-mediated inflammation eventually leads to tissue remodeling including neointima formation in intragraft arteries. We previously showed that recipient-derived neointimal alpha-SMA(+) smooth muscle-like cells are present in human renal

  16. Basally activated nonselective cation currents regulate the resting membrane potential in human and monkey colonic smooth muscle

    Science.gov (United States)

    Dwyer, Laura; Rhee, Poong-Lyul; Lowe, Vanessa; Zheng, Haifeng; Peri, Lauren; Ro, Seungil; Sanders, Kenton M.

    2011-01-01

    Resting membrane potential (RMP) plays an important role in determining the basal excitability of gastrointestinal smooth muscle. The RMP in colonic muscles is significantly less negative than the equilibrium potential of K+, suggesting that it is regulated not only by K+ conductances but by inward conductances such as Na+ and/or Ca2+. We investigated the contribution of nonselective cation channels (NSCC) to the RMP in human and monkey colonic smooth muscle cells (SMC) using voltage- and current-clamp techniques. Qualitative reverse transcriptase-polymerase chain reaction was performed to examine potential molecular candidates for these channels among the transient receptor potential (TRP) channel superfamily. Spontaneous transient inward currents and holding currents were recorded in human and monkey SMC. Replacement of extracellular Na+ with equimolar tetraethylammonium or Ca2+ with Mn2+ inhibited basally activated nonselective cation currents. Trivalent cations inhibited these channels. Under current clamp, replacement of extracellular Na+ with N-methyl-d-glucamine or addition of trivalent cations caused hyperpolarization. Three unitary conductances of NSCC were observed in human and monkey colonic SMC. Molecular candidates for basally active NSCC were TRPC1, C3, C4, C7, M2, M4, M6, M7, V1, and V2 in human and monkey SMC. Comparison of the biophysical properties of these TRP channels with basally active NSCC (bINSCC) suggests that TRPM4 and specific TRPC heteromultimer combinations may underlie the three single-channel conductances of bINSCC. In conclusion, these findings suggest that basally activated NSCC contribute to the RMP in human and monkey colonic SMC and therefore may play an important role in determining basal excitability of colonic smooth muscle. PMID:21566016

  17. In-depth evaluation of commercially available human vascular smooth muscle cells phenotype: Implications for vascular tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Timraz, Sara B.H., E-mail: sara.timraz@kustar.ac.ae [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Farhat, Ilyas A.H., E-mail: ilyas.farhat@outlook.com [Department of Applied Mathematics and Sciences, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Alhussein, Ghada, E-mail: ghada.alhussein@kustar.ac.ae [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Christoforou, Nicolas, E-mail: nicolas.christoforou@kustar.ac.ae [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Department of Biomedical Engineering, Duke University, Durham, NC 27708 (United States); Teo, Jeremy C.M., E-mail: jeremy.teo@kustar.ac.ae [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates)

    2016-05-01

    In vitro research on vascular tissue engineering has extensively used isolated primary human or animal smooth muscle cells (SMC). Research programs that lack such facilities tend towards commercially available primary cells sources. Here, we aim to evaluate the capacity of commercially available human SMC to maintain their contractile phenotype, and determine if dedifferentiation towards the synthetic phenotype occurs in response to conventional cell culture and passaging without any external biochemical or mechanical stimuli. Lower passage SMC adopted a contractile phenotype marked by a relatively slower proliferation rate, higher expression of proteins of the contractile apparatus and smoothelin, elongated morphology, and reduced deposition of collagen types I and III. As the passage number increased, migratory capacity was enhanced, average cell speed, total distance and net distance travelled increased up to passage 8. Through the various assays, corroborative evidence pinpoints SMC at passage 7 as the transition point between the contractile and synthetic phenotypes, while passage 8 distinctly and consistently exhibited characteristics of synthetic phenotype. This knowledge is particularly useful in selecting SMC of appropriate passage number for the target vascular tissue engineering application, for example, a homeostatic vascular graft for blood vessel replacement versus recreating atherosclerotic blood vessel model in vitro. - Highlights: • Ability of human smooth muscle cells to alter phenotype in culture is evaluated. • Examined the effect of passaging human smooth muscle cells on phenotype. • Phenotype is assessed based on morphology, proliferation, markers, and migration. • Multi-resolution assessment methodology, single-cell and cell-population. • Lower and higher passages than P7 adopted a contractile and synthetic phenotype respectively.

  18. In-depth evaluation of commercially available human vascular smooth muscle cells phenotype: Implications for vascular tissue engineering

    International Nuclear Information System (INIS)

    Timraz, Sara B.H.; Farhat, Ilyas A.H.; Alhussein, Ghada; Christoforou, Nicolas; Teo, Jeremy C.M.

    2016-01-01

    In vitro research on vascular tissue engineering has extensively used isolated primary human or animal smooth muscle cells (SMC). Research programs that lack such facilities tend towards commercially available primary cells sources. Here, we aim to evaluate the capacity of commercially available human SMC to maintain their contractile phenotype, and determine if dedifferentiation towards the synthetic phenotype occurs in response to conventional cell culture and passaging without any external biochemical or mechanical stimuli. Lower passage SMC adopted a contractile phenotype marked by a relatively slower proliferation rate, higher expression of proteins of the contractile apparatus and smoothelin, elongated morphology, and reduced deposition of collagen types I and III. As the passage number increased, migratory capacity was enhanced, average cell speed, total distance and net distance travelled increased up to passage 8. Through the various assays, corroborative evidence pinpoints SMC at passage 7 as the transition point between the contractile and synthetic phenotypes, while passage 8 distinctly and consistently exhibited characteristics of synthetic phenotype. This knowledge is particularly useful in selecting SMC of appropriate passage number for the target vascular tissue engineering application, for example, a homeostatic vascular graft for blood vessel replacement versus recreating atherosclerotic blood vessel model in vitro. - Highlights: • Ability of human smooth muscle cells to alter phenotype in culture is evaluated. • Examined the effect of passaging human smooth muscle cells on phenotype. • Phenotype is assessed based on morphology, proliferation, markers, and migration. • Multi-resolution assessment methodology, single-cell and cell-population. • Lower and higher passages than P7 adopted a contractile and synthetic phenotype respectively.

  19. Assessment of noninvasive predictors of bladder detrusor underactivity in BPH/LUTs patients.

    Science.gov (United States)

    Luo, Fei; Sun, Hong-Hong; Su, Yan-Hui; Zhang, Zhi-Hua; Wang, Ya-Shen; Zhao, Zhen; Li, Jian

    2017-05-01

    To retrospectively assess the diagnostic predictive value of clinical characteristics to improve the diagnostic accuracy of bladder detrusor underactivity (DU) among benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) patients who cannot undergo urodynamic examinations. A total of 704 BPH/LUTS patients at Tianjin Medical Union Center from January 2013 through June 2016 were enrolled in the study. All cases were stratified by maximum detrusor pressure (Pdet.max) into two groups (DU and control). Patient and clinical variables were analyzed in both groups. One hundred twelve and 592 cases were classified into the DU and control group, respectively. PV (OR 0.976, 95% CI 0.961-0.991, P = 0.002) and PVR (OR 1.004, 95% CI 1.001-1.007, P = 0.004) were independent predictors of DU. In addition, Pdet.max was positively correlated with HTN (≥10 years) (r = 0.373, P = 0.001), smoking (r = 0.108, P = 0.039), IPSS (20-23) (r = 0.257, P = 0.013), PV (r = 0.305, P 76 years) (r = -0.265, P = 0.015), BMI (21-23) (r = -0.382, P = 0.001), DM (0-20 years) (r = 0.365, P = 0.009) and PVR (50-400 mL) (r = 0.423, P = 0.001). The AUCs for BMI, PV, tPSA, PSAD, Q max , and PVR were 0.762, 0.739, 0.727, 0.681, 0.749, and 0.716, respectively. Combined ROC analysis showed the AUC for PV + PVR was 0.774 with sensitivity of 77.78% and specificity of 73.68%. Clinical factors were effective for predicting DU and could help improve the diagnostic accuracy for BPH/LUTS patients who cannot undergo urodynamic examinations.

  20. Smooth Muscle-Like Cells Generated from Human Mesenchymal Stromal Cells Display Marker Gene Expression and Electrophysiological Competence Comparable to Bladder Smooth Muscle Cells.

    Science.gov (United States)

    Brun, Juliane; Lutz, Katrin A; Neumayer, Katharina M H; Klein, Gerd; Seeger, Tanja; Uynuk-Ool, Tatiana; Wörgötter, Katharina; Schmid, Sandra; Kraushaar, Udo; Guenther, Elke; Rolauffs, Bernd; Aicher, Wilhelm K; Hart, Melanie L

    2015-01-01

    The use of mesenchymal stromal cells (MSCs) differentiated toward a smooth muscle cell (SMC) phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP)-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late) myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs. Within 1-2 weeks of myogenic differentiation, differentiating MSCs significantly expressed alpha smooth muscle actin (αSMA; ACTA2), transgelin (TAGLN), calponin (CNN1), and smooth muscle myosin heavy chain (SM-MHC; MYH11) according to qRT-PCR and/or immunofluorescence and Western blot. Voltage-gated Na+ current levels also increased within the same time period following myogenic differentiation. In contrast to undifferentiated MSCs, differentiated MSCs and bladder SMCs exhibited elevated cytosolic Ca2+ transients in response to K+-induced depolarization and contracted in response to K+ indicating functional maturation of differentiated MSCs. Depolarization was suppressed by Cd2+, an inhibitor of voltage-gated Ca2+-channels. The expression of Na+-channels was pharmacologically identified as the Nav1.4 subtype, while the K+ and Ca2+ ion channels were identified by gene expression of KCNMA1, CACNA1C and CACNA1H which encode for the large conductance Ca2+-activated K+ channel BKCa channels, Cav1.2 L-type Ca2+ channels and Cav3.2 T-type Ca2+ channels, respectively. This protocol may be used to differentiate adult MSCs into smooth muscle-like cells with an intermediate-to-late SMC contractile phenotype exhibiting voltage-gated ion channel

  1. Smooth Muscle-Like Cells Generated from Human Mesenchymal Stromal Cells Display Marker Gene Expression and Electrophysiological Competence Comparable to Bladder Smooth Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Juliane Brun

    Full Text Available The use of mesenchymal stromal cells (MSCs differentiated toward a smooth muscle cell (SMC phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs. Within 1-2 weeks of myogenic differentiation, differentiating MSCs significantly expressed alpha smooth muscle actin (αSMA; ACTA2, transgelin (TAGLN, calponin (CNN1, and smooth muscle myosin heavy chain (SM-MHC; MYH11 according to qRT-PCR and/or immunofluorescence and Western blot. Voltage-gated Na+ current levels also increased within the same time period following myogenic differentiation. In contrast to undifferentiated MSCs, differentiated MSCs and bladder SMCs exhibited elevated cytosolic Ca2+ transients in response to K+-induced depolarization and contracted in response to K+ indicating functional maturation of differentiated MSCs. Depolarization was suppressed by Cd2+, an inhibitor of voltage-gated Ca2+-channels. The expression of Na+-channels was pharmacologically identified as the Nav1.4 subtype, while the K+ and Ca2+ ion channels were identified by gene expression of KCNMA1, CACNA1C and CACNA1H which encode for the large conductance Ca2+-activated K+ channel BKCa channels, Cav1.2 L-type Ca2+ channels and Cav3.2 T-type Ca2+ channels, respectively. This protocol may be used to differentiate adult MSCs into smooth muscle-like cells with an intermediate-to-late SMC contractile phenotype exhibiting voltage-gated ion

  2. Iptakalim inhibits PDGF-BB-induced human airway smooth muscle cells proliferation and migration

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wenrui; Kong, Hui; Zeng, Xiaoning; Wang, Jingjing; Wang, Zailiang; Yan, Xiaopei; Wang, Yanli; Xie, Weiping, E-mail: wpxie@njmu.edu.cn; Wang, Hong, E-mail: hongwang@njmu.edu.cn

    2015-08-15

    Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (K{sub ATP}) channels have been identified in ASMCs. Mount evidence has suggested that K{sub ATP} channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K{sup +} channels triggers K{sup +} efflux, which leading to membrane hyperpolarization, preventing Ca{sup 2+}entry through closing voltage-operated Ca{sup 2+} channels. Intracellular Ca{sup 2+} is the most important regulator of muscle contraction, cell proliferation and migration. K{sup +} efflux decreases Ca{sup 2+} influx, which consequently influences ASMCs proliferation and migration. As a K{sub ATP} channel opener, iptakalim (Ipt) has been reported to restrain the proliferation of pulmonary arterial smooth muscle cells (PASMCs) involved in vascular remodeling, while little is known about its impact on ASMCs. The present study was designed to investigate the effects of Ipt on human ASMCs and the mechanisms underlying. Results obtained from cell counting kit-8 (CCK-8), flow cytometry and 5-ethynyl-2′-deoxyuridine (EdU) incorporation showed that Ipt significantly inhibited platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation. ASMCs migration induced by PDGF-BB was also suppressed by Ipt in transwell migration and scratch assay. Besides, the phosphorylation of Ca{sup 2+}/calmodulin-dependent kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (Akt), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were as well alleviated by Ipt administration. Furthermore, we found that the inhibition of Ipt on the PDGF-BB-induced proliferation and migration in human ASMCs was blocked by glibenclamide (Gli), a selective K{sub ATP} channel antagonist. These findings provide a strong evidence to support that Ipt

  3. Interstitial cells of Cajal in human small intestine. Ultrastructural identification and organization between the main smooth muscle layers

    DEFF Research Database (Denmark)

    Rumessen, J J; Thuneberg, L

    1991-01-01

    with elastin fibers. The organization shown in this study strongly supports the concept of interstitial cells of Cajal as important regulatory cells also in the human small intestine. The characteristic cytology and organization of interstitial cells of Cajal may provide a basis for future morphological......Previous morphological and electrophysiological studies have supported the hypothesis that interstitial cells of Cajal have important regulatory (pacemaker) functions in the gut. In the current study, interstitial cells of Cajal associated with Auerbach's plexus in human small intestine were...... studied. Freshly resected intestine was examined by light and electron microscopy. The interstitial cells of Cajal resembled modified smooth muscle cells. They had caveolae and dense bodies, an incomplete basal lamina, a very well-developed smooth endoplasmic reticulum, and abundant intermediate (10 nm...

  4. Proliferation and extracellular matrix synthesis of smooth muscle cells cultured from human coronary atherosclerotic and restenotic lesions

    NARCIS (Netherlands)

    D.C. MacLeod (Donald); B.H. Strauss (Bradley); J. Escaned (Javier); V.A.W.M. Umans (Victor); R-J. van Suylen (Robert-Jan); A. Verkerk (Anton); P.J. de Feyter (Pim); P.W.J.C. Serruys (Patrick); M. de Jong (Marcel)

    1994-01-01

    textabstractOBJECTIVES. The purpose of this study was to examine the proliferative capacity and extracellular matrix synthesis of human coronary plaque cells in vitro. BACKGROUND. Common to both primary atherosclerosis and restenosis are vascular smooth muscle cell proliferation and production of

  5. Adenovirus-assisted lipofection: efficient in vitro gene transfer of luciferase and cytosine deaminase to human smooth muscle cells.

    Science.gov (United States)

    Kreuzer, J; Denger, S; Reifers, F; Beisel, C; Haack, K; Gebert, J; Kübler, W

    1996-07-01

    Smooth muscle cells (SMC) are a central cell type involved in multiple processes of coronary artery diseases including restenosis and therefore are major target cells for different aspects of gene transfer. Previous attempts to transfect primary arterial cells using different techniques like liposomes, CaPO4 and electroporation resulted in only low transfection efficiency. The development of recombinant adenoviruses dramatically improved the delivery of foreign genes into different cell types including SMC. However, cloning and identification of recombinants remain difficult and time-consuming techniques. The present study demonstrates that a complex consisting of reporter plasmid encoding firefly luciferase (pLUC), polycationic liposomes and replication-deficient adenovirus was able to yield very high in vitro transfection of primary human smooth muscle cells under optimized conditions. The technique of adenovirus-assisted lipofection (AAL) increases transfer and expression of plasmid DNA in human smooth muscle cells in vitro up to 1000-fold compared to lipofection. To verify the applicability of AAL for gene transfer into human smooth muscle cells we studied a gene therapy approach to suppress proliferation of SMC in vitro, using the prokaryotic cytosine deaminase gene (CD) which enables transfected mammalian cells to deaminate 5-fluorocytosine (5-FC) to the highly toxic 5-fluorouracil (5-FU). The effect of a transient CD expression on RNA synthesis was investigated by means of a cotransfection with a RSV-CD expression plasmid and the luciferase reporter plasmid. Western blot analysis demonstrated high expression of CD protein in transfected SMC. Cotransfected SMC demonstrated two-fold less luciferase activity in the presence of 5-FC (5 mmol/l) after 48 h compared to cells transfected with a non-CD coding plasmid. The data demonstrate that a transient expression of CD could be sufficient to reduce the capacity of protein synthesis in human SMC. This simple and

  6. LPS, but not Angiotensin ll, lnduces Direct Pro-lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

    DEFF Research Database (Denmark)

    Outzen, Emilie M; Zaki, Marina; Mehryar, Rahila

    2017-01-01

    resistance-sized arteries (MRA) supported by experiments in cultured human primary endothelial and vascular smooth muscle cells. Results showed that 24-hr organ culture of mouse MRA with 10 nM Ang II had, unlike 100 ng/mL LPS, no effects on IL-6 or MCP-1 secretion, VCAM1 mRNA expression or endothelial......]-Ang II had no concentration- or time-dependent effects on IL-6 and MCP-1 secretion in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMC). AGTR1 or AGTR2 mRNA expression were undetectable in HUVEC, whereas HASMC expressed only AGTR1 mRNA. In summary, contrary...... rights reserved....

  7. Combined treatment with a β3 -adrenergic receptor agonist and a muscarinic receptor antagonist inhibits detrusor overactivity induced by cold stress in spontaneously hypertensive rats.

    Science.gov (United States)

    Imamura, Tetsuya; Ogawa, Teruyuki; Minagawa, Tomonori; Nagai, Takashi; Suzuki, Toshiro; Saito, Tetsuichi; Yokoyama, Hitoshi; Nakazawa, Masaki; Ishizuka, Osamu

    2017-04-01

    This study determined if combined treatment with the muscarinic receptor (MR) antagonist solifenacin and the β 3 -adrenergic receptor (AR) agonist mirabegron could inhibit detrusor overactivity induced by cold stress in spontaneously hypertensive rats (SHRs). Thirty-two female 10-week-old SHRs were fed an 8% NaCl-supplemented diet for 4 weeks. Cystometric measurements of the unanesthetized, unrestricted rats were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then intravenously administered vehicle, 0.1 mg/kg solifenacin alone, 0.1 mg/kg mirabegron alone, or the combination of 0.1 mg/kg mirabegron and 0.1 mg/kg solifenacin (n = 8 each group). Five minutes later, the treated rats were exposed to low temperature (LT, 4 ± 2°C) for 40 min. Finally, the rats were returned to RT. After the cystometric investigations, the β 3 -ARs and M 3 -MRs expressed within the urinary bladders were analyzed. Just after transfer from RT to LT, vehicle-, solifenacin-, and mirabegron-treated SHRs exhibited detrusor overactivity that significantly decreased voiding interval and bladder capacity. However, treatment with the combination of solifenacin and mirabegron partially inhibited the cold stress-induced detrusor overactivity patterns. The decreases of voiding interval and bladder capacity in the combination-treated rats were significantly inhibited compared to other groups. Within the urinary bladders, there were no differences between expression levels of M 3 -MR and β 3 -AR mRNA. The tissue distribution of M 3 -MRs was similar to that of the β 3 -ARs. This study suggested that the combination of solifenacin and mirabegron act synergistically to inhibit the cold stress-induced detrusor overactivity in SHRs. Neurourol. Urodynam. 36:1026-1033, 2017. © 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc. © 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.

  8. Effects of the dual TP receptor antagonist and thromboxane synthase inhibitor EV-077 on human endothelial and vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Petri, Marcelo H.; Tellier, Céline; Michiels, Carine; Ellertsen, Ingvill; Dogné, Jean-Michel; Bäck, Magnus

    2013-01-01

    Highlights: •EV-077 reduced TNF-α induced inflammation in endothelial cells. •The thromboxane mimetic U69915 enhanced vascular smooth muscle cell proliferation. •EV-077 inhibited smooth muscle cell proliferation. -- Abstract: The prothrombotic mediator thromboxane A 2 is derived from arachidonic acid metabolism through the cyclooxygenase and thromboxane synthase pathways, and transduces its effect through the thromboxane prostanoid (TP) receptor. The aim of this study was to determine the effect of the TP receptor antagonist and thromboxane synthase inhibitor EV-077 on inflammatory markers in human umbilical vein endothelial cells and on human coronary artery smooth muscle cell proliferation. To this end, mRNA levels of different proinflammatory mediators were studied by real time quantitative PCR, supernatants were analyzed by enzyme immune assay, and cell proliferation was assessed using WST-1. EV-077 significantly decreased mRNA levels of ICAM-1 and PTX3 after TNFα incubation, whereas concentrations of 6-keto PGF1α in supernatants of endothelial cells incubated with TNFα were significantly increased after EV-077 treatment. Although U46619 did not alter coronary artery smooth muscle cell proliferation, this thromboxane mimetic enhanced the proliferation induced by serum, insulin and growth factors, which was significantly inhibited by EV-077. In conclusion, EV-077 inhibited TNFα-induced endothelial inflammation and reduced the enhancement of smooth muscle cell proliferation induced by a thromboxane mimetic, supporting that the thromboxane pathway may be associated with early atherosclerosis in terms of endothelial dysfunction and vascular hypertrophy

  9. Effects of the dual TP receptor antagonist and thromboxane synthase inhibitor EV-077 on human endothelial and vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Petri, Marcelo H. [Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm (Sweden); Tellier, Céline; Michiels, Carine [NARILIS, URBC, University of Namur, Namur (Belgium); Ellertsen, Ingvill [Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm (Sweden); Dogné, Jean-Michel [Department of Pharmacy, Namur Thrombosis and Hemostasis Center, University of Namur, Namur (Belgium); Bäck, Magnus, E-mail: Magnus.Back@ki.se [Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm (Sweden)

    2013-11-15

    Highlights: •EV-077 reduced TNF-α induced inflammation in endothelial cells. •The thromboxane mimetic U69915 enhanced vascular smooth muscle cell proliferation. •EV-077 inhibited smooth muscle cell proliferation. -- Abstract: The prothrombotic mediator thromboxane A{sub 2} is derived from arachidonic acid metabolism through the cyclooxygenase and thromboxane synthase pathways, and transduces its effect through the thromboxane prostanoid (TP) receptor. The aim of this study was to determine the effect of the TP receptor antagonist and thromboxane synthase inhibitor EV-077 on inflammatory markers in human umbilical vein endothelial cells and on human coronary artery smooth muscle cell proliferation. To this end, mRNA levels of different proinflammatory mediators were studied by real time quantitative PCR, supernatants were analyzed by enzyme immune assay, and cell proliferation was assessed using WST-1. EV-077 significantly decreased mRNA levels of ICAM-1 and PTX3 after TNFα incubation, whereas concentrations of 6-keto PGF1α in supernatants of endothelial cells incubated with TNFα were significantly increased after EV-077 treatment. Although U46619 did not alter coronary artery smooth muscle cell proliferation, this thromboxane mimetic enhanced the proliferation induced by serum, insulin and growth factors, which was significantly inhibited by EV-077. In conclusion, EV-077 inhibited TNFα-induced endothelial inflammation and reduced the enhancement of smooth muscle cell proliferation induced by a thromboxane mimetic, supporting that the thromboxane pathway may be associated with early atherosclerosis in terms of endothelial dysfunction and vascular hypertrophy.

  10. Oxytocin receptors expressed and coupled to Ca2+ signalling in a human vascular smooth muscle cell line.

    Science.gov (United States)

    Yazawa, H; Hirasawa, A; Horie, K; Saita, Y; Iida, E; Honda, K; Tsujimoto, G

    1996-03-01

    1. In a human vascular smooth muscle cell line (HVSMC), binding experiments with [3H]-arginine8-vasopressin (AVP) have shown the existence of a homogeneous population of binding sites with affinity (Kd value) of 0.65 nM and a maximum number of binding sites (Bmax) of 122 fmol mg-1 protein. 2. Nonlabelled compounds compete for [3H]-AVP binding in the HVSMC membrane with an order of potency of oxytocin > lyspressin > or = AVP > Thr4, Gly7-oxytocin > (beta-mercapto-beta-beta-cyclopentamethylenepropionyl-O-Me Tyr2, Arg8) vasopressin > desmopressin > OPC21268 > OPC31260. This order was markedly different from that observed in rat vascular smooth muscle cells (A10), a well-established V1A receptor system. 3. In HVSMC both oxytocin and AVP increased inositol 1,4,5-trisphosphate (IP3) production and [Ca2+]i response, but the efficacy of the responses was greater for oxytocin than AVP. 4. Reverse transcription-polymerase chain reaction (RT-PCR) assay detected only oxytocin receptor but not V1A or V2 receptors in HVSMC, whereas only V1A receptors were found in A10 cells. 5. In conclusion, in HVSMC only oxytocin receptors are expressed among the vasopressin receptor family, and they coupled to phosphatidyl inositol (PI) turnover/Ca2+ signalling. This unexpected observation should provide new insight into the functional role of the oxytocin receptor in a human vascular smooth muscle cell line.

  11. Immunoexpression of adrenergic receptors in detrusor from patients with prune belly syndrome: a digital quantification.

    Science.gov (United States)

    Schneider-Monteiro, Edison D; Dénes, Francisco T; Hampel, Christian; Leite, Katia R M; Thüroff, Joachim W; Srougi, Miguel

    2010-06-01

    Prune belly syndrome (PBS) presents with large-capacity bladders, high compliance and post-void residual volumes. Operative and conservative treatments are controversial. When histologically compared to normal bladder, bladder outlet obstruction results in an up- or down-regulation of adrenoceptors. Our goal was to study the immunoexpression of adrenoceptors in detrusor from patients with PBS. Bladder domes from PBS patients (n=14) were studied (PBG). For normal controls, bladder specimens were obtained at adult surgery (n=13) (CG1) and at child autopsy (n=5) (CG2). Staining was performed using antibodies to alpha1a, alpha1b, alpha1d and beta3 adrenoceptors. Five to 10 images were captured on an optic microscope with a digital camera and analysed with Photoshop. The immunocyhistochemical index with arbitrary units was calculated and compared. Mean age was 1.28, 64 and 1.41 years for PBG, CG1 and CG2, respectively. The immunohistochemical index with arbitrary units of alpha1a receptors was 0.06 in PBG, 0.16 in CG1 and 0.14 in CG2 (p=0.008); of alpha1b 0.06, 0.06 and 0.07 (p=0.781); and of alpha1d 0.04, 0.04 and 0.05 (p=0.618). Regarding beta3 the respective values were 0.07, 0.14 and 0.10 (p=0.378). Our results show a decrease in alpha1a-adrenoceptor immunostaining intensity in detrusor from children with PBS. Further in vitro studies are needed to determine whether these observations are physiologically significant. Copyright (c) 2010 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  12. Mixed incontinence: does preoperative urodynamic detrusor overactivity affect postoperative quality of life after pubovaginal sling?

    Directory of Open Access Journals (Sweden)

    John T. Stoffel

    2008-12-01

    Full Text Available OBJECTIVE: Our purpose was to determine if women with mixed urinary incontinence (MUI and urodynamic detrusor overactivity (DO have less improvement in urinary symptoms after pubovaginal sling surgery (PVS, compared to MUI without DO. MATERIALS AND METHODS: Women with preoperative MUI symptoms prior to PVS were identified through retrospective review. DO was defined as a symptomatic 5 cm H20 detrusor pressure or greater rise during urodynamics. MUI patients with and without DO before PVS were divided into Groups A and B, respectively. All patients had returned a completed Urogenital Distress Inventory 6 (UDI-6 questionnaire and a 3-day diary of pad usage before surgery and at each postoperative visit. Study endpoints included change in total UDI-6 score, and change in number of pad use/day after PVS. RESULTS: 73 patients were identified, 31 in Group A and 42 in Group B. Mean follow-up after PVS was 15 and 16 months, respectively (p = 0.59. Preoperative total UDI-6 scores were 11.8 and 12.7 (p = 0.30 for Group A and B. Mean changes in total UDI-6 after PVS were - 8.0 and - 10.2 (p = 0.030, respectively. After PVS, both groups reported similar mean reduction in pad/day usage from preoperative baseline (-2.57 vs. --2.49, p = 0.83. There were no differences between the groups when comparing demographic, urodynamic, or operative data. CONCLUSION: MUI patients had improved continence and quality of life after PVS. However, MUI patients with DO had less improvement in UDI-6 scores after PVS, despite a similar reduction to pad use/day.

  13. A systematic review of the diagnosis and treatment of patients with neurogenic hyperactivity of the detrusor muscle.

    Science.gov (United States)

    Borau, A; Adot, J M; Allué, M; Arlandis, S; Castro, D; Esteban, M; Salinas, J

    Neurogenic detrusor hyperactivity (NDH) is a urodynamic observation characterised by involuntary detrusor contractions during the filling phase that are caused by an underlying neurological disease. The common and severe complications that can result from NDH warrant the preparation of healthcare protocols for the proper management of patients with NDH. The aim of this study is to standardise the criteria for the decision-making process in the management of patients with diagnosed or suspected NDH, providing personalised medical care. We performed a systematic noncomprehensive literature review on the aspects of the diagnosis and treatment of NDH. Based on the review, recommendations were issued by nominal consensus of a group of urology specialists. In general, the diagnosis of NDH is arrived at by a proper review of the medical history, physical examination and voiding diary before performing any diagnostic study. The main treatment objectives are to protect the upper urinary tract, restore function of the lower tract and improve these patients' continence and quality of life. The treatment consists of several steps aimed at obtaining proper bladder storage that allows for sufficiently spaced voidings. The follow-up should be personalised based on each patient's needs. The identification and management of NDH is important for positively redirecting the function of the lower urinary tract, in terms of filling and voiding, thereby improving the patients' quality of life. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  14. Tissue-Engineered Vascular Rings from Human iPSC-Derived Smooth Muscle Cells

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    Biraja C. Dash

    2016-07-01

    Full Text Available There is an urgent need for an efficient approach to obtain a large-scale and renewable source of functional human vascular smooth muscle cells (VSMCs to establish robust, patient-specific tissue model systems for studying the pathogenesis of vascular disease, and for developing novel therapeutic interventions. Here, we have derived a large quantity of highly enriched functional VSMCs from human induced pluripotent stem cells (hiPSC-VSMCs. Furthermore, we have engineered 3D tissue rings from hiPSC-VSMCs using a facile one-step cellular self-assembly approach. The tissue rings are mechanically robust and can be used for vascular tissue engineering and disease modeling of supravalvular aortic stenosis syndrome. Our method may serve as a model system, extendable to study other vascular proliferative diseases for drug screening. Thus, this report describes an exciting platform technology with broad utility for manufacturing cell-based tissues and materials for various biomedical applications.

  15. Pleiotropic effects of statins in distal human pulmonary artery smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Butrous Ghazwan S

    2011-10-01

    Full Text Available Abstract Background Recent clinical data suggest statins have transient but significant effects in patients with pulmonary arterial hypertension. In this study we explored the molecular effects of statins on distal human pulmonary artery smooth muscle cells (PASMCs and their relevance to proliferation and apoptosis in pulmonary arterial hypertension. Methods Primary distal human PASMCs from patients and controls were treated with lipophilic (simvastatin, atorvastatin, mevastatin and fluvastatin, lipophobic (pravastatin and nitric-oxide releasing statins and studied in terms of their DNA synthesis, proliferation, apoptosis, matrix metalloproteinase-9 and endothelin-1 release. Results Treatment of human PASMCs with selected statins inhibited DNA synthesis, proliferation and matrix metalloproteinase-9 production in a concentration-dependent manner. Statins differed in their effectiveness, the rank order of anti-mitogenic potency being simvastatin > atorvastatin > > pravastatin. Nevertheless, a novel nitric oxide-releasing derivative of pravastatin (NCX 6550 was effective. Lipophilic statins, such as simvastatin, also enhanced the anti-proliferative effects of iloprost and sildenafil, promoted apoptosis and inhibited the release of the mitogen and survival factor endothelin-1. These effects were reversed by mevalonate and the isoprenoid intermediate geranylgeranylpyrophosphate and were mimicked by inhibitors of the Rho and Rho-kinase. Conclusions Lipophilic statins exert direct effects on distal human PASMCs and are likely to involve inhibition of Rho GTPase signalling. These findings compliment some of the recently documented effects in patients with pulmonary arterial hypertension.

  16. Human mast cell and airway smooth muscle cell interactions: implications for asthma.

    Science.gov (United States)

    Page, S; Ammit, A J; Black, J L; Armour, C L

    2001-12-01

    Asthma is characterized by inflammation, hyperresponsiveness, and remodeling of the airway. Human mast cells (HMCs) play a central role in all of these changes by releasing mediators that cause exaggerated bronchoconstriction, induce human airway smooth muscle (HASM) cell proliferation, and recruit and activate inflammatory cells. Moreover, the number of HMCs present on asthmatic HASM is increased compared with that on nonasthmatic HASM. HASM cells also have the potential to actively participate in the inflammatory process by synthesizing cytokines and chemokines and expressing surface molecules, which have the capacity to perpetuate the inflammatory mechanisms present in asthma. This review specifically examines how the mediators of HMCs have the capacity to modulate many functions of HASM; how the synthetic function of HASM, particularly through the release and expression of stem cell factor, has the potential to influence HMC number and activation in an extraordinarily potent and proinflammatory manner; and how these interactions between HMCs and HASM have potential consequences for airway structure and inflammation relevant to the disease process of asthma.

  17. Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection

    Directory of Open Access Journals (Sweden)

    King Nicholas JC

    2006-05-01

    Full Text Available Abstract Background Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV are the predominant virus type. Airway smooth muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human airway smooth muscle cells (HASM. We hypothesised that rhinovirus induction of inflammatory cytokine release from airway smooth muscle is augmented and differentially regulated in asthmatic compared to normal HASM cells. Methods HASM cells, isolated from either asthmatic or non-asthmatic subjects, were infected with rhinovirus. Cytokine production was assayed by ELISA, ICAM-1 cell surface expression was assessed by FACS, and the transcription regulation of IL-6 was measured by luciferase activity. Results RV-induced IL-6 release was significantly greater in HASM cells derived from asthmatic subjects compared to non-asthmatic subjects. This response was RV specific, as 5% serum- induced IL-6 release was not different in the two cell types. Whilst serum stimulated IL-8 production in cells from both subject groups, RV induced IL-8 production in only asthmatic derived HASM cells. The transcriptional induction of IL-6 was differentially regulated via C/EBP in the asthmatic and NF-κB + AP-1 in the non-asthmatic HASM cells. Conclusion This study demonstrates augmentation and differential transcriptional regulation of RV specific innate immune response in HASM cells derived from asthmatic and non-asthmatics, and may give valuable insight into the mechanisms of RV-induced asthma exacerbations.

  18. Neuron-derived orphan receptor 1 promoted human pulmonary artery smooth muscle cells proliferation.

    Science.gov (United States)

    Wang, Chang-Guo; Lei, Wei; Li, Chang; Zeng, Da-Xiong; Huang, Jian-An

    2015-05-01

    As a transcription factor of the nuclear receptor superfamily, neuron-derived orphan receptor 1 (NOR1) is induced rapidly in response to various extracellular stimuli. But, it is still unclear its role in pulmonary artery smooth muscle cells proliferation. Human PASMCs were cultured in vitro and stimulated by serum. The special antisense oligodeoxynucleotides (AS-ODNs) were used to knockdown human NOR1 gene expression. Real-time PCR and Western-blot were used to evaluate the gene expression and protein levels. Fetal bovine serum (FBS) induced human PASMCs proliferation in a dose dependent manner. Furthermore, FBS promoted NOR1 gene expression in a dose dependent manner and a time dependent manner. 10% FBS induced a maximal NOR1 mRNA levels at 2 h. FBS also induced a significant higher NOR1 protein levels as compared with control. The NOR1 over-expressed plasmid significantly promoted DNA synthesis and cells proliferation. Moreover, the special AS-ODNs against human NOR1 not only prevented NOR1 expression but also inhibited DNA synthesis and cells proliferation significantly. The NOR1 over-expression plasmid could up-regulate cyclin D1 expression markedly, but the AS-ODNs inhibited cyclin D1 expression significantly. So, we concluded that NOR1 could promote human PASMCs proliferation. Cyclin D1 might be involved in this process.

  19. Oxidative and nonoxidative metabolism of polycyclic aromatic hydrocarbons in rabbit and chicken aortas and in human fetal smooth-muscle cells

    International Nuclear Information System (INIS)

    Bond, J.A.; Kocan, R.M.; Benditt, E.P.; Juchau, M.R.

    1980-01-01

    A description of the various enzyme systems in aortas of rabbits and chickens and in human fetal smooth muscle cells in culture which are responsible overall for the metabolism of F, 12-dimethylbenz(a)anthracene and benzo(a)pyrene-4, 5-oxide are provided

  20. The chemokine and scavenger receptor CXCL16/SR-PSOX is expressed in human vascular smooth muscle cells and is induced by interferon γ

    International Nuclear Information System (INIS)

    Wagsaeter, Dick; Olofsson, Peder S.; Norgren, Lars; Stenberg, Bjoern; Sirsjoe, Allan

    2004-01-01

    Atherosclerosis is an inflammatory disease that is characterised by the involvement of chemokines that are important for the recruitment of leukocytes and scavenger receptors that mediate foam cell formation. Several cytokines are involved in the regulation of chemokines and scavenger receptors in atherosclerosis. CXCL16 is a chemokine and scavenger receptor and found in macrophages in human atherosclerotic lesions. Using double-labelled immunohistochemistry, we identified that smooth muscle cells in human lesions express CXCL16. We then analysed the effects of IFN-γ, TNF-α, IL-12, IL-15, IL-18, and LPS on CXCL16 expression in cultured aortic smooth muscle cells. IFN-γ was the most potent CXCL16 inducer and increased mRNA, soluble form, membrane form, and total cellular levels of CXCL16. The IFN-γ induction of CXCL16 was also associated with increased uptake of oxLDL into these cells. Taken together, smooth muscle cells express CXCL16 in atherosclerotic lesions, which may play a role in the attraction of T cells to atherosclerotic lesions and contribute to the cellular internalisation of modified LDL

  1. Detrusor instability in children with recurrent urinary tract infection and/or enuresis. II

    DEFF Research Database (Denmark)

    Qvist, N; Nielsen, K K; Kristensen, E S

    1986-01-01

    Of 41 children, aged 5-15 years, referred consecutively because of recurrent urinary tract infections (UTIs) and/or enuresis, 18 (44%) showed detrusor instability (DI) in at least 2 of 6 CO2 cystometries. One child was excluded from the study because of lack of follow-up. Four children with less...... pronounced DI (instability during less than or equal to 50% of the cystometries performed) and frequent UTIs were given antibiotics prophylactically for 3 months. In the remaining 13 children, DI was found during more than half the cystometries performed, and 11 of these children, who also had urge...... incontinence, were treated with emepronium bromide, 400-600 mg daily (10-12 mg/kg) for 3 months. In 7 of the patients this treatment was supplemented by antibiotics prophylactically because of frequent UTIs. Two children with special problems received other types of treatment. All children were free from...

  2. Efficacy of peripheral lidocaine application (neural therapy) in the treatment of neurogenic detrusor overactivity in multiple sclerosis patients.

    Science.gov (United States)

    Tamam, Yusuf; Özdemir, Hasan Hüseyin; Gedik, Abdullah; Tamam, Cüneyt; Nazlıkul, Hüseyin

    2017-09-01

    Many agents and treatments are used in the treatment of neurogenic detrusor overactivity (NDO) in MS patients, but no study has been conducted on the use of peripheric lidocaine (neural therapy-NT) on MS patients. We evaluated the effects of local administration of lidocaine on NDO in Multiple Sclerosis (MS) patients. For each patient local anesthetic lidocaine was injected at each session. Sessions were held once a week for 5 weeks. At each session, Th 10-L1, urogenital segment intradermal injections, Frankenhauser, and sacral epidural injections were given. The patients had clinical and urodynamic assessment 1 month before and 3, 9, and 12 months after NT. In addition, multiple sclerosis quality of life inventory (MSQL-54) and bladder control scale (BLCS) was performed for patients. Twenty-eight patients were included in the study (8 males, 20 females). The patients' average age was 31.7 ± 8.1 years. The injection therapy significantly improved volume at first involuntary bladder contraction (FCV), maximal detrusor pression during filling (P det. max.), maximal cystometric bladder capacity (MCC) after 3 months. Also, the MSQL-54 and BLCS scores were improved with treatment. However, these improvements reached a maximum 3 months after treatment, but from the 9 month a regression was seen in the parameters, and after 12 months the findings were seen to be slightly above their basal levels. These results suggest that NDO treatment in MS patients could be an effective treatment which is easy and has very few side effects, and is cost effective. © 2017 Wiley Periodicals, Inc.

  3. Use of Optical Mapping to Evaluate Mechanisms and New Therapies for Bladder Dysfunction Due to Spinal Cord Injury

    Science.gov (United States)

    2014-12-01

    propria, between detrusor muscle bundles (intra- muscular ), within muscle bundles (inter- muscular )27 and around blood vessels (perivascular)6 (Fig. 1...osmotic distension , signals propagated from the urothelial to smooth muscle. When the ICs were removed, the smooth muscle did not respond to stretch...calcium channels. Br J Pharmacol 1995;115:1020–6. 37. Ghoneim MA, Fretin JA, Gagnon DJ, et al. The influence of vesical distension on the urethral

  4. Antiproliferative effect of UTP on human arterial and venous smooth muscle cells.

    Science.gov (United States)

    White, P J; Kumari, R; Porter, K E; London, N J; Ng, L L; Boarder, M R

    2000-12-01

    We have investigated the hypothesis that responses associated with proliferation are regulated by extracellular nucleotides such as ATP and UTP in cultured human vascular smooth muscle cells (VSMC) derived from internal mammary artery (IMA) and saphenous vein (SV). Platelet-derived growth factor (PDGF), ATP, and UTP each generated an increase in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in both IMA- and SV-derived cells in the absence of detectable inositol 1,4,5-trisphosphate production. ATP alone had no effect on [(3)H]thymidine incorporation into DNA, but with a submaximal concentration of PDGF it raised [(3)H]thymidine incorporation in SV- but not IMA-derived cells. UTP alone also was without effect on [(3)H]thymidine incorporation or cell number. However, in both SV- and IMA-derived cells, UTP reduced the PDGF-stimulated [(3)H]thymidine response and PDGF-stimulated cell proliferation. This cannot be explained by an inhibitory effect on the p42/p44 mitogen-activated protein kinase (MAPK) cascade, since this response to PDGF was not attenuated by UTP. We conclude that, in human VSMC of both arterial and venous origin, UTP acts as an anti-proliferative regulator.

  5. Stimulation of aortic smooth muscle cell mitogenesis by serotonin

    International Nuclear Information System (INIS)

    Nemecek, G.M.; Coughlin, S.R.; Handley, D.A.; Moskowitz, M.A.

    1986-01-01

    Bovine aortic smooth muscle cells in vitro responded to 1 nM to 10 μM serotonin with increased incorporation of [ 3 H]thymidine into DNA. The mitogenic effect of serotonin was half-maximal at 80 nM and maximal above 1 μM. At a concentration of 1 μM, serotonin stimulated smooth muscle cell mitogenesis to the same extent as human platelet-derived growth factor (PDGF) at 12 ng/ml. Tryptamine was ≅ 1/10th as potent as serotonin as a mitogen for smooth muscle cells. Other indoles that are structurally related to serotonin (D- and L-tryptophan, 5-hydroxy-L-tryptophan, N-acetyl-5-hydroxytryptamine, melatonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol) and quipazine were inactive. The stimulatory effect of serotonin on smooth muscle cell DNA synthesis required prolonged (20-24 hr) exposure to the agonist and was attenuated in the presence of serotonin D receptor antagonists. When smooth muscle cells were incubated with submaximal concentrations of serotonin and PDGF, synergistic rather than additive mitogenic responses were observed. These data indicate that serotonin has a significant mitogenic effect on smooth muscle cells in vitro, which appears to be mediated by specific plasma membrane receptors

  6. Tetraspanin CD9 regulates cell contraction and actin arrangement via RhoA in human vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Michael J Herr

    Full Text Available The most prevalent cardiovascular diseases arise from alterations in vascular smooth muscle cell (VSMC morphology and function. Tetraspanin CD9 has been previously implicated in regulating vascular pathologies; however, insight into how CD9 may regulate adverse VSMC phenotypes has not been provided. We utilized a human model of aortic smooth muscle cells to understand the consequences of CD9 deficiency on VSMC phenotypes. Upon knocking down CD9, the cells developed an abnormally small and rounded morphology. We determined that this morphological change was due to a lack of typical parallel actin arrangement. We also found similar total RhoA but decreased GTP-bound (active RhoA levels in CD9 deficient cells. As a result, cells lacking a full complement of CD9 were less contractile than their control treated counterparts. Upon restoration of RhoA activity in the CD9 deficient cells, the phenotype was reversed and cell contraction was restored. Conversely, inhibition of RhoA activity in the control cells mimicked the CD9-deficient cell phenotype. Thus, alteration in CD9 expression was sufficient to profoundly disrupt cellular actin arrangement and endogenous cell contraction by interfering with RhoA signaling. This study provides insight into how CD9 may regulate previously described vascular smooth muscle cell pathophysiology.

  7. Evidence Supports Tradition: The in Vitro Effects of Roman Chamomile on Smooth Muscles

    Directory of Open Access Journals (Sweden)

    Zsolt Sándor

    2018-04-01

    Full Text Available The dried flowers of Chamaemelum nobile (L. All. have been used in traditional medicine for different conditions related to the spasm of the gastrointestinal system. However, there have been no experimental studies to support the smooth muscle relaxant effect of this plant. The aim of our research was to assess the effects of the hydroethanolic extract of Roman chamomile, its fractions, four of its flavonoids (apigenin, luteolin, hispidulin, and eupafolin, and its essential oil on smooth muscles. The phytochemical compositions of the extract and its fractions were characterized and quantified by HPLC-DAD, the essential oil was characterized by GC and GC-MS. Neuronally mediated and smooth muscle effects were tested in isolated organ bath experiments on guinea pig, rat, and human smooth muscle preparations. The crude herbal extract induced an immediate, moderate, and transient contraction of guinea pig ileum via the activation of cholinergic neurons of the gut wall. Purinoceptor and serotonin receptor antagonists did not influence this effect. The more sustained relaxant effect of the extract, measured after pre-contraction of the preparations, was remarkable and was not affected by an adrenergic beta receptor antagonist. The smooth muscle-relaxant activity was found to be associated with the flavonoid content of the fractions. The essential oil showed only the relaxant effect, but no contracting activity. The smooth muscle-relaxant effect was also detected on rat gastrointestinal tissues, as well as on strip preparations of human small intestine. These results suggest that Roman chamomile extract has a direct and prolonged smooth muscle-relaxant effect on guinea pig ileum which is related to its flavonoid content. In some preparations, a transient stimulation of enteric cholinergic motoneurons was also detected. The essential oil also had a remarkable smooth muscle relaxant effect in this setting. Similar relaxant effects were also detected on

  8. Evidence Supports Tradition: The in Vitro Effects of Roman Chamomile on Smooth Muscles.

    Science.gov (United States)

    Sándor, Zsolt; Mottaghipisheh, Javad; Veres, Katalin; Hohmann, Judit; Bencsik, Tímea; Horváth, Attila; Kelemen, Dezső; Papp, Róbert; Barthó, Loránd; Csupor, Dezső

    2018-01-01

    The dried flowers of Chamaemelum nobile (L.) All. have been used in traditional medicine for different conditions related to the spasm of the gastrointestinal system. However, there have been no experimental studies to support the smooth muscle relaxant effect of this plant. The aim of our research was to assess the effects of the hydroethanolic extract of Roman chamomile, its fractions, four of its flavonoids (apigenin, luteolin, hispidulin, and eupafolin), and its essential oil on smooth muscles. The phytochemical compositions of the extract and its fractions were characterized and quantified by HPLC-DAD, the essential oil was characterized by GC and GC-MS. Neuronally mediated and smooth muscle effects were tested in isolated organ bath experiments on guinea pig, rat, and human smooth muscle preparations. The crude herbal extract induced an immediate, moderate, and transient contraction of guinea pig ileum via the activation of cholinergic neurons of the gut wall. Purinoceptor and serotonin receptor antagonists did not influence this effect. The more sustained relaxant effect of the extract, measured after pre-contraction of the preparations, was remarkable and was not affected by an adrenergic beta receptor antagonist. The smooth muscle-relaxant activity was found to be associated with the flavonoid content of the fractions. The essential oil showed only the relaxant effect, but no contracting activity. The smooth muscle-relaxant effect was also detected on rat gastrointestinal tissues, as well as on strip preparations of human small intestine. These results suggest that Roman chamomile extract has a direct and prolonged smooth muscle-relaxant effect on guinea pig ileum which is related to its flavonoid content. In some preparations, a transient stimulation of enteric cholinergic motoneurons was also detected. The essential oil also had a remarkable smooth muscle relaxant effect in this setting. Similar relaxant effects were also detected on other visceral

  9. Estrogen receptor beta signaling inhibits PDGF induced human airway smooth muscle proliferation.

    Science.gov (United States)

    Ambhore, Nilesh Sudhakar; Katragadda, Rathnavali; Raju Kalidhindi, Rama Satyanarayana; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S; Sathish, Venkatachalem

    2018-04-20

    Airway smooth muscle (ASM) cell hyperplasia driven by persistent inflammation is a hallmark feature of remodeling in asthma. Sex steroid signaling in the lungs is of considerable interest, given epidemiological data showing more asthma in pre-menopausal women and aging men. Our previous studies demonstrated that estrogen receptor (ER) expression increases in asthmatic human ASM; however, very limited data are available regarding differential roles of ERα vs. ERβ isoforms in human ASM cell proliferation. In this study, we evaluated the effect of selective ERα and ERβ modulators on platelet-derived growth factor (PDGF)-stimulated ASM proliferation and the mechanisms involved. Asthmatic and non-asthmatic primary human ASM cells were treated with PDGF, 17β-estradiol, ERα-agonist and/or ERβ-agonist and/or G-protein-coupled estrogen receptor 30 (GPR30/GPER) agonist and proliferation was measured using MTT and CyQuant assays followed by cell cycle analysis. Transfection of small interfering RNA (siRNA) ERα and ERβ significantly altered the human ASM proliferation. The specificity of siRNA transfection was confirmed by Western blot analysis. Gene and protein expression of cell cycle-related antigens (PCNA and Ki67) and C/EBP were measured by RT-PCR and Western analysis, along with cell signaling proteins. PDGF significantly increased ASM proliferation in non-asthmatic and asthmatic cells. Treatment with PPT showed no significant effect on PDGF-induced proliferation, whereas WAY interestingly suppressed proliferation via inhibition of ERK1/2, Akt, and p38 signaling. PDGF-induced gene expression of PCNA, Ki67 and C/EBP in human ASM was significantly lower in cells pre-treated with WAY. Furthermore, WAY also inhibited PDGF-activated PCNA, C/EBP, cyclin-D1, and cyclin-E. Overall, we demonstrate ER isoform-specific signaling in the context of ASM proliferation. Activation of ERβ can diminish remodeling in human ASM by inhibiting pro-proliferative signaling pathways

  10. Female urinary incontinence at orgasm: a possible marker of a more severe form of detrusor overactivity. Can ultrasound measurement of bladder wall thickness explain it?

    Science.gov (United States)

    Serati, Maurizio; Salvatore, Stefano; Cattoni, Elena; Siesto, Gabriele; Soligo, Marco; Braga, Andrea; Sorice, Paola; Cromi, Antonella; Ghezzi, Fabio; Cardozo, Linda; Bolis, Pierfrancesco

    2011-06-01

    Coital incontinence (CI) during orgasm is a form of urinary incontinence possibly because of detrusor overactivity (DO), as the underlying pathophysiological condition. Women with this symptom usually show a pharmacological lower cure rate than those with DO alone. The ultrasound measurement of the bladder wall thickness (BWT) allows an indirect evaluation of detrusor muscle thickness, giving a potential index of detrusor activity. We wanted to understand if CI at orgasm could be a marker of severity of DO by comparing BWT in women with both DO and CI at orgasm vs. women with DO alone. In addition we aimed to confirm if CI during orgasm is related to antimuscarinics treatment failure. This is a prospective cohort study performed in two tertiary urogynecological referral departments, recruiting consecutive patients seeking treatment for symptomatic DO. All patients were thoroughly assessed including physical examination, urodynamic evaluation, and BWT measurement according to the International Continence Society/International Urogynecological Association and ICI recommendations. Solifenacine 5 mg once daily was then prescribed and follow-up was scheduled to evaluate treatment. Multiple logistic regression (MLR) was performed to identify risk factors for treatment failure. Between September 2007 and March 2010, 31 (22.6%) and 106 (77.4%) women with DO with and without CI at orgasm were enrolled. Women complaining of CI at orgasm had significantly higher BWT than the control group (5.8 ± 0.6 mm vs. 5.2 ± 1.2 mm [P=0.007]). In patients with CI at orgasm, the nonresponder rate to antimuscarinics was significantly higher than controls (P=0.01). After MLR, CI at orgasm was the only independent predictor decreasing antimuscarinics efficacy (odds ratio [OR] 3.16 [95% CI 1.22-8.18], P=0.02). Women with DO and CI at orgasm showed a significantly higher BWT values and worse cure rates than women with DO alone. CI at orgasm could be a marker of a more severe form of DO.

  11. Smooth manifolds

    CERN Document Server

    Sinha, Rajnikant

    2014-01-01

    This book offers an introduction to the theory of smooth manifolds, helping students to familiarize themselves with the tools they will need for mathematical research on smooth manifolds and differential geometry. The book primarily focuses on topics concerning differential manifolds, tangent spaces, multivariable differential calculus, topological properties of smooth manifolds, embedded submanifolds, Sard’s theorem and Whitney embedding theorem. It is clearly structured, amply illustrated and includes solved examples for all concepts discussed. Several difficult theorems have been broken into many lemmas and notes (equivalent to sub-lemmas) to enhance the readability of the book. Further, once a concept has been introduced, it reoccurs throughout the book to ensure comprehension. Rank theorem, a vital aspect of smooth manifolds theory, occurs in many manifestations, including rank theorem for Euclidean space and global rank theorem. Though primarily intended for graduate students of mathematics, the book ...

  12. Oxytocin receptors expressed and coupled to Ca2+ signalling in a human vascular smooth muscle cell line.

    OpenAIRE

    Yazawa, H.; Hirasawa, A.; Horie, K.; Saita, Y.; Iida, E.; Honda, K.; Tsujimoto, G.

    1996-01-01

    1. In a human vascular smooth muscle cell line (HVSMC), binding experiments with [3H]-arginine8-vasopressin (AVP) have shown the existence of a homogeneous population of binding sites with affinity (Kd value) of 0.65 nM and a maximum number of binding sites (Bmax) of 122 fmol mg-1 protein. 2. Nonlabelled compounds compete for [3H]-AVP binding in the HVSMC membrane with an order of potency of oxytocin > lyspressin > or = AVP > Thr4, Gly7-oxytocin > (beta-mercapto-beta-beta-cyclopentamethylenep...

  13. A role for mitochondrial oxidants in stress-induced premature senescence of human vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Yogita Mistry

    2013-01-01

    Full Text Available Mitochondria are a major source of cellular oxidants and have been implicated in aging and associated pathologies, notably cardiovascular diseases. Vascular cell senescence is observed in experimental and human cardiovascular pathologies. Our previous data highlighted a role for angiotensin II in the induction of telomere-dependent and -independent premature senescence of human vascular smooth muscle cells and suggested this was due to production of superoxide by NADPH oxidase. However, since a role for mitochondrial oxidants was not ruled out we hypothesise that angiotensin II mediates senescence by mitochondrial superoxide generation and suggest that inhibition of superoxide may prevent vascular smooth muscle cell aging in vitro. Cellular senescence was induced using a stress-induced premature senescence protocol consisting of three successive once-daily exposure of cells to 1×10−8 mol/L angiotensin II and was dependent upon the type-1 angiotensin II receptor. Angiotensin stimulated NADPH-dependent superoxide production as estimated using lucigenin chemiluminescence in cell lysates and this was attenuated by the mitochondrial electron transport chain inhibitor, rotenone. Angiotensin also resulted in an increase in mitoSOX fluorescence indicating stimulation of mitochondrial superoxide. Significantly, the induction of senescence by angiotensin II was abrogated by rotenone and by the mitochondria-targeted superoxide dismutase mimetic, mitoTEMPO. These data suggest that mitochondrial superoxide is necessary for the induction of stress-induced premature senescence by angiotensin II and taken together with other data suggest that mitochondrial cross-talk with NADPH oxidases, via as yet unidentified signalling pathways, is likely to play a key role.

  14. GM-CSF production from human airway smooth muscle cells is potentiated by human serum

    Directory of Open Access Journals (Sweden)

    Maria B. Sukkar

    2000-01-01

    Full Text Available Recent evidence suggests that airway smooth muscle cells (ASMC actively participate in the airway inflammatory process in asthma. Interleukin–1β (IL–1β and tumour necrosis factor–α (TNF–α induce ASMC to release inflammatory mediators in vitro. ASMC mediator release in vivo, however, may be influenced by features of the allergic asthmatic phenotype. We determined whether; (1 allergic asthmatic serum (AAS modulates ASMC mediator release in response to IL–1β and TNF–α, and (2 IL–1β/TNF–α prime ASMC to release mediators in response to AAS. IL–5 and GMCSF were quantified by ELISA in culture supernatants of; (1 ASMC pre-incubated with either AAS, non-allergic non-asthmatic serum (NAS or MonomedTM (a serum substitute and subsequently stimulated with IL–1β and TNF–α and (2 ASMC stimulated with IL–1β/TNF–α and subsequently exposed to either AAS, NAS or MonomedTM. IL-1g and TNF–α induced GM-CSF release in ASMC pre-incubated with AAS was not greater than that in ASMC pre-incubated with NAS or MonomedTM. IL–1β and TNF–α, however, primed ASMC to release GM-CSF in response to human serum. GM-CSF production following IL–1β/TNF–α and serum exposure (AAS or NAS was significantly greater than that following IL–1β /TNF–α and MonomedTM exposure or IL–1β/TNF–α exposure only. Whilst the potentiating effects of human serum were not specific to allergic asthma, these findings suggest that the secretory capacity of ASMC may be up-regulated during exacerbations of asthma, where there is evidence of vascular leakage.

  15. Smooth Tubercle Bacilli: Neglected Opportunistic Tropical Pathogens

    Directory of Open Access Journals (Sweden)

    Djaltou eAboubaker

    2016-01-01

    Full Text Available Smooth tubercle bacilli (STB including ‘‘Mycobacterium canettii’’ are members of the Mycobacterium tuberculosis complex (MTBC which cause non-contagious tuberculosis in human. This group comprises less than one hundred isolates characterized by smooth colonies and cordless organisms. Most STB isolates have been obtained from patients exposed to the Republic of Djibouti but seven isolates, including the three seminal ones obtained by Georges Canetti between 1968 and 1970, were recovered from patients in France, Madagascar, Sub-Sahara East Africa and French Polynesia. STB form a genetically heterogeneous group of MTBC organisms with large 4.48 ± 0.05 Mb genomes which may link Mycobacterium kansasii to MTBC organisms. Lack of inter-human transmission suggested a yet unknown environmental reservoir. Clinical data indicate a respiratory tract route of contamination and the digestive tract as an alternative route of contamination. Further epidemiological and clinical studies are warranted to elucidate areas of uncertainty regarding these unusual mycobacteria and the tuberculosis they cause.

  16. TIMP-1 stimulates proliferation of human aortic smooth muscle cells and Ras effector pathways

    International Nuclear Information System (INIS)

    Akahane, Takemi; Akahane, Manabu; Shah, Amy; Thorgeirsson, Unnur P.

    2004-01-01

    Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a multifunctional protein, which is found in most tissues and body fluids. Here, we demonstrated that recombinant TIMP-1 but not the synthetic matrix metalloproteinase inhibitor, GM6001, stimulated proliferation of human aortic smooth muscle cells (AoSMC) in a dose-dependent manner. The mitogenic effect was associated with activation of Ras, increased phosphorylation of ERK, and stimulation of cyclin D1 expression. The phosphatidylinositol 3-kinase (PI3K) signaling pathway was also involved since the PI3K inhibitor, LY294002, abolished the TIMP-1-mediated growth stimulation. These data suggest that TIMP-1 activates Ras, which then turns on the ERK and PI3K signaling pathways to promote cell cycle progression of the AoSMC

  17. Comparison of Surgical Outcomes Between Holmium Laser Enucleation and Transurethral Resection of the Prostate in Patients With Detrusor Underactivity

    Directory of Open Access Journals (Sweden)

    Myeong Jin Woo

    2017-03-01

    Full Text Available Purpose Currently, holmium laser enucleation of the prostate (HoLEP and transurethral resection of the prostate (TURP are the standard surgical procedures used to treat benign prostatic hyperplasia (BPH. Several recent studies have demonstrated that the surgical management of BPH in patients with detrusor underactivity (DU can effectively improve voiding symptoms, but comparative data on the efficacy of HoLEP and TURP are insufficient. Therefore, we compared the short-term surgical outcomes of HoLEP and TURP in patients with DU. Methods From January 2010 to May 2015, 352 patients underwent HoLEP or TURP in procedures performed by a single surgeon. Of these patients, 56 patients with both BPH and DU were enrolled in this study (HoLEP, n=24; TURP, n=32. Surgical outcomes were retrospectively compared between the 2 groups. DU was defined as a detrusor pressure at maximal flow rate of <40 cm H2O as measured by a pressure flow study. Results The preoperative characteristics of patients and the presence of comorbidities were comparable between the 2 groups. The TURP group showed a significantly shorter operative time than the HoLEP group (P=0.033. The weight of the resected prostate was greater in the HoLEP group, and postoperative voiding parameters, including peak flow rate and postvoid residual urine volume were significantly better in the HoLEP group than in the TURP group. Conclusions HoLEP can be effectively and safely performed in patients with DU and can be expected to have better surgical outcomes than TURP in terms of the improvement in lower urinary tract symptoms.

  18. TNF-α activates death pathway in human aorta smooth muscle cell in the presence of 7-ketocholesterol

    International Nuclear Information System (INIS)

    Lee, Hyun Sun; Chang, Jong Sun; Baek, Jin Ah; Chung, Mi Yeon; Lee, Han Cheol; Rhim, Byung Yong; Sok, Dai Eun; Rho, Mun-Chual; Kim, Young Kook; Kim, Koanhoi

    2005-01-01

    This study was undertaken to investigate whether a physiologically compatible concentration of 7-ketocholesterol had any effect on human vascular smooth muscle cells (HVSMCs). We found that 7-ketocholesterol changed the viability of human aorta smooth muscle cells (HAoSMC) not by cytotoxicity but by activation of tumor necrosis factor-α receptor (TNFR)-mediated death. Whereas TNF-α did not affect the viability in the presence of 7α-hydroxycholesterol or cholesterol, the cytokine induced HAoSMC death in the presence of 7-ketocholesterol as detected by morphology, viability, and fragmentation of chromosomal DNA. The HAoSMC death was inhibited by a neutralizing anti-TNF receptor 1 (TNFR1) antibody and by the caspase inhibitors of z-VAD and z-DEVD. Activations of caspase-8 and -3 were detected from dying HAoSMCs. 7-Ketocholesterol inhibited translocation of the nuclear factor κB (NF-κB) subunits of p65 and p50 from the cytosol into the nucleus, increase of NF-κB activity, and expression of caspase-8 homolog Fas ligand interleukin-1-converting enzyme inhibitory protein by TNF-α. We also found that X-chromosome-linked inhibitor of apoptosis protein was degraded in dying HAoSMC. The present study proposes that 7-ketocholesterol would contribute to the disappearance of HVSMC in the atherosclerotic lesions by enhancing receptor-mediated death. This is the first report demonstrating induction of TNF-α-mediated death by oxysterol in cells

  19. The influence of propofol, remifentanil and lidocaine on the tone of human bronchial smooth muscle.

    Science.gov (United States)

    Rogliani, Paola; Calzetta, Luigino; Rendina, Erino A; Massullo, Domenico; Dauri, Mario; Rinaldi, Barbara; Capuano, Annalisa; Matera, Maria Gabriella

    2013-06-01

    Bronchoscopy is generally a safe procedure, but the induction of anaesthesia can induce bronchospasm. Consequently we investigated the influence of propofol, remifentanil and lidocaine on the tone of the human bronchial smooth muscle. The influence of propofol, remifentanil and lidocaine on the contractile response of human bronchial smooth muscle to electrical field stimulation (EFS) has been evaluated. The role of capsaicin-sensitive sensory nerves and of inducible nitric oxide synthase has also been assessed. Furthermore, the interaction between these three dugs has been measured by Bliss Independence (BI) theory. Statistical significance (P < 0.05) was assessed by Student's t test or ANOVA. Propofol (1.3 μg ml(-1)) and lidocaine (1 mg ml(-1)) reduced the baseline tone of bronchial rings (-14.45 ± 4.53% and -33.40 ± 1.07%, respectively, P < 0.05), whereas remifentanil had not such effect. Aminoguanidine prevented the relaxant effect of propofol. Propofol did not alter the bronchial contractile response to EFS following 30 min of treatment, whereas remifentanil enhanced the bronchial tension (133.83 ± 9.38%, control 101.93 ± 6.82%, P < 0.05 P < 0.05) and lidocaine completely abolished the contractility at 1 mg ml(-1) (P < 0.05). The desensitization of capsaicin-sensitive sensory nerves normalized the hyperresponsiveness induced by remifentanil (-26.77 ± 1.68%, P < 0.05). Significant BI antagonism (P < 0.001) was detected for propofol and lidocaine on the bronchial hyperresponsiveness induced by remifentanil. Propofol and remifentanil may be used safely for bronchoscopy, although remifentanil should be associated with propofol or lidocaine to prevent the potential opioid-mediated bronchospasm. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Smooth polyhedral surfaces

    KAUST Repository

    Gü nther, Felix; Jiang, Caigui; Pottmann, Helmut

    2017-01-01

    Polyhedral surfaces are fundamental objects in architectural geometry and industrial design. Whereas closeness of a given mesh to a smooth reference surface and its suitability for numerical simulations were already studied extensively, the aim of our work is to find and to discuss suitable assessments of smoothness of polyhedral surfaces that only take the geometry of the polyhedral surface itself into account. Motivated by analogies to classical differential geometry, we propose a theory of smoothness of polyhedral surfaces including suitable notions of normal vectors, tangent planes, asymptotic directions, and parabolic curves that are invariant under projective transformations. It is remarkable that seemingly mild conditions significantly limit the shapes of faces of a smooth polyhedral surface. Besides being of theoretical interest, we believe that smoothness of polyhedral surfaces is of interest in the architectural context, where vertices and edges of polyhedral surfaces are highly visible.

  1. Smooth polyhedral surfaces

    KAUST Repository

    Günther, Felix

    2017-03-15

    Polyhedral surfaces are fundamental objects in architectural geometry and industrial design. Whereas closeness of a given mesh to a smooth reference surface and its suitability for numerical simulations were already studied extensively, the aim of our work is to find and to discuss suitable assessments of smoothness of polyhedral surfaces that only take the geometry of the polyhedral surface itself into account. Motivated by analogies to classical differential geometry, we propose a theory of smoothness of polyhedral surfaces including suitable notions of normal vectors, tangent planes, asymptotic directions, and parabolic curves that are invariant under projective transformations. It is remarkable that seemingly mild conditions significantly limit the shapes of faces of a smooth polyhedral surface. Besides being of theoretical interest, we believe that smoothness of polyhedral surfaces is of interest in the architectural context, where vertices and edges of polyhedral surfaces are highly visible.

  2. SmoothMoves : Smooth pursuits head movements for augmented reality

    NARCIS (Netherlands)

    Esteves, Augusto; Verweij, David; Suraiya, Liza; Islam, Rasel; Lee, Youryang; Oakley, Ian

    2017-01-01

    SmoothMoves is an interaction technique for augmented reality (AR) based on smooth pursuits head movements. It works by computing correlations between the movements of on-screen targets and the user's head while tracking those targets. The paper presents three studies. The first suggests that head

  3. Can we predict detrusor overactivity in women with lower urinary tract symptoms? The King's Detrusor Overactivity Score (KiDOS).

    Science.gov (United States)

    Giarenis, Ilias; Musonda, Patrick; Mastoroudes, Heleni; Robinson, Dudley; Cardozo, Linda

    2016-10-01

    Traditionally, urodynamic studies (UDS) have been used to assess lower urinary tract symptoms (LUTS), but their routine use is now discouraged. While urodynamic stress incontinence is strongly associated with the symptom of stress urinary incontinence (SUI) and a positive cough test, there is a weak relationship between symptoms of overactive bladder and detrusor overactivity (DO). The aim of our study was to develop a model to predict DO in women with LUTS. This prospective study included consecutive women with LUTS attending a urodynamic clinic. All women underwent a comprehensive clinical and urodynamic assessment. The effect of each variable on the odds of DO was estimated both by univariate analysis and adjusted analysis using logistic regression. 1006 women with LUTS were included in the study with 374 patients (37%) diagnosed with DO. The factors considered to be the best predictors of DO were urgency urinary incontinence, urge rating/void and parity (p-value<0.01). The absence of SUI, vaginal bulging and previous continence surgery were also good predictors of DO (p-value<0.01). We have created a prediction model for DO based on our best predictors. In our scoring system, presence of UUI scores 5; mean urge rating/void≥3 scores 3; parity≥2 scores 2; previous continence surgery scores -1; presence of SUI scores -1; and the complaint of vaginal bulging scores -1. If a criterion is absent, then the score is 0 and the total score can vary from a value of -3 to +10. The Receiver Operating Characteristic (ROC) analysis for the overall cut-off points revealed an area under the curve of 0.748 (95%CI 0.741, 0.755). This model is able to predict DO more accurately than a symptomatic diagnosis alone, in women with LUTS. The introduction of this scoring system as a screening tool into clinical practice may reduce the need for expensive and invasive tests to diagnose DO, but cannot replace UDS completely. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Smoothing a Piecewise-Smooth: An Example from Plankton Population Dynamics

    DEFF Research Database (Denmark)

    Piltz, Sofia Helena

    2016-01-01

    In this work we discuss a piecewise-smooth dynamical system inspired by plankton observations and constructed for one predator switching its diet between two different types of prey. We then discuss two smooth formulations of the piecewise-smooth model obtained by using a hyperbolic tangent funct...... function and adding a dimension to the system. We compare model behaviour of the three systems and show an example case where the steepness of the switch is determined from a comparison with data on freshwater plankton....

  5. Metabolism of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in cultured human fetal aortic smooth muscle cells

    International Nuclear Information System (INIS)

    Bond, J.A.; Kocan, R.M.; Benditt, E.P.; Juchau, M.R.

    1979-01-01

    Cultured human fetal aortic smooth muscle cells derived from the abdominal aorta converted benzo[a]pyrene (BaP) and 7,12-dimethylbenz[a]anthracene (DMBA) via cytochrome P-450-dependent monooxygenation to metabolites detectable by both a highly sensitive radiometric assay and high pressure liquid chromatography (HPLC). Cells incubated with 3 H-BaP transformed this substrate primarily to phenols. 14 C-DMBA was converted to metabolites that cochromatographed with 12-hydroxymethyl-methylbenz[a]anthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene, 7- 7,12-dihydroxymethylbenz[a]anthracene, and trans-8,9-dihydrodiol-7,12-DMBA. Exposure of cells in culture to 13 μM 1,2-benz[a]anthracene resulted in increased oxidative metabolism of both BaP and DMBA. In the case of BaP, total phenol formation was increased, while with DMBA all metabolites detected by HPLC were increased. Support for the potential role of metabolism of polycyclic aromatic hydrocarbons by aortic smooth muscle cells in the etiology of atherosclerosis was obtained

  6. Molecular Expression and Pharmacological Evidence for a Functional Role of Kv7 Channel Subtypes in Guinea Pig Urinary Bladder Smooth Muscle

    Science.gov (United States)

    Afeli, Serge A. Y.; Malysz, John; Petkov, Georgi V.

    2013-01-01

    Voltage-gated Kv7 (KCNQ) channels are emerging as essential regulators of smooth muscle excitability and contractility. However, their physiological role in detrusor smooth muscle (DSM) remains to be elucidated. Here, we explored the molecular expression and function of Kv7 channel subtypes in guinea pig DSM by RT-PCR, qRT-PCR, immunohistochemistry, electrophysiology, and isometric tension recordings. In whole DSM tissue, mRNAs for all Kv7 channel subtypes were detected in a rank order: Kv7.1~Kv7.2Kv7.3~Kv7.5Kv7.4. In contrast, freshly-isolated DSM cells showed mRNA expression of: Kv7.1~Kv7.2Kv7.5Kv7.3~Kv7.4. Immunohistochemical confocal microscopy analyses of DSM, conducted by using co-labeling of Kv7 channel subtype-specific antibodies and α-smooth muscle actin, detected protein expression for all Kv7 channel subtypes, except for the Kv7.4, in DSM cells. L-364373 (R-L3), a Kv7.1 channel activator, and retigabine, a Kv7.2-7.5 channel activator, inhibited spontaneous phasic contractions and the 10-Hz electrical field stimulation (EFS)-induced contractions of DSM isolated strips. Linopiridine and XE991, two pan-Kv7 (effective at Kv7.1-Kv7.5 subtypes) channel inhibitors, had opposite effects increasing DSM spontaneous phasic and 10 Hz EFS-induced contractions. EFS-induced DSM contractions generated by a wide range of stimulation frequencies were decreased by L-364373 (10 µM) or retigabine (10 µM), and increased by XE991 (10 µM). Retigabine (10 µM) induced hyperpolarization and inhibited spontaneous action potentials in freshly-isolated DSM cells. In summary, Kv7 channel subtypes are expressed at mRNA and protein levels in guinea pig DSM cells. Their pharmacological modulation can control DSM contractility and excitability; therefore, Kv7 channel subtypes provide potential novel therapeutic targets for urinary bladder dysfunction. PMID:24073284

  7. Immunohistochemical characterization of endometriosis-associated smooth muscle cells in human peritoneal endometriotic lesions.

    Science.gov (United States)

    Barcena de Arellano, Maria L; Gericke, Jessica; Reichelt, Uta; Okuducu, Ali Fuat; Ebert, Andreas D; Chiantera, Vito; Schneider, Achim; Mechsner, Sylvia

    2011-10-01

    Smooth muscle cells (SMC) are common components of endometriotic lesions. SMC have been characterized previously in peritoneal, ovarian and deep infiltrating endometriotic lesions and adenomyosis. The aim of this retrospective study was to investigate the extent of differentiation in endometriosis-associated SMC (EMaSMC) in peritoneal endometriotic lesions. We obtained biopsies from peritoneal endometriotic lesions (n = 60) and peritoneal sites distant from the endometriotic lesion (n = 60), as well as healthy peritoneum from patients without endometriosis (control tissue, n = 10). These controls were hysterectomy specimens from patients without endometriosis or adenomyosis. Histopathological examination of peritoneal specimens using antibodies against oxytocin receptor (OTR), vasopressin receptor (VPR), smooth muscle myosin heavy chain (SM-MHC), estrogen receptor (ER) or progesterone receptor (PR) was performed. To identify SMC and their level of differentiation, antibodies for smooth muscle actin desmin and caldesmon were used. SMC were detected in all endometriotic lesions. SMC were more abundant in unaffected peritoneum of women with endometriosis (38%) compared with women without endometriosis (6%; P endometriosis.

  8. Ureter smooth muscle cell orientation in rat is predominantly longitudinal.

    Directory of Open Access Journals (Sweden)

    Bart Spronck

    Full Text Available In ureter peristalsis, the orientation of the contracting smooth muscle cells is essential, yet current descriptions of orientation and composition of the smooth muscle layer in human as well as in rat ureter are inconsistent. The present study aims to improve quantification of smooth muscle orientation in rat ureters as a basis for mechanistic understanding of peristalsis. A crucial step in our approach is to use two-photon laser scanning microscopy and image analysis providing objective, quantitative data on smooth muscle cell orientation in intact ureters, avoiding the usual sectioning artifacts. In 36 rat ureter segments, originating from a proximal, middle or distal site and from a left or right ureter, we found close to the adventitia a well-defined longitudinal smooth muscle orientation. Towards the lamina propria, the orientation gradually became slightly more disperse, yet the main orientation remained longitudinal. We conclude that smooth muscle cell orientation in rat ureter is predominantly longitudinal, though the orientation gradually becomes more disperse towards the proprial side. These findings do not support identification of separate layers. The observed longitudinal orientation suggests that smooth muscle contraction would rather cause local shortening of the ureter, than cause luminal constriction. However, the net-like connective tissue of the ureter wall may translate local longitudinal shortening into co-local luminal constriction, facilitating peristalsis. Our quantitative, minimally invasive approach is a crucial step towards more mechanistic insight into ureter peristalsis, and may also be used to study smooth muscle cell orientation in other tube-like structures like gut and blood vessels.

  9. Ureter smooth muscle cell orientation in rat is predominantly longitudinal.

    Science.gov (United States)

    Spronck, Bart; Merken, Jort J; Reesink, Koen D; Kroon, Wilco; Delhaas, Tammo

    2014-01-01

    In ureter peristalsis, the orientation of the contracting smooth muscle cells is essential, yet current descriptions of orientation and composition of the smooth muscle layer in human as well as in rat ureter are inconsistent. The present study aims to improve quantification of smooth muscle orientation in rat ureters as a basis for mechanistic understanding of peristalsis. A crucial step in our approach is to use two-photon laser scanning microscopy and image analysis providing objective, quantitative data on smooth muscle cell orientation in intact ureters, avoiding the usual sectioning artifacts. In 36 rat ureter segments, originating from a proximal, middle or distal site and from a left or right ureter, we found close to the adventitia a well-defined longitudinal smooth muscle orientation. Towards the lamina propria, the orientation gradually became slightly more disperse, yet the main orientation remained longitudinal. We conclude that smooth muscle cell orientation in rat ureter is predominantly longitudinal, though the orientation gradually becomes more disperse towards the proprial side. These findings do not support identification of separate layers. The observed longitudinal orientation suggests that smooth muscle contraction would rather cause local shortening of the ureter, than cause luminal constriction. However, the net-like connective tissue of the ureter wall may translate local longitudinal shortening into co-local luminal constriction, facilitating peristalsis. Our quantitative, minimally invasive approach is a crucial step towards more mechanistic insight into ureter peristalsis, and may also be used to study smooth muscle cell orientation in other tube-like structures like gut and blood vessels.

  10. Endogenous laminin is required for human airway smooth muscle cell maturation

    Directory of Open Access Journals (Sweden)

    Tran Thai

    2006-09-01

    Full Text Available Abstract Background Airway smooth muscle (ASM contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. Methods Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. Results Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. Conclusion While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the

  11. Comparative study of the organisation and phenotypes of bladder interstitial cells in human, mouse and rat.

    Science.gov (United States)

    Gevaert, Thomas; Neuhaus, Jochen; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Der Aa, Frank Van; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Pintelon, Isabel; De Ridder, Dirk

    2017-12-01

    With most research on interstitial cells (IC) in the bladder being conducted on animal models, it remains unclear whether all structural and functional data on IC from animal models can be translated to the human context. This prompted us to compare the structural and immunohistochemical properties of IC in bladders from mouse, rat and human. Tissue samples were obtained from the bladder dome and subsequently processed for immunohistochemistry and electron microscopy. The ultrastructural properties of IC were compared by means of electron microscopy and IC were additionally characterized with single/double immunohistochemistry/immunofluorescence. Our results reveal a similar organization of the IC network in the upper lamina propria (ULP), the deep lamina propria (DLP) and the detrusor muscle in human, rat and mouse bladders. Furthermore, despite several similarities in IC phenotypes, we also found several obvious inter-species differences in IC, especially in the ULP. Most remarkably in this respect, ULP IC in human bladder predominantly displayed a myoid phenotype with abundant presence of contractile micro-filaments, while those in rat and mouse bladders showed a fibroblast phenotype. In conclusion, the organization of ULP IC, DLP IC and detrusor IC is comparable in human, rat and mouse bladders, although several obvious inter-species differences in IC phenotypes were found. The present data show that translating research data on IC in laboratory animals to the human setting should be carried out with caution.

  12. Is the male dog comparable to human? A histological study of the muscle systems of the lower urinary tract.

    Science.gov (United States)

    Stolzenburg, Jens-Uwe; Schwalenberg, Thilo; Do, Minh; Dorschner, Wolfgang; Salomon, Franz-Viktor; Jurina, Konrad; Neuhaus, Jochen

    2002-08-01

    Because of their superficial anatomical resemblance, the male dog seems to be suitable for studying the physiologic and pathological alterations of the bladder neck of human males. The present study was carried out to compare and contrast the muscular anatomy of the male dog lower urinary tract with that of humans. The complete lower urinary tract, including the surrounding organs (bulb of penis, prostate, rectum and musculature of the pelvic floor) were removed from adult and newborn male dogs and histologically processed using serial section technique. Based on our own histological investigations, three-dimensional (3D)-models of the anatomy of the lower urinary tract were constructed to depict the corresponding structures and the differences between the species. The results of this study confirm that the lower urinary tract of the male dog bears some anatomical resemblance (musculus detrusor vesicae, prostate, prostatic and membranous urethra) to man. As with human males, the two parts of the musculus sphincter urethrae (glaber and transversostriatus) are evident in the canine bladder neck. Nevertheless, considerable differences in formation of individual muscles should be noted. In male dogs, no separate anatomic entity can be identified as vesical or internal sphincter. The individual course of the ventral and lateral longitudinal musculature and of the circularly arranged smooth musculature of the urethra is different to that of humans. Differences in the anatomy of individual muscles of the bladder neck in the male dog and man suggest that physiological interpretations of urethral functions obtained in one species cannot be attributed without qualification to the other.

  13. Expression of smooth muscle and non-muscle myosin heavy chain isoforms in cultured vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Rovner, A.S.; Murphy, R.A.; Owens, G.K.

    1986-01-01

    Immunocytochemical studies of cultured smooth muscle cells (SMCs) have disagreed on the nature of myosin expression. This investigation was undertaken to test for the presence of heterogeneous myosin heavy chain (MHC) isoforms in cell culture as a possible explanation for these results. Previously, Rovner et al. detected two MHCs in intact smooth muscles which differed in molecular weight by ca. 4000 daltons (SM1 and SM2) using a 3-4% acrylamide gradient SDS gel system. When sub-confluent primary cultures of rat aorta SMCs were assayed by this system, SM1 and SM2 were seen, along with large amounts of a third, unique MHC, NM, which closely resembled the MHC from human platelet in size and antigenicity. Data from 35 S-methionine autoradiograms showed that the log growth phase SMC cultures were producing almost exclusively NM, but the growth arrest, post-confluent cultures synthesized increased relative amounts of the SM MHC forms and contained comparable amounts of SM1, SM2, and NM. The same patterns of MHC synthesis were seen in sub-passaged SMCs. The expression of the SM-specific forms of myosin in quiescent, post-confluent cultures parallels that of smooth muscle actin suggesting that density induced growth arrest promotes cytodifferentiation in cultured vascular SMCs

  14. Polysaccharide from Fuzi protects against Ox-LDL-induced calcification of human vascular smooth muscle cells by increasing autophagic activity

    Science.gov (United States)

    Liao, Lizhen; Zhuang, Xiaodong; Li, Weidong; Su, Qibiao; Zhao, Jie; Liu, Ying

    2018-01-01

    Polysaccharide from Fuzi (FPS) is a water-soluble polysaccharide isolated from the traditional Chinese herbal medicine Fuzi. It has been demonstrated to protect hepatocytes against ischemia-reperfusion injury through its potent antioxidant effects, and to attenuate starvation-induced cytotoxicity in H9c2 cells by increasing autophagic activity. In the present study, Alizarin Red S staining was used to detect mineral deposition and reverse transcription-quantitative polymerase chain reaction was used to detect the core binding factor α1 and smooth muscle 22α mRNA expression. To analyze autophagic activity, western blotting was used to detect microtubule-associated protein 1A/1B light chain 3 and nucleoporin P62 expression. In addition, green fluorescent protein-LC3 dots-per-cell was observed by fluorescence microscopy. It was demonstrated that oxidized low-density lipoprotein (Ox-LDL) could increase the calcification of human vascular smooth muscle cells (VSMCs) in a concentration-dependent manner, and that FPS treatment had a significant protective effect against Ox-LDL-induced calcification of human VSMCs. Furthermore, FPS treatment alleviated the Ox-LDL-induced downregulation of autophagic activity, and the protective effect of FPS on Ox-LDL-induced calcification was attenuated by the autophagy inhibitor 3-methyladenine. In conclusion, the present study demonstrated for the first time to the best of the authors' knowledge that FPS can protect against Ox-LDL-induced vascular calcification in human VSMCs, and that this likely occurs via the activation of autophagy. This supports the hypothesis that autophagy may be an endogenous protective mechanism counteracting vascular calcification, and that FPS may be used as a potential therapeutic for vascular calcification. PMID:29393437

  15. Classification of smooth Fano polytopes

    DEFF Research Database (Denmark)

    Øbro, Mikkel

    A simplicial lattice polytope containing the origin in the interior is called a smooth Fano polytope, if the vertices of every facet is a basis of the lattice. The study of smooth Fano polytopes is motivated by their connection to toric varieties. The thesis concerns the classification of smooth...... Fano polytopes up to isomorphism. A smooth Fano -polytope can have at most vertices. In case of vertices an explicit classification is known. The thesis contains the classification in case of vertices. Classifications of smooth Fano -polytopes for fixed exist only for . In the thesis an algorithm...... for the classification of smooth Fano -polytopes for any given is presented. The algorithm has been implemented and used to obtain the complete classification for ....

  16. Comparative immunohistochemical characterization of interstitial cells in the urinary bladder of human, guinea pig and pig.

    Science.gov (United States)

    Steiner, Clara; Gevaert, Thomas; Ganzer, Roman; De Ridder, Dirk; Neuhaus, Jochen

    2018-05-01

    Interstitial cells (ICs) are thought to play a functional role in urinary bladder. Animal models are commonly used to elucidate bladder physiology and pathophysiology. However, inter-species comparative studies on ICs are rare. We therefore analyzed ICs and their distribution in the upper lamina propria (ULP), the deeper lamina propria (DLP) and the detrusor muscular layer (DET) of human, guinea pig (GP) and pig. Paraffin slices were examined by immunohistochemistry and 3D confocal immunofluorescence of the mesenchymal intermediate filament vimentin (VIM), alpha-smooth muscle actin (αSMA), platelet-derived growth factor receptor alpha (PDGFRα) and transient receptor potential cation channel A1 (TRPA1). Image stacks were processed for analysis using Huygens software; quantitative analysis was performed with Fiji macros. ICs were identified by immunoreactivity for VIM (excluding blood vessels). In all species ≥ 75% of ULP ICs were VIM + /PDGFRα + and ≥ 90% were VIM + /TRPA1 + . In human and pig ≥ 74% of ULP ICs were VIM + /αSMA + , while in GP the percentage differed significantly with only 37% VIM + /αSMA + ICs. Additionally, over 90% of αSMA + ICs were also TRPA1 + and PDGFRα + in human, GP and pig. In all three species, TRPA1 + and PDGFRα + ICs point to an active role for these cells in bladder physiology, regarding afferent signaling processes and signal modification. We hypothesize that decline in αSMA-positivity in GP reflects adaptation of bladder histology to smaller bladder size. In our experiments, pig bladder proved to be highly comparable to human urinary bladder and seems to provide safer interpretation of experimental findings than GP.

  17. Major vault protein in cardiac and smooth muscle.

    Science.gov (United States)

    Shults, Nataliia V; Das, Dividutta; Suzuki, Yuichiro J

    Major vault protein (MVP) is the major component of the vault particle whose functions are not well understood. One proposed function of the vault is to serve as a mechanism of drug transport, which confers drug resistance in cancer cells. We show that MVP can be found in cardiac and smooth muscle. In human airway smooth muscle cells, knocking down MVP was found to cause cell death, suggesting that MVP serves as a cell survival factor. Further, our laboratory found that MVP is S-glutathionylated in response to ligand/receptor-mediated cell signaling. The S-glutathionylation of MVP appears to regulate protein-protein interactions between MVP and a protein called myosin heavy chain 9 (MYH9). Through MYH9 and Vsp34, MVP may form a complex with Beclin-1 that regulates autophagic cell death. In pulmonary vascular smooth muscle, proteasome inhibition promotes the ubiquitination of MVP, which may function as a mechanism of proteasome inhibition-mediated cell death. Investigating the functions and the regulatory mechanisms of MVP and vault particles is an exciting new area of research in cardiovascular/pulmonary pathophysiology.

  18. Contrast and assimilation in motion perception and smooth pursuit eye movements.

    Science.gov (United States)

    Spering, Miriam; Gegenfurtner, Karl R

    2007-09-01

    The analysis of visual motion serves many different functions ranging from object motion perception to the control of self-motion. The perception of visual motion and the oculomotor tracking of a moving object are known to be closely related and are assumed to be controlled by shared brain areas. We compared perceived velocity and the velocity of smooth pursuit eye movements in human observers in a paradigm that required the segmentation of target object motion from context motion. In each trial, a pursuit target and a visual context were independently perturbed simultaneously to briefly increase or decrease in speed. Observers had to accurately track the target and estimate target speed during the perturbation interval. Here we show that the same motion signals are processed in fundamentally different ways for perception and steady-state smooth pursuit eye movements. For the computation of perceived velocity, motion of the context was subtracted from target motion (motion contrast), whereas pursuit velocity was determined by the motion average (motion assimilation). We conclude that the human motion system uses these computations to optimally accomplish different functions: image segmentation for object motion perception and velocity estimation for the control of smooth pursuit eye movements.

  19. PM2.5 promotes human bronchial smooth muscle cell migration via the sonic hedgehog signaling pathway.

    Science.gov (United States)

    Ye, Xiuqin; Hong, Wei; Hao, Binwei; Peng, Gongyong; Huang, Lingmei; Zhao, Zhuxiang; Zhou, Yumin; Zheng, Mengning; Li, Chenglong; Liang, Chunxiao; Yi, Erkang; Pu, Jinding; Li, Bing; Ran, Pixin

    2018-03-02

    The contribution of airway remodeling in chronic obstructive pulmonary disease (COPD) has been well documented, with airway smooth muscle cell proliferation and migration playing a role in the remodeling process. Here, we aimed to verify the effects of fine particulate matter (PM2.5) on human bronchial smooth muscle cell (HBSMC) migration and to explore the underlying signaling pathways. HBSMC apoptosis, proliferation and migration were measured using flow cytometry, cell counting and transwell migration assays, respectively. The role of the hedgehog pathway in cell migration was assessed by western blotting to measure the expression of Sonic hedgehog (Shh), Gli1 and Snail. Furthermore, siRNA was used to knock down Gli1 or Snail expression. PM2.5 induced HBSMC apoptosis in a dose-dependent manner, although certain concentrations of PM2.5 did not induce HBSMC proliferation or apoptosis. Interestingly, cell migration was stimulated by PM2.5 doses far below those that induced apoptosis. Additional experiments revealed that these PM2.5 doses enhanced the expression of Shh, Gli1 and Snail in HBSMCs. Furthermore, PM2.5-induced cell migration and protein expression were enhanced by recombinant Shh and attenuated by cyclopamine. Similar results were obtained by knocking down Gli1 or Snail. These findings suggest that PM2.5, which may exert its effects through the Shh signaling pathway, is necessary for the migration of HBSMCs. These data define a novel role for PM2.5 in airway remodeling in COPD.

  20. Cue-dependent memory-based smooth-pursuit in normal human subjects: importance of extra-retinal mechanisms for initial pursuit.

    Science.gov (United States)

    Ito, Norie; Barnes, Graham R; Fukushima, Junko; Fukushima, Kikuro; Warabi, Tateo

    2013-08-01

    Using a cue-dependent memory-based smooth-pursuit task previously applied to monkeys, we examined the effects of visual motion-memory on smooth-pursuit eye movements in normal human subjects and compared the results with those of the trained monkeys. These results were also compared with those during simple ramp-pursuit that did not require visual motion-memory. During memory-based pursuit, all subjects exhibited virtually no errors in either pursuit-direction or go/no-go selection. Tracking eye movements of humans and monkeys were similar in the two tasks, but tracking eye movements were different between the two tasks; latencies of the pursuit and corrective saccades were prolonged, initial pursuit eye velocity and acceleration were lower, peak velocities were lower, and time to reach peak velocities lengthened during memory-based pursuit. These characteristics were similar to anticipatory pursuit initiated by extra-retinal components during the initial extinction task of Barnes and Collins (J Neurophysiol 100:1135-1146, 2008b). We suggest that the differences between the two tasks reflect differences between the contribution of extra-retinal and retinal components. This interpretation is supported by two further studies: (1) during popping out of the correct spot to enhance retinal image-motion inputs during memory-based pursuit, pursuit eye velocities approached those during simple ramp-pursuit, and (2) during initial blanking of spot motion during memory-based pursuit, pursuit components appeared in the correct direction. Our results showed the importance of extra-retinal mechanisms for initial pursuit during memory-based pursuit, which include priming effects and extra-retinal drive components. Comparison with monkey studies on neuronal responses and model analysis suggested possible pathways for the extra-retinal mechanisms.

  1. Tungstate-targeting of BKαβ1 channels tunes ERK phosphorylation and cell proliferation in human vascular smooth muscle.

    Directory of Open Access Journals (Sweden)

    Ana Isabel Fernández-Mariño

    Full Text Available Despite the substantial knowledge on the antidiabetic, antiobesity and antihypertensive actions of tungstate, information on its primary target/s is scarce. Tungstate activates both the ERK1/2 pathway and the vascular voltage- and Ca2+-dependent large-conductance BKαβ1 potassium channel, which modulates vascular smooth muscle cell (VSMC proliferation and function, respectively. Here, we have assessed the possible involvement of BKαβ1 channels in the tungstate-induced ERK phosphorylation and its relevance for VSMC proliferation. Western blot analysis in HEK cell lines showed that expression of vascular BKαβ1 channels potentiates the tungstate-induced ERK1/2 phosphorylation in a Gi/o protein-dependent manner. Tungstate activated BKαβ1 channels upstream of G proteins as channel activation was not altered by the inhibition of G proteins with GDPβS or pertussis toxin. Moreover, analysis of Gi/o protein activation measuring the FRET among heterologously expressed Gi protein subunits suggested that tungstate-targeting of BKαβ1 channels promotes G protein activation. Single channel recordings on VSMCs from wild-type and β1-knockout mice indicated that the presence of the regulatory β1 subunit was essential for the tungstate-mediated activation of BK channels in VSMCs. Moreover, the specific BK channel blocker iberiotoxin lowered tungstate-induced ERK phosphorylation by 55% and partially reverted (by 51% the tungstate-produced reduction of platelet-derived growth factor (PDGF-induced proliferation in human VSMCs. Our observations indicate that tungstate-targeting of BKαβ1 channels promotes activation of PTX-sensitive Gi proteins to enhance the tungstate-induced phosphorylation of ERK, and inhibits PDGF-stimulated cell proliferation in human vascular smooth muscle.

  2. Bayesian Exponential Smoothing.

    OpenAIRE

    Forbes, C.S.; Snyder, R.D.; Shami, R.S.

    2000-01-01

    In this paper, a Bayesian version of the exponential smoothing method of forecasting is proposed. The approach is based on a state space model containing only a single source of error for each time interval. This model allows us to improve current practices surrounding exponential smoothing by providing both point predictions and measures of the uncertainty surrounding them.

  3. Anti-smooth muscle antibody

    Science.gov (United States)

    ... gov/ency/article/003531.htm Anti-smooth muscle antibody To use the sharing features on this page, please enable JavaScript. Anti-smooth muscle antibody is a blood test that detects the presence ...

  4. Smooth functors vs. differential forms

    NARCIS (Netherlands)

    Schreiber, U.; Waldorf, K.

    2011-01-01

    We establish a relation between smooth 2-functors defined on the path 2-groupoid of a smooth manifold and differential forms on this manifold. This relation can be understood as a part of a dictionary between fundamental notions from category theory and differential geometry. We show that smooth

  5. Expression and proliferation profiles of PKC, JNK and p38MAPK in physiologically stretched human bladder smooth muscle cells

    International Nuclear Information System (INIS)

    Wazir, Romel; Luo, De-Yi; Dai, Yi; Yue, Xuan; Tian, Ye; Wang, Kun-Jie

    2013-01-01

    Highlights: •Stretch induces proliferation in human bladder smooth muscle cells (HBSMC). •5% Equibiaxial elongation produces maximum proliferation. •Physiologic stretch decreases apoptotic cell death. •PKC is involved in functional modulation of bladder. •JNK and p38 are not involved in proliferating HBSMC. -- Abstract: Objective: To determine protein kinase C (PKC), c-Jun NH2-Terminal Kinase (JNK) and P38 mitogen-activated protein kinases (p38MAPK) expression levels and effects of their respective inhibitors on proliferation of human bladder smooth muscle cells (HBSMCs) when physiologically stretched in vitro. Materials and methods: HBSMCs were grown on silicone membrane and stretch was applied under varying conditions; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (frequency: 0.05, 0.1, 0.2, 0.5, 1 Hz). Optimal physiological stretch was established by assessing proliferation with 5-Bromo-2-deoxyuridine (BrdU) assay and flow cytometry. PKC, JNK and p38 expression levels were analyzed by Western blot. Specificity was maintained by employing specific inhibitors; (GF109203X for PKC, SP600125 for JNK and SB203580 for p38MAPK), in some experiments. Results: Optimum proliferation was observed at 5% equibiaxial stretch (BrdU: 0.837 ± 0.026 (control) to 1.462 ± 0.023)%, (P 0.05 SP600125) and (1.461 ± 0.01, P > 0.05 SB203580). These findings show that mechanical stretch can promote magnitude-dependent proliferative modulation through PKC and possibly JNK but not via p38MAPK in hBSMCs

  6. PPARγ ligand ciglitazone inhibits TNFα-induced ICAM-1 in human airway smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Chien-Da Huang

    2014-08-01

    Full Text Available Background: Modification of human airway smooth muscle (ASM function by proinflammatory cytokines has been regarded as a potential mechanism underlying bronchial hyperresponsiveness in asthma. Human ASM cells express intercellular adhesion molecule (ICAM-1 in response to cytokines. Synthetic ligands for peroxisome proliferator-activated receptor (PPARγ reportedly possess anti-inflammatory and immunomodulatory properties. In this study, we examined whether ciglitazone, a synthetic PPARγ ligand, can modulate the basal and tumor necrosis factor (TNFα-induced ICAM1 gene expression in human ASM cells. Methods: Human ASM cells were treated with TNFα. ICAM-1 expression was assessed by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR analysis. PPARγ activity was inhibited by target-specific small interfering (si RNA targeting PPARγ and GW9662, a PPARγ antagonist. Activity of nuclear factor (NF-κB was assessed by using immunoblot analysis, immune-confocal images, and electrophoretic mobility shift assay (EMSA. Results: By flow cytometry, ciglitazone alone had no effect on ICAM-1 expression in ASM cells, but inhibited ICAM-1 expression in response to TNFα (10 ng/ml in a dose-dependent manner (1-10 μM. It also inhibited TNFα-induced ICAM1 gene expression by RT-PCR analysis. Knockdown of PPARγ gene by target-specific siRNA targeting PPARγ enhanced ICAM-1 expression and the inhibitory effect of ciglitazone on TNFα-induced ICAM-1 expression was reversed by PPARγ siRNA and GW9662. SN-50 (10 μg/ml, an inhibitor for nuclear translocation of NF-κB, inhibited TNFα-induced ICAM-1 expression. Ciglitazone did not prevent TNFα-induced degradation of the cytosolic inhibitor of NF-κB (IκB, but inhibited the nuclear translocation of p65 induced by TNFα and suppressed the NF-κB/DNA binding activity. Conclusion: These findings suggest that ciglitazone inhibits TNFα-induced ICAM1 gene expression in human ASM cells through

  7. Interstitial cells of Cajal in human small intestine. Ultrastructural identification and organization between the main smooth muscle layers

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johannes; Thuneberg, Lars

    1991-01-01

    Anatomy, interstitial cells of Cajal, small intestine, gut motility, pacemaker cells, smooth muscle......Anatomy, interstitial cells of Cajal, small intestine, gut motility, pacemaker cells, smooth muscle...

  8. Smoothness in Binomial Edge Ideals

    Directory of Open Access Journals (Sweden)

    Hamid Damadi

    2016-06-01

    Full Text Available In this paper we study some geometric properties of the algebraic set associated to the binomial edge ideal of a graph. We study the singularity and smoothness of the algebraic set associated to the binomial edge ideal of a graph. Some of these algebraic sets are irreducible and some of them are reducible. If every irreducible component of the algebraic set is smooth we call the graph an edge smooth graph, otherwise it is called an edge singular graph. We show that complete graphs are edge smooth and introduce two conditions such that the graph G is edge singular if and only if it satisfies these conditions. Then, it is shown that cycles and most of trees are edge singular. In addition, it is proved that complete bipartite graphs are edge smooth.

  9. Urinary incontinence at orgasm: relation to detrusor overactivity and treatment efficacy.

    Science.gov (United States)

    Serati, Maurizio; Salvatore, Stefano; Uccella, Stefano; Cromi, Antonella; Khullar, Vik; Cardozo, Linda; Bolis, Pierfrancesco

    2008-10-01

    To understand the pathophysiological mechanism of incontinence during orgasm and to compare women affected by symptomatic detrusor overactivity (DO) with and without incontinence at orgasm in terms of efficacy of antimuscarinic treatment. All consecutive sexually active women with incontinence during intercourse were prospectively included and divided into two groups: women with coital incontinence at orgasm or at penetration. The two forms of coital incontinence were correlated to the urodynamic finding of DO. Women complaining of overactive bladder (OAB) symptoms, with urinary incontinence at orgasm and urodynamically proven DO (cases), were prescribed tolterodine 4 mg extended release for at least 12 wk. The cases were compared in terms of efficacy of treatment on OAB symptoms to consecutive patients with symptomatic DO without coital incontinence (control group). Among the 1133 women who underwent urodynamic testings during the study period, 132 patients were eligible for final analysis. A significant difference in DO was observed in women with incontinence at orgasm (34 of 49; 69.4%) compared with women with incontinence during penetration (24 of 83; 28.9%) (porgasm associated with DO were given antimuscarinics treatment and were compared with 53 controls. Fourteen of 34 (41.2%) and 9 of 53 (17%) women did not respond to antimuscarinics in the cases and in the control group, respectively (p=0.023). Incontinence at orgasm is associated with DO in the majority of cases. This is the first study showing an inferior efficacy of antimuscarinic treatment in women with DO complaining of incontinence at orgasm.

  10. Essential Roles of Raf/Extracellular Signal-regulated Kinase/Mitogen-activated Protein Kinase Pathway, YY1, and Ca2+ Influx in Growth Arrest of Human Vascular Smooth Muscle Cells by Bilirubin*

    Science.gov (United States)

    Stoeckius, Marlon; Erat, Anna; Fujikawa, Tatsuya; Hiromura, Makoto; Koulova, Anna; Otterbein, Leo; Bianchi, Cesario; Tobiasch, Edda; Dagon, Yossi; Sellke, Frank W.; Usheva, Anny

    2012-01-01

    The biological effects of bilirubin, still poorly understood, are concentration-dependent ranging from cell protection to toxicity. Here we present data that at high nontoxic physiological concentrations, bilirubin inhibits growth of proliferating human coronary artery smooth muscle cells by three events. It impairs the activation of Raf/ERK/MAPK pathway and the cellular Raf and cyclin D1 content that results in retinoblastoma protein hypophosphorylation on amino acids S608 and S780. These events impede the release of YY1 to the nuclei and its availability to regulate the expression of genes and to support cellular proliferation. Moreover, altered calcium influx and calpain II protease activation leads to proteolytical degradation of transcription factor YY1. We conclude that in the serum-stimulated human vascular smooth muscle primary cell cultures, bilirubin favors growth arrest, and we propose that this activity is regulated by its interaction with the Raf/ERK/MAPK pathway, effect on cyclin D1 and Raf content, altered retinoblastoma protein profile of hypophosphorylation, calcium influx, and YY1 proteolysis. We propose that these activities together culminate in diminished 5 S and 45 S ribosomal RNA synthesis and cell growth arrest. The observations provide important mechanistic insight into the molecular mechanisms underlying the transition of human vascular smooth muscle cells from proliferative to contractile phenotype and the role of bilirubin in this transition. PMID:22262839

  11. Smooth halos in the cosmic web

    Energy Technology Data Exchange (ETDEWEB)

    Gaite, José, E-mail: jose.gaite@upm.es [Physics Dept., ETSIAE, IDR, Universidad Politécnica de Madrid, Pza. Cardenal Cisneros 3, E-28040 Madrid (Spain)

    2015-04-01

    Dark matter halos can be defined as smooth distributions of dark matter placed in a non-smooth cosmic web structure. This definition of halos demands a precise definition of smoothness and a characterization of the manner in which the transition from smooth halos to the cosmic web takes place. We introduce entropic measures of smoothness, related to measures of inequality previously used in economy and with the advantage of being connected with standard methods of multifractal analysis already used for characterizing the cosmic web structure in cold dark matter N-body simulations. These entropic measures provide us with a quantitative description of the transition from the small scales portrayed as a distribution of halos to the larger scales portrayed as a cosmic web and, therefore, allow us to assign definite sizes to halos. However, these ''smoothness sizes'' have no direct relation to the virial radii. Finally, we discuss the influence of N-body discreteness parameters on smoothness.

  12. Smooth halos in the cosmic web

    International Nuclear Information System (INIS)

    Gaite, José

    2015-01-01

    Dark matter halos can be defined as smooth distributions of dark matter placed in a non-smooth cosmic web structure. This definition of halos demands a precise definition of smoothness and a characterization of the manner in which the transition from smooth halos to the cosmic web takes place. We introduce entropic measures of smoothness, related to measures of inequality previously used in economy and with the advantage of being connected with standard methods of multifractal analysis already used for characterizing the cosmic web structure in cold dark matter N-body simulations. These entropic measures provide us with a quantitative description of the transition from the small scales portrayed as a distribution of halos to the larger scales portrayed as a cosmic web and, therefore, allow us to assign definite sizes to halos. However, these ''smoothness sizes'' have no direct relation to the virial radii. Finally, we discuss the influence of N-body discreteness parameters on smoothness

  13. Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?

    Science.gov (United States)

    Park, Song-Young; Gifford, Jayson R; Andtbacka, Robert H I; Trinity, Joel D; Hyngstrom, John R; Garten, Ryan S; Diakos, Nikolaos A; Ives, Stephen J; Dela, Flemming; Larsen, Steen; Drakos, Stavros; Richardson, Russell S

    2014-08-01

    Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial respiration. Therefore, the present study examined mitochondrial respiratory rates in smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth muscles were harvested from a total of 22 subjects (53 ± 6 yr), and mitochondrial respiration was assessed in permeabilized fibers. Complex I + II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac to skeletal to smooth muscles (54 ± 1, 39 ± 4, and 15 ± 1 pmol·s(-1)·mg(-1), P respiration rates were normalized by CS (respiration per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, complex I state 2 normalized for CS activity, an index of nonphosphorylating respiration per mitochondrial content, increased progressively from cardiac to skeletal to smooth muscles, such that the respiratory control ratio, state 3/state 2 respiration, fell progressively from cardiac to skeletal to smooth muscles (5.3 ± 0.7, 3.2 ± 0.4, and 1.6 ± 0.3 pmol·s(-1)·mg(-1), P respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially alter ROS production.

  14. Comparison of some nonlinear smoothing methods

    International Nuclear Information System (INIS)

    Bell, P.R.; Dillon, R.S.

    1977-01-01

    Due to the poor quality of many nuclear medicine images, computer-driven smoothing procedures are frequently employed to enhance the diagnostic utility of these images. While linear methods were first tried, it was discovered that nonlinear techniques produced superior smoothing with little detail suppression. We have compared four methods: Gaussian smoothing (linear), two-dimensional least-squares smoothing (linear), two-dimensional least-squares bounding (nonlinear), and two-dimensional median smoothing (nonlinear). The two dimensional least-squares procedures have yielded the most satisfactorily enhanced images, with the median smoothers providing quite good images, even in the presence of widely aberrant points

  15. Inhibition of human arterial smooth muscle (HASM) cell proliferation and collagen synthesis by protamine

    International Nuclear Information System (INIS)

    Drucker, D.E.; Graham, M.F.; Diegelmann, R.F.; Greenfield, L.J.

    1986-01-01

    Atherosclerotic plaques result from vascular smooth muscle cell proliferation and collagen deposition. The authors have been studying factors which modulate HASM cell proliferation and collagen synthesis. HASM cells were isolated from the media of normal human thoracic and infrarenal aortas and grown in vitro. Cell numbers were determined by direct counting and collagen synthesis was measured by incorporation of 3 H-proline into collagenase-digestible protein. In this study, protamine (200 μg/ml) was tested and found to cause a 55% reduction of HASM cell proliferation which was reversible when the cells were returned to control medium or when heparin (100 μg/ml) was added with protamine. Protamine caused a constant 33% decrease in non-collagen protein (NCP) synthesis per cell. In contrast, collagen synthesis was inhibited in dose dependent fashion (88% reduction at 200 μg/ml). Protamine blocks HASM cell proliferation and specifically inhibits collagen production. The exact mechanism of this inhibition is unclear but may be related to a transcriptional event since protamine has a high affinity for DNA

  16. Long Non-Coding RNA MEG3 Downregulation Triggers Human Pulmonary Artery Smooth Muscle Cell Proliferation and Migration via the p53 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Zengxian Sun

    2017-08-01

    Full Text Available Background/Aims: Increasing evidence has demonstrated a significant role of long non-coding RNAs (lncRNAs in diverse biological processes, and many of which are likely to have functional roles in vascular remodeling. However, their functions in pulmonary arterial hypertension (PAH remain largely unknown. Pulmonary vascular remodeling is an important pathological feature of PAH, leading to increased vascular resistance and reduced compliance. Pulmonary artery smooth muscle cells (PASMCs dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of PASMCs function. Herein, we determined whether long noncoding RNA–maternally expressed gene 3 (MEG3 was involved in PAH-related vascular remodeling. Methods: The arterial wall thickness was examined by hematoxylin and eosin (H&E staining in distal pulmonary arteries (PAs isolated from lungs of healthy volunteers and PAH patients. The expression level of MEG3 was analyzed by qPCR. The effects of MEG3 on human PASMCs were assessed by cell counting Kit-8 assay, BrdU incorporation assay, flow cytometry, scratch-wound assay, immunofluorescence, and western blotting in human PASMCs. Results: We revealed that the expression of MEG3 was significantly downregulated in lung and PAs of patients with PAH. MEG3 knockdown affected PASMCs proliferation and migration in vitro. Moreover, inhibition of MEG3 regulated the cell cycle progression and made more smooth muscle cells from the G0/G1 phase to the G2/M+S phase and the process could stimulate the expression of PCNA, Cyclin A and Cyclin E. In addition, we found that the p53 pathway was involved in MEG3–induced smooth muscle cell proliferation. Conclusions: This study identified MEG3 as a critical regulator in PAH and demonstrated the potential of gene therapy and drug development for treating PAH.

  17. A 310-bp minimal promoter mediates smooth muscle cell-specific expression of telokin.

    Science.gov (United States)

    Smith, A F; Bigsby, R M; Word, R A; Herring, B P

    1998-05-01

    A cell-specific promoter located in an intron of the smooth muscle myosin light chain kinase gene directs transcription of telokin exclusively in smooth muscle cells. Transgenic mice were generated in which a 310-bp rabbit telokin promoter fragment, extending from -163 to +147, was used to drive expression of simian virus 40 large T antigen. Smooth muscle-specific expression of the T-antigen transgene paralleled that of the endogenous telokin gene in all smooth muscle tissues except uterus. The 310-bp promoter fragment resulted in very low levels of transgene expression in uterus; in contrast, a transgene driven by a 2.4-kb fragment (-2250 to +147) resulted in high levels of transgene expression in uterine smooth muscle. Telokin expression levels correlate with the estrogen status of human myometrial tissues, suggesting that deletion of an estrogen response element (ERE) may account for the low levels of transgene expression driven by the 310-bp rabbit telokin promoter in uterine smooth muscle. Experiments in A10 smooth muscle cells directly showed that reporter gene expression driven by the 2.4-kb, but not 310-bp, promoter fragment could be stimulated two- to threefold by estrogen. This stimulation was mediated through an ERE located between -1447 and -1474. Addition of the ERE to the 310-bp fragment restored estrogen responsiveness in A10 cells. These data demonstrate that in addition to a minimal 310-bp proximal promoter at least one distal cis-acting regulatory element is required for telokin expression in uterine smooth muscle. The distal element may include an ERE between -1447 and -1474.

  18. Smooth and non-smooth travelling waves in a nonlinearly dispersive Boussinesq equation

    International Nuclear Information System (INIS)

    Shen Jianwei; Xu Wei; Lei Youming

    2005-01-01

    The dynamical behavior and special exact solutions of nonlinear dispersive Boussinesq equation (B(m,n) equation), u tt -u xx -a(u n ) xx +b(u m ) xxxx =0, is studied by using bifurcation theory of dynamical system. As a result, all possible phase portraits in the parametric space for the travelling wave system, solitary wave, kink and anti-kink wave solutions and uncountably infinite many smooth and non-smooth periodic wave solutions are obtained. It can be shown that the existence of singular straight line in the travelling wave system is the reason why smooth waves converge to cusp waves, finally. When parameter are varied, under different parametric conditions, various sufficient conditions guarantee the existence of the above solutions are given

  19. Angiogenesis is induced by airway smooth muscle strain.

    Science.gov (United States)

    Hasaneen, Nadia A; Zucker, Stanley; Lin, Richard Z; Vaday, Gayle G; Panettieri, Reynold A; Foda, Hussein D

    2007-10-01

    Angiogenesis is an important feature of airway remodeling in both chronic asthma and chronic obstructive pulmonary disease (COPD). Airways in those conditions are exposed to excessive mechanical strain during periods of acute exacerbations. We recently reported that mechanical strain of human airway smooth muscle (HASM) led to an increase in their proliferation and migration. Sustained growth in airway smooth muscle in vivo requires an increase in the nutritional supply to these muscles, hence angiogenesis. In this study, we examined the hypothesis that cyclic mechanical strain of HASM produces factors promoting angiogenic events in the surrounding vascular endothelial cells. Our results show: 1) a significant increase in human lung microvascular endothelial cell (HMVEC-L) proliferation, migration, and tube formation following incubation in conditioned media (CM) from HASM cells exposed to mechanical strain; 2) mechanical strain of HASM cells induced VEGF expression and release; 3) VEGF neutralizing antibodies inhibited the proliferation, migration, and tube formations of HMVEC-L induced by the strained airway smooth muscle CM; 4) mechanical strain of HASM induced a significant increase in hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA and protein, a transcription factor required for VEGF gene transcription; and 5) mechanical strain of HASM induced HIF-1alpha/VEGF through dual phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and ERK pathways. In conclusion, exposing HASM cells to mechanical strain induces signal transduction pathway through PI3K/Akt/mTOR and ERK pathways that lead to an increase in HIF-1alpha, a transcription factor required for VEGF expression. VEGF release by mechanical strain of HASM may contribute to the angiogenesis seen with repeated exacerbation of asthma and COPD.

  20. Differential expression of caveolin-1 in human myometrial and uterine leiomyoma smooth muscle.

    Science.gov (United States)

    Zhou, Yu; Ren, Yuanyuan; Cui, Lihua; Li, Zongjin; Zhu, Yingjun; Lin, Wanjun; Wang, Yuebing

    2014-11-01

    Uterine leiomyomas, the most common neoplasms of the female genital tract, are benign tumors of the uterus arising from the smooth muscle cells (SMCs) of the myometrium with an involvement of estrogen. Caveolin-1 (Cav-1), a major protein component in caveolae membrane lipid rafts, is down-regulated in several estrogen-related cancer cells, and overexpression of Cav-1 inhibits proliferation of cancer cells and vascular SMCs as well. Therefore, we hypothesize that Cav-1 is down-regulated in human uterine leiomyoma. Western blot using tissues from clinical patients showed that Cav-1 expression was significantly lower or undetectable in uterine leiomyoma compared with their matched myometrium (P leiomyomas was also significantly lower as detected by reverse transcription-quantitative polymerase chain reaction analysis (P = .001). To further study the underlying mechanism, we performed primary cell culture, and found that the expression of Cav-1 remained low in cultured leiomyoma SMCs (P = .009). Serum withdrawal did not change Cav-1 expression in leiomyoma SMCs, but increased expression in myometrial SMCs (P = .006). 17-β estradiol inhibited the expression of Cav-1 protein (P = .047) and mRNA (P = .007) in leiomyoma SMCs, whereas it stimulated expression in myometrial SMCs (P = .043). 17-β estradiol, although activating the mitogen-activated protein kinase pathway in both SMCs, did not stimulate their proliferation. We conclude that human uterine leiomyomas in vitro express low levels of Cav-1, which may result from estrogen inhibition. This effect of estrogen may contribute to the pathogenesis of uterine leiomyoma. Further studies in vivo are needed to verify these results. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone.

    Science.gov (United States)

    Pearson, Helen; Britt, Rodney D; Pabelick, Christine M; Prakash, Y S; Amrani, Yassine; Pandya, Hitesh C

    2015-12-01

    Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Cultured fetal human ASM cells stimulated with TNF-α (0-20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases.

  2. Birth weight and characteristics of endothelial and smooth muscle cell cultures from human umbilical cord vessels

    Directory of Open Access Journals (Sweden)

    Lurbe Empar

    2009-04-01

    Full Text Available Abstract Background Low birth weight has been related to an increased risk for developing high blood pressure in adult life. The molecular and cellular analysis of umbilical cord artery and vein may provide information about the early vascular characteristics of an individual. We have assessed several phenotype characteristics of the four vascular cell types derived from human umbilical cords of newborns with different birth weight. Further follow-up studies could show the association of those vascular properties with infancy and adulthood blood pressure. Methods Endothelial and smooth muscle cell cultures were obtained from umbilical cords from two groups of newborns of birth weight less than 2.8 kg or higher than 3.5 kg. The expression of specific endothelial cell markers (von Willebrand factor, CD31, and the binding and internalization of acetylated low-density lipoprotein and the smooth muscle cell specific α-actin have been evaluated. Cell culture viability, proliferation kinetic, growth fraction (expression of Ki67 and percentage of senescent cells (detection of β-galactosidase activity at pH 6.0 have been determined. Endothelial cell projection area was determined by morphometric analysis of cell cultures after CD31 immunodetection. Results The highest variation was found in cell density at the confluence of endothelial cell cultures derived from umbilical cord arteries (66,789 ± 5,093 cells/cm2 vs. 45,630 ± 11,927 cells/cm2, p 2, p Conclusion The analysis of umbilical cord artery endothelial cells, which demonstrated differences in cell size related to birth weight, can provide hints about the cellular and molecular links between lower birth weight and increased adult high blood pressure risk.

  3. Resembling a viper: implications of mimicry for conservation of the endangered smooth snake.

    Science.gov (United States)

    Valkonen, Janne K; Mappes, Johanna

    2014-12-01

    The phenomenon of Batesian mimicry, where a palatable animal gains protection against predation by resembling an unpalatable model, has been a core interest of evolutionary biologists for 150 years. An extensive range of studies has focused on revealing mechanistic aspects of mimicry (shared education and generalization of predators) and the evolutionary dynamics of mimicry systems (co-operation vs. conflict) and revealed that protective mimicry is widespread and is important for individual fitness. However, according to our knowledge, there are no case studies where mimicry theories have been applied to conservation of mimetic species. Theoretically, mimicry affects, for example, frequency dependency of predator avoidance learning and human induced mortality. We examined the case of the protected, endangered, nonvenomous smooth snake (Coronella austriaca) that mimics the nonprotected venomous adder (Vipera berus), both of which occur in the Åland archipelago, Finland. To quantify the added predation risk on smooth snakes caused by the rarity of vipers, we calculated risk estimates from experimental data. Resemblance of vipers enhances survival of smooth snakes against bird predation because many predators avoid touching venomous vipers. Mimetic resemblance is however disadvantageous against human predators, who kill venomous vipers and accidentally kill endangered, protected smooth snakes. We found that the effective population size of the adders in Åland is very low relative to its smooth snake mimic (28.93 and 41.35, respectively).Because Batesian mimicry is advantageous for the mimic only if model species exist in sufficiently high numbers, it is likely that the conservation program for smooth snakes will fail if adders continue to be destroyed. Understanding the population consequences of mimetic species may be crucial to the success of endangered species conservation. We suggest that when a Batesian mimic requires protection, conservation planners should

  4. multiscale smoothing in supervised statistical learning

    Indian Academy of Sciences (India)

    Optimum level of smoothing is chosen based on the entire training sample, while a good choice of smoothing parameter may also depend on the observation to be classified. One may like to assess the strength of evidence in favor of different competing class at different scale of smoothing. In allows only one single ...

  5. Smoothness of limit functors

    Indian Academy of Sciences (India)

    Abstract. Let S be a scheme. Assume that we are given an action of the one dimen- sional split torus Gm,S on a smooth affine S-scheme X. We consider the limit (also called attractor) subfunctor Xλ consisting of points whose orbit under the given action. 'admits a limit at 0'. We show that Xλ is representable by a smooth ...

  6. RELM-β promotes human pulmonary artery smooth muscle cell proliferation via FAK-stimulated surviving

    International Nuclear Information System (INIS)

    Lin, Chunlong; Li, Xiaohui; Luo, Qiong; Yang, Hui; Li, Lun; Zhou, Qiong; Li, Yue; Tang, Hao; Wu, Lifu

    2017-01-01

    Resistin-like molecule-β (RELM-β), focal adhesion kinase (FAK), and survivin may be involved in the proliferation of cultured human pulmonary artery smooth muscle cells (HPAMSCs), which is involved in pulmonary hypertension. HPAMSCs were treated with human recombinant RELM-β (rhRELM-β). siRNAs against FAK and survivin were transfected into cultured HPASMCs. Expression of FAK and survivin were examined by RT-PCR and western blot. Immunofluorescence was used to localize FAK. Flow cytometry was used to examine cell cycle distribution and cell death. Compared to the control group, all rhRELM-β-treated groups demonstrated significant increases in the expression of FAK and survivin (P<0.05). rhRELM-β significantly increased the proportion of HPASMCs in the S phase and decreased the proportion in G0/G1. FAK siRNA down-regulated survivin expression while survivin siRNA did not affect FAK expression. FAK siRNA effectively inhibited FAK and survivin expression in RELM-β-treated HPASMCs and partially suppressed cell proliferation. RELM-β promoted HPASMC proliferation and upregulated FAK and survivin expression. In conclusion, results suggested that FAK is upstream of survivin in the signaling pathway mediating cell proliferation. FAK seems to be important in RELM-β-induced HPASMC proliferation, partially by upregulating survivin expression. - Highlights: • rhRELM-β increased the expression of FAK and survivin. • rhRELM-β increased the proportion of HPASMCs in the S phase. • FAK is upstream of survivin in the signaling pathway mediating cell proliferation. • FAK is important in RELM-β-induced HPASMC proliferation, partly via survivin.

  7. RELM-β promotes human pulmonary artery smooth muscle cell proliferation via FAK-stimulated surviving

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chunlong, E-mail: lclmd@sina.com; Li, Xiaohui; Luo, Qiong; Yang, Hui; Li, Lun; Zhou, Qiong; Li, Yue; Tang, Hao; Wu, Lifu

    2017-02-01

    Resistin-like molecule-β (RELM-β), focal adhesion kinase (FAK), and survivin may be involved in the proliferation of cultured human pulmonary artery smooth muscle cells (HPAMSCs), which is involved in pulmonary hypertension. HPAMSCs were treated with human recombinant RELM-β (rhRELM-β). siRNAs against FAK and survivin were transfected into cultured HPASMCs. Expression of FAK and survivin were examined by RT-PCR and western blot. Immunofluorescence was used to localize FAK. Flow cytometry was used to examine cell cycle distribution and cell death. Compared to the control group, all rhRELM-β-treated groups demonstrated significant increases in the expression of FAK and survivin (P<0.05). rhRELM-β significantly increased the proportion of HPASMCs in the S phase and decreased the proportion in G0/G1. FAK siRNA down-regulated survivin expression while survivin siRNA did not affect FAK expression. FAK siRNA effectively inhibited FAK and survivin expression in RELM-β-treated HPASMCs and partially suppressed cell proliferation. RELM-β promoted HPASMC proliferation and upregulated FAK and survivin expression. In conclusion, results suggested that FAK is upstream of survivin in the signaling pathway mediating cell proliferation. FAK seems to be important in RELM-β-induced HPASMC proliferation, partially by upregulating survivin expression. - Highlights: • rhRELM-β increased the expression of FAK and survivin. • rhRELM-β increased the proportion of HPASMCs in the S phase. • FAK is upstream of survivin in the signaling pathway mediating cell proliferation. • FAK is important in RELM-β-induced HPASMC proliferation, partly via survivin.

  8. A Model of the Smooth Pursuit Eye Movement with Prediction and Learning

    Directory of Open Access Journals (Sweden)

    Davide Zambrano

    2010-01-01

    Full Text Available Smooth pursuit is one of the five main eye movements in humans, consisting of tracking a steadily moving visual target. Smooth pursuit is a good example of a sensory-motor task that is deeply based on prediction: tracking a visual target is not possible by correcting the error between the eye and the target position or velocity with a feedback loop, but it is only possible by predicting the trajectory of the target. This paper presents a model of smooth pursuit based on prediction and learning. It starts from amodel of the neuro-physiological system proposed by Shibata and Schaal (Shibata et al., Neural Networks, vol. 18, pp. 213-224, 2005. The learning component added here decreases the prediction time in the case of target dynamics already experienced by the system. In the implementation described here, the convergence time is, after the learning phase, 0.8 s.

  9. Bone morphogenetic proteins regulate osteoprotegerin and its ligands in human vascular smooth muscle cells

    DEFF Research Database (Denmark)

    Knudsen, Kirsten Quyen Nguyen; Olesen, Ping; Ledet, Thomas

    2007-01-01

    The bone-related protein osteoprotegerin (OPG) may be involved in the development of vascular calcifications, especially in diabetes, where it has been found in increased amounts in the arterial wall. Experimental studies suggest that members of the TGF-superfamily are involved in the transformat......The bone-related protein osteoprotegerin (OPG) may be involved in the development of vascular calcifications, especially in diabetes, where it has been found in increased amounts in the arterial wall. Experimental studies suggest that members of the TGF-superfamily are involved...... in the transformation of human vascular smooth muscle cells (HVSMC) to osteoblast-like cells. In this study, we evaluated the effect of BMP-2, BMP-7 and transforming growth factor beta (TGF-beta1) on the secretion and mRNA expression of OPG and its ligands receptor activator of nuclear factor-kappabeta ligand (RANKL......) and TNF-related apoptosis-inducing ligand (TRAIL) in HVSMC. All three growth factors decreased OPG protein production significantly; these results were paralleled by reduced OPG mRNA expression. TRAIL mRNA levels were also decreased. RANKL mRNA expression declined when treated with TGF-beta1 but were...

  10. Calcium dynamics in vascular smooth muscle

    OpenAIRE

    Amberg, Gregory C.; Navedo, Manuel F.

    2013-01-01

    Smooth muscle cells are ultimately responsible for determining vascular luminal diameter and blood flow. Dynamic changes in intracellular calcium are a critical mechanism regulating vascular smooth muscle contractility. Processes influencing intracellular calcium are therefore important regulators of vascular function with physiological and pathophysiological consequences. In this review we discuss the major dynamic calcium signals identified and characterized in vascular smooth muscle cells....

  11. The Relationship between Intellectual Capital and Income Smoothing and Stock Returns (Case in Medical Companies

    Directory of Open Access Journals (Sweden)

    Dr. H. Vakilifard

    2013-05-01

    Full Text Available This article examines the relationship between intellectual capital, income smoothing and stock returns. We are capturing income smoothing through total accruals. Income smoothing firms have significantly higher abnormal returns around earnings announcement. In the knowledge economy, intellectual capital has become one of the primary sources of competitive advantage for a firm. Given the remarkable shift in the underlying production factors of a business within the new knowledge economy, it is important for firms to be aware of the elements of intellectual capital that would lead to value creation. So we associated relationship between intellectual capital and income smoothing and stock returns. The sample includes 108 firm-year observations from 2006 to 2011.We have used five variables: three variables to measure IC, and two variables to measure stock returns and income smoothing. Initial data analyses were conducted through SPSS. The results of our study showed that there was relationship between physical capital and stock returns but they did not provide support for the positive relationship between structural capital, human capital and firm’s financial performance.

  12. Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque.

    Science.gov (United States)

    Bonin, L R; Madden, K; Shera, K; Ihle, J; Matthews, C; Aziz, S; Perez-Reyes, N; McDougall, J K; Conroy, S C

    1999-03-01

    The study of atherogenesis in humans has been restricted by the limited availability and brief in vitro life span of plaque smooth muscle cells (SMCs). We describe plaque SMC lines with extended life spans generated by the expression of the human papillomavirus (HPV)-16 E6 and E7 genes, which has been shown to extend the life span of normal adult human aortic SMCs. Resulting cell lines (pdSMC1A and 2) demonstrated at least 10-fold increases in life span; pdSMC1A became immortal. The SMC identity of both pdSMC lines was confirmed by SM22 mRNA expression. pdSMC2 were generally diploid but with various structural and numerical alterations; pdSMC1A demonstrated several chromosomal abnormalities, most commonly -Y, +7, -13, anomalies previously reported in both primary pdSMCs and atherosclerotic tissue. Confluent pdSMC2 appeared grossly similar to HPV-16 E6/E7-expressing normal adult aortic SMCs (AASMCs), exhibiting typical SMC morphology/growth patterns; pdSMC1A displayed irregular cell shape/organization with numerous mitotic figures. Dedifferentiation to a synthetic/proliferative phenotype has been hypothesized as a critical step in atherogenesis, because rat neonatal SMCs and adult intimal SMCs exhibit similar gene expression patterns. To confirm that our pdSMC lines likewise express this apparent plaque phenotype, osteopontin, platelet-derived growth factor B, and elastin mRNA levels were determined in pdSMC1A, pdSMC2, and AASMCs. However, no significant increases in osteopontin or platelet-derived growth factor B expression levels were observed in either pdSMC compared with AASMCs. pdSMC2 alone expressed high levels of elastin mRNA. Lower levels of SM22 mRNA in pdSMC1A suggested greater dedifferentiation and/or additional population doublings in pdSMC1A relative to pdSMC2. Both pdSMC lines (particularly 1A) demonstrated high message levels for matrix Gla protein, previously reported to be highly expressed by human neointimal SMCs in vitro. These results describe 2

  13. Effect of smoothing on robust chaos.

    Science.gov (United States)

    Deshpande, Amogh; Chen, Qingfei; Wang, Yan; Lai, Ying-Cheng; Do, Younghae

    2010-08-01

    In piecewise-smooth dynamical systems, situations can arise where the asymptotic attractors of the system in an open parameter interval are all chaotic (e.g., no periodic windows). This is the phenomenon of robust chaos. Previous works have established that robust chaos can occur through the mechanism of border-collision bifurcation, where border is the phase-space region where discontinuities in the derivatives of the dynamical equations occur. We investigate the effect of smoothing on robust chaos and find that periodic windows can arise when a small amount of smoothness is present. We introduce a parameter of smoothing and find that the measure of the periodic windows in the parameter space scales linearly with the parameter, regardless of the details of the smoothing function. Numerical support and a heuristic theory are provided to establish the scaling relation. Experimental evidence of periodic windows in a supposedly piecewise linear dynamical system, which has been implemented as an electronic circuit, is also provided.

  14. α-Trinositol inhibits FGF-stimulated growth of smooth muscle and breast cancer cells

    International Nuclear Information System (INIS)

    Siren, Matti J.; Vainiomaeki, Maija; Vaeaenaenen, Kalervo; Haerkoenen, Pirkko

    2004-01-01

    α-Trinositol (D-myo-inositol-1,2,6-trisphosphate), an isomer of the intracellular messenger IP 3 , has been studied for its anti-inflammatory and other effects in animal experiments and in human. The mechanisms of action remain unknown. Several human pathologies are associated with uncontrolled production of fibroblast growth factors (FGFs). FGF-2 induces vascular smooth muscle cell proliferation, which contributes to restenosis after coronary balloon angioplasty. The expression of several FGFs is also increased in tumors. We studied the effects of the water- and lipid-soluble derivatives of α-trinositol on the FGF-2- and/or FGF-8-induced proliferation of human pulmonary artery smooth muscle cells (HPASMC) and S115 mouse breast cancer cells. α-Trinositol decreased the FGF-mediated proliferation of HPASMC and S115 cells. Membrane permeability did not seem obligatory since the lipid-soluble form of α-trinositol was less effective than the water-soluble derivative. These results suggest a new biological function for certain phosphoinositides in the modulation of FGF-regulated processes

  15. Intermediate filaments in smooth muscle from pregnant and non-pregnant human uterus.

    OpenAIRE

    Leoni, P; Carli, F; Halliday, D

    1990-01-01

    The intermediate filament proteins desmin and vimentin from pregnant and non-pregnant uterine muscle and smooth-muscle cells in culture were analysed using SDS/PAGE. The desmin content in uterine muscle increases dramatically during pregnancy, whereas vimentin remains unchanged or changes very little. When muscle cells are kept in culture, a considerable increase in vimentin content is observed as compared with vimentin in freshly isolated non-pregnant uterine tissue. Our results strengthen t...

  16. Smooth surfaces from rational bilinear patches

    KAUST Repository

    Shi, Ling

    2014-01-01

    Smooth freeform skins from simple panels constitute a challenging topic arising in contemporary architecture. We contribute to this problem area by showing how to approximate a negatively curved surface by smoothly joined rational bilinear patches. The approximation problem is solved with help of a new computational approach to the hyperbolic nets of Huhnen-Venedey and Rörig and optimization algorithms based on it. We also discuss its limits which lie in the topology of the input surface. Finally, freeform deformations based on Darboux transformations are used to generate smooth surfaces from smoothly joined Darboux cyclide patches; in this way we eliminate the restriction to surfaces with negative Gaussian curvature. © 2013 Elsevier B.V.

  17. Functional vascular smooth muscle cells derived from human induced pluripotent stem cells via mesenchymal stem cell intermediates

    Science.gov (United States)

    Bajpai, Vivek K.; Mistriotis, Panagiotis; Loh, Yuin-Han; Daley, George Q.; Andreadis, Stelios T.

    2012-01-01

    Aims Smooth muscle cells (SMC) play an important role in vascular homeostasis and disease. Although adult mesenchymal stem cells (MSC) have been used as a source of contractile SMC, they suffer from limited proliferation potential and culture senescence, particularly when originating from older donors. By comparison, human induced pluripotent stem cells (hiPSC) can provide an unlimited source of functional SMC for autologous cell-based therapies and for creating models of vascular disease. Our goal was to develop an efficient strategy to derive functional, contractile SMC from hiPSC. Methods and results We developed a robust, stage-wise, feeder-free strategy for hiPSC differentiation into functional SMC through an intermediate stage of multipotent MSC, which could be coaxed to differentiate into fat, bone, cartilage, and muscle. At this stage, the cells were highly proliferative and displayed higher clonogenic potential and reduced senescence when compared with parental hair follicle mesenchymal stem cells. In addition, when exposed to differentiation medium, the myogenic proteins such as α-smooth muscle actin, calponin, and myosin heavy chain were significantly upregulated and displayed robust fibrillar organization, suggesting the development of a contractile phenotype. Indeed, tissue constructs prepared from these cells exhibited high levels of contractility in response to receptor- and non-receptor-mediated agonists. Conclusion We developed an efficient stage-wise strategy that enabled hiPSC differentiation into contractile SMC through an intermediate population of clonogenic and multipotent MSC. The high yield of MSC and SMC derivation suggests that our strategy may facilitate an acquisition of the large numbers of cells required for regenerative medicine or for studying vascular disease pathophysiology. PMID:22941255

  18. Smooth leader or sharp follower? Playing the mirror game with a robot.

    Science.gov (United States)

    Kashi, Shir; Levy-Tzedek, Shelly

    2018-01-01

    The increasing number of opportunities for human-robot interactions in various settings, from industry through home use to rehabilitation, creates a need to understand how to best personalize human-robot interactions to fit both the user and the task at hand. In the current experiment, we explored a human-robot collaborative task of joint movement, in the context of an interactive game. We set out to test people's preferences when interacting with a robotic arm, playing a leader-follower imitation game (the mirror game). Twenty two young participants played the mirror game with the robotic arm, where one player (person or robot) followed the movements of the other. Each partner (person and robot) was leading part of the time, and following part of the time. When the robotic arm was leading the joint movement, it performed movements that were either sharp or smooth, which participants were later asked to rate. The greatest preference was given to smooth movements. Half of the participants preferred to lead, and half preferred to follow. Importantly, we found that the movements of the robotic arm primed the subsequent movements performed by the participants. The priming effect by the robot on the movements of the human should be considered when designing interactions with robots. Our results demonstrate individual differences in preferences regarding the role of the human and the joint motion path of the robot and the human when performing the mirror game collaborative task, and highlight the importance of personalized human-robot interactions.

  19. [Studies on the interaction of blood components with ultra-smooth polymer surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, T.H. [New Mexico Univ., Albuquerque, NM (United States). School of Medicine

    1989-04-17

    This report is in three parts, though each is briefly described data is provided. The three parts address (1) radioiodination of human thrombin and fibrinogen; (2) interaction of blood components with ultra- smooth polymer surfaces; and (3) initial studies of Tecoflex and treated Tecoflex cups with normal serum samples.

  20. Bifurcations of non-smooth systems

    Science.gov (United States)

    Angulo, Fabiola; Olivar, Gerard; Osorio, Gustavo A.; Escobar, Carlos M.; Ferreira, Jocirei D.; Redondo, Johan M.

    2012-12-01

    Non-smooth systems (namely piecewise-smooth systems) have received much attention in the last decade. Many contributions in this area show that theory and applications (to electronic circuits, mechanical systems, …) are relevant to problems in science and engineering. Specially, new bifurcations have been reported in the literature, and this was the topic of this minisymposium. Thus both bifurcation theory and its applications were included. Several contributions from different fields show that non-smooth bifurcations are a hot topic in research. Thus in this paper the reader can find contributions from electronics, energy markets and population dynamics. Also, a carefully-written specific algebraic software tool is presented.

  1. SREBP inhibits VEGF expression in human smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Motoyama, Koka [Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka (Japan); Fukumoto, Shinya [Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka (Japan); Koyama, Hidenori [Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka (Japan); Emoto, Masanori [Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka (Japan); Shimano, Hitoshi [Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki (Japan); Maemura, Koji [Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo (Japan); Nishizawa, Yoshiki [Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka (Japan)

    2006-03-31

    Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate expression of genes encoding enzymes for lipid biosynthesis. SREBPs are activated by HMG-CoA reductase inhibitors (statins). Statins have been also reported to suppress vascular endothelial growth factor (VEGF) expression in vascular smooth muscle cells (VSMCs). Therefore, we hypothesized that SREBPs are involved in statin-mediated regulation of VEGF production in VSMCs. SREBP1 was robustly expressed, and was activated by atorvastatin in VSMCs, as demonstrated by increased levels of the mature nuclear form of SREBP1, and increased promoter activities of a reporter containing sterol regulatory elements by atorvastatin. Moreover, overexpression of SREBP1a dose-dependently suppressed VEGF promoter activity. Site-specific mutation or deletion of the proximal Sp1 sites reduced the inhibitory effects of SREBP1a on VEGF promoter activity. These data demonstrated that SREBP1, activated by atorvastatin, suppressed VEGF expression through the indirect interaction with the proximal tandem Sp1 sites in VSMCs.

  2. SREBP inhibits VEGF expression in human smooth muscle cells

    International Nuclear Information System (INIS)

    Motoyama, Koka; Fukumoto, Shinya; Koyama, Hidenori; Emoto, Masanori; Shimano, Hitoshi; Maemura, Koji; Nishizawa, Yoshiki

    2006-01-01

    Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate expression of genes encoding enzymes for lipid biosynthesis. SREBPs are activated by HMG-CoA reductase inhibitors (statins). Statins have been also reported to suppress vascular endothelial growth factor (VEGF) expression in vascular smooth muscle cells (VSMCs). Therefore, we hypothesized that SREBPs are involved in statin-mediated regulation of VEGF production in VSMCs. SREBP1 was robustly expressed, and was activated by atorvastatin in VSMCs, as demonstrated by increased levels of the mature nuclear form of SREBP1, and increased promoter activities of a reporter containing sterol regulatory elements by atorvastatin. Moreover, overexpression of SREBP1a dose-dependently suppressed VEGF promoter activity. Site-specific mutation or deletion of the proximal Sp1 sites reduced the inhibitory effects of SREBP1a on VEGF promoter activity. These data demonstrated that SREBP1, activated by atorvastatin, suppressed VEGF expression through the indirect interaction with the proximal tandem Sp1 sites in VSMCs

  3. A SAS IML Macro for Loglinear Smoothing

    Science.gov (United States)

    Moses, Tim; von Davier, Alina

    2011-01-01

    Polynomial loglinear models for one-, two-, and higher-way contingency tables have important applications to measurement and assessment. They are essentially regarded as a smoothing technique, which is commonly referred to as loglinear smoothing. A SAS IML (SAS Institute, 2002a) macro was created to implement loglinear smoothing according to…

  4. Mechanical stretch modulates microRNA 21 expression, participating in proliferation and apoptosis in cultured human aortic smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Jian tao Song

    Full Text Available OBJECTIVES: Stretch affects vascular smooth muscle cell proliferation and apoptosis, and several responsible genes have been proposed. We tested whether the expression of microRNA 21 (miR-21 is modulated by stretch and is involved in stretch-induced proliferation and apoptosis of human aortic smooth muscle cells (HASMCs. METHODS AND RESULTS: RT-PCR revealed that elevated stretch (16% elongation, 1 Hz increased miR-21 expression in cultured HASMCs, and moderate stretch (10% elongation, 1 Hz decreased the expression. BrdU incorporation assay and cell counting showed miR-21 involved in the proliferation of HASMCs mediated by stretch, likely by regulating the expression of p27 and phosphorylated retinoblastoma protein (p-Rb. FACS analysis revealed that the complex of miR-21 and programmed cell death protein 4 (PDCD4 participated in regulating apoptosis with stretch. Stretch increased the expression of primary miR-21 and pre-miR-21 in HASMCs. Electrophoretic mobility shift assay (EMSA demonstrated that stretch increased NF-κB and AP-1 activities in HASMCs, and blockade of AP-1 activity by c-jun siRNA significantly suppressed stretch-induced miR-21 expression. CONCLUSIONS: Cyclic stretch modulates miR-21 expression in cultured HASMCs, and miR-21 plays important roles in regulating proliferation and apoptosis mediated by stretch. Stretch upregulates miR-21 expression at least in part at the transcription level and AP-1 is essential for stretch-induced miR-21 expression.

  5. Stimulatory interactions between human coronary smooth muscle cells and dendritic cells.

    Directory of Open Access Journals (Sweden)

    Sara Paccosi

    Full Text Available Despite inflammatory and immune mechanisms participating to atherogenesis and dendritic cells (DCs driving immune and non-immune tissue injury response, the interactions between DCs and vascular smooth muscle cells (VSMCs possibly relevant to vascular pathology including atherogenesis are still unclear. To address this issue, immature DCs (iDCs generated from CD14+ cells isolated from healthy donors were matured either with cytokines (mDCs, or co-cultured (ccDCs with human coronary artery VSMCs (CASMCs using transwell chambers. Co-culture induced DC immunophenotypical and functional maturation similar to cytokines, as demonstrated by flow cytometry and mixed lymphocyte reaction. In turn, factors from mDCs and ccDCs induced CASMC migration. MCP-1 and TNFα, secreted from DCs, and IL-6 and MCP-1, secreted from CASMCs, were primarily involved. mDCs adhesion to CASMCs was enhanced by CASMC pre-treatment with IFNγ and TNFα ICAM-1 and VCAM-1 were involved, since the expression of specific mRNAs for these molecules increased and adhesion was inhibited by neutralizing antibodies to the counter-receptors CD11c and CD18. Adhesion was also inhibited by CASMC pre-treatment with the HMG-CoA-reductase inhibitor atorvastatin and the PPARγ agonist rosiglitazone, which suggests a further mechanism for the anti-inflammatory action of these drugs. Adhesion of DCs to VSMCs was shown also in vivo in rat carotid 7 to 21 days after crush and incision injury. The findings indicate that DCs and VSMCs can interact with reciprocal stimulation, possibly leading to perpetuate inflammation and vascular wall remodelling, and that the interaction is enhanced by a cytokine-rich inflammatory environment and down-regulated by HMGCoA-reductase inhibitors and PPARγ agonists.

  6. MicroRNA Mediated Chemokine Responses in Human Airway Smooth Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Mythili Dileepan

    Full Text Available Airway smooth muscle (ASM cells play a critical role in the pathophysiology of asthma due to their hypercontractility and their ability to proliferate and secrete inflammatory mediators. microRNAs (miRNAs are gene regulators that control many signaling pathways and thus serve as potential therapeutic alternatives for many diseases. We have previously shown that miR-708 and miR-140-3p regulate the MAPK and PI3K signaling pathways in human ASM (HASM cells following TNF-α exposure. In this study, we investigated the regulatory effect of these miRNAs on other asthma-related genes. Microarray analysis using the Illumina platform was performed with total RNA extracted from miR-708 (or control miR-transfected HASM cells. Inhibition of candidate inflammation-associated gene expression was further validated by qPCR and ELISA. The most significant biologic functions for the differentially expressed gene set included decreased inflammatory response, cytokine expression and signaling. qPCR revealed inhibition of expression of CCL11, CXCL10, CCL2 and CXCL8, while the release of CCL11 was inhibited in miR-708-transfected cells. Transfection of cells with miR-140-3p resulted in inhibition of expression of CCL11, CXCL12, CXCL10, CCL5 and CXCL8 and of TNF-α-induced CXCL12 release. In addition, expression of RARRES2, CD44 and ADAM33, genes known to contribute to the pathophysiology of asthma, were found to be inhibited in miR-708-transfected cells. These results demonstrate that miR-708 and miR-140-3p exert distinct effects on inflammation-associated gene expression and biological function of ASM cells. Targeting these miRNA networks may provide a novel therapeutic mechanism to down-regulate airway inflammation and ASM proliferation in asthma.

  7. Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition

    Science.gov (United States)

    Rothdiener, Miriam; Hegemann, Miriam; Uynuk-Ool, Tatiana; Walters, Brandan; Papugy, Piruntha; Nguyen, Phong; Claus, Valentin; Seeger, Tanja; Stoeckle, Ulrich; Boehme, Karen A.; Aicher, Wilhelm K.; Stegemann, Jan P.; Hart, Melanie L.; Kurz, Bodo; Klein, Gerd; Rolauffs, Bernd

    2016-10-01

    Using matrix elasticity and cyclic stretch have been investigated for inducing mesenchymal stromal cell (MSC) differentiation towards the smooth muscle cell (SMC) lineage but not in combination. We hypothesized that combining lineage-specific stiffness with cyclic stretch would result in a significantly increased expression of SMC markers, compared to non-stretched controls. First, we generated dense collagen type I sheets by mechanically compressing collagen hydrogels. Atomic force microscopy revealed a nanoscale stiffness range known to support myogenic differentiation. Further characterization revealed viscoelasticity and stable biomechanical properties under cyclic stretch with >99% viable adherent human MSC. MSCs on collagen sheets demonstrated a significantly increased mRNA but not protein expression of SMC markers, compared to on culture flasks. However, cyclic stretch of MSCs on collagen sheets significantly increased both mRNA and protein expression of α-smooth muscle actin, transgelin, and calponin versus plastic and non-stretched sheets. Thus, lineage-specific stiffness and cyclic stretch can be applied together for inducing MSC differentiation towards SMCs without the addition of recombinant growth factors or other soluble factors. This represents a novel stimulation method for modulating the phenotype of MSCs towards SMCs that could easily be incorporated into currently available methodologies to obtain a more targeted control of MSC phenotype.

  8. Income and Consumption Smoothing among US States

    DEFF Research Database (Denmark)

    Sørensen, Bent; Yosha, Oved

    within regions but not between regions. This suggests that capital markets transcend regional barriers while credit markets are regional in their nature. Smoothing within the club of rich states is accomplished mainly via capital markets whereas consumption smoothing is dominant within the club of poor...... states. The fraction of a shock to gross state products smoothed by the federal tax-transfer system is the same for various regions and other clubs of states. We calculate the scope for consumption smoothing within various regions and clubs, finding that most gains from risk sharing can be achieved...

  9. Assessment of smoothed spectra using autocorrelation function

    International Nuclear Information System (INIS)

    Urbanski, P.; Kowalska, E.

    2006-01-01

    Recently, data and signal smoothing became almost standard procedures in the spectrometric and chromatographic methods. In radiometry, the main purpose to apply smoothing is minimisation of the statistical fluctuation and avoid distortion. The aim of the work was to find a qualitative parameter, which could be used, as a figure of merit for detecting distortion of the smoothed spectra, based on the linear model. It is assumed that as long as the part of the raw spectrum removed by the smoothing procedure (v s ) will be of random nature, the smoothed spectrum can be considered as undistorted. Thanks to this feature of the autocorrelation function, drifts of the mean value in the removed noise vs as well as its periodicity can be more easily detected from the autocorrelogram than from the original data

  10. Microtissues Enhance Smooth Muscle Differentiation and Cell Viability of hADSCs for Three Dimensional Bioprinting

    Directory of Open Access Journals (Sweden)

    Jin Yipeng

    2017-07-01

    Full Text Available Smooth muscle differentiated human adipose derived stem cells (hADSCs provide a crucial stem cell source for urinary tissue engineering, but the induction of hADSCs for smooth muscle differentiation still has several issues to overcome, including a relatively long induction time and equipment dependence, which limits access to abundant stem cells within a short period of time for further application. Three-dimensional (3D bioprinting holds great promise in regenerative medicine due to its controllable construction of a designed 3D structure. When evenly mixed with bioink, stem cells can be spatially distributed within a bioprinted 3D structure, thus avoiding drawbacks such as, stem cell detachment in a conventional cell-scaffold strategy. Notwithstanding the advantages mentioned above, cell viability is often compromised during 3D bioprinting, which is often due to pressure during the bioprinting process. The objective of our study was to improve the efficiency of hADSC smooth muscle differentiation and cell viability of a 3D bioprinted structure. Here, we employed the hanging-drop method to generate hADSC microtissues in a smooth muscle inductive medium containing human transforming growth factor β1 and bioprinted the induced microtissues onto a 3D structure. After 3 days of smooth muscle induction, the expression of α-smooth muscle actin and smoothelin was higher in microtissues than in their counterpart monolayer cultured hADSCs, as confirmed by immunofluorescence and western blotting analysis. The semi-quantitative assay showed that the expression of α-smooth muscle actin (α-SMA was 0.218 ± 0.077 in MTs and 0.082 ± 0.007 in Controls; smoothelin expression was 0.319 ± 0.02 in MTs and 0.178 ± 0.06 in Controls. Induced MTs maintained their phenotype after the bioprinting process. Live/dead and cell count kit 8 assays showed that cell viability and cell proliferation in the 3D structure printed with microtissues were higher at all time

  11. Smooth surfaces from rational bilinear patches

    KAUST Repository

    Shi, Ling; Wang, Jun; Pottmann, Helmut

    2014-01-01

    Smooth freeform skins from simple panels constitute a challenging topic arising in contemporary architecture. We contribute to this problem area by showing how to approximate a negatively curved surface by smoothly joined rational bilinear patches

  12. TAX SMOOTHING: TESTS ON INDONESIAN DATA

    Directory of Open Access Journals (Sweden)

    Rudi Kurniawan

    2011-01-01

    Full Text Available This paper contributes to the literature of public debt management by testing for tax smoothing behaviour in Indonesia. Tax smoothing means that the government smooths the tax rate across all future time periods to minimize the distortionary costs of taxation over time for a given path of government spending. In a stochastic economy with an incomplete bond market, tax smoothing implies that the tax rate approximates a random walk and changes in the tax rate are nearly unpredictable. For that purpose, two tests were performed. First, random walk behaviour of the tax rate was examined by undertaking unit root tests. The null hypothesis of unit root cannot be rejected, indicating that the tax rate is nonstationary and, hence, it follows a random walk. Second, the predictability of the tax rate was examined by regressing changes in the tax rate on its own lagged values and also on lagged values of changes in the goverment expenditure ratio, and growth of real output. They are found to be not significant in predicting changes in the tax rate. Taken together, the present evidence seems to be consistent with the tax smoothing, therefore provides support to this theory.

  13. Smoothing of respiratory motion traces for motion-compensated radiotherapy.

    Science.gov (United States)

    Ernst, Floris; Schlaefer, Alexander; Schweikard, Achim

    2010-01-01

    The CyberKnife system has been used successfully for several years to radiosurgically treat tumors without the need for stereotactic fixation or sedation of the patient. It has been shown that tumor motion in the lung, liver, and pancreas can be tracked with acceptable accuracy and repeatability. However, highly precise targeting for tumors in the lower abdomen, especially for tumors which exhibit strong motion, remains problematic. Reasons for this are manifold, like the slow tracking system operating at 26.5 Hz, and using the signal from the tracking camera "as is." Since the motion recorded with the camera is used to compensate for system latency by prediction and the predicted signal is subsequently used to infer the tumor position from a correlation model based on x-ray imaging of gold fiducials around the tumor, camera noise directly influences the targeting accuracy. The goal of this work is to establish the suitability of a new smoothing method for respiratory motion traces used in motion-compensated radiotherapy. The authors endeavor to show that better prediction--With a lower rms error of the predicted signal--and/or smoother prediction is possible using this method. The authors evaluated six commercially available tracking systems (NDI Aurora, PolarisClassic, Polaris Vicra, MicronTracker2 H40, FP5000, and accuTrack compact). The authors first tracked markers both stationary and while in motion to establish the systems' noise characteristics. Then the authors applied a smoothing method based on the a trous wavelet decomposition to reduce the devices' noise level. Additionally, the smoothed signal of the moving target and a motion trace from actual human respiratory motion were subjected to prediction using the MULIN and the nLMS2 algorithms. The authors established that the noise distribution for a static target is Gaussian and that when the probe is moved such as to mimic human respiration, it remains Gaussian with the exception of the FP5000 and the

  14. Smoothing of respiratory motion traces for motion-compensated radiotherapy

    International Nuclear Information System (INIS)

    Ernst, Floris; Schlaefer, Alexander; Schweikard, Achim

    2010-01-01

    Purpose: The CyberKnife system has been used successfully for several years to radiosurgically treat tumors without the need for stereotactic fixation or sedation of the patient. It has been shown that tumor motion in the lung, liver, and pancreas can be tracked with acceptable accuracy and repeatability. However, highly precise targeting for tumors in the lower abdomen, especially for tumors which exhibit strong motion, remains problematic. Reasons for this are manifold, like the slow tracking system operating at 26.5 Hz, and using the signal from the tracking camera ''as is''. Since the motion recorded with the camera is used to compensate for system latency by prediction and the predicted signal is subsequently used to infer the tumor position from a correlation model based on x-ray imaging of gold fiducials around the tumor, camera noise directly influences the targeting accuracy. The goal of this work is to establish the suitability of a new smoothing method for respiratory motion traces used in motion-compensated radiotherapy. The authors endeavor to show that better prediction--With a lower rms error of the predicted signal--and/or smoother prediction is possible using this method. Methods: The authors evaluated six commercially available tracking systems (NDI Aurora, PolarisClassic, Polaris Vicra, MicronTracker2 H40, FP5000, and accuTrack compact). The authors first tracked markers both stationary and while in motion to establish the systems' noise characteristics. Then the authors applied a smoothing method based on the a trous wavelet decomposition to reduce the devices' noise level. Additionally, the smoothed signal of the moving target and a motion trace from actual human respiratory motion were subjected to prediction using the MULIN and the nLMS 2 algorithms. Results: The authors established that the noise distribution for a static target is Gaussian and that when the probe is moved such as to mimic human respiration, it remains Gaussian with the

  15. Nodular smooth muscle metaplasia in multiple peritoneal endometriosis

    OpenAIRE

    Kim, Hyun-Soo; Yoon, Gun; Ha, Sang Yun; Song, Sang Yong

    2015-01-01

    We report here an unusual presentation of peritoneal endometriosis with smooth muscle metaplasia as multiple protruding masses on the lateral pelvic wall. Smooth muscle metaplasia is a common finding in rectovaginal endometriosis, whereas in peritoneal endometriosis, smooth muscle metaplasia is uncommon and its nodular presentation on the pelvic wall is even rarer. To the best of our knowledge, this is the first case of nodular smooth muscle metaplasia occurring in peritoneal endometriosis. A...

  16. Human Lung Mast Cell Products Regulate Airway Smooth Muscle CXCL10 Levels.

    Science.gov (United States)

    Alkhouri, H; Cha, V; Tong, K; Moir, L M; Armour, C L; Hughes, J M

    2014-01-01

    In asthma, the airway smooth muscle (ASM) produces CXCL10 which may attract CXCR3(+) mast/T cells to it. Our aim was to investigate the effects of mast cell products on ASM cell CXCL10 production. ASM cells from people with and without asthma were stimulated with IL-1 β , TNF- α , and/or IFN γ and treated with histamine (1-100  μ M) ± chlorpheniramine (H1R antagonist; 1  μ M) or ranitidine (H2R antagonist; 50  μ M) or tryptase (1 nM) ± leupeptin (serine protease inhibitor; 50  μ M), heat-inactivated tryptase, or vehicle for 4 h or 24 h. Human lung mast cells (MC) were isolated and activated with IgE/anti-IgE and supernatants were collected after 2 h or 24 h. The supernatants were added to ASM cells for 48 h and ASM cell CXCL10 production detected using ELISA (protein) and real-time PCR (mRNA). Histamine reduced IL-1 β /TNF- α -induced CXCL10 protein, but not mRNA, levels independent of H1 and H2 receptor activation, whereas tryptase and MC 2 h supernatants reduced all cytokine-induced CXCL10. Tryptase also reduced CXCL10 levels in a cell-free system. Leupeptin inhibited the effects of tryptase and MC 2 h supernatants. MC 24 h supernatants contained TNF- α and amplified IFN γ -induced ASM cell CXCL10 production. This is the first evidence that MC can regulate ASM cell CXCL10 production and its degradation. Thus MC may regulate airway myositis in asthma.

  17. Contextual effects on smooth-pursuit eye movements.

    Science.gov (United States)

    Spering, Miriam; Gegenfurtner, Karl R

    2007-02-01

    Segregating a moving object from its visual context is particularly relevant for the control of smooth-pursuit eye movements. We examined the interaction between a moving object and a stationary or moving visual context to determine the role of the context motion signal in driving pursuit. Eye movements were recorded from human observers to a medium-contrast Gaussian dot that moved horizontally at constant velocity. A peripheral context consisted of two vertically oriented sinusoidal gratings, one above and one below the stimulus trajectory, that were either stationary or drifted into the same or opposite direction as that of the target at different velocities. We found that a stationary context impaired pursuit acceleration and velocity and prolonged pursuit latency. A drifting context enhanced pursuit performance, irrespective of its motion direction. This effect was modulated by context contrast and orientation. When a context was briefly perturbed to move faster or slower eye velocity changed accordingly, but only when the context was drifting along with the target. Perturbing a context into the direction orthogonal to target motion evoked a deviation of the eye opposite to the perturbation direction. We therefore provide evidence for the use of absolute and relative motion cues, or motion assimilation and motion contrast, for the control of smooth-pursuit eye movements.

  18. Epigallocatechin Gallate Attenuates Proliferation and Oxidative Stress in Human Vascular Smooth Muscle Cells Induced by Interleukin-1β via Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)

    Po-Len Liu

    2014-01-01

    Full Text Available Proliferation of vascular smooth muscle cells (VSMCs triggered by inflammatory stimuli and oxidative stress contributes importantly to atherogenesis. The association of green tea consumption with cardiovascular protection has been well documented in epidemiological observations, however, the underlying mechanisms remain unclear. This study aimed to elucidate the effects of the most active green tea catechin derivative, (−-epigallocatechin-3-gallate (EGCG, in human aortic smooth muscle cells (HASMCs, focusing particularly on the role of a potent anti-inflammatory and antioxidative enzyme heme oxygenase-1 (HO-1. We found that pretreatment of EGCG dose- and time-dependently induced HO-1 protein levels in HASMCs. EGCG inhibited interleukin- (IL-1β-induced HASMC proliferation and oxidative stress in a dose-dependent manner. The HO-1 inducer CoPPIX decreased IL-1β-induced cell proliferation, whereas the HO-1 enzyme inhibitor ZnPPIX significantly reversed EGCG-caused growth inhibition in IL-1β-treated HASMCs. At the molecular level, EGCG treatment significantly activated nuclear factor erythroid-2-related factor (Nrf2 transcription activities. These results suggest that EGCG might serve as a complementary and alternative medicine in the treatment of these pathologies by inducing HO-1 expression and subsequently decreasing VSMC proliferation.

  19. Smoothed Analysis of Local Search Algorithms

    NARCIS (Netherlands)

    Manthey, Bodo; Dehne, Frank; Sack, Jörg-Rüdiger; Stege, Ulrike

    2015-01-01

    Smoothed analysis is a method for analyzing the performance of algorithms for which classical worst-case analysis fails to explain the performance observed in practice. Smoothed analysis has been applied to explain the performance of a variety of algorithms in the last years. One particular class of

  20. 16-dimensional smooth projective planes with large collineation groups

    OpenAIRE

    Bödi, Richard

    1998-01-01

    Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch) Smooth projective planes are projective planes defined on smooth manifolds (i.e. the set of points and the set of lines are smooth manifolds) such that the geometric operations of join and intersection are smooth. A systematic study of such planes and of their collineation groups can be found in previous works of the author. We prove in this paper that a 16-dimensional smooth projective plane which admits a ...

  1. Radial Basis Function Based Quadrature over Smooth Surfaces

    Science.gov (United States)

    2016-03-24

    Radial Basis Functions φ(r) Piecewise Smooth (Conditionally Positive Definite) MN Monomial |r|2m+1 TPS thin plate spline |r|2mln|r| Infinitely Smooth...smooth surfaces using polynomial interpolants, while [27] couples Thin - Plate Spline interpolation (see table 1) with Green’s integral formula [29

  2. Non-parametric smoothing of experimental data

    International Nuclear Information System (INIS)

    Kuketayev, A.T.; Pen'kov, F.M.

    2007-01-01

    Full text: Rapid processing of experimental data samples in nuclear physics often requires differentiation in order to find extrema. Therefore, even at the preliminary stage of data analysis, a range of noise reduction methods are used to smooth experimental data. There are many non-parametric smoothing techniques: interval averages, moving averages, exponential smoothing, etc. Nevertheless, it is more common to use a priori information about the behavior of the experimental curve in order to construct smoothing schemes based on the least squares techniques. The latter methodology's advantage is that the area under the curve can be preserved, which is equivalent to conservation of total speed of counting. The disadvantages of this approach include the lack of a priori information. For example, very often the sums of undifferentiated (by a detector) peaks are replaced with one peak during the processing of data, introducing uncontrolled errors in the determination of the physical quantities. The problem is solvable only by having experienced personnel, whose skills are much greater than the challenge. We propose a set of non-parametric techniques, which allows the use of any additional information on the nature of experimental dependence. The method is based on a construction of a functional, which includes both experimental data and a priori information. Minimum of this functional is reached on a non-parametric smoothed curve. Euler (Lagrange) differential equations are constructed for these curves; then their solutions are obtained analytically or numerically. The proposed approach allows for automated processing of nuclear physics data, eliminating the need for highly skilled laboratory personnel. Pursuant to the proposed approach is the possibility to obtain smoothing curves in a given confidence interval, e.g. according to the χ 2 distribution. This approach is applicable when constructing smooth solutions of ill-posed problems, in particular when solving

  3. Role of Myoendothelial Gap Junctions in the Regulation of Human Coronary Artery Smooth Muscle Cell Differentiation by Laminar Shear Stress

    Directory of Open Access Journals (Sweden)

    Zongqi Zhang

    2016-07-01

    Full Text Available Background/Aims: Smooth muscle cells may dedifferentiate into the synthetic phenotype and promote atherosclerosis. Here, we explored the role of myoendothelial gap junctions in phenotypic switching of human coronary artery smooth muscle cells (HCASMCs co-cultured with human coronary artery endothelial cells (HCAECs exposed to shear stress. Methods: HCASMCs and HCAECs were seeded on opposite sides of Transwell inserts, and HCAECs were exposed to laminar shear stress of 12 dyn/cm2 or 5 dyn/cm2. The myoendothelial gap junctions were evaluated by using a multi-photon microscope. Results: In co-culture with HCAECs, HCASMCs exhibited a contractile phenotype, and maintained the expression of differentiation markers MHC and H1-calponin. HCASMCs and HCAECs formed functional intercellular junctions, as evidenced by colocalization of connexin(Cx40 and Cx43 on cellular projections inside the Transwell membrane and biocytin transfer from HCAECs to HCASMCs. Cx40 siRNA and 18-α-GA attenuated protein expression of MHC and H1-calponin in HCASMCs. Shear stress of 5 dyn/cm2 increased Cx43 and decreased Cx40 expression in HCAECs, and partly inhibited biocytin transfer from HCAECs to HCASMCs, which could be completely blocked by Cx43 siRNA or restored by Cx40 DNA transfected into HCAECs. The exposure of HCAECs to shear stress of 5 dyn/cm2 promoted HCASMC phenotypic switching, manifested by morphological changes, decrease in MHC and H1-calponin expression, and increase in platelet-derived growth factor (PDGF-BB release, which was partly rescued by Cx43 siRNA or Cx40 DNA or PDGF receptor signaling inhibitor. Conclusions: The exposure of HCAECs to shear stress of 5 dyn/cm2 caused the dysfunction of Cx40/Cx43 heterotypic myoendothelial gap junctions, which may be replaced by homotypic Cx43/Cx43 channels, and induced HCASMC transition to the synthetic phenotype associated with the activation of PDGF receptor signaling, which may contribute to shear stress

  4. A fibroblast-associated antigen: Characterization in fibroblasts and immunoreactivity in smooth muscle differentiated stromal cells

    DEFF Research Database (Denmark)

    Rønnov-Jessen, Lone; Celis, Julio E.; van Deurs, Bo

    1992-01-01

    major brands migrating at apparent Mr of 38,000, 45,000, and 80,000, in addition to many minor bands between Mr 45,000 and 97,000, including Mr 52,000. The Mr 45,000 and 38,000 were associated with the cell membrane and Mr 52,000 as well as Mr 38,000 were associated with the lysosomes. The 1B10......Fibroblasts with smooth muscle differentiation are frequently derived from human breast tissue. Immunofluorescence cytochemistry of a fibroblast-associated antigen recognized by a monoclonal antibody (MAb), 1B10, was analyzed with a view to discriminating smooth muscle differentiated fibroblasts...

  5. Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzaki, Shinichi [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Ishizuka, Tamotsu, E-mail: tamotsui@showa.gunma-u.ac.jp [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Yamada, Hidenori; Kamide, Yosuke; Hisada, Takeshi; Ichimonji, Isao; Aoki, Haruka; Yatomi, Masakiyo [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Komachi, Mayumi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Tsurumaki, Hiroaki; Ono, Akihiro; Koga, Yasuhiko [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Dobashi, Kunio [Gunma University Graduate School of Health Sciences, Maebashi 371-8511 (Japan); Mogi, Chihiro; Sato, Koichi; Tomura, Hideaki [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Mori, Masatomo [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Okajima, Fumikazu [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)

    2011-10-07

    Highlights: {yields} The involvement of extracellular acidification in airway remodeling was investigated. {yields} Extracellular acidification alone induced CTGF production in human ASMCs. {yields} Extracellular acidification enhanced TGF-{beta}-induced CTGF production in human ASMCs. {yields} Proton-sensing receptor OGR1 was involved in acidic pH-stimulated CTGF production. {yields} OGR1 may play an important role in airway remodeling in asthma. -- Abstract: Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-{beta}-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G{sub q/11} protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP{sub 3}) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G{sub q/11} protein and inositol-1,4,5-trisphosphate-induced Ca{sup 2+} mobilization in human ASMCs.

  6. Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells

    International Nuclear Information System (INIS)

    Matsuzaki, Shinichi; Ishizuka, Tamotsu; Yamada, Hidenori; Kamide, Yosuke; Hisada, Takeshi; Ichimonji, Isao; Aoki, Haruka; Yatomi, Masakiyo; Komachi, Mayumi; Tsurumaki, Hiroaki; Ono, Akihiro; Koga, Yasuhiko; Dobashi, Kunio; Mogi, Chihiro; Sato, Koichi; Tomura, Hideaki; Mori, Masatomo; Okajima, Fumikazu

    2011-01-01

    Highlights: → The involvement of extracellular acidification in airway remodeling was investigated. → Extracellular acidification alone induced CTGF production in human ASMCs. → Extracellular acidification enhanced TGF-β-induced CTGF production in human ASMCs. → Proton-sensing receptor OGR1 was involved in acidic pH-stimulated CTGF production. → OGR1 may play an important role in airway remodeling in asthma. -- Abstract: Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-β-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G q/11 protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP 3 ) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G q/11 protein and inositol-1,4,5-trisphosphate-induced Ca 2+ mobilization in human ASMCs.

  7. Doing smooth pursuit paradigms in Windows 7

    DEFF Research Database (Denmark)

    Wilms, Inge Linda

    predict strengths or deficits in perception and attention. However, smooth pursuit movements have been difficult to study and very little normative data is available for smooth pursuit performance in children and adults. This poster describes the challenges in setting up a smooth pursuit paradigm...... in Windows 7 with live capturing of eye movements using a Tobii TX300 eye tracker. In particular, the poster describes the challenges and limitations created by the hardware and the software...

  8. Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors

    NARCIS (Netherlands)

    Burgess, J. K.; Ketheson, A.; Faiz, A.; Rempel, K. A. Limbert; Oliver, B. G.; Ward, J. P. T.; Halayko, A. J.

    2018-01-01

    Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness

  9. Differential regulation of protease activated receptor-1 and tissue plasminogen activator expression by shear stress in vascular smooth muscle cells

    Science.gov (United States)

    Papadaki, M.; Ruef, J.; Nguyen, K. T.; Li, F.; Patterson, C.; Eskin, S. G.; McIntire, L. V.; Runge, M. S.

    1998-01-01

    Recent studies have demonstrated that vascular smooth muscle cells are responsive to changes in their local hemodynamic environment. The effects of shear stress on the expression of human protease activated receptor-1 (PAR-1) and tissue plasminogen activator (tPA) mRNA and protein were investigated in human aortic smooth muscle cells (HASMCs). Under conditions of low shear stress (5 dyn/cm2), PAR-1 mRNA expression was increased transiently at 2 hours compared with stationary control values, whereas at high shear stress (25 dyn/cm2), mRNA expression was decreased (to 29% of stationary control; Pmuscle cells, indicating that the effects of shear stress on human PAR-1 were not species-specific. Flow cytometry and ELISA techniques using rat smooth muscle cells and HASMCs, respectively, provided evidence that shear stress exerted similar effects on cell surface-associated PAR-1 and tPA protein released into the conditioned media. The decrease in PAR-1 mRNA and protein had functional consequences for HASMCs, such as inhibition of [Ca2+] mobilization in response to thrombin stimulation. These data indicate that human PAR-1 and tPA gene expression are regulated differentially by shear stress, in a pattern consistent with their putative roles in several arterial vascular pathologies.

  10. Nodular smooth muscle metaplasia in multiple peritoneal endometriosis.

    Science.gov (United States)

    Kim, Hyun-Soo; Yoon, Gun; Ha, Sang Yun; Song, Sang Yong

    2015-01-01

    We report here an unusual presentation of peritoneal endometriosis with smooth muscle metaplasia as multiple protruding masses on the lateral pelvic wall. Smooth muscle metaplasia is a common finding in rectovaginal endometriosis, whereas in peritoneal endometriosis, smooth muscle metaplasia is uncommon and its nodular presentation on the pelvic wall is even rarer. To the best of our knowledge, this is the first case of nodular smooth muscle metaplasia occurring in peritoneal endometriosis. As observed in this case, when performing laparoscopic surgery in order to excise malignant tumors of intra-abdominal or pelvic organs, it can be difficult for surgeons to distinguish the metastatic tumors from benign nodular pelvic wall lesions, including endometriosis, based on the gross findings only. Therefore, an intraoperative frozen section biopsy of the pelvic wall nodules should be performed to evaluate the peritoneal involvement by malignant tumors. Moreover, this report implies that peritoneal endometriosis, as well as rectovaginal endometriosis, can clinically present as nodular lesions if obvious smooth muscle metaplasia is present. The pathological investigation of smooth muscle cells in peritoneal lesions can contribute not only to the precise diagnosis but also to the structure and function of smooth muscle cells and related cells involved in the histogenesis of peritoneal endometriosis.

  11. Smooth pursuit eye movements and schizophrenia: literature review.

    Science.gov (United States)

    Franco, J G; de Pablo, J; Gaviria, A M; Sepúlveda, E; Vilella, E

    2014-09-01

    To review the scientific literature about the relationship between impairment on smooth pursuit eye movements and schizophrenia. Narrative review that includes historical articles, reports about basic and clinical investigation, systematic reviews, and meta-analysis on the topic. Up to 80% of schizophrenic patients have impairment of smooth pursuit eye movements. Despite the diversity of test protocols, 65% of patients and controls are correctly classified by their overall performance during this pursuit. The smooth pursuit eye movements depend on the ability to anticipate the target's velocity and the visual feedback, as well as on learning and attention. The neuroanatomy implicated in smooth pursuit overlaps to some extent with certain frontal cortex zones associated with some clinical and neuropsychological characteristics of the schizophrenia, therefore some specific components of smooth pursuit anomalies could serve as biomarkers of the disease. Due to their sedative effect, antipsychotics have a deleterious effect on smooth pursuit eye movements, thus these movements cannot be used to evaluate the efficacy of the currently available treatments. Standardized evaluation of smooth pursuit eye movements on schizophrenia will allow to use specific aspects of that pursuit as biomarkers for the study of its genetics, psychopathology, or neuropsychology. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  12. Smoothing-Norm Preconditioning for Regularizing Minimum-Residual Methods

    DEFF Research Database (Denmark)

    Hansen, Per Christian; Jensen, Toke Koldborg

    2006-01-01

    take into account a smoothing norm for the solution. This technique is well established for CGLS, but it does not immediately carry over to minimum-residual methods when the smoothing norm is a seminorm or a Sobolev norm. We develop a new technique which works for any smoothing norm of the form $\\|L...

  13. Bifurcation theory for finitely smooth planar autonomous differential systems

    Science.gov (United States)

    Han, Maoan; Sheng, Lijuan; Zhang, Xiang

    2018-03-01

    In this paper we establish bifurcation theory of limit cycles for planar Ck smooth autonomous differential systems, with k ∈ N. The key point is to study the smoothness of bifurcation functions which are basic and important tool on the study of Hopf bifurcation at a fine focus or a center, and of Poincaré bifurcation in a period annulus. We especially study the smoothness of the first order Melnikov function in degenerate Hopf bifurcation at an elementary center. As we know, the smoothness problem was solved for analytic and C∞ differential systems, but it was not tackled for finitely smooth differential systems. Here, we present their optimal regularity of these bifurcation functions and their asymptotic expressions in the finite smooth case.

  14. Smooth solutions of the Navier-Stokes equations

    International Nuclear Information System (INIS)

    Pokhozhaev, S I

    2014-01-01

    We consider smooth solutions of the Cauchy problem for the Navier-Stokes equations on the scale of smooth functions which are periodic with respect to x∈R 3 . We obtain existence theorems for global (with respect to t>0) and local solutions of the Cauchy problem. The statements of these depend on the smoothness and the norm of the initial vector function. Upper bounds for the behaviour of solutions in both classes, which depend on t, are also obtained. Bibliography: 10 titles

  15. Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors.

    Science.gov (United States)

    Burgess, J K; Ketheson, A; Faiz, A; Limbert Rempel, K A; Oliver, B G; Ward, J P T; Halayko, A J

    2018-01-16

    Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness of hTERT immortalisation of human ASM cells as a research tool. Specifically we compared proliferative capacity, inflammatory mediator release and extracellular matrix (ECM) production in hTERT immortalised and parent primary ASM cells from asthmatic and non-asthmatic donors. Our studies revealed no significant differences in proliferation, IL-6 and eotaxin-1 production, or CTGF synthesis between donor-matched parent and hTERT immortalised ASM cell lines. However, deposition of ECM proteins fibronectin and fibulin-1 was significantly lower in immortalised ASM cells compared to corresponding primary cells. Notably, previously reported differences in proliferation and inflammatory mediator release between asthmatic and non-asthmatic ASM cells were retained, but excessive ECM protein deposition in asthmatic ASM cells was lost in hTERT ASM cells. This study shows that hTERT immortalised ASM cells mirror primary ASM cells in proliferation and inflammatory profile characteristics. Moreover, we demonstrate both strengths and weaknesses of this immortalised cell model as a representation of primary ASM cells for future asthma pathophysiological research.

  16. A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening.

    Science.gov (United States)

    An, Steven S; Askovich, Peter S; Zarembinski, Thomas I; Ahn, Kwangmi; Peltier, John M; von Rechenberg, Moritz; Sahasrabudhe, Sudhir; Fredberg, Jeffrey J

    2011-01-13

    A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20) and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma. Using a high-throughput fluorescence polarization (FP) assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM). Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds. Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell in vitro and attenuated active force development of intact tissue ex vivo. This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.

  17. A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening

    Directory of Open Access Journals (Sweden)

    von Rechenberg Moritz

    2011-01-01

    Full Text Available Abstract Background A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20 and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma. Methods Using a high-throughput fluorescence polarization (FP assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM. Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds. Results Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell in vitro and attenuated active force development of intact tissue ex vivo. Conclusions This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.

  18. Quantum key distribution with finite resources: Smooth Min entropy vs. Smooth Renyi entropy

    Energy Technology Data Exchange (ETDEWEB)

    Mertz, Markus; Abruzzo, Silvestre; Bratzik, Sylvia; Kampermann, Hermann; Bruss, Dagmar [Institut fuer Theoretische Physik III, Duesseldorf (Germany)

    2010-07-01

    We consider different entropy measures that play an important role in the analysis of the security of QKD with finite resources. The smooth min entropy leads to an optimal bound for the length of a secure key. Another bound on the secure key length was derived by using Renyi entropies. Unfortunately, it is very hard or even impossible to calculate these entropies for realistic QKD scenarios. To estimate the security rate it becomes important to find computable bounds on these entropies. Here, we compare a lower bound for the smooth min entropy with a bound using Renyi entropies. We compare these entropies for the six-state protocol with symmetric attacks.

  19. Artichoke, Cynarin and Cyanidin Downregulate the Expression of Inducible Nitric Oxide Synthase in Human Coronary Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Ning Xia

    2014-03-01

    Full Text Available Artichoke (Cynara scolymus L. is one of the world’s oldest medicinal plants with multiple health benefits. We have previously shown that artichoke leaf extracts and artichoke flavonoids upregulate the gene expression of endothelial-type nitric oxide synthase (eNOS in human endothelial cells. Whereas NO produced by the eNOS is a vasoprotective molecule, NO derived from the inducible iNOS plays a pro-inflammatory role in the vasculature. The present study was aimed to investigate the effects of artichoke on iNOS expression in human coronary artery smooth muscle cells (HCASMC. Incubation of HCASMC with a cytokine mixture led to an induction of iNOS mRNA expression. This iNOS induction was concentration- and time-dependently inhibited by an artichoke leaf extract (1–100 µg/mL, 6 h or 24 h. Consistently, the artichoke leaf extract also reduced cytokine-induced iNOS promoter activation and iNOS protein expression. In addition, treatment of HCASMC with four well-known artichoke compounds (cynarin > cyanidin > luteolin ≈ cynaroside led to a downregulation iNOS mRNA and protein expression, with cynarin being the most potent one. In conclusion, artichoke contains both eNOS-upregulating and iNOS-downregulating compounds. Such compounds may contribute to the beneficial effects of artichoke and may per se have therapeutic potentials.

  20. Artichoke, cynarin and cyanidin downregulate the expression of inducible nitric oxide synthase in human coronary smooth muscle cells.

    Science.gov (United States)

    Xia, Ning; Pautz, Andrea; Wollscheid, Ursula; Reifenberg, Gisela; Förstermann, Ulrich; Li, Huige

    2014-03-24

    Artichoke (Cynara scolymus L.) is one of the world's oldest medicinal plants with multiple health benefits. We have previously shown that artichoke leaf extracts and artichoke flavonoids upregulate the gene expression of endothelial-type nitric oxide synthase (eNOS) in human endothelial cells. Whereas NO produced by the eNOS is a vasoprotective molecule, NO derived from the inducible iNOS plays a pro-inflammatory role in the vasculature. The present study was aimed to investigate the effects of artichoke on iNOS expression in human coronary artery smooth muscle cells (HCASMC). Incubation of HCASMC with a cytokine mixture led to an induction of iNOS mRNA expression. This iNOS induction was concentration- and time-dependently inhibited by an artichoke leaf extract (1-100 µg/mL, 6 h or 24 h). Consistently, the artichoke leaf extract also reduced cytokine-induced iNOS promoter activation and iNOS protein expression. In addition, treatment of HCASMC with four well-known artichoke compounds (cynarin > cyanidin > luteolin ≈ cynaroside) led to a downregulation iNOS mRNA and protein expression, with cynarin being the most potent one. In conclusion, artichoke contains both eNOS-upregulating and iNOS-downregulating compounds. Such compounds may contribute to the beneficial effects of artichoke and may per se have therapeutic potentials.

  1. Smoothness without smoothing: why Gaussian naive Bayes is not naive for multi-subject searchlight studies.

    Directory of Open Access Journals (Sweden)

    Rajeev D S Raizada

    Full Text Available Spatial smoothness is helpful when averaging fMRI signals across multiple subjects, as it allows different subjects' corresponding brain areas to be pooled together even if they are slightly misaligned. However, smoothing is usually not applied when performing multivoxel pattern-based analyses (MVPA, as it runs the risk of blurring away the information that fine-grained spatial patterns contain. It would therefore be desirable, if possible, to carry out pattern-based analyses which take unsmoothed data as their input but which produce smooth images as output. We show here that the Gaussian Naive Bayes (GNB classifier does precisely this, when it is used in "searchlight" pattern-based analyses. We explain why this occurs, and illustrate the effect in real fMRI data. Moreover, we show that analyses using GNBs produce results at the multi-subject level which are statistically robust, neurally plausible, and which replicate across two independent data sets. By contrast, SVM classifiers applied to the same data do not generate a replication, even if the SVM-derived searchlight maps have smoothing applied to them. An additional advantage of GNB classifiers for searchlight analyses is that they are orders of magnitude faster to compute than more complex alternatives such as SVMs. Collectively, these results suggest that Gaussian Naive Bayes classifiers may be a highly non-naive choice for multi-subject pattern-based fMRI studies.

  2. microRNA expression profile in human coronary smooth muscle cell-derived microparticles is a source of biomarkers.

    Science.gov (United States)

    de Gonzalo-Calvo, David; Cenarro, Ana; Civeira, Fernando; Llorente-Cortes, Vicenta

    2016-01-01

    microRNA (miRNA) expression profile of extracellular vesicles is a potential tool for clinical practice. Despite the key role of vascular smooth muscle cells (VSMC) in cardiovascular pathology, there is limited information about the presence of miRNAs in microparticles secreted by this cell type, including human coronary artery smooth muscle cells (HCASMC). Here, we tested whether HCASMC-derived microparticles contain miRNAs and the value of these miRNAs as biomarkers. HCASMC and explants from atherosclerotic or non-atherosclerotic areas were obtained from coronary arteries of patients undergoing heart transplant. Plasma samples were collected from: normocholesterolemic controls (N=12) and familial hypercholesterolemia (FH) patients (N=12). Both groups were strictly matched for age, sex and cardiovascular risk factors. Microparticle (0.1-1μm) isolation and characterization was performed using standard techniques. VSMC-enriched miRNAs expression (miR-21-5p, -143-3p, -145-5p, -221-3p and -222-3p) was analyzed using RT-qPCR. Total RNA isolated from HCASMC-derived microparticles contained small RNAs, including VSMC-enriched miRNAs. Exposition of HCASMC to pathophysiological conditions, such as hypercholesterolemia, induced a decrease in the expression level of miR-143-3p and miR-222-3p in microparticles, not in cells. Expression levels of miR-222-3p were lower in circulating microparticles from FH patients compared to normocholesterolemic controls. Microparticles derived from atherosclerotic plaque areas showed a decreased level of miR-143-3p and miR-222-3p compared to non-atherosclerotic areas. We demonstrated for the first time that microparticles secreted by HCASMC contain microRNAs. Hypercholesterolemia alters the microRNA profile of HCASMC-derived microparticles. The miRNA signature of HCASMC-derived microparticles is a source of cardiovascular biomarkers. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights

  3. Basic mechanisms of urgency: roles and benefits of pharmacotherapy.

    Science.gov (United States)

    Michel, Martin Christian; Chapple, Christopher R

    2009-12-01

    Since urgency is key to the overactive bladder syndrome, we have reviewed the mechanisms underlying how bladder filling and urgency are sensed, what causes urgency and how this relates to medical therapy. Review of published literature. As urgency can only be assessed in cognitively intact humans, mechanistic studies of urgency often rely on proxy or surrogate parameters, such as detrusor overactivity, but these may not necessarily be reliable. There is an increasing evidence base to suggest that the sensation of ‘urgency’ differs from the normal physiological urge to void upon bladder filling. While the relative roles of alterations in afferent processes, central nervous processing, efferent mechanisms and in intrinsic bladder smooth muscle function remain unclear, and not necessarily mutually exclusive, several lines of evidence support an important role for the latter. A better understanding of urgency and its causes may help to develop more effective treatments for voiding dysfunction.

  4. Some splines produced by smooth interpolation

    Czech Academy of Sciences Publication Activity Database

    Segeth, Karel

    2018-01-01

    Roč. 319, 15 February (2018), s. 387-394 ISSN 0096-3003 R&D Projects: GA ČR GA14-02067S Institutional support: RVO:67985840 Keywords : smooth data approximation * smooth data interpolation * cubic spline Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 1.738, year: 2016 http://www. science direct.com/ science /article/pii/S0096300317302746?via%3Dihub

  5. Some splines produced by smooth interpolation

    Czech Academy of Sciences Publication Activity Database

    Segeth, Karel

    2018-01-01

    Roč. 319, 15 February (2018), s. 387-394 ISSN 0096-3003 R&D Projects: GA ČR GA14-02067S Institutional support: RVO:67985840 Keywords : smooth data approximation * smooth data interpolation * cubic spline Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 1.738, year: 2016 http://www.sciencedirect.com/science/article/pii/S0096300317302746?via%3Dihub

  6. Early Transcriptomic Response to LDL and oxLDL in Human Vascular Smooth Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Salvador Damián-Zamacona

    Full Text Available Although nowadays it is well known that the human transcriptome can importantly vary according to external or environmental condition, the reflection of this concept when studying oxidative stress and its direct relationship with gene expression profiling during the process of atherogenesis has not been thoroughly achieved.The ability to analyze genome-wide gene expression through transcriptomics has shown that the genome responds dynamically to diverse stimuli. Here, we describe the transcriptome of human vascular smooth muscle cells (hVSMC stimulated by native and oxidized low-density lipoprotein (nLDL and oxLDL respectively, with the aim of assessing the early molecular changes that induce a response in this cell type resulting in a transcriptomic transformation. This expression has been demonstrated in atherosclerotic plaques in vivo and in vitro, particularly in the light of the oxidative modification hypothesis of atherosclerosis.Total RNA was isolated with TRIzol reagent (Life Technologies and quality estimated using an Agilent 2100 bioanalyzer. The transcriptome of hVSMC under different experimental conditions (1,5 and 24 hours for nLDL and oxLDL was obtained using the GeneChip Human Gene 1.0 ST (Affymetrix designed to measure gene expression of 28,869 well-annotated genes. A fixed fold-change cut-off corresponding to ± 2 was used to identify genes exhibiting the most significant variation and statistical significance (P< 0.05, and 8 genes validated by qPCR using Taqman probes.10 molecular processes were significantly affected in hVSMC: Apoptosis and cell cycle, extracellular matrix remodeling, DNA repair, cholesterol efflux, cGMP biosynthesis, endocytic mechanisms, calcium homeostasis, redox balance, membrane trafficking and finally, the immune response to inflammation. The evidence we present supporting the hypothesis for the involvement of oxidative modification of several processes and metabolic pathways in atherosclerosis is

  7. Smooth Phase Interpolated Keying

    Science.gov (United States)

    Borah, Deva K.

    2007-01-01

    Smooth phase interpolated keying (SPIK) is an improved method of computing smooth phase-modulation waveforms for radio communication systems that convey digital information. SPIK is applicable to a variety of phase-shift-keying (PSK) modulation schemes, including quaternary PSK (QPSK), octonary PSK (8PSK), and 16PSK. In comparison with a related prior method, SPIK offers advantages of better performance and less complexity of implementation. In a PSK scheme, the underlying information waveform that one seeks to convey consists of discrete rectangular steps, but the spectral width of such a waveform is excessive for practical radio communication. Therefore, the problem is to smooth the step phase waveform in such a manner as to maintain power and bandwidth efficiency without incurring an unacceptably large error rate and without introducing undesired variations in the amplitude of the affected radio signal. Although the ideal constellation of PSK phasor points does not cause amplitude variations, filtering of the modulation waveform (in which, typically, a rectangular pulse is converted to a square-root raised cosine pulse) causes amplitude fluctuations. If a power-efficient nonlinear amplifier is used in the radio communication system, the fluctuating-amplitude signal can undergo significant spectral regrowth, thus compromising the bandwidth efficiency of the system. In the related prior method, one seeks to solve the problem in a procedure that comprises two major steps: phase-value generation and phase interpolation. SPIK follows the two-step approach of the related prior method, but the details of the steps are different. In the phase-value-generation step, the phase values of symbols in the PSK constellation are determined by a phase function that is said to be maximally smooth and that is chosen to minimize the spectral spread of the modulated signal. In this step, the constellation is divided into two groups by assigning, to information symbols, phase values

  8. Efficient computation of smoothing splines via adaptive basis sampling

    KAUST Repository

    Ma, Ping

    2015-06-24

    © 2015 Biometrika Trust. Smoothing splines provide flexible nonparametric regression estimators. However, the high computational cost of smoothing splines for large datasets has hindered their wide application. In this article, we develop a new method, named adaptive basis sampling, for efficient computation of smoothing splines in super-large samples. Except for the univariate case where the Reinsch algorithm is applicable, a smoothing spline for a regression problem with sample size n can be expressed as a linear combination of n basis functions and its computational complexity is generally O(n3). We achieve a more scalable computation in the multivariate case by evaluating the smoothing spline using a smaller set of basis functions, obtained by an adaptive sampling scheme that uses values of the response variable. Our asymptotic analysis shows that smoothing splines computed via adaptive basis sampling converge to the true function at the same rate as full basis smoothing splines. Using simulation studies and a large-scale deep earth core-mantle boundary imaging study, we show that the proposed method outperforms a sampling method that does not use the values of response variables.

  9. Efficient computation of smoothing splines via adaptive basis sampling

    KAUST Repository

    Ma, Ping; Huang, Jianhua Z.; Zhang, Nan

    2015-01-01

    © 2015 Biometrika Trust. Smoothing splines provide flexible nonparametric regression estimators. However, the high computational cost of smoothing splines for large datasets has hindered their wide application. In this article, we develop a new method, named adaptive basis sampling, for efficient computation of smoothing splines in super-large samples. Except for the univariate case where the Reinsch algorithm is applicable, a smoothing spline for a regression problem with sample size n can be expressed as a linear combination of n basis functions and its computational complexity is generally O(n3). We achieve a more scalable computation in the multivariate case by evaluating the smoothing spline using a smaller set of basis functions, obtained by an adaptive sampling scheme that uses values of the response variable. Our asymptotic analysis shows that smoothing splines computed via adaptive basis sampling converge to the true function at the same rate as full basis smoothing splines. Using simulation studies and a large-scale deep earth core-mantle boundary imaging study, we show that the proposed method outperforms a sampling method that does not use the values of response variables.

  10. The Smoothing Hypothesis, Stock Returns and Risk in Brazil

    Directory of Open Access Journals (Sweden)

    Antonio Lopo Martinez

    2011-01-01

    Full Text Available Income smoothing is defined as the deliberate normalization of income in order to reach a desired trend. If the smoothing causes more information to be reflected in the stock price, it is likely to improve the allocation of resources and can be a critical factor in investment decisions. This study aims to build metrics to determine the degree of smoothing in Brazilian public companies, to classify them as smoothing and non-smoothing companies and additionally to present evidence on the long-term relationship between the smoothing hypothesis and stock return and risk. Using the Economatica and CVM databases, this study focuses on 145 companies in the period 1998-2007. We find that Brazilian smoothers have a smaller degree of systemic risk than non-smoothers. In average terms, the beta of smoothers is significantly lower than non-smoothers. Regarding return, we find that the abnormal annualized returns of smoothers are significantly higher. We confirm differences in the groups by nonparametric and parametric tests in cross section or as time series, indicating that there is a statistically significant difference in performance in the Brazilian market between firms that do and do not engage in smoothing.

  11. Investigation of angular and axial smoothing of PET data

    International Nuclear Information System (INIS)

    Daube-Witherspoon, M.E.; Carson, R.E.

    1996-01-01

    Radial filtering of emission and transmission data is routinely performed in PET during reconstruction in order to reduce image noise. Angular smoothing is not typically done, due to the introduction of a non-uniform resolution loss; axial filtering is also not usually performed on data acquired in 2D mode. The goal of this paper was to assess the effects of angular and axial smoothing on noise and resolution. Angular and axial smoothing was incorporated into the reconstruction process on the Scanditronix PC2048-15B brain PET scanner. In-plane spatial resolution and noise reduction were measured for different amounts of radial and angular smoothing. For radial positions away from the center of the scanner, noise reduction and degraded tangential resolution with no loss of radial resolution were seen. Near the center, no resolution loss was observed, but there was also no reduction in noise for angular filters up to a 7 degrees FWHM. These results can be understood by considering the combined effects of smoothing projections across rows (angles) and then summing (backprojecting). Thus, angular smoothing is not optimal due to its anisotropic noise reduction and resolution degradation properties. However, uniform noise reduction comparable to that seen with radial filtering can be achieved with axial smoothing of transmission data. The axial results suggest that combined radial and axial transmission smoothing could lead to improved noise characteristics with more isotropic resolution degradation

  12. Mechanisms of mechanical strain memory in airway smooth muscle.

    Science.gov (United States)

    Kim, Hak Rim; Hai, Chi-Ming

    2005-10-01

    We evaluated the hypothesis that mechanical deformation of airway smooth muscle induces structural remodeling of airway smooth muscle cells, thereby modulating mechanical performance in subsequent contractions. This hypothesis implied that past experience of mechanical deformation was retained (or "memorized") as structural changes in airway smooth muscle cells, which modulated the cell's subsequent contractile responses. We termed this phenomenon mechanical strain memory. Preshortening has been found to induce attenuation of both force and isotonic shortening velocity in cholinergic receptor-activated airway smooth muscle. Rapid stretching of cholinergic receptor-activated airway smooth muscle from an initial length to a final length resulted in post-stretch force and myosin light chain phosphorylation that correlated significantly with initial length. Thus post-stretch muscle strips appeared to retain memory of the initial length prior to rapid stretch (mechanical strain memory). Cytoskeletal recruitment of actin- and integrin-binding proteins and Erk 1/2 MAPK appeared to be important mechanisms of mechanical strain memory. Sinusoidal length oscillation led to force attenuation during oscillation and in subsequent contractions in intact airway smooth muscle, and p38 MAPK appeared to be an important mechanism. In contrast, application of local mechanical strain to cultured airway smooth muscle cells induced local actin polymerization and cytoskeletal stiffening. It is conceivable that deep inspiration-induced bronchoprotection may be a manifestation of mechanical strain memory such that mechanical deformation from past breathing cycles modulated the mechanical performance of airway smooth muscle in subsequent cycles in a continuous and dynamic manner.

  13. Observations on human smooth muscle cell cultures from hyperplastic lesions of prosthetic bypass grafts: Production of a platelet-derived growth factor-like mitogen and expression of a gene for a platelet-derived growth factor receptor--a preliminary study

    International Nuclear Information System (INIS)

    Birinyi, L.K.; Warner, S.J.; Salomon, R.N.; Callow, A.D.; Libby, P.

    1989-01-01

    Prosthetic bypass grafts placed to the distal lower extremity often fail because of an occlusive tissue response in the perianastomotic region. The origin of the cells that comprise this occlusive lesion and the causes of the cellular proliferation are not known. To increase our understanding of this process we cultured cells from hyperplastic lesions obtained from patients at the time of reexploration for lower extremity graft failure, and we studied their identity and growth factor production in tissue culture. These cultures contain cells that express muscle-specific actin isoforms, shown by immunohistochemical staining, consistent with vascular smooth muscle origin. These cultures also released material that stimulated smooth muscle cell growth. A portion of this activity was similar to platelet-derived growth factor, since preincubation with antibody-to-human platelet-derived growth factor partially blocked the mitogenic effect of medium conditioned by human anastomotic hyperplastic cells. These conditioned media also contained material that competed with platelet-derived growth factor for its receptor, as measured in a radioreceptor assay. Northern blot analysis showed that these cells contain messenger RNA that encodes the A chain but not the B chain of platelet-derived growth factor. In addition, these cells contain messenger RNA that encodes a platelet-derived growth factor receptor. We conclude that cultured smooth muscle cells from human anastomotic hyperplastic lesions express genes for platelet-derived growth factor A chain and a platelet-derived growth factor receptor and secrete biologically active molecules similar to platelet-derived growth factor

  14. Surface smoothness

    DEFF Research Database (Denmark)

    Tummala, Sudhakar; Dam, Erik B.

    2010-01-01

    accuracy, such novel markers must therefore be validated against clinically meaningful end-goals such as the ability to allow correct diagnosis. We present a method for automatic cartilage surface smoothness quantification in the knee joint. The quantification is based on a curvature flow method used....... We demonstrate that the fully automatic markers eliminate the time required for radiologist annotations, and in addition provide a diagnostic marker superior to the evaluated semi-manual markers....

  15. Effects of nifedipine on anorectal smooth muscle in vitro.

    Science.gov (United States)

    Cook, T A; Brading, A F; Mortensen, N J

    1999-06-01

    Glyceryl trinitrate reduces anal resting pressure and aids the healing of anal fissures. However, some patients develop tachyphylaxis and the fissure fails to heal, suggesting that other agents are needed. This study assesses the effects of nifedipine (a calcium channel antagonist) in modulating resting tone and agonist-induced contractions in human internal anal sphincter (IAS) and rectal circular muscle. Smooth muscle strips from the IAS and rectal circular muscle from ten patients undergoing surgical resection were mounted for isometric tension recording in a superfusion organ bath. The effects of noradrenaline and carbachol were assessed in the presence of various perfusates. LAS strips developed tone and spontaneous activity. Noradrenaline produced dose-dependent contractions. In calcium-free Krebs solution, tone and activity were abolished and no contractions were elicited in response to noradrenaline. Nifedipine also abolished tone and spontaneous activity, but contractions to noradrenaline were only slightly attenuated. In contrast, rectal smooth muscle strips developed spontaneous activity but no resting tone and contracted in response to carbachol. In calcium-free Krebs solution, the spontaneous activity and carbachol contractions were abolished. Addition of nifedipine to the perfusate abolished spontaneous activity and greatly reduced contractions. These data suggest that spontaneous activity and resting tone are dependent on extracellular calcium and flux across the cells. Agonist-induced contraction in the IAS is attributable mainly to the release of calcium from intracellular stores, whereas rectal circular smooth muscle depends principally on extracellular calcium entering the cell for contraction. The attenuation of contractions in both tissues and the abolition of resting tone in the IAS suggest that nifedipine may be useful in the management of patients with anorectal disorders.

  16. Experimental investigation of smoothing by spectral dispersion

    International Nuclear Information System (INIS)

    Regan, Sean P.; Marozas, John A.; Kelly, John H.; Boehly, Thomas R.; Donaldson, William R.; Jaanimagi, Paul A.; Keck, Robert L.; Kessler, Terrance J.; Meyerhofer, David D.; Seka, Wolf

    2000-01-01

    Measurements of smoothing rates for smoothing by spectral dispersion (SSD) of high-power, solid-state laser beams used for inertial confinement fusion (ICF) research are reported. Smoothing rates were obtained from the intensity distributions of equivalent target plane images for laser pulses of varying duration. Simulations of the experimental data with the known properties of the phase plates and the frequency modulators are in good agreement with the experimental data. These results inspire confidence in extrapolating to higher bandwidths and other SSD configurations that may be suitable for ICF experiments and ultimately for direct-drive laser-fusion ignition. (c) 2000 Optical Society of America

  17. Fast compact algorithms and software for spline smoothing

    CERN Document Server

    Weinert, Howard L

    2012-01-01

    Fast Compact Algorithms and Software for Spline Smoothing investigates algorithmic alternatives for computing cubic smoothing splines when the amount of smoothing is determined automatically by minimizing the generalized cross-validation score. These algorithms are based on Cholesky factorization, QR factorization, or the fast Fourier transform. All algorithms are implemented in MATLAB and are compared based on speed, memory use, and accuracy. An overall best algorithm is identified, which allows very large data sets to be processed quickly on a personal computer.

  18. Direct numerical simulation of open channel flow over smooth-to-rough and rough-to-smooth step changes

    Science.gov (United States)

    Rouhi, Amirreza; Chung, Daniel; Hutchins, Nicholas

    2017-11-01

    Direct numerical simulations (DNSs) are reported for open channel flow over streamwise-alternating patches of smooth and fully rough walls. Owing to the streamwise periodicity, the flow configuration is composed of a step change from smooth to rough, and a step change from rough to smooth. The friction Reynolds number varies from 443 over the smooth patch to 715 over the rough patch. The flow is thoroughly studied by mean and fluctuation profiles, and spectrograms. The detailed flow from DNS reveals discrepancies of up to 50% among the various definitions of the internal-layer thickness, with apparent power-law exponents differing by up to 60%. The definition based on the logarithmic slope of the velocity profile, as proposed by Chamorro et al. (Boundary-Layer Meteorol., vol. 130, 2009, pp. 29-41), is most consistent with the physical notion of the internal layer; this is supported by the defect similarity based on this internal-layer thickness, and the streamwise homogeneity of the dissipation length-scale within this internal layer. The statistics inside this internal-layer, and the growth of the internal layer itself, are minimally affected by the streamwise periodicity when the patch length is at least six times the channel height.

  19. CURRENT OPPORTUNITIES FOR COMBINATION TREATMENT OF LOWER URINARY TRACT SYMPTOMS DUE TO BENIGN PROSTATIC HYPERPLASIA IN MEN

    Directory of Open Access Journals (Sweden)

    G. R. Kasyan

    2016-01-01

    Full Text Available Lower urinary tract symptoms (LUTS associated with benign prostatic hyperplasia (BPH are widely presented, particularly among elderly men. It was commonly accepted that LUTS are directly or indirectly connected with the prostate. Recent studies have shown that mild andsevere forms of LUTS may have a different etiology, such as, bladder related problems: overactive bladder (OAB/detrusor overactivity or, conversely, an underactive bladder due to compromised contractions of the detrusor. There are three main groups of LUTS: storage symptoms, voiding symptoms and post-micturition symptoms. Patients with LUTS/BPH who are not sufficiently respond to monotherapy with alpha-blockers should receive additional treatment with M‑anticholinergics in accordance with the European urological guidelines. Current studies show that up to 65% of patients with LUTS/BPH with symptoms of urgency and frequency do not have sufficient reduction of symptoms after 3 months of treatment with alphablocker as monotherapy. Until recently, alpha-blockers and M‑anticholinergic medications were prescribed in combination therapy as a two separate pills. Vesomni is a combination of antimuscarinic drug solifenacin 6 mg with α1‑blocker tamsulosin OCAS 0.4 mg in one tablet. It is developed to relieve storage (urgency and frequency and voiding symptoms in men with LUTS/BPH. Solifenacin suppresses the overactivity of the detrusor and reduces storage symptoms. Tamsulosin OCAS relaxes smooth muscle of the prostate, prostatic urethra and bladder neck, and eliminates most voiding symptoms and, to a lesser extent, storage symptoms.

  20. Revealed smooth nontransitive preferences

    DEFF Research Database (Denmark)

    Keiding, Hans; Tvede, Mich

    2013-01-01

    In the present paper, we are concerned with the behavioural consequences of consumers having nontransitive preference relations. Data sets consist of finitely many observations of price vectors and consumption bundles. A preference relation rationalizes a data set provided that for every observed...... consumption bundle, all strictly preferred bundles are more expensive than the observed bundle. Our main result is that data sets can be rationalized by a smooth nontransitive preference relation if and only if prices can normalized such that the law of demand is satisfied. Market data sets consist of finitely...... many observations of price vectors, lists of individual incomes and aggregate demands. We apply our main result to characterize market data sets consistent with equilibrium behaviour of pure-exchange economies with smooth nontransitive consumers....

  1. Generalizing smooth transition autoregressions

    DEFF Research Database (Denmark)

    Chini, Emilio Zanetti

    We introduce a variant of the smooth transition autoregression - the GSTAR model - capable to parametrize the asymmetry in the tails of the transition equation by using a particular generalization of the logistic function. A General-to-Specific modelling strategy is discussed in detail, with part......We introduce a variant of the smooth transition autoregression - the GSTAR model - capable to parametrize the asymmetry in the tails of the transition equation by using a particular generalization of the logistic function. A General-to-Specific modelling strategy is discussed in detail......, with particular emphasis on two different LM-type tests for the null of symmetric adjustment towards a new regime and three diagnostic tests, whose power properties are explored via Monte Carlo experiments. Four classical real datasets illustrate the empirical properties of the GSTAR, jointly to a rolling...

  2. Effects of contrast on smooth pursuit eye movements.

    Science.gov (United States)

    Spering, Miriam; Kerzel, Dirk; Braun, Doris I; Hawken, Michael J; Gegenfurtner, Karl R

    2005-05-20

    It is well known that moving stimuli can appear to move more slowly when contrast is reduced (P. Thompson, 1982). Here we address the question whether changes in stimulus contrast also affect smooth pursuit eye movements. Subjects were asked to smoothly track a moving Gabor patch. Targets varied in velocity (1, 8, and 15 deg/s), spatial frequency (0.1, 1, 4, and 8 c/deg), and contrast, ranging from just below individual thresholds to maximum contrast. Results show that smooth pursuit eye velocity gain rose significantly with increasing contrast. Below a contrast level of two to three times threshold, pursuit gain, acceleration, latency, and positional accuracy were severely impaired. Therefore, the smooth pursuit motor response shows the same kind of slowing at low contrast that was demonstrated in previous studies on perception.

  3. Smooth incidence maps give valuable insight into Q fever outbreaks in The Netherlands

    Directory of Open Access Journals (Sweden)

    Wim van der Hoek

    2012-11-01

    Full Text Available From 2007 through 2009, The Netherlands faced large outbreaks of human Q fever. Control measures focused primarily on dairy goat farms because these were implicated as the main source of infection for the surrounding population. However, in other countries, outbreaks have mainly been associated with non-dairy sheep and The Netherlands has many more sheep than goats. Therefore, a public discussion arose about the possible role of non-dairy (meat sheep in the outbreaks. To inform decision makers about the relative importance of different infection sources, we developed accurate and high-resolution incidence maps for detection of Q fever hot spots. In the high incidence area in the south of the country, full postal codes of notified Q fever patients with onset of illness in 2009, were georeferenced. Q fever cases (n = 1,740 were treated as a spatial point process. A 500 x 500 m grid was imposed over the area of interest. The number of cases and the population number were counted in each cell. The number of cases was modelled as an inhomogeneous Poisson process where the underlying incidence was estimated by 2-dimensional P-spline smoothing. Modelling of numbers of Q fever cases based on residential addresses and population size produced smooth incidence maps that clearly showed Q fever hotspots around infected dairy goat farms. No such increased incidence was noted around infected meat sheep farms. We conclude that smooth incidence maps of human notifications give valuable information about the Q fever epidemic and are a promising method to provide decision support for the control of other infectious diseases with an environmental source.

  4. Polarization beam smoothing for inertial confinement fusion

    International Nuclear Information System (INIS)

    Rothenberg, Joshua E.

    2000-01-01

    For both direct and indirect drive approaches to inertial confinement fusion (ICF) it is imperative to obtain the best possible drive beam uniformity. The approach chosen for the National Ignition Facility uses a random-phase plate to generate a speckle pattern with a precisely controlled envelope on target. A number of temporal smoothing techniques can then be employed to utilize bandwidth to rapidly change the speckle pattern, and thus average out the small-scale speckle structure. One technique which generally can supplement other smoothing methods is polarization smoothing (PS): the illumination of the target with two distinct and orthogonally polarized speckle patterns. Since these two polarizations do not interfere, the intensity patterns add incoherently, and the rms nonuniformity can be reduced by a factor of (√2). A number of PS schemes are described and compared on the basis of the aggregate rms and the spatial spectrum of the focused illumination distribution. The (√2) rms nonuniformity reduction of PS is present on an instantaneous basis and is, therefore, of particular interest for the suppression of laser plasma instabilities, which have a very rapid response time. When combining PS and temporal methods, such as smoothing by spectral dispersion (SSD), PS can reduce the rms of the temporally smoothed illumination by an additional factor of (√2). However, it has generally been thought that in order to achieve this reduction of (√2), the increased divergence of the beam from PS must exceed the divergence of SSD. It is also shown here that, over the time scales of interest to direct or indirect drive ICF, under some conditions PS can reduce the smoothed illumination rms by nearly (√2) even when the PS divergence is much smaller than that of SSD. (c) 2000 American Institute of Physics

  5. Damage Mechanism in Counter Pairs Caused by Bionic Non-smoothed Surface

    Directory of Open Access Journals (Sweden)

    ZHANG Zhan-hui

    2016-08-01

    Full Text Available Four biomimetic non-smoothed surface specimens with different shapes were prepared by laser processing. Tests were conducted on MMU-5G wear and abrasion test machine to study the influencing rule of non-smoothed surfaces on counter pairs. The results show that the mass loss of the friction pair matching with the non-smoothed units is much greater than the ones matching with the smooth specimens. The pairs matching with different non-smoothed units suffer differently. The non-smoothed surface protruding zone exerts micro cutting on counter pairs. The striation causes the greatest mass loss of the pairs than the other non-smoothed units, which almost doubles the damage of the grid ones suffering the least. The difference in pairs damage is attributed to the different mechanism of undertaking the load in the process of wear. The damage can be alleviated effectively by changing the shapes of the units without increasing or decreasing the area ratio of the non-smoothed units.

  6. The optical smoothing for high power laser chain. Fundamental concepts and analytical modeling, computerized simulations, experiments on smoothing by multimode optical fiber

    International Nuclear Information System (INIS)

    Videau, Laurent

    1998-01-01

    Laser-plasma interaction experiments require a focal spot whose spatial width is imposed and whose energy distribution is uniform. Optical smoothing techniques have been developed for high power laser chains in order to reach the required uniformity level. We present theoretical principles for optical smoothing and we develop a statistical approach which allows a precise study of smoothing techniques. This study deals with the contrast of the time-integrated pattern and with the hot spot motion and their life time. We give more details about the technique of Smoothing by Optical Fiber (SOF). A broadband pulse is injected into a multimode optical fiber. At the output of the fiber, the spatial modes, correlated to a propagation angle in the core of the fiber, are statistically independent and produce a speckle pattern. The speckles move because of the temporal incoherence and the time-integrated pattern is smoothed. The smoothing is characterized by the spectral correlation width defined as the width of the spectral correlation function. We show a smoothing difference between the fiber image plane and the convergence one which is the Fourier plane. Furthermore, we analyze the mode coupling into the core of the fiber which allows an explanation of experimental results compared to theoretical ones. A second study presents experimental results of Smoothing by Optical Fiber on a high power laser chain. In fact, SOF implies amplitude modulations in spatial and temporal domains which induce nonlinear effects. We show that the amplification efficiency decreases and we compare experimental results with an analytic model which takes into account spatial and temporal incoherencies. Finally, we propose a different setup using the cascading effect which creates spatially and/or temporally incoherent pulses. (author) [fr

  7. Smooth embeddings with Stein surface images

    OpenAIRE

    Gompf, Robert E.

    2011-01-01

    A simple characterization is given of open subsets of a complex surface that smoothly perturb to Stein open subsets. As applications, complex 2-space C^2 contains domains of holomorphy (Stein open subsets) that are exotic R^4's, and others homotopy equivalent to the 2-sphere but cut out by smooth, compact 3-manifolds. Pseudoconvex embeddings of Brieskorn spheres and other 3-manifolds into complex surfaces are constructed, as are pseudoconcave holomorphic fillings (with disagreeing contact and...

  8. Optimal Smooth Consumption and Annuity Design

    DEFF Research Database (Denmark)

    Bruhn, Kenneth; Steffensen, Mogens

    2013-01-01

    We propose an optimization criterion that yields extraordinary consumption smoothing compared to the well known results of the life-cycle model. Under this criterion we solve the related consumption and investment optimization problem faced by individuals with preferences for intertemporal stabil...... stability in consumption. We find that the consumption and investment patterns demanded under the optimization criterion is in general offered as annuity benefits from products in the class of ‘Formula Based Smoothed Investment-Linked Annuities’....

  9. Lyapunov exponents and smooth ergodic theory

    CERN Document Server

    Barreira, Luis

    2001-01-01

    This book is a systematic introduction to smooth ergodic theory. The topics discussed include the general (abstract) theory of Lyapunov exponents and its applications to the stability theory of differential equations, stable manifold theory, absolute continuity, and the ergodic theory of dynamical systems with nonzero Lyapunov exponents (including geodesic flows). The authors consider several non-trivial examples of dynamical systems with nonzero Lyapunov exponents to illustrate some basic methods and ideas of the theory. This book is self-contained. The reader needs a basic knowledge of real analysis, measure theory, differential equations, and topology. The authors present basic concepts of smooth ergodic theory and provide complete proofs of the main results. They also state some more advanced results to give readers a broader view of smooth ergodic theory. This volume may be used by those nonexperts who wish to become familiar with the field.

  10. PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from human airway smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Halayko Andrew J

    2009-09-01

    Full Text Available Abstract Background Airway smooth muscle contributes to the pathogenesis of pulmonary diseases by secreting inflammatory mediators such as interleukin-8 (IL-8. IL-8 production is in part regulated via activation of Gq-and Gs-coupled receptors. Here we study the role of the cyclic AMP (cAMP effectors protein kinase A (PKA and exchange proteins directly activated by cAMP (Epac1 and Epac2 in the bradykinin-induced IL-8 release from a human airway smooth muscle cell line and the underlying molecular mechanisms of this response. Methods IL-8 release was assessed via ELISA under basal condition and after stimulation with bradykinin alone or in combination with fenoterol, the Epac activators 8-pCPT-2'-O-Me-cAMP and Sp-8-pCPT-2'-O-Me-cAMPS, the PKA activator 6-Bnz-cAMP and the cGMP analog 8-pCPT-2'-O-Me-cGMP. Where indicated, cells were pre-incubated with the pharmacological inhibitors Clostridium difficile toxin B-1470 (GTPases, U0126 (extracellular signal-regulated kinases ERK1/2 and Rp-8-CPT-cAMPS (PKA. The specificity of the cyclic nucleotide analogs was confirmed by measuring phosphorylation of the PKA substrate vasodilator-stimulated phosphoprotein. GTP-loading of Rap1 and Rap2 was evaluated via pull-down technique. Expression of Rap1, Rap2, Epac1 and Epac2 was assessed via western blot. Downregulation of Epac protein expression was achieved by siRNA. Unpaired or paired two-tailed Student's t test was used. Results The β2-agonist fenoterol augmented release of IL-8 by bradykinin. The PKA activator 6-Bnz-cAMP and the Epac activator 8-pCPT-2'-O-Me-cAMP significantly increased bradykinin-induced IL-8 release. The hydrolysis-resistant Epac activator Sp-8-pCPT-2'-O-Me-cAMPS mimicked the effects of 8-pCPT-2'-O-Me-cAMP, whereas the negative control 8-pCPT-2'-O-Me-cGMP did not. Fenoterol, forskolin and 6-Bnz-cAMP induced VASP phosphorylation, which was diminished by the PKA inhibitor Rp-8-CPT-cAMPS. 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP induced GTP

  11. Aging may negatively impact movement smoothness during stair negotiation.

    Science.gov (United States)

    Dixon, P C; Stirling, L; Xu, X; Chang, C C; Dennerlein, J T; Schiffman, J M

    2018-05-26

    Stairs represent a barrier to safe locomotion for some older adults, potentially leading to the adoption of a cautious gait strategy that may lack fluidity. This strategy may be characterized as unsmooth; however, stair negotiation smoothness has yet to be quantified. The aims of this study were to assess age- and task-related differences in head and body center of mass (COM) acceleration patterns and smoothness during stair negotiation and to determine if smoothness was associated with the timed "Up and Go" (TUG) test of functional movement. Motion data from nineteen older and twenty young adults performing stair ascent, stair descent, and overground straight walking trials were analyzed and used to compute smoothness based on the log-normalized dimensionless jerk (LDJ) and the velocity spectral arc length (SPARC) metrics. The associations between TUG and smoothness measures were evaluated using Pearson's correlation coefficient (r). Stair tasks increased head and body COM acceleration pattern differences across groups, compared to walking (p < 0.05). LDJ smoothness for the head and body COM decreased in older adults during stair descent, compared to young adults (p ≤ 0.015) and worsened with increasing TUG for all tasks (-0.60 ≤ r ≤ -0.43). SPARC smoothness of the head and body COM increased in older adults, regardless of task (p < 0.001), while correlations showed improved SPARC smoothness with increasing TUG for some tasks (0.33 ≤ r ≤ 0.40). The LDJ outperforms SPARC in identifying age-related stair negotiation adaptations and is associated with performance on a clinical test of gait. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Vardenafil inhibiting parasympathetic function of tracheal smooth muscle.

    Science.gov (United States)

    Lee, Fei-Peng; Chao, Pin-Zhir; Wang, Hsing-Won

    2018-07-01

    Levitra, a phosphodiesterase-5 (PDE5) inhibitor, is the trade name of vardenafil. Nowadays, it is applied to treatment of erectile dysfunction. PDE5 inhibitors are employed to induce dilatation of the vascular smooth muscle. The effect of Levitra on impotency is well known; however, its effect on the tracheal smooth muscle has rarely been explored. When administered for sexual symptoms via oral intake or inhalation, Levitra might affect the trachea. This study assessed the effects of Levitra on isolated rat tracheal smooth muscle by examining its effect on resting tension of tracheal smooth muscle, contraction caused by 10 -6  M methacholine as a parasympathetic mimetic, and electrically induced tracheal smooth muscle contractions. The results showed that adding methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of Levitra at doses of 10 -5  M or above elicited a significant relaxation response to 10 -6  M methacholine-induced contraction. Levitra could inhibit electrical field stimulation-induced spike contraction. It alone had minimal effect on the basal tension of the trachea as the concentration increased. High concentrations of Levitra could inhibit parasympathetic function of the trachea. Levitra when administered via oral intake might reduce asthma attacks in impotent patients because it might inhibit parasympathetic function and reduce methacholine-induced contraction of the tracheal smooth muscle. Copyright © 2018. Published by Elsevier Taiwan LLC.

  13. Carrier tracking by smoothing filter improves symbol SNR

    Science.gov (United States)

    Pomalaza-Raez, Carlos A.; Hurd, William J.

    1986-01-01

    The potential benefit of using a smoothing filter to estimate carrier phase over use of phase locked loops (PLL) is determined. Numerical results are presented for the performance of three possible configurations of the deep space network advanced receiver. These are residual carrier PLL, sideband aided residual carrier PLL, and finally sideband aiding with a Kalman smoother. The average symbol signal to noise ratio (SNR) after losses due to carrier phase estimation error is computed for different total power SNRs, symbol rates and symbol SNRs. It is found that smoothing is most beneficial for low symbol SNRs and low symbol rates. Smoothing gains up to 0.4 dB over a sideband aided residual carrier PLL, and the combined benefit of smoothing and sideband aiding relative to a residual carrier loop is often in excess of 1 dB.

  14. Impact of spectral smoothing on gamma radiation portal alarm probabilities

    International Nuclear Information System (INIS)

    Burr, T.; Hamada, M.; Hengartner, N.

    2011-01-01

    Gamma detector counts are included in radiation portal monitors (RPM) to screen for illicit nuclear material. Gamma counts are sometimes smoothed to reduce variance in the estimated underlying true mean count rate, which is the 'signal' in our context. Smoothing reduces total error variance in the estimated signal if the bias that smoothing introduces is more than offset by the variance reduction. An empirical RPM study for vehicle screening applications is presented for unsmoothed and smoothed gamma counts in low-resolution plastic scintillator detectors and in medium-resolution NaI detectors. - Highlights: → We evaluate options for smoothing counts from gamma detectors deployed for portal monitoring. → A new multiplicative bias correction (MBC) is shown to reduce bias in peak and valley regions. → Performance is measured using mean squared error and detection probabilities for sources. → Smoothing with the MBC improves detection probabilities and the mean squared error.

  15. Some asymptotic theory for variance function smoothing | Kibua ...

    African Journals Online (AJOL)

    Simple selection of the smoothing parameter is suggested. Both homoscedastic and heteroscedastic regression models are considered. Keywords: Asymptotic, Smoothing, Kernel, Bandwidth, Bias, Variance, Mean squared error, Homoscedastic, Heteroscedastic. > East African Journal of Statistics Vol. 1 (1) 2005: pp. 9-22 ...

  16. Mechanical properties of mammalian single smooth muscle cells. I. A low cost large range microforce transducer.

    NARCIS (Netherlands)

    J.J. Glerum (Jacobus); R. van Mastrigt (Ron)

    1990-01-01

    textabstractA transducer has been developed for measuring the minute forces generated during isometric contractions (1.0-10.0 microN) of single smooth muscle cells from the pig urinary bladder and the human uterus. In addition to its high sensitivity, resolution and stability (100 mV microN-1, and

  17. Bitter Taste Receptors in The Wrong Place: Novel Airway Smooth Muscle Targets For Treating Asthma

    OpenAIRE

    Liggett, Stephen B.

    2014-01-01

    There is a need to expand the classes of drugs used to treat obstructive lung diseases to achieve better outcomes. With only one class of direct bronchodilators (β-agonists), we sought to find receptors on human airway smooth muscle (ASM) that act via a unique mechanism to relax the muscle, have a diverse agonist binding profile to enhance the probability of finding new therapeutics, and relax ASM with equal or greater efficacy than β-agonists. We have found that human and mouse ASM express s...

  18. Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy.

    Science.gov (United States)

    Li, Chao; Vu, Kent; Hazelgrove, Krystina; Kuemmerle, John F

    2015-12-01

    The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were increased in muscle cells isolated from fibrostenotic intestine under regulation by endogenous TGF-β1. Erk5 and MEF2C were phosphorylated in vivo in fibrostenotic muscle; both were phosphorylated and colocalized to nucleus in response to synthetic MGF in vitro. Smooth muscle-specific protein expression of α-smooth muscle actin, γ-smooth muscle actin, and smoothelin was increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth muscle-specific gene expression and hypertrophy induced by synthetic MGF. Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The results indicate that TGF-β1-dependent IGF-IEc expression and MGF production in patients with fibrostenotic Crohn's disease regulates smooth muscle cell hypertrophy a critical factor that contributes to intestinal stricture formation. Copyright © 2015 the American Physiological Society.

  19. Divergent effects of 17-β-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-α-induced neointima formation

    International Nuclear Information System (INIS)

    Nintasen, Rungrat; Riches, Kirsten; Mughal, Romana S.; Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa; Turner, Neil A.; Porter, Karen E.

    2012-01-01

    Highlights: ► TNF-α augments neointimal hyperplasia in human saphenous vein. ► TNF-α induces detrimental effects on endothelial and smooth muscle cell function. ► Estradiol exerts modulatory effects on TNF-induced vascular cell functions. ► The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α). TNF-α can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-α on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-α (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-α, an effect that was abolished by co-culture with E2. TNF-α increased SV–SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1–50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV–SMC proliferation to a level comparable to that of TNF-α alone. SV–EC migration was significantly impaired by TNF-α (42% of control), and co-culture with E2 partially restored the ability of SV–EC to migrate and repair the wound. In contrast, TNF-α increased SV–SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-α potently induced ICAM-1 and VCAM-1 expression in both SV–EC and SV–SMC. However there was no modulation by E2 in either cell-type. In conclusion, TNF-α induced SV neointima formation, increased SMC proliferation and migration, impaired

  20. A Fourier transform method for the selection of a smoothing interval

    International Nuclear Information System (INIS)

    Kekre, H.B.; Madan, V.K.; Bairi, B.R.

    1989-01-01

    A novel method for the selection of a smoothing interval for the widely used Savitzky and Golay's smoothing filter is proposed. Complementary bandwidths for the nuclear spectral data and the smoothing filter are defined. The criterion for the selection of smoothing interval is based on matching the bandwidths of the spectral data to the filter. Using the above method five real observed spectral peaks of different full width at half maximum, viz. 23.5, 19.5, 17, 8.5 and 6.5 channels, were smoothed and the results are presented. (orig.)

  1. Full Waveform Inversion Using Nonlinearly Smoothed Wavefields

    KAUST Repository

    Li, Y.; Choi, Yun Seok; Alkhalifah, Tariq Ali; Li, Z.

    2017-01-01

    The lack of low frequency information in the acquired data makes full waveform inversion (FWI) conditionally converge to the accurate solution. An initial velocity model that results in data with events within a half cycle of their location in the observed data was required to converge. The multiplication of wavefields with slightly different frequencies generates artificial low frequency components. This can be effectively utilized by multiplying the wavefield with itself, which is nonlinear operation, followed by a smoothing operator to extract the artificially produced low frequency information. We construct the objective function using the nonlinearly smoothed wavefields with a global-correlation norm to properly handle the energy imbalance in the nonlinearly smoothed wavefield. Similar to the multi-scale strategy, we progressively reduce the smoothing width applied to the multiplied wavefield to welcome higher resolution. We calculate the gradient of the objective function using the adjoint-state technique, which is similar to the conventional FWI except for the adjoint source. Examples on the Marmousi 2 model demonstrate the feasibility of the proposed FWI method to mitigate the cycle-skipping problem in the case of a lack of low frequency information.

  2. Full Waveform Inversion Using Nonlinearly Smoothed Wavefields

    KAUST Repository

    Li, Y.

    2017-05-26

    The lack of low frequency information in the acquired data makes full waveform inversion (FWI) conditionally converge to the accurate solution. An initial velocity model that results in data with events within a half cycle of their location in the observed data was required to converge. The multiplication of wavefields with slightly different frequencies generates artificial low frequency components. This can be effectively utilized by multiplying the wavefield with itself, which is nonlinear operation, followed by a smoothing operator to extract the artificially produced low frequency information. We construct the objective function using the nonlinearly smoothed wavefields with a global-correlation norm to properly handle the energy imbalance in the nonlinearly smoothed wavefield. Similar to the multi-scale strategy, we progressively reduce the smoothing width applied to the multiplied wavefield to welcome higher resolution. We calculate the gradient of the objective function using the adjoint-state technique, which is similar to the conventional FWI except for the adjoint source. Examples on the Marmousi 2 model demonstrate the feasibility of the proposed FWI method to mitigate the cycle-skipping problem in the case of a lack of low frequency information.

  3. Myosin light chain kinase phosphorylation in tracheal smooth muscle

    International Nuclear Information System (INIS)

    Stull, J.T.; Hsu, L.C.; Tansey, M.G.; Kamm, K.E.

    1990-01-01

    Purified myosin light chain kinase from smooth muscle is phosphorylated by cyclic AMP-dependent protein kinase, protein kinase C, and the multifunctional calmodulin-dependent protein kinase II. Because phosphorylation in a specific site (site A) by any one of these kinases desensitizes myosin light chain kinase to activation by Ca2+/calmodulin, kinase phosphorylation could play an important role in regulating smooth muscle contractility. This possibility was investigated in 32 P-labeled bovine tracheal smooth muscle. Treatment of tissues with carbachol, KCl, isoproterenol, or phorbol 12,13-dibutyrate increased the extent of kinase phosphorylation. Six primary phosphopeptides (A-F) of myosin light chain kinase were identified. Site A was phosphorylated to an appreciable extent only with carbachol or KCl, agents which contract tracheal smooth muscle. The extent of site A phosphorylation correlated to increases in the concentration of Ca2+/calmodulin required for activation. These results show that cyclic AMP-dependent protein kinase and protein kinase C do not affect smooth muscle contractility by phosphorylating site A in myosin light chain kinase. It is proposed that phosphorylation of myosin light chain kinase in site A in contracting tracheal smooth muscle may play a role in the reported desensitization of contractile elements to activation by Ca2+

  4. Optical smoothing of laser imprinting in planar-target experiments on OMEGA EP using multi-FM 1-D smoothing by spectral dispersion

    Energy Technology Data Exchange (ETDEWEB)

    Hohenberger, M., E-mail: mhoh@lle.rochester.edu; Shvydky, A.; Marozas, J. A.; Bonino, M. J.; Canning, D.; Collins, T. J. B.; Dorrer, C.; Kessler, T. J.; Kruschwitz, B. E.; McKenty, P. W.; Regan, S. P.; Sangster, T. C.; Zuegel, J. D. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road Rochester, Rochester, New York 14623 (United States); Fiksel, G. [Nuclear Engineering and Radiological Sciences (NERS), University of Michigan, Ann Arbor, Michigan 48109 (United States); Meyerhofer, D. D. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

    2016-09-15

    Direct-drive ignition on the National Ignition Facility (NIF) requires single-beam smoothing to minimize imprinting of laser nonuniformities that can negatively affect implosion performance. One-dimensional, multi-FM smoothing by spectral dispersion (SSD) has been proposed to provide the required smoothing [Marozas et al., Bull. Am. Phys. Soc. 55, 294 (2010)]. A prototype multi-FM SSD system has been integrated into the NIF-like beamline of the OMEGA EP Laser System. Experiments have been performed to verify the smoothing performance by measuring Rayleigh–Taylor growth rates in planar targets of laser-imprinted and preimposed surface modulations. Multi-FM 1-D SSD has been observed to reduce imprint levels by ∼50% compared to the nominal OMEGA EP SSD system. The experimental results are in agreement with 2-D DRACO simulations using realistic, time-dependent far-field spot-intensity calculations that emulate the effect of SSD.

  5. Six-term exact sequences for smooth generalized crossed products

    DEFF Research Database (Denmark)

    Gabriel, Olivier; Grensing, Martin

    2013-01-01

    We define smooth generalized crossed products and prove six-term exact sequences of Pimsner–Voiculescu type. This sequence may, in particular, be applied to smooth subalgebras of the quantum Heisenberg manifolds in order to compute the generators of their cyclic cohomology. Further, our results...... include the known results for smooth crossed products. Our proof is based on a combination of arguments from the setting of (Cuntz–)Pimsner algebras and the Toeplitz proof of Bott periodicity....

  6. LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-β.

    Science.gov (United States)

    Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

    2012-11-14

    Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer's disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in endothelial cells in transcytosing Aβ out of the brain across the BBB; however, whether this represents a significant pathway for brain Aβ clearance remains controversial. Here, we demonstrate that Aβ can be cleared locally in the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle cells. The uptake and degradation of both endogenous and exogenous Aβ were significantly reduced in LRP1-suppressed human brain vascular smooth muscle cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain Aβ accumulation and exacerbated Aβ deposition as amyloid plaques and CAA without affecting Aβ production. Our results demonstrate that LRP1 is a major Aβ clearance receptor in cerebral vascular smooth muscle cell and a disturbance of this pathway contributes to Aβ accumulation. These studies establish critical functions of the cerebrovasculature system in Aβ metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA.

  7. Large area smoothing of surfaces by ion bombardment: fundamentals and applications

    International Nuclear Information System (INIS)

    Frost, F; Fechner, R; Ziberi, B; Voellner, J; Flamm, D; Schindler, A

    2009-01-01

    Ion beam erosion can be used as a process for achieving surface smoothing at microscopic length scales and for the preparation of ultrasmooth surfaces, as an alternative to nanostructuring of various surfaces via self-organization. This requires that in the evolution of the surface topography different relaxation mechanisms dominate over the roughening, and smoothing of initially rough surfaces can occur. This contribution focuses on the basic mechanisms as well as potential applications of surface smoothing using low energy ion beams. In the first part, the fundamentals for the smoothing of III/V semiconductors, Si and quartz glass surfaces using low energy ion beams (ion energy: ≤2000 eV) are reviewed using examples. The topography evolution of these surfaces with respect to different process parameters (ion energy, ion incidence angle, erosion time, sample rotation) has been investigated. On the basis of the time evolution of different roughness parameters, the relevant surface relaxation mechanisms responsible for surface smoothing are discussed. In this context, physical constraints as regards the effectiveness of surface smoothing by direct ion bombardment will also be addressed and furthermore ion beam assisted smoothing techniques are introduced. In the second application-orientated part, recent technological developments related to ion beam assisted smoothing of optically relevant surfaces are summarized. It will be demonstrated that smoothing by direct ion bombardment in combination with the use of sacrificial smoothing layers and the utilization of appropriate broad beam ion sources enables the polishing of various technologically important surfaces down to 0.1 nm root mean square roughness level, showing great promise for large area surface processing. Specific examples are given for ion beam smoothing of different optical surfaces, especially for substrates used for advanced optical applications (e.g., in x-ray optics and components for extreme

  8. Discrimination of curvature from motion during smooth pursuit eye movements and fixation.

    Science.gov (United States)

    Ross, Nicholas M; Goettker, Alexander; Schütz, Alexander C; Braun, Doris I; Gegenfurtner, Karl R

    2017-09-01

    Smooth pursuit and motion perception have mainly been investigated with stimuli moving along linear trajectories. Here we studied the quality of pursuit movements to curved motion trajectories in human observers and examined whether the pursuit responses would be sensitive enough to discriminate various degrees of curvature. In a two-interval forced-choice task subjects pursued a Gaussian blob moving along a curved trajectory and then indicated in which interval the curve was flatter. We also measured discrimination thresholds for the same curvatures during fixation. Motion curvature had some specific effects on smooth pursuit properties: trajectories with larger amounts of curvature elicited lower open-loop acceleration, lower pursuit gain, and larger catch-up saccades compared with less curved trajectories. Initially, target motion curvatures were underestimated; however, ∼300 ms after pursuit onset pursuit responses closely matched the actual curved trajectory. We calculated perceptual thresholds for curvature discrimination, which were on the order of 1.5 degrees of visual angle (°) for a 7.9° curvature standard. Oculometric sensitivity to curvature discrimination based on the whole pursuit trajectory was quite similar to perceptual performance. Oculometric thresholds based on smaller time windows were higher. Thus smooth pursuit can quite accurately follow moving targets with curved trajectories, but temporal integration over longer periods is necessary to reach perceptual thresholds for curvature discrimination. NEW & NOTEWORTHY Even though motion trajectories in the real world are frequently curved, most studies of smooth pursuit and motion perception have investigated linear motion. We show that pursuit initially underestimates the curvature of target motion and is able to reproduce the target curvature ∼300 ms after pursuit onset. Temporal integration of target motion over longer periods is necessary for pursuit to reach the level of precision found

  9. Intracellular interactions of umeclidinium and vilanterol in human airway smooth muscle

    Directory of Open Access Journals (Sweden)

    Shaikh N

    2017-06-01

    Full Text Available Nooreen Shaikh,1,2 Malcolm Johnson,3 David A Hall,4 Kian Fan Chung,1,2 John H Riley,3 Sally Worsley,5 Pankaj K Bhavsar1,2 1Experimental Studies, National Heart and Lung Institute, Imperial College London, 2Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, 3Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, 4Fibrosis and Lung Injury Development Planning Unit, GlaxoSmithKline, Stevenage, 5Respiratory Research & Development, GlaxoSmithKline, Uxbridge, UK Background: Intracellular mechanisms of action of umeclidinium (UMEC, a long-acting muscarinic receptor antagonist, and vilanterol (VI, a long-acting β2-adrenoceptor (β2R agonist, were investigated in target cells: human airway smooth-muscle cells (ASMCs. Materials and methods: ASMCs from tracheas of healthy lung-transplant donors were treated with VI, UMEC, UMEC and VI combined, or control compounds (salmeterol, propranolol, ICI 118.551, or methacholine [MCh]. Cyclic adenosine monophosphate (cAMP was measured using an enzyme-linked immunosorbent assay, intracellular free calcium ([Ca2+]i using a fluorescence assay, and regulator of G-protein signaling 2 (RGS2 messenger RNA using real-time quantitative polymerase chain reaction. Results: VI and salmeterol (10–12–10–6 M induced cAMP production from ASMCs in a concentration-dependent manner, which was greater for VI at all concentrations. β2R antagonism by propranolol or ICI 118.551 (10–12–10–4 M resulted in concentration-dependent inhibition of VI-induced cAMP production, and ICI 118.551 was more potent. MCh (5×10–6 M, 30 minutes attenuated VI-induced cAMP production (P<0.05, whereas pretreatment with UMEC (10–8 M, 1 hour restored the magnitude of VI-induced cAMP production. ASMC stimulation with MCh (10–11–5×10–6 M resulted in a concentration-dependent increase in [Ca2+]i, which was attenuated with UMEC pretreatment. Reduction of MCh-induced [Ca2+]i release was greater with UMEC + VI versus

  10. Bandwidth selection in smoothing functions | Kibua | East African ...

    African Journals Online (AJOL)

    ... inexpensive and, hence, worth adopting. We argue that the bandwidth parameter is determined by two factors: the kernel function and the length of the smoothing region. We give an illustrative example of its application using real data. Keywords: Kernel, Smoothing functions, Bandwidth > East African Journal of Statistics ...

  11. Intermittent Smoothing Approaches for Wind Power Output: A Review

    Directory of Open Access Journals (Sweden)

    Muhammad Jabir

    2017-10-01

    Full Text Available Wind energy is one of the most common types of renewable energy resource. Due to its sustainability and environmental benefits, it is an emerging source for electric power generation. Rapid and random changes of wind speed makes it an irregular and inconsistent power source when connected to the grid, causing different technical problems in protection, power quality and generation dispatch control. Due to these problems, effective intermittent smoothing approaches for wind power output are crucially needed to minimize such problems. This paper reviews various intermittent smoothing approaches used in smoothing the output power fluctuations caused by wind energy. Problems associated with the inclusion of wind energy resources to grid are also briefly reviewed. From this review, it has been found that battery energy storage system is the most suitable and effective smoothing approach, provided that an effective control strategy is available for optimal utilization of battery energy system. This paper further demonstrates different control strategies built for battery energy storage system to obtain the smooth output wind power.

  12. Existence and smoothness of solutions to second initial boundary value problems for Schrodinger systems in cylinders with non-smooth bases

    Directory of Open Access Journals (Sweden)

    Nguyen Manh Hung

    2008-03-01

    Full Text Available In this paper, we consider the second initial boundary value problem for strongly general Schrodinger systems in both the finite and the infinite cylinders $Q_T, 0smooth base $Omega$. Some results on the existence, uniqueness and smoothness with respect to time variable of generalized solution of this problem are given.

  13. On smoothed analysis of quicksort and Hoare's find

    NARCIS (Netherlands)

    Fouz, Mahmoud; Kufleitner, Manfred; Manthey, Bodo; Zeini Jahromi, Nima; Ngo, H.Q.

    2009-01-01

    We provide a smoothed analysis of Hoare’s find algorithm and we revisit the smoothed analysis of quicksort. Hoare’s find algorithm – often called quickselect – is an easy-to-implement algorithm for finding the $k$-th smallest element of a sequence. While the worst-case number of comparisons that

  14. Dynamics of wetting on smooth and rough surfaces.

    NARCIS (Netherlands)

    Cazabat, A.M.; Cohen Stuart, M.A.

    1987-01-01

    The rate of spreading of non-volatile liquids on smooth and on rough surfaces was investigated. The radius of the wetted spot was found to agree with recently proposed scaling laws (t 1/10 for capillarity driven andt 1/8 for gravity driven spreading) when the surface was smooth. However, the

  15. Vascular wall-resident CD44+ multipotent stem cells give rise to pericytes and smooth muscle cells and contribute to new vessel maturation.

    Directory of Open Access Journals (Sweden)

    Diana Klein

    Full Text Available Here, we identify CD44(+CD90(+CD73(+CD34(-CD45(- cells within the adult human arterial adventitia with properties of multipotency which were named vascular wall-resident multipotent stem cells (VW-MPSCs. VW-MPSCs exhibit typical mesenchymal stem cell characteristics including cell surface markers in immunostaining and flow cytometric analyses, and differentiation into adipocytes, chondrocytes and osteocytes under culture conditions. Particularly, TGFß1 stimulation up-regulates smooth muscle cell markers in VW-MPSCs. Using fluorescent cell labelling and co-localisation studies we show that VW-MPSCs differentiate to pericytes/smooth muscle cells which cover the wall of newly formed endothelial capillary-like structures in vitro. Co-implantation of EGFP-labelled VW-MPSCs and human umbilical vein endothelial cells into SCID mice subcutaneously via Matrigel results in new vessels formation which were covered by pericyte- or smooth muscle-like cells generated from implanted VW-MPSCs. Our results suggest that VW-MPSCs are of relevance for vascular morphogenesis, repair and self-renewal of vascular wall cells and for local capacity of neovascularization in disease processes.

  16. Non-smooth dynamical systems

    CERN Document Server

    2000-01-01

    The book provides a self-contained introduction to the mathematical theory of non-smooth dynamical problems, as they frequently arise from mechanical systems with friction and/or impacts. It is aimed at applied mathematicians, engineers, and applied scientists in general who wish to learn the subject.

  17. Additional Smooth and Rough Water Trials of SKI-CAT.

    Science.gov (United States)

    1981-08-01

    REPORT & PERIOD COVERED ADDITIONAL SMOOTH AND ROUGH WATER TRIALS OF FINAL SKI- CAT S. PERFORMING ORO. REPORT NUMSER 7. AUTHOR() I. CONTRACT OR GRANT NUMUr...Identif by bloc membe) ’ " -Further tests of SKI- CAT were made in smooth and rough water. Smooth water results confirmed the performance results of...reductions in the accelerations and motions of SKI- CAT over against the head seasreut DD , +A ,3 1473 EDITION OF I NOVS IS OBSOLETE UNCIbSJFIED SIME 0102-014

  18. Role of Smooth Muscle in Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Stephen M Collins

    1996-01-01

    Full Text Available The notion that smooth muscle function is altered in inflammation is prompted by clinical observations of altered motility in patients with inflammatory bowel disease (IBD. While altered motility may reflect inflammation-induced changes in intrinsic or extrinsic nerves to the gut, changes in gut hormone release and changes in muscle function, recent studies have provided in vitro evidence of altered muscle contractility in muscle resected from patients with ulcerative colitis or Crohn’s disease. In addition, the observation that smooth muscle cells are more numerous and prominent in the strictured bowel of IBD patients compared with controls suggests that inflammation may alter the growth of intestinal smooth muscle. Thus, inflammation is associated with changes in smooth muscle growth and contractility that, in turn, contribute to important symptoms of IBD including diarrhea (from altered motility and pain (via either altered motility or stricture formation. The involvement of smooth muscle in this context may be as an innocent bystander, where cells and products of the inflammatory process induce alterations in muscle contractility and growth. However, it is likely that intestinal muscle cells play a more active role in the inflammatory process via the elaboration of mediators and trophic factors, including cytokines, and via the production of collagen. The concept of muscle cells as active participants in the intestinal inflammatory process is a new concept that is under intense study. This report summarizes current knowledge as it relates to these two aspects of altered muscle function (growth and contractility in the inflamed intestine, and will focus on mechanisms underlying these changes, based on data obtained from animal models of intestinal inflammation.

  19. Modeling the dispersion effects of contractile fibers in smooth muscles

    Science.gov (United States)

    Murtada, Sae-Il; Kroon, Martin; Holzapfel, Gerhard A.

    2010-12-01

    Micro-structurally based models for smooth muscle contraction are crucial for a better understanding of pathological conditions such as atherosclerosis, incontinence and asthma. It is meaningful that models consider the underlying mechanical structure and the biochemical activation. Hence, a simple mechanochemical model is proposed that includes the dispersion of the orientation of smooth muscle myofilaments and that is capable to capture available experimental data on smooth muscle contraction. This allows a refined study of the effects of myofilament dispersion on the smooth muscle contraction. A classical biochemical model is used to describe the cross-bridge interactions with the thin filament in smooth muscles in which calcium-dependent myosin phosphorylation is the only regulatory mechanism. A novel mechanical model considers the dispersion of the contractile fiber orientations in smooth muscle cells by means of a strain-energy function in terms of one dispersion parameter. All model parameters have a biophysical meaning and may be estimated through comparisons with experimental data. The contraction of the middle layer of a carotid artery is studied numerically. Using a tube the relationships between the internal pressure and the stretches are investigated as functions of the dispersion parameter, which implies a strong influence of the orientation of smooth muscle myofilaments on the contraction response. It is straightforward to implement this model in a finite element code to better analyze more complex boundary-value problems.

  20. Multiple predictor smoothing methods for sensitivity analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Helton, Jon Craig; Storlie, Curtis B.

    2006-08-01

    The use of multiple predictor smoothing methods in sampling-based sensitivity analyses of complex models is investigated. Specifically, sensitivity analysis procedures based on smoothing methods employing the stepwise application of the following nonparametric regression techniques are described: (1) locally weighted regression (LOESS), (2) additive models, (3) projection pursuit regression, and (4) recursive partitioning regression. The indicated procedures are illustrated with both simple test problems and results from a performance assessment for a radioactive waste disposal facility (i.e., the Waste Isolation Pilot Plant). As shown by the example illustrations, the use of smoothing procedures based on nonparametric regression techniques can yield more informative sensitivity analysis results than can be obtained with more traditional sensitivity analysis procedures based on linear regression, rank regression or quadratic regression when nonlinear relationships between model inputs and model predictions are present.

  1. Multiple predictor smoothing methods for sensitivity analysis

    International Nuclear Information System (INIS)

    Helton, Jon Craig; Storlie, Curtis B.

    2006-01-01

    The use of multiple predictor smoothing methods in sampling-based sensitivity analyses of complex models is investigated. Specifically, sensitivity analysis procedures based on smoothing methods employing the stepwise application of the following nonparametric regression techniques are described: (1) locally weighted regression (LOESS), (2) additive models, (3) projection pursuit regression, and (4) recursive partitioning regression. The indicated procedures are illustrated with both simple test problems and results from a performance assessment for a radioactive waste disposal facility (i.e., the Waste Isolation Pilot Plant). As shown by the example illustrations, the use of smoothing procedures based on nonparametric regression techniques can yield more informative sensitivity analysis results than can be obtained with more traditional sensitivity analysis procedures based on linear regression, rank regression or quadratic regression when nonlinear relationships between model inputs and model predictions are present

  2. Adsorption on smooth electrodes: A radiotracer study

    International Nuclear Information System (INIS)

    Rice-Jackson, L.M.

    1990-01-01

    Adsorption on solids is a complicated process and in most cases, occurs as the early stage of other more complicated processes, i.e. chemical reactions, electrooxidation, electroreduction. The research reported here combines the electroanalytical method, cyclic voltammetry, and the use of radio-labeled isotopes, soft beta emitters, to study adsorption processes at smooth electrodes. The in-situ radiotracer method is highly anion (molecule) specific and provides information on the structure and composition of the electric double layer. The emphasis of this research was on studying adsorption processes at smooth electrodes of copper, gold, and platinum. The application of the radiotracer method to these smooth surfaces have led to direct in-situ measurements from which surface coverage was determined; anions and molecules were identified; and weak interactions of adsorbates with the surface of the electrodes were readily monitored. 179 refs

  3. Neurophysiology and Neuroanatomy of Smooth Pursuit: Lesion Studies

    Science.gov (United States)

    Sharpe, James A.

    2008-01-01

    Smooth pursuit impairment is recognized clinically by the presence of saccadic tracking of a small object and quantified by reduction in pursuit gain, the ratio of smooth eye movement velocity to the velocity of a foveal target. Correlation of the site of brain lesions, identified by imaging or neuropathological examination, with defective smooth…

  4. Modeling Cerebrovascular Pathophysiology in Amyloid-β Metabolism using Neural-Crest-Derived Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Christine Cheung

    2014-10-01

    Full Text Available Summary: There is growing recognition of cerebrovascular contributions to neurodegenerative diseases. In the walls of cerebral arteries, amyloid-beta (Aβ accumulation is evident in a majority of aged people and patients with cerebral amyloid angiopathy. Here, we leverage human pluripotent stem cells to generate vascular smooth muscle cells (SMCs from neural crest progenitors, recapitulating brain-vasculature-specific attributes of Aβ metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural-crest-derived SMCs to mediate Aβ uptake and intracellular lysosomal degradation. Hypoxia significantly compromises the contribution of SMCs to Aβ clearance by suppressing LRP1 expression. This enabled us to develop an assay of Aβ uptake by using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high-throughput format, demonstrating the value of stem-cell-based phenotypic screening for novel therapeutics and drug repurposing, aimed at alleviating amyloid burden. : The contribution of blood vessel pathologies to neurodegenerative disorders is relatively neglected, partly due to inadequate human tissues for research. By using human stem cells, Cheung et al. establish a method of generating vascular smooth muscle cells (SMCs from neural crest progenitors, the primary precursors that give rise to brain blood vessels. These stem-cell-derived SMCs display defective amyloid processing under chronic hypoxia, a phenomenon well documented in the cerebral vasculatures of aged people and patients with Alzheimer’s disease.

  5. Smooth massless limit of field theories

    International Nuclear Information System (INIS)

    Fronsdal, C.

    1980-01-01

    The massless limit of Fierz-Pauli field theories, describing fields with fixed mass and spin interacting with external sources, is examined. Results are obtained for spins, 1, 3/2, 2 and 3 using conventional models, and then for all half-integral spins in a relatively model-independent manner. It is found that the massless limit is smooth provided that the sources satisfy certain conditions. In the massless limit these conditions reduce to the conservation laws required by internal consistency of massless field theory. Smoothness simply requires that quantities that vanish in the massless case approach zero in a certain well-defined manner. (orig.)

  6. Mapping of Agricultural Crops from Single High-Resolution Multispectral Images—Data-Driven Smoothing vs. Parcel-Based Smoothing

    Directory of Open Access Journals (Sweden)

    Asli Ozdarici-Ok

    2015-05-01

    Full Text Available Mapping agricultural crops is an important application of remote sensing. However, in many cases it is based either on hyperspectral imagery or on multitemporal coverage, both of which are difficult to scale up to large-scale deployment at high spatial resolution. In the present paper, we evaluate the possibility of crop classification based on single images from very high-resolution (VHR satellite sensors. The main objective of this work is to expose performance difference between state-of-the-art parcel-based smoothing and purely data-driven conditional random field (CRF smoothing, which is yet unknown. To fulfill this objective, we perform extensive tests with four different classification methods (Support Vector Machines, Random Forest, Gaussian Mixtures, and Maximum Likelihood to compute the pixel-wise data term; and we also test two different definitions of the pairwise smoothness term. We have performed a detailed evaluation on different multispectral VHR images (Ikonos, QuickBird, Kompsat-2. The main finding of this study is that pairwise CRF smoothing comes close to the state-of-the-art parcel-based method that requires parcel boundaries (average difference ≈ 2.5%. Our results indicate that a single multispectral (R, G, B, NIR image is enough to reach satisfactory classification accuracy for six crop classes (corn, pasture, rice, sugar beet, wheat, and tomato in Mediterranean climate. Overall, it appears that crop mapping using only one-shot VHR imagery taken at the right time may be a viable alternative, especially since high-resolution multitemporal or hyperspectral coverage as well as parcel boundaries are in practice often not available.

  7. A User Guide for Smoothing Air Traffic Radar Data

    Science.gov (United States)

    Bach, Ralph E.; Paielli, Russell A.

    2014-01-01

    Matlab software was written to provide smoothing of radar tracking data to simulate ADS-B (Automatic Dependent Surveillance-Broadcast) data in order to test a tactical conflict probe. The probe, called TSAFE (Tactical Separation-Assured Flight Environment), is designed to handle air-traffic conflicts left undetected or unresolved when loss-of-separation is predicted to occur within approximately two minutes. The data stream that is down-linked from an aircraft equipped with an ADS-B system would include accurate GPS-derived position and velocity information at sample rates of 1 Hz. Nation-wide ADS-B equipage (mandated by 2020) should improve surveillance accuracy and TSAFE performance. Currently, position data are provided by Center radar (nominal 12-sec samples) and Terminal radar (nominal 4.8-sec samples). Aircraft ground speed and ground track are estimated using real-time filtering, causing lags up to 60 sec, compromising performance of a tactical resolution tool. Offline smoothing of radar data reduces wild-point errors, provides a sample rate as high as 1 Hz, and yields more accurate and lag-free estimates of ground speed, ground track, and climb rate. Until full ADS-B implementation is available, smoothed radar data should provide reasonable track estimates for testing TSAFE in an ADS-B-like environment. An example illustrates the smoothing of radar data and shows a comparison of smoothed-radar and ADS-B tracking. This document is intended to serve as a guide for using the smoothing software.

  8. Carrier tracking by smoothing filter can improve symbol SNR

    Science.gov (United States)

    Hurd, W. J.; Pomalaza-Raez, C. A.

    1985-01-01

    The potential benefit of using a smoothing filter to estimate carrier phase over use of phase locked loops (PLL) is determined. Numerical results are presented for the performance of three possible configurations of the deep space network advanced receiver. These are residual carrier PLL, sideband aided residual carrier PLL, and finally sideband aiding with a Kalman smoother. The average symbol signal to noise ratio (CNR) after losses due to carrier phase estimation error is computed for different total power SNRs, symbol rates and symbol SNRs. It is found that smoothing is most beneficial for low symbol SNRs and low symbol rates. Smoothing gains up to 0.4 dB over a sideband aided residual carrier PLL, and the combined benefit of smoothing and sideband aiding relative to a residual carrier loop is often in excess of 1 dB.

  9. Effective Five Directional Partial Derivatives-Based Image Smoothing and a Parallel Structure Design.

    Science.gov (United States)

    Choongsang Cho; Sangkeun Lee

    2016-04-01

    Image smoothing has been used for image segmentation, image reconstruction, object classification, and 3D content generation. Several smoothing approaches have been used at the pre-processing step to retain the critical edge, while removing noise and small details. However, they have limited performance, especially in removing small details and smoothing discrete regions. Therefore, to provide fast and accurate smoothing, we propose an effective scheme that uses a weighted combination of the gradient, Laplacian, and diagonal derivatives of a smoothed image. In addition, to reduce computational complexity, we designed and implemented a parallel processing structure for the proposed scheme on a graphics processing unit (GPU). For an objective evaluation of the smoothing performance, the images were linearly quantized into several layers to generate experimental images, and the quantized images were smoothed using several methods for reconstructing the smoothly changed shape and intensity of the original image. Experimental results showed that the proposed scheme has higher objective scores and better successful smoothing performance than similar schemes, while preserving and removing critical and trivial details, respectively. For computational complexity, the proposed smoothing scheme running on a GPU provided 18 and 16 times lower complexity than the proposed smoothing scheme running on a CPU and the L0-based smoothing scheme, respectively. In addition, a simple noise reduction test was conducted to show the characteristics of the proposed approach; it reported that the presented algorithm outperforms the state-of-the art algorithms by more than 5.4 dB. Therefore, we believe that the proposed scheme can be a useful tool for efficient image smoothing.

  10. Microscopic changes induced by Cr-VI in smooth muscles of albino mice

    International Nuclear Information System (INIS)

    Nabeel, H.

    2007-01-01

    Chromium is believed to be an essential trace element in human nutrition. Evidence suggests that it plays an important role in normal carbohydrate metabolism. It was found that patients receiving long-term total parenteral nutrition (TPN) without chromium developed glucose intolerance, weight loss and peripheral neuropathy Chromium is present in a normal diet at trace (but essential) levels. Occupational exposure is related to the industrial uses of chrome compounds in production and use of steels, pigments, leather tanning and wood preservation solutions, plating chemicals, and cement. Toxicity is predominantly associated with industrial exposures. Hexavalent chromium compounds appear to have greatest toxicity and almost all tissues of body are affected. To evaluate the effects on smooth muscles, present study was carried out. The mice of experimental group (2wks, 4wks, 6wks ,and 8wks) were injected Potassium dichromate (K/sub 2/Cr/sub 2/O/sub 7/) intraperitoneally according to experimental design. The drug caused slight to marked inflammation of smooth muscle fibers and vaculations of nuclei was also observed indicating degenerative changes. (author)

  11. Layer-dependent role of collagen recruitment during loading of the rat bladder wall.

    Science.gov (United States)

    Cheng, Fangzhou; Birder, Lori A; Kullmann, F Aura; Hornsby, Jack; Watton, Paul N; Watkins, Simon; Thompson, Mark; Robertson, Anne M

    2018-04-01

    In this work, we re-evaluated long-standing conjectures as to the source of the exceptionally large compliance of the bladder wall. Whereas these conjectures were based on indirect measures of loading mechanisms, in this work we take advantage of advances in bioimaging to directly assess collagen fibers and wall architecture during biaxial loading. A custom biaxial mechanical testing system compatible with multiphoton microscopy was used to directly measure the layer-dependent collagen fiber recruitment in bladder tissue from 9 male Fischer rats (4 adult and 5 aged). As for other soft tissues, the bladder loading curve was exponential in shape and could be divided into toe, transition and high stress regimes. The relationship between collagen recruitment and loading curves was evaluated in the context of the inner (lamina propria) and outer (detrusor smooth muscle) layers. The large extensibility of the bladder was found to be possible due to folds in the wall (rugae) that provide a mechanism for low resistance flattening without any discernible recruitment of collagen fibers throughout the toe regime. For more extensible bladders, as the loading extended into the transition regime, a gradual coordinated recruitment of collagen fibers between the lamina propria layer and detrusor smooth muscle layer was found. A second important finding was that wall extensibility could be lost by premature recruitment of collagen in the outer wall that cut short the toe region. This change was correlated with age. This work provides, for the first time, a mechanistic understanding of the role of collagen recruitment in determining bladder extensibility and capacitance.

  12. Comparison of optical beam smoothing techniques for inertial confinement fusion and improvement of smoothing by the use of zero-correlation masks

    International Nuclear Information System (INIS)

    Lehmberg, R. H.; Rothenberg, J. E.

    2000-01-01

    We present analytic theory and numerical simulations comparing the optical beam smoothing capabilities of the smoothing by spectral dispersion (SSD) technique using random temporal phase modulation, with that of the induced spatial incoherence technique. The analytic theory provides a simple formula for the SSD mode spectrum in the usual case where the phase mask at the focusing lens is random, and its asymptotic limit quantitatively relates the long wavelength mode smoothing to the width of the angular dispersion. With parameters and phase aberration relevant to the National Ignition Facility beams, the SSD simulations show that the large long wavelength components, which are also found in earlier simulations, can be significantly reduced by replacing the independent random phase masks in each pair of adjacent beams by a conjugate pair of zero-correlation masks. These simulations suggest that one can combine zero-correlation masks with random temporal phase modulation and multiple color cycles to achieve SSD smoothing approaching the optical bandwidth limit at all spatial frequencies, without using large angular dispersions. (c) 2000 American Institute of Physics

  13. On smoothness-asymmetric null infinities

    International Nuclear Information System (INIS)

    Valiente Kroon, Juan Antonio

    2006-01-01

    We discuss the existence of asymptotically Euclidean initial data sets for the vacuum Einstein field equations which would give rise (modulo an existence result for the evolution equations near spatial infinity) to developments with a past and a future null infinity of different smoothness. For simplicity, the analysis is restricted to the class of conformally flat, axially symmetric initial data sets. It is shown how the free parameters in the second fundamental form of the data can be used to satisfy certain obstructions to the smoothness of null infinity. The resulting initial data sets could be interpreted as those of some sort of (nonlinearly) distorted Schwarzschild black hole. Their developments would be that they admit a peeling future null infinity, but at the same time have a polyhomogeneous (non-peeling) past null infinity

  14. Diagnosis of osteoarthritis by cartilage surface smoothness quantified automatically from knee MRI

    DEFF Research Database (Denmark)

    Tummala, Sudhakar; Bay-Jensen, Anne-Christine; Karsdal, Morten A.

    2011-01-01

    Objective: We investigated whether surface smoothness of articular cartilage in the medial tibiofemoral compartment quantified from magnetic resonance imaging (MRI) could be appropriate as a diagnostic marker of osteoarthritis (OA). Method: At baseline, 159 community-based subjects aged 21 to 81...... with normal or OA-affected knees were recruited to provide a broad range of OA states. Smoothness was quantified using an automatic framework from low-field MRI in the tibial, femoral, and femoral subcompartments. Diagnostic ability of smoothness was evaluated by comparison with conventional OA markers......, correlations between smoothness and pain values and smoothness loss and cartilage loss supported a link to progression of OA. Thereby, smoothness markers may allow detection and monitoring of OA-supplemented currently accepted markers....

  15. Classification of smooth structures on a homotopy complex ...

    Indian Academy of Sciences (India)

    Abstract. We classify, up to diffeomorphism, all closed smooth manifolds homeo- morphic to the complex projective n-space CPn, where n = 3 and 4. Let M2n be a closed smooth 2n-manifold homotopy equivalent to CPn. We show that, up to diffeo- morphism, M6 has a unique differentiable structure and M8 has at most two ...

  16. Classification of smooth structures on a homotopy complex ...

    Indian Academy of Sciences (India)

    We classify, up to diffeomorphism, all closed smooth manifolds homeomorphic to the complex projective n -space C P n , where n = 3 and 4. Let M 2 n be a closed smooth 2 n -manifold homotopy equivalent to C P n . We show that, up to diffeomorphism, M 6 has a unique differentiable structure and M 8 has at most two ...

  17. Vestibular-related frontal cortical areas and their roles in smooth-pursuit eye movements: representation of neck velocity, neck-vestibular interactions and memory-based smooth-pursuit

    Directory of Open Access Journals (Sweden)

    Kikuro eFukushima

    2011-12-01

    Full Text Available Smooth-pursuit eye movements are voluntary responses to small slow-moving objects in the fronto-parallel plane. They evolved in primates, who possess high-acuity foveae, to ensure clear vision about the moving target. The primate frontal cortex contains two smooth-pursuit related areas; the caudal part of the frontal eye fields (FEF and the supplementary eye fields (SEF. Both areas receive vestibular inputs. We review functional differences between the two areas in smooth-pursuit. Most FEF pursuit neurons signal pursuit parameters such as eye velocity and gaze-velocity, and are involved in cancelling the vestibulo-ocular reflex by linear addition of vestibular and smooth-pursuit responses. In contrast, gaze-velocity signals are rarely represented in the SEF. Most FEF pursuit neurons receive neck velocity inputs, while discharge modulation during pursuit and trunk-on-head rotation adds linearly. Linear addition also occurs between neck velocity responses and vestibular responses during head-on-trunk rotation in a task-dependent manner. During cross-axis pursuit-vestibular interactions, vestibular signals effectively initiate predictive pursuit eye movements. Most FEF pursuit neurons discharge during the interaction training after the onset of pursuit eye velocity, making their involvement unlikely in the initial stages of generating predictive pursuit. Comparison of representative signals in the two areas and the results of chemical inactivation during a memory-based smooth-pursuit task indicate they have different roles; the SEF plans smooth-pursuit including working memory of motion-direction, whereas the caudal FEF generates motor commands for pursuit eye movements. Patients with idiopathic Parkinson’s disease were asked to perform this task, since impaired smooth-pursuit and visual working memory deficit during cognitive tasks have been reported in most patients. Preliminary results suggested specific roles of the basal ganglia in memory

  18. Cyclic mechanical strain-induced proliferation and migration of human airway smooth muscle cells: role of EMMPRIN and MMPs.

    Science.gov (United States)

    Hasaneen, Nadia A; Zucker, Stanley; Cao, Jian; Chiarelli, Christian; Panettieri, Reynold A; Foda, Hussein D

    2005-09-01

    Airway smooth muscle (ASM) proliferation and migration are major components of airway remodeling in asthma. Asthmatic airways are exposed to mechanical strain, which contributes to their remodeling. Matrix metalloproteinase (MMP) plays an important role in remodeling. In the present study, we examined if the mechanical strain of human ASM (HASM) cells contributes to their proliferation and migration and the role of MMPs in this process. HASM were exposed to mechanical strain using the FlexCell system. HASM cell proliferation, migration and MMP release, activation, and expression were assessed. Our results show that cyclic strain increased the proliferation and migration of HASM; cyclic strain increased release and activation of MMP-1, -2, and -3 and membrane type 1-MMP; MMP release was preceded by an increase in extracellular MMP inducer; Prinomastat [a MMP inhibitor (MMPI)] significantly decreased cyclic strain-induced proliferation and migration of HASM; and the strain-induced increase in the release of MMPs was accompanied by an increase in tenascin-C release. In conclusion, cyclic mechanical strain plays an important role in HASM cell proliferation and migration. This increase in proliferation and migration is through an increase in MMP release and activation. Pharmacological MMPIs should be considered in the pursuit of therapeutic options for airway remodeling in asthma.

  19. Human mesenchymal stem cells cultured on silk hydrogels with variable stiffness and growth factor differentiate into mature smooth muscle cell phenotype.

    Science.gov (United States)

    Floren, Michael; Bonani, Walter; Dharmarajan, Anirudh; Motta, Antonella; Migliaresi, Claudio; Tan, Wei

    2016-02-01

    Cell-matrix and cell-biomolecule interactions play critical roles in a diversity of biological events including cell adhesion, growth, differentiation, and apoptosis. Evidence suggests that a concise crosstalk of these environmental factors may be required to direct stem cell differentiation toward matured cell type and function. However, the culmination of these complex interactions to direct stem cells into highly specific phenotypes in vitro is still widely unknown, particularly in the context of implantable biomaterials. In this study, we utilized tunable hydrogels based on a simple high pressure CO2 method and silk fibroin (SF) the structural protein of Bombyx mori silk fibers. Modification of SF protein starting water solution concentration results in hydrogels of variable stiffness while retaining key structural parameters such as matrix pore size and β-sheet crystallinity. To further resolve the complex crosstalk of chemical signals with matrix properties, we chose to investigate the role of 3D hydrogel stiffness and transforming growth factor (TGF-β1), with the aim of correlating the effects on the vascular commitment of human mesenchymal stem cells. Our data revealed the potential to upregulate matured vascular smooth muscle cell phenotype (myosin heavy chain expression) of hMSCs by employing appropriate matrix stiffness and growth factor (within 72h). Overall, our observations suggest that chemical and physical stimuli within the cellular microenvironment are tightly coupled systems involved in the fate decisions of hMSCs. The production of tunable scaffold materials that are biocompatible and further specialized to mimic tissue-specific niche environments will be of considerable value to future tissue engineering platforms. This article investigates the role of silk fibroin hydrogel stiffness and transforming growth factor (TGF-β1), with the aim of correlating the effects on the vascular commitment of human mesenchymal stem cells. Specifically, we

  20. Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation

    Energy Technology Data Exchange (ETDEWEB)

    Nintasen, Rungrat [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University (Thailand); Riches, Kirsten; Mughal, Romana S. [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa [Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University (Thailand); Turner, Neil A. [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Porter, Karen E., E-mail: medkep@leeds.ac.uk [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} augments neointimal hyperplasia in human saphenous vein. Black-Right-Pointing-Pointer TNF-{alpha} induces detrimental effects on endothelial and smooth muscle cell function. Black-Right-Pointing-Pointer Estradiol exerts modulatory effects on TNF-induced vascular cell functions. Black-Right-Pointing-Pointer The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}). TNF-{alpha} can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-{alpha} on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-{alpha} (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-{alpha}, an effect that was abolished by co-culture with E2. TNF-{alpha} increased SV-SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV-SMC proliferation to a level comparable to that of TNF-{alpha} alone. SV-EC migration was significantly impaired by TNF-{alpha} (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-{alpha} increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-{alpha} potently induced ICAM-1 and VCAM-1 expression in both SV-EC and SV-SMC. However there

  1. Three-phase electric drive with modified electronic smoothing inductor

    DEFF Research Database (Denmark)

    Singh, Yash Veer; Rasmussen, Peter Omand; Andersen, Torben Ole

    2010-01-01

    This paper presents a three-phase electric drive with a modified electronic smoothing inductor (MESI) having reduced size of passive components. The classical electronic smoothing inductor (ESI) is able to control a diode bridge output current and also reduce not only mains current harmonics...

  2. EXCHANGE-RATES FORECASTING: EXPONENTIAL SMOOTHING TECHNIQUES AND ARIMA MODELS

    Directory of Open Access Journals (Sweden)

    Dezsi Eva

    2011-07-01

    Full Text Available Exchange rates forecasting is, and has been a challenging task in finance. Statistical and econometrical models are widely used in analysis and forecasting of foreign exchange rates. This paper investigates the behavior of daily exchange rates of the Romanian Leu against the Euro, United States Dollar, British Pound, Japanese Yen, Chinese Renminbi and the Russian Ruble. Smoothing techniques are generated and compared with each other. These models include the Simple Exponential Smoothing technique, as the Double Exponential Smoothing technique, the Simple Holt-Winters, the Additive Holt-Winters, namely the Autoregressive Integrated Moving Average model.

  3. Smooth invariant densities for random switching on the torus

    Science.gov (United States)

    Bakhtin, Yuri; Hurth, Tobias; Lawley, Sean D.; Mattingly, Jonathan C.

    2018-04-01

    We consider a random dynamical system obtained by switching between the flows generated by two smooth vector fields on the 2d-torus, with the random switchings happening according to a Poisson process. Assuming that the driving vector fields are transversal to each other at all points of the torus and that each of them allows for a smooth invariant density and no periodic orbits, we prove that the switched system also has a smooth invariant density, for every switching rate. Our approach is based on an integration by parts formula inspired by techniques from Malliavin calculus.

  4. Smoothing optimization of supporting quadratic surfaces with Zernike polynomials

    Science.gov (United States)

    Zhang, Hang; Lu, Jiandong; Liu, Rui; Ma, Peifu

    2018-03-01

    A new optimization method to get a smooth freeform optical surface from an initial surface generated by the supporting quadratic method (SQM) is proposed. To smooth the initial surface, a 9-vertex system from the neighbor quadratic surface and the Zernike polynomials are employed to establish a linear equation system. A local optimized surface to the 9-vertex system can be build by solving the equations. Finally, a continuous smooth optimization surface is constructed by stitching the above algorithm on the whole initial surface. The spot corresponding to the optimized surface is no longer discrete pixels but a continuous distribution.

  5. Some remarks on smooth renormings of Banach spaces

    Czech Academy of Sciences Publication Activity Database

    Hájek, Petr Pavel; Russo, T.

    2017-01-01

    Roč. 455, č. 2 (2017), s. 1272-1284 ISSN 0022-247X R&D Projects: GA ČR GA16-07378S Institutional support: RVO:67985840 Keywords : Fréchet smooth * approximation of norms * Ck-smooth norm Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 1.064, year: 2016 http://www.sciencedirect.com/science/article/pii/S0022247X17305462?via%3Dihub

  6. Star Products with Separation of Variables Admitting a Smooth Extension

    Science.gov (United States)

    Karabegov, Alexander

    2012-08-01

    Given a complex manifold M with an open dense subset Ω endowed with a pseudo-Kähler form ω which cannot be smoothly extended to a larger open subset, we consider various examples where the corresponding Kähler-Poisson structure and a star product with separation of variables on (Ω, ω) admit smooth extensions to M. We give a simple criterion of the existence of a smooth extension of a star product and apply it to these examples.

  7. Star products with separation of variables admitting a smooth extension

    OpenAIRE

    Karabegov, Alexander

    2010-01-01

    Given a complex manifold $M$ with an open dense subset $\\Omega$ endowed with a pseudo-Kaehler form $\\omega$ which cannot be smoothly extended to a larger open subset, we consider various examples where the corresponding Kaehler-Poisson structure and a star product with separation of variables on $(\\Omega, \\omega)$ admit smooth extensions to $M$. We suggest a simple criterion of the existence of a smooth extension of a star product and apply it to these examples.

  8. Spatial analysis on human brucellosis incidence in mainland China: 2004–2010

    Science.gov (United States)

    Zhang, Junhui; Yin, Fei; Zhang, Tao; Yang, Chao; Zhang, Xingyu; Feng, Zijian; Li, Xiaosong

    2014-01-01

    Objectives China has experienced a sharply increasing rate of human brucellosis in recent years. Effective spatial monitoring of human brucellosis incidence is very important for successful implementation of control and prevention programmes. The purpose of this paper is to apply exploratory spatial data analysis (ESDA) methods and the empirical Bayes (EB) smoothing technique to monitor county-level incidence rates for human brucellosis in mainland China from 2004 to 2010 by examining spatial patterns. Methods ESDA methods were used to characterise spatial patterns of EB smoothed incidence rates for human brucellosis based on county-level data obtained from the China Information System for Disease Control and Prevention (CISDCP) in mainland China from 2004 to 2010. Results EB smoothed incidence rates for human brucellosis were spatially dependent during 2004–2010. The local Moran test identified significantly high-risk clusters of human brucellosis (all p values brucellosis incidence. PMID:24713215

  9. Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Yun-Yun Ma

    Full Text Available Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification.

  10. HSP20 phosphorylation and airway smooth muscle relaxation

    Directory of Open Access Journals (Sweden)

    Mariam Ba

    2009-06-01

    Full Text Available Mariam Ba1, Cherie A Singer1, Manoj Tyagi2, Colleen Brophy3, Josh E Baker4, Christine Cremo4, Andrew Halayko5, William T Gerthoffer21Department of Pharmacology, University of Nevada School of Medicine, Reno, NV, USA; 2Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL, USA; 3Harrington Department of Biochemistry, Arizona State University, Tempe, AZ, USA; 4Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV, USA; 5Departments of Physiology and Internal Medicine, University of Manitoba, Winnipeg, MB, CanadaAbstract: HSP20 (HSPB6 is a small heat shock protein expressed in smooth muscles that is hypothesized to inhibit contraction when phosphorylated by cAMP-dependent protein kinase. To investigate this hypothesis in airway smooth muscle (ASM we showed that HSP20 was constitutively expressed as well as being inducible in cultured hASM cells by treatment with 1 µM isoproterenol or 10 µM salmeterol. In contrast, a mixture of proinflammatory mediators (interleukin-1β, tumor necrosis factor α, and interferon γ inhibited expression of HSP20 by about 50% in 48 hours. To determine whether phosphorylation of HSP20 is sufficient to induce relaxation, canine tracheal smooth muscle was treated with a cell permeant phosphopeptide that mimics the phosphorylation of HSP20. The HSP20 phosphopeptide antagonized carbacholinduced contraction by 60% with no change in myosin light chain phosphorylation. Recombinant full length HSP20 inhibited skeletal actin binding to smooth muscle myosin subfragment 1 (S1, and recombinant cell permeant TAT-HSP20 S16D mutant reduced F-actin filaments in cultured hASM cells. Carbachol stimulation of canine tracheal smooth muscle tissue caused redistribution of HSP20 from large macromolecular complexes (200–500 kDa to smaller complexes (<60 kDa. The results are consistent with HSP20 expression and macromolecular structure being dynamically regulated in airway

  11. Automatic smoothing parameter selection in GAMLSS with an application to centile estimation.

    Science.gov (United States)

    Rigby, Robert A; Stasinopoulos, Dimitrios M

    2014-08-01

    A method for automatic selection of the smoothing parameters in a generalised additive model for location, scale and shape (GAMLSS) model is introduced. The method uses a P-spline representation of the smoothing terms to express them as random effect terms with an internal (or local) maximum likelihood estimation on the predictor scale of each distribution parameter to estimate its smoothing parameters. This provides a fast method for estimating multiple smoothing parameters. The method is applied to centile estimation where all four parameters of a distribution for the response variable are modelled as smooth functions of a transformed explanatory variable x This allows smooth modelling of the location, scale, skewness and kurtosis parameters of the response variable distribution as functions of x. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Return Smoothing Mechanisms in Life and Pension Insurance

    DEFF Research Database (Denmark)

    Montserrat, Guillén; Jørgensen, Peter Løchte; Nielsen, Jens Perch

    2006-01-01

    pricing theory. We explore the properties of this pension scheme in detail and find that in terms of market value, smoothing is an illusion, but also that the return smoothing mechanism implies a dynamic asset allocation strategy which corresponds with traditional pension saving advice......Traditional with-profits pension saving schemes have been criticized for their opacity, plagued by embedded options and guarantees, and have recently created enormous problems for the solvency of the life insurance and pension industry. This has fueled creativity in the industry's product...... development departments, and this paper analyzes a representative member of a family of new pension schemes that have been introduced in the new millennium to alleviate these problems. The complete transparency of the new scheme's smoothing mechanism means that it can be analyzed using contingent claims...

  13. Panel Smooth Transition Regression Models

    DEFF Research Database (Denmark)

    González, Andrés; Terasvirta, Timo; Dijk, Dick van

    We introduce the panel smooth transition regression model. This new model is intended for characterizing heterogeneous panels, allowing the regression coefficients to vary both across individuals and over time. Specifically, heterogeneity is allowed for by assuming that these coefficients are bou...

  14. Second-order numerical methods for multi-term fractional differential equations: Smooth and non-smooth solutions

    Science.gov (United States)

    Zeng, Fanhai; Zhang, Zhongqiang; Karniadakis, George Em

    2017-12-01

    Starting with the asymptotic expansion of the error equation of the shifted Gr\\"{u}nwald--Letnikov formula, we derive a new modified weighted shifted Gr\\"{u}nwald--Letnikov (WSGL) formula by introducing appropriate correction terms. We then apply one special case of the modified WSGL formula to solve multi-term fractional ordinary and partial differential equations, and we prove the linear stability and second-order convergence for both smooth and non-smooth solutions. We show theoretically and numerically that numerical solutions up to certain accuracy can be obtained with only a few correction terms. Moreover, the correction terms can be tuned according to the fractional derivative orders without explicitly knowing the analytical solutions. Numerical simulations verify the theoretical results and demonstrate that the new formula leads to better performance compared to other known numerical approximations with similar resolution.

  15. Income smoothing by Dutch hospitals

    NARCIS (Netherlands)

    Boterenbrood, D.R.

    2014-01-01

    Research indicates that hospitals manage their earnings. However, these findings might be influenced by methodological issues. In this study, I exploit specific features of Dutch hospitals to study income smoothing while limiting these methodological issues. The managers of Dutch hospitals have the

  16. An adaptive segment method for smoothing lidar signal based on noise estimation

    Science.gov (United States)

    Wang, Yuzhao; Luo, Pingping

    2014-10-01

    An adaptive segmentation smoothing method (ASSM) is introduced in the paper to smooth the signal and suppress the noise. In the ASSM, the noise is defined as the 3σ of the background signal. An integer number N is defined for finding the changing positions in the signal curve. If the difference of adjacent two points is greater than 3Nσ, the position is recorded as an end point of the smoothing segment. All the end points detected as above are recorded and the curves between them will be smoothed separately. In the traditional method, the end points of the smoothing windows in the signals are fixed. The ASSM creates changing end points in different signals and the smoothing windows could be set adaptively. The windows are always set as the half of the segmentations and then the average smoothing method will be applied in the segmentations. The Iterative process is required for reducing the end-point aberration effect in the average smoothing method and two or three times are enough. In ASSM, the signals are smoothed in the spacial area nor frequent area, that means the frequent disturbance will be avoided. A lidar echo was simulated in the experimental work. The echo was supposed to be created by a space-born lidar (e.g. CALIOP). And white Gaussian noise was added to the echo to act as the random noise resulted from environment and the detector. The novel method, ASSM, was applied to the noisy echo to filter the noise. In the test, N was set to 3 and the Iteration time is two. The results show that, the signal could be smoothed adaptively by the ASSM, but the N and the Iteration time might be optimized when the ASSM is applied in a different lidar.

  17. PHYSICAL CONTACT BETWEEN HUMAN VASCULAR ENDOTHELIAL AND SMOOTH MUSCLE CELLS MODULATES CYTOSOLIC AND NUCLEAR CALCIUM HOMEOSTASIS.

    Science.gov (United States)

    Hassan, Ghada S; Jacques, Danielle; D'Orleans-Juste, Pedro; Magder, Sheldon; Bkaily, Ghassan

    2018-05-14

    The interaction between vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) plays an important role in the modulation of vascular tone. There is however no information on whether direct physical communication regulates the intracellular calcium levels of human VECs (hVECs) and/or hVSMCs . Thus, the objective of the study is to verify whether co-culture of hVECs and hVSMCs modulates cytosolic ([Ca2+]c) and nuclear calcium ([Ca2+]n) levels via physical contact and/or factors released by both cell types. Quantitative 3D confocal microscopy for [Ca2+]c and [Ca2+]n measurement was performed in cultured hVECs or hVSMCs or in co-culture of hVECs-hVSMCs. Our results show that: 1) physical contact between hVECs-hVECs or hVSMCs-hVSMCs does not affect [Ca2+]c and [Ca2+]n in these two cell types; 2) physical contact between hVECs and hVSMCs induces a significant increase only of [Ca2+]n of hVECs without affecting the level of [Ca2+]c and [Ca2+]n of hVSMCs; and 3) preconditioned culture medium of hVECs or hVSMCs does not affect [Ca2+]c and [Ca2+]n of both types of cells. We concluded that physical contact between hVECs and hVSMCs only modulates [Ca2+]n in hVECs. The increase of [Ca2+]n in hVECs may modulate nuclear functions that are calcium dependent.

  18. Induction of CTGF by TGF-β1 in normal and radiation enteritis human smooth muscle cells: Smad/Rho balance and therapeutic perspectives

    International Nuclear Information System (INIS)

    Haydont, Valerie; Mathe, Denis; Bourgier, Celine; Abdelali, Jalil; Aigueperse, Jocelyne; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine

    2005-01-01

    Background and purpose: Transforming Growth Factor β1 (TGF-β1) and its downstream effector Connective Tissue Growth Factor (CTGF/CCN2), are well known fibrogenic activators and we previously showed that the Rho/ROCK pathway controls CTGF expression in intestinal smooth muscle cells isolated from patients with delayed radiation enteritis. The aim of the present work was to investigate the balance between Smad and Rho signalling pathways in the TGF-β1 CTGF induction and modulation of radiation-induced fibrogenic differentiation after addition of pravastatin, an inhibitor of Rho isoprenylation. Patients and methods: Primary human smooth muscle cells isolated from normal (N-SMC) or radiation enteritis (RE-SMC) biopsies were incubated with TGF-β1 (10 ng/ml). Induction of CTGF, as well as nucleo-cytoplasmic distribution of phospho-Smad2/3, Smad2/3 and Smad4 were analysed by Western blot and immunocytochemistry. Smad DNA binding was assessed by EMSA and Rho activation was measured by pull-down assay. Results: After TGF-β1 addition, Smads were translocated to the nucleus in both cell types. Nuclear accumulation of Smad as well as their DNA-binding activity were higher in N-SMC than in RE-SMC, whereas the opposite was observed for Rho activation, suggesting a main involvement of Rho pathway in sustained fibrogenic differentiation. This hypothesis was further supported by the antifibrotic effect observed in vitro after cell treatment with pravastatin (i.e. decreased expression of CTGF, TGF-β1 and Collagen Iα2). Conclusions: Our results suggest that TGF-β1-induced CTGF transactivation mainly depends on the Smad pathway in N-SMC, whereas in RE-SMC, Smad and Rho pathways are involved. Inhibition of Rho activity by pravastatin alters fibrogenic differentiation in vitro which opens up new therapeutic perspectives

  19. The angiotensin-(1-7/Mas axis counteracts angiotensin II-dependent and –independent pro-inflammatory signaling in human vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Laura A Villalobos

    2016-12-01

    Full Text Available Background and aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7 is a member of the renin-angiotensin system (RAS that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7 to counteract human aortic smooth muscle cell (HASMC inflammation triggered by RAS-dependent and –independent stimuli, such as Ang II or interleukin (IL-1.Methods and Results: In cultured HASMC, the expression of iNOS and the release of nitric oxide were stimulated by both Ang II and IL-1, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7 in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7, suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and NF-B. Indeed, Ang-(1-7 markedly inhibited the activation of the NADPH oxidase and subsequently of NF-B, as determined by lucigenin-derived chemiluminiscence and electromobility shift assay, respectively.Conclusion: Ang-(1-7 can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.

  20. Full-waveform inversion using a nonlinearly smoothed wavefield

    KAUST Repository

    Li, Yuanyuan

    2017-12-08

    Conventional full-waveform inversion (FWI) based on the least-squares misfit function faces problems in converging to the global minimum when using gradient methods because of the cycle-skipping phenomena. An initial model producing data that are at most a half-cycle away from the observed data is needed for convergence to the global minimum. Low frequencies are helpful in updating low-wavenumber components of the velocity model to avoid cycle skipping. However, low enough frequencies are usually unavailable in field cases. The multiplication of wavefields of slightly different frequencies adds artificial low-frequency components in the data, which can be used for FWI to generate a convergent result and avoid cycle skipping. We generalize this process by multiplying the wavefield with itself and then applying a smoothing operator to the multiplied wavefield or its square to derive the nonlinearly smoothed wavefield, which is rich in low frequencies. The global correlation-norm-based objective function can mitigate the dependence on the amplitude information of the nonlinearly smoothed wavefield. Therefore, we have evaluated the use of this objective function when using the nonlinearly smoothed wavefield. The proposed objective function has much larger convexity than the conventional objective functions. We calculate the gradient of the objective function using the adjoint-state technique, which is similar to that of the conventional FWI except for the adjoint source. We progressively reduce the smoothing width applied to the nonlinear wavefield to naturally adopt the multiscale strategy. Using examples on the Marmousi 2 model, we determine that the proposed FWI helps to generate convergent results without the need for low-frequency information.

  1. Comparative Analysis for Robust Penalized Spline Smoothing Methods

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2014-01-01

    Full Text Available Smoothing noisy data is commonly encountered in engineering domain, and currently robust penalized regression spline models are perceived to be the most promising methods for coping with this issue, due to their flexibilities in capturing the nonlinear trends in the data and effectively alleviating the disturbance from the outliers. Against such a background, this paper conducts a thoroughly comparative analysis of two popular robust smoothing techniques, the M-type estimator and S-estimation for penalized regression splines, both of which are reelaborated starting from their origins, with their derivation process reformulated and the corresponding algorithms reorganized under a unified framework. Performances of these two estimators are thoroughly evaluated from the aspects of fitting accuracy, robustness, and execution time upon the MATLAB platform. Elaborately comparative experiments demonstrate that robust penalized spline smoothing methods possess the capability of resistance to the noise effect compared with the nonrobust penalized LS spline regression method. Furthermore, the M-estimator exerts stable performance only for the observations with moderate perturbation error, whereas the S-estimator behaves fairly well even for heavily contaminated observations, but consuming more execution time. These findings can be served as guidance to the selection of appropriate approach for smoothing the noisy data.

  2. MicroRNA-31 controls phenotypic modulation of human vascular smooth muscle cells by regulating its target gene cellular repressor of E1A-stimulated genes

    International Nuclear Information System (INIS)

    Wang, Jie; Yan, Cheng-Hui; Li, Yang; Xu, Kai; Tian, Xiao-Xiang; Peng, Cheng-Fei; Tao, Jie; Sun, Ming-Yu; Han, Ya-Ling

    2013-01-01

    Phenotypic modulation of vascular smooth muscle cells (VSMCs) plays a critical role in the pathogenesis of a variety of proliferative vascular diseases. The cellular repressor of E1A-stimulated genes (CREG) has been shown to play an important role in phenotypic modulation of VSMCs. However, the mechanism regulating CREG upstream signaling remains unclear. MicroRNAs (miRNAs) have recently been found to play a critical role in cell differentiation via target-gene regulation. This study aimed to identify a miRNA that binds directly to CREG, and may thus be involved in CREG-mediated VSMC phenotypic modulation. Computational analysis indicated that miR-31 bound to the CREG mRNA 3′ untranslated region (3′-UTR). miR-31 was upregulated in quiescent differentiated VSMCs and downregulated in proliferative cells stimulated by platelet-derived growth factor and serum starvation, demonstrating a negative relationship with the VSMC differentiation marker genes, smooth muscle α-actin, calponin and CREG. Using gain-of-function and loss-of-function approaches, CREG and VSMC differentiation marker gene expression levels were shown to be suppressed by a miR-31 mimic, but increased by a miR-31 inhibitor at both protein and mRNA levels. Notably, miR-31 overexpression or inhibition affected luciferase expression driven by the CREG 3′-UTR containing the miR-31 binding site. Furthermore, miR-31-mediated VSMC phenotypic modulation was inhibited in CREG-knockdown human VSMCs. We also determined miR-31 levels in the serum of patients with coronary artery disease (CAD), with or without in stent restenosis and in healthy controls. miR-31 levels were higher in the serum of CAD patients with restenosis compared to CAD patients without restenosis and in healthy controls. In summary, these data demonstrate that miR-31 not only directly binds to its target gene CREG and modulates the VSMC phenotype through this interaction, but also can be an important biomarker in diseases involving VSMC

  3. Sodium leak channel, non-selective contributes to the leak current in human myometrial smooth muscle cells from pregnant women.

    Science.gov (United States)

    Reinl, Erin L; Cabeza, Rafael; Gregory, Ismail A; Cahill, Alison G; England, Sarah K

    2015-10-01

    Uterine contractions are tightly regulated by the electrical activity of myometrial smooth muscle cells (MSMCs). These cells require a depolarizing current to initiate Ca(2+) influx and induce contraction. Cationic leak channels, which permit a steady flow of cations into a cell, are known to cause membrane depolarization in many tissue types. Previously, a Gd(3+)-sensitive, Na(+)-dependent leak current was identified in the rat myometrium, but the presence of such a current in human MSMCs and the specific ion channel conducting this current was unknown. Here, we report the presence of a Na(+)-dependent leak current in human myometrium and demonstrate that the Na(+)-leak channel, NALCN, contributes to this current. We performed whole-cell voltage-clamp on fresh and cultured MSMCs from uterine biopsies of term, non-laboring women and isolated the leak currents by using Ca(2+) and K(+) channel blockers in the bath solution. Ohmic leak currents were identified in freshly isolated and cultured MSMCs with normalized conductances of 14.6 pS/pF and 10.0 pS/pF, respectively. The myometrial leak current was significantly reduced (P < 0.01) by treating cells with 10 μM Gd(3+) or by superfusing the cells with a Na(+)-free extracellular solution. Reverse transcriptase PCR and immunoblot analysis of uterine biopsies from term, non-laboring women revealed NALCN messenger RNA and protein expression in the myometrium. Notably, ∼90% knockdown of NALCN protein expression with lentivirus-delivered shRNA reduced the Gd(3+)-sensitive leak current density by 42% (P < 0.05). Our results reveal that NALCN, in part, generates the leak current in MSMCs and provide the basis for future research assessing NALCN as a potential molecular target for modulating uterine excitability. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Kinematic evaluation of movement smoothness in golf: relationship between the normalized jerk cost of body joints and the clubhead.

    Science.gov (United States)

    Choi, Ahnryul; Joo, Su-Bin; Oh, Euichaul; Mun, Joung Hwan

    2014-02-26

    When the human body is introduced to a new motion or movement, it learns the placement of different body parts, sequential muscle control, and coordination between muscles to achieve necessary positions, and it hones this new skill over time and repetition. Previous studies have demonstrated definite differences in the smoothness of body movements with different levels of training, i.e., amateurs compared with professionals. Therefore, we tested the hypothesis that skilled golfers swing a driver with a smoother motion than do unskilled golfers. In addition, the relationship between the smoothness of body joints and that of the clubhead was evaluated to provide further insight into the mechanism of smooth golf swing. Two subject groups (skilled and unskilled) participated in the experiment. The skilled group comprised 20 male professional golfers registered with the Korea Professional Golf Association, and the unskilled group comprised 19 amateur golfers who enjoy golf as a hobby. Six infrared cameras (VICON460 system) were used to record the 3D trajectories of markers attached to the clubhead and body segments, and the resulting data was evaluated with kinematic analysis. A physical quantity called jerk was calculated to investigate differences in smoothness during downswing between the two study groups. The hypothesis that skilled golfers swing a driver with a smoother motion than do unskilled golfers was supported. The normalized jerk of the clubhead of skilled golfers was lower than that of unskilled golfers in the anterior/posterior, medial/lateral, and proximal/distal directions. Most human joints, especially in the lower body, had statistically significant lower normalized jerk values in the skilled group. In addition, the normalized jerk of the skilled group's lower body joints had a distinct positive correlation with the normalized jerk of the clubhead with r = 0.657 (p golf swings and, eventually, to improve golf performance.

  5. Covariances of smoothed observational data

    Czech Academy of Sciences Publication Activity Database

    Vondrák, Jan; Čepek, A.

    2000-01-01

    Roč. 40, 5-6 (2000), s. 42-44 ISSN 1210-2709 R&D Projects: GA ČR GA205/98/1104 Institutional research plan: CEZ:AV0Z1003909 Keywords : digital filter * smoothing * estimation of uncertainties Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics

  6. A Note on the Definition of a Smooth Curve

    Science.gov (United States)

    Euler, Russell; Sadek, Jawad

    2005-01-01

    In many elementary calculus textbooks in use today, the definition of a "smooth curve" is slightly ambiguous from the students' perspective. Even when smoothness is defined carefully, there is a shortage of relevant exercises that would serve to elaborate on related subtle points which many students may find confusing. In this article, the authors…

  7. An approach for spherical harmonic analysis of non-smooth data

    Science.gov (United States)

    Wang, Hansheng; Wu, Patrick; Wang, Zhiyong

    2006-12-01

    A method is proposed to evaluate the spherical harmonic coefficients of a global or regional, non-smooth, observable dataset sampled on an equiangular grid. The method is based on an integration strategy using new recursion relations. Because a bilinear function is used to interpolate points within the grid cells, this method is suitable for non-smooth data; the slope of the data may be piecewise continuous, with extreme changes at the boundaries. In order to validate the method, the coefficients of an axisymmetric model are computed, and compared with the derived analytical expressions. Numerical results show that this method is indeed reasonable for non-smooth models, and that the maximum degree for spherical harmonic analysis should be empirically determined by several factors including the model resolution and the degree of non-smoothness in the dataset, and it can be several times larger than the total number of latitudinal grid points. It is also shown that this method is appropriate for the approximate analysis of a smooth dataset. Moreover, this paper provides the program flowchart and an internet address where the FORTRAN code with program specifications are made available.

  8. Smoothing of, and parameter estimation from, noisy biophysical recordings.

    Directory of Open Access Journals (Sweden)

    Quentin J M Huys

    2009-05-01

    Full Text Available Biophysically detailed models of single cells are difficult to fit to real data. Recent advances in imaging techniques allow simultaneous access to various intracellular variables, and these data can be used to significantly facilitate the modelling task. These data, however, are noisy, and current approaches to building biophysically detailed models are not designed to deal with this. We extend previous techniques to take the noisy nature of the measurements into account. Sequential Monte Carlo ("particle filtering" methods, in combination with a detailed biophysical description of a cell, are used for principled, model-based smoothing of noisy recording data. We also provide an alternative formulation of smoothing where the neural nonlinearities are estimated in a non-parametric manner. Biophysically important parameters of detailed models (such as channel densities, intercompartmental conductances, input resistances, and observation noise are inferred automatically from noisy data via expectation-maximization. Overall, we find that model-based smoothing is a powerful, robust technique for smoothing of noisy biophysical data and for inference of biophysical parameters in the face of recording noise.

  9. An analysis of 1-D smoothed particle hydrodynamics kernels

    International Nuclear Information System (INIS)

    Fulk, D.A.; Quinn, D.W.

    1996-01-01

    In this paper, the smoothed particle hydrodynamics (SPH) kernel is analyzed, resulting in measures of merit for one-dimensional SPH. Various methods of obtaining an objective measure of the quality and accuracy of the SPH kernel are addressed. Since the kernel is the key element in the SPH methodology, this should be of primary concern to any user of SPH. The results of this work are two measures of merit, one for smooth data and one near shocks. The measure of merit for smooth data is shown to be quite accurate and a useful delineator of better and poorer kernels. The measure of merit for non-smooth data is not quite as accurate, but results indicate the kernel is much less important for these types of problems. In addition to the theory, 20 kernels are analyzed using the measure of merit demonstrating the general usefulness of the measure of merit and the individual kernels. In general, it was decided that bell-shaped kernels perform better than other shapes. 12 refs., 16 figs., 7 tabs

  10. Exponential smoothing weighted correlations

    Science.gov (United States)

    Pozzi, F.; Di Matteo, T.; Aste, T.

    2012-06-01

    In many practical applications, correlation matrices might be affected by the "curse of dimensionality" and by an excessive sensitiveness to outliers and remote observations. These shortcomings can cause problems of statistical robustness especially accentuated when a system of dynamic correlations over a running window is concerned. These drawbacks can be partially mitigated by assigning a structure of weights to observational events. In this paper, we discuss Pearson's ρ and Kendall's τ correlation matrices, weighted with an exponential smoothing, computed on moving windows using a data-set of daily returns for 300 NYSE highly capitalized companies in the period between 2001 and 2003. Criteria for jointly determining optimal weights together with the optimal length of the running window are proposed. We find that the exponential smoothing can provide more robust and reliable dynamic measures and we discuss that a careful choice of the parameters can reduce the autocorrelation of dynamic correlations whilst keeping significance and robustness of the measure. Weighted correlations are found to be smoother and recovering faster from market turbulence than their unweighted counterparts, helping also to discriminate more effectively genuine from spurious correlations.

  11. Root surface smoothness or roughness following open debridement. An in vivo study.

    Science.gov (United States)

    Schlageter, L; Rateitschak-Plüss, E M; Schwarz, J P

    1996-05-01

    Consensus has not been reached on the desired characteristics of the root surface following cleaning. It is also not clear what degree of roughness or smoothness results from use of different instruments. In the present human clinical study, various instruments for root surface cleaning were evaluated. 18 teeth destined for extraction for periodontal reasons were utilized. After reflection of soft tissue flaps, the 72 root surface aspects of the 18 teeth were uniformally treated with one of the following instruments: Gracey curette (GC), piezo ultrasonic scaler (PUS), Perioplaner curette (PPC), sonic scaler (SS), 75 microns diamond (75 D) and 15 microns diamond (15.D). The degree of roughness of each surface was measured after extraction. A planimetry apparatus was used to establish the average surface roughness (Ra) and the mean depth of the roughness profile (Rz). It was demonstrated that hand- and machine-driven curettes as well as very fine rotating diamonds created the smoothest root surfaces, while "vibrating" instruments such as sonic and ultrasonic scalers, as well as coarse diamonds, tended to roughen the root surface. Whether the root surface should be rough or smooth in order to enhance tissue healing remains an open question.

  12. Walking smoothness is associated with self-reported function after accounting for gait speed.

    Science.gov (United States)

    Lowry, Kristin A; Vanswearingen, Jessie M; Perera, Subashan; Studenski, Stephanie A; Brach, Jennifer S

    2013-10-01

    Gait speed has shown to be an indicator of functional status in older adults; however, there may be aspects of physical function not represented by speed but by the quality of movement. The purpose of this study was to determine the relations between walking smoothness, an indicator of the quality of movement based on trunk accelerations, and physical function. Thirty older adults (mean age, 77.7±5.1 years) participated. Usual gait speed was measured using an instrumented walkway. Walking smoothness was quantified by harmonic ratios derived from anteroposterior, vertical, and mediolateral trunk accelerations recorded during overground walking. Self-reported physical function was recorded using the function subscales of the Late-Life Function and Disability Instrument. Anteroposterior smoothness was positively associated with all function components of the Late-Life Function and Disability Instrument, whereas mediolateral smoothness exhibited negative associations. Adjusting for gait speed, anteroposterior smoothness remained associated with the overall and lower extremity function subscales, whereas mediolateral smoothness remained associated with only the advanced lower extremity subscale. These findings indicate that walking smoothness, particularly the smoothness of forward progression, represents aspects of the motor control of walking important for physical function not represented by gait speed alone.

  13. Some properties of the smoothed Wigner function

    International Nuclear Information System (INIS)

    Soto, F.; Claverie, P.

    1981-01-01

    Recently it has been proposed a modification of the Wigner function which consists in smoothing it by convolution with a phase-space gaussian function; this smoothed Wigner function is non-negative if the gaussian parameters Δ and delta satisfy the condition Δdelta > h/2π. We analyze in this paper the predictions of this modified Wigner function for the harmonic oscillator, for anharmonic oscillator and finally for the hydrogen atom. We find agreement with experiment in the linear case, but for strongly nonlinear systems, such as the hydrogen atom, the results obtained are completely wrong. (orig.)

  14. Cardiac, Skeletal, and smooth muscle mitochondrial respiration

    DEFF Research Database (Denmark)

    Park, Song-Young; Gifford, Jayson R; Andtbacka, Robert H I

    2014-01-01

    , skeletal, and smooth muscle was harvested from a total of 22 subjects (53±6 yrs) and mitochondrial respiration assessed in permeabilized fibers. Complex I+II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac, skeletal, to smooth muscle (54±1; 39±4; 15......±1 pmol•s(-1)•mg (-1), prespiration rates were normalized by CS (respiration...... per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, Complex I state 2 normalized for CS activity, an index of non-phosphorylating respiration per mitochondrial content, increased progressively from cardiac, skeletal...

  15. Effects of Piecewise Spatial Smoothing in 4-D SPECT Reconstruction

    Science.gov (United States)

    Qi, Wenyuan; Yang, Yongyi; King, Michael A.

    2014-02-01

    In nuclear medicine, cardiac gated SPECT images are known to suffer from significantly increased noise owing to limited data counts. Consequently, spatial (and temporal) smoothing has been indispensable for suppressing the noise artifacts in SPECT reconstruction. However, recently we demonstrated that the benefit of spatial processing in motion-compensated reconstruction of gated SPECT (aka 4-D) could be outweighed by its adverse effects on the myocardium, which included degraded wall motion and perfusion defect detectability. In this work, we investigate whether we can alleviate these adverse effects by exploiting an alternative spatial smoothing prior in 4-D based on image total variation (TV). TV based prior is known to induce piecewise smoothing which can preserve edge features (such as boundaries of the heart wall) in reconstruction. However, it is not clear whether such a property would necessarily be beneficial for improving the accuracy of the myocardium in 4-D reconstruction. In particular, it is unknown whether it would adversely affect the detectability of perfusion defects that are small in size or low in contrast. In our evaluation study, we first use Monte Carlo simulated imaging with 4-D NURBS-based cardiac-torso (NCAT) phantom wherein the ground truth is known for quantitative comparison. We evaluated the accuracy of the reconstructed myocardium using a number of metrics, including regional and overall accuracy of the myocardium, accuracy of the phase activity curve (PAC) of the LV wall for wall motion, uniformity and spatial resolution of the LV wall, and detectability of perfusion defects using a channelized Hotelling observer (CHO). For lesion detection, we simulated perfusion defects with different sizes and contrast levels with the focus being on perfusion defects that are subtle. As a preliminary demonstration, we also tested on three sets of clinical acquisitions. From the quantitative results, it was demonstrated that TV smoothing could

  16. Calcium signaling in smooth muscle.

    Science.gov (United States)

    Hill-Eubanks, David C; Werner, Matthias E; Heppner, Thomas J; Nelson, Mark T

    2011-09-01

    Changes in intracellular Ca(2+) are central to the function of smooth muscle, which lines the walls of all hollow organs. These changes take a variety of forms, from sustained, cell-wide increases to temporally varying, localized changes. The nature of the Ca(2+) signal is a reflection of the source of Ca(2+) (extracellular or intracellular) and the molecular entity responsible for generating it. Depending on the specific channel involved and the detection technology employed, extracellular Ca(2+) entry may be detected optically as graded elevations in intracellular Ca(2+), junctional Ca(2+) transients, Ca(2+) flashes, or Ca(2+) sparklets, whereas release of Ca(2+) from intracellular stores may manifest as Ca(2+) sparks, Ca(2+) puffs, or Ca(2+) waves. These diverse Ca(2+) signals collectively regulate a variety of functions. Some functions, such as contractility, are unique to smooth muscle; others are common to other excitable cells (e.g., modulation of membrane potential) and nonexcitable cells (e.g., regulation of gene expression).

  17. Physiological and pharmacological characterization of transmembrane acid extruders in cultured human umbilical artery smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Gunng-Shinng Chen

    2015-01-01

    Full Text Available Background: Intracellular pH (pH i is a pivotal factor for cellular functions and homeostasis. Apart from passive intracellular buffering capacity, active transmembrane transporters responsible for kinetic changes of pH i impacts. Acid extrusion transporters such as Na + /H + exchanger (NHE and Na + /HCO3− cotransporter (NBC have been found to be activated when cells are in an acidic condition in different cell types. However, such far, the pH i regulators have not been characterized in human umbilical artery smooth muscle cells (HUASMCs. Materials and Methods: We, therefore, investigated the mechanism of pH i recovery from intracellular acidosis, induced by NH 4 Cl-prepulse, using pH-sensitive fluorescence dye: 2′,7′-bis(2-carboxethyl-5(6-carboxy-fluorescein in HUASMCs. Cultured HUASMCs were derived from the segments of the human umbilical artery that were obtained from women undergoing children delivery. Results: The resting pH i is 7.23 ± 0.03 when cells in HEPES (nominally HCO 3− -free buffered solution. The resting pH i is higher as 7.27 ± 0.03 when cells in CO 2 /HCO3− -buffered solution. In HEPES-buffered solution, a pH i recovery following induced intracellular acidosis could be inhibited completely by 30 μM HOE 694 (a specific NHE inhibitor or by removing [Na +]o . In 5% CO2/HCO3− -buffered solution, 30 μM HOE 694 slowed the pH i recovery from the induced intracellular acidosis only. On the contrary, HOE 694 adding together with 0.2 mM 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (a specific NBC inhibitor or removal of [Na +]o entirely blocked the acid extrusion. By using Western blot technique, we demonstrated that four different isoforms of NBC, that is, SLC4A8 (NBCBE, SLC4A7 (NBCn1, SLC4A5 (NBCe2 and SLC4A4 (NBCe1, co-exist in the HUASMCs. Conclusions: We demonstrate, for the 1 st time, that apart from the housekeeping NHE1, another Na + couple HCO3− -transporter, that is, NBC, functionally coexists to

  18. Fuzzy Logic Based Edge Detection in Smooth and Noisy Clinical Images.

    Directory of Open Access Journals (Sweden)

    Izhar Haq

    Full Text Available Edge detection has beneficial applications in the fields such as machine vision, pattern recognition and biomedical imaging etc. Edge detection highlights high frequency components in the image. Edge detection is a challenging task. It becomes more arduous when it comes to noisy images. This study focuses on fuzzy logic based edge detection in smooth and noisy clinical images. The proposed method (in noisy images employs a 3 × 3 mask guided by fuzzy rule set. Moreover, in case of smooth clinical images, an extra mask of contrast adjustment is integrated with edge detection mask to intensify the smooth images. The developed method was tested on noise-free, smooth and noisy images. The results were compared with other established edge detection techniques like Sobel, Prewitt, Laplacian of Gaussian (LOG, Roberts and Canny. When the developed edge detection technique was applied to a smooth clinical image of size 270 × 290 pixels having 24 dB 'salt and pepper' noise, it detected very few (22 false edge pixels, compared to Sobel (1931, Prewitt (2741, LOG (3102, Roberts (1451 and Canny (1045 false edge pixels. Therefore it is evident that the developed method offers improved solution to the edge detection problem in smooth and noisy clinical images.

  19. Determining the Optimal Values of Exponential Smoothing Constants--Does Solver Really Work?

    Science.gov (United States)

    Ravinder, Handanhal V.

    2013-01-01

    A key issue in exponential smoothing is the choice of the values of the smoothing constants used. One approach that is becoming increasingly popular in introductory management science and operations management textbooks is the use of Solver, an Excel-based non-linear optimizer, to identify values of the smoothing constants that minimize a measure…

  20. Smooth surfaces from bilinear patches: Discrete affine minimal surfaces

    KAUST Repository

    Käferböck, Florian

    2013-06-01

    Motivated by applications in freeform architecture, we study surfaces which are composed of smoothly joined bilinear patches. These surfaces turn out to be discrete versions of negatively curved affine minimal surfaces and share many properties with their classical smooth counterparts. We present computational design approaches and study special cases which should be interesting for the architectural application. 2013 Elsevier B.V.

  1. Reoxygenation of human coronary smooth muscle cells suppresses HIF-1{alpha} gene expression and augments radiation-induced growth delay and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Grumann, T.; Arab, A.; Bode, C.; Hehrlein, C. [Dept. of Cardiology, Univ. Clinic of Freiburg (Germany); Guttenberger, R. [Dept. of Radiotherapy, Univ. Clinic of Freiburg (Germany)

    2006-01-01

    Background and Purpose: Catheter-based coronary brachytherapy with {beta}- and {gamma}-radiation is an evidence-based method to prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA) and stent implantation, but the outcome may be PTCA are hypoxic. A lack of oxygen decreases the effect of low LET (linear energy transfer) irradiation. The authors assumed that reoxygenation of hypoxic human coronary smooth muscle cells (HCSMCs) improves the results of coronary brachytherapy. The expression of hypoxia-inducible factor 1{alpha} (HIF-1{alpha}) gene, and the rates of growth and apoptosis of hypoxic and reoxygenated HCSMCs after {gamma}-iradiation were therefore analyzed. Material and Methods: An in vitro model of megacolonies of HCSMCs was developed. After exposure to chronic hypoxia the HCSMCs were irradiated with graded doses of 2, 4, 8, and 16 Gy using a {sup 60}Co source either under hypoxia (pO{sub 2}<3 mmHg) or after reoxygenation (pO{sub 2}{approx}150 mmHg). RT-PCR (reverse transcription-polymerase chain reaction) analysis was used to quantify HIF-1{alpha} gene expression and the growth of HCSMC megacolonies was measured serially. The oxygen enhancement ratio (OER) was calculate from the specific growth delay. Apoptosis of HCSMCs was quantified by counting cells with specific DNA strand breaks using the TUNEL assy. Results: HIF-1{alpha} gene expression was markedly suppressed in reoxygenated cells versus hypoxic cells 30 min after {gamma}-irradiation at all radiation doses (158{+-}46% vs. 1,675{+-}1,211%; p<0.01). Apoptosis was markedly increased in reoxygenated HCSMCs. The OER was 1.8(95% CI[confidence interval]1.3-2.4). Therefore, reoxygenated HCSMCs require 44% less radiation dose to achieve the equivalent biological radiation effect compared to hypoxic HCSMCs. Conclusion: Reoxygenation of coronary smooth muscle cells should be considered an option to increase efficacy of coronary brachytherapy. This could be used to reduce radiation dose

  2. The persistence of active smooth muscle in the female rat cervix through pregnancy.

    Science.gov (United States)

    Ferland, David J; Darios, Emma S; Watts, Stephanie W

    2015-02-01

    A controversy exists as to whether functional smooth muscle exists in the cervix before and during pregnancy, potentially continuous with the uterus. We hypothesized that cervical smooth muscle persists through pregnancy and is functional. Uteri and cervices were taken from female virgin, 11 day, and 20 day (near labor) pregnant rats. All experiments used the uterus as a positive control. Three different smooth muscle proteins (smooth muscle α-actin, SM-22α, and calponin-1) allowed immunohistochemical detection of the continuous nature of the smooth muscle from the vagina, cervix, and uterus. Tissues were also hung in isolated tissue baths for the measurement of isometric smooth muscle contraction. Uterine and cervical homogenates were also used in Western analyses to measure protein expression. Immunohistochemistry revealed there to be smooth muscle as validated by an expression of all 3 markers in the cervix. This smooth muscle was continuous with that of the vagina and uterus. Smooth muscle α-actin was detected in virgin tissue (291.3 ± 32.2 arbitrary densitometry units/β-actin), day 11 (416.8 ± 19.5), and day 20 pregnant tissue (293.0 ± 34.4). The virgin, day 11, and day 20 cervices contracted 2.18 ± 0.24 g, 1.46 ± 0.08 g, and 3.88 ± 0.49 g (respectively) to depolarizing KCl. Cervices contracted at day 20 to the cholinergic muscarinic agonist carbamylcholine (maximum, 133% ± 18.2% KCl contraction, n = 4). These findings strongly support that smooth muscle is present in the cervix through pregnancy and continuous with the uterus. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Electrochemically replicated smooth aluminum foils for anodic alumina nanochannel arrays

    International Nuclear Information System (INIS)

    Biring, Sajal; Tsai, K-T; Sur, Ujjal Kumar; Wang, Y-L

    2008-01-01

    A fast electrochemical replication technique has been developed to fabricate large-scale ultra-smooth aluminum foils by exploiting readily available large-scale smooth silicon wafers as the masters. Since the adhesion of aluminum on silicon depends on the time of surface pretreatment in water, it is possible to either detach the replicated aluminum from the silicon master without damaging the replicated aluminum and master or integrate the aluminum film to the silicon substrate. Replicated ultra-smooth aluminum foils are used for the growth of both self-organized and lithographically guided long-range ordered arrays of anodic alumina nanochannels without any polishing pretreatment

  4. Optimal Smoothing in Adaptive Location Estimation

    OpenAIRE

    Mammen, Enno; Park, Byeong U.

    1997-01-01

    In this paper higher order performance of kernel basedadaptive location estimators are considered. Optimalchoice of smoothing parameters is discussed and it isshown how much is lossed in efficiency by not knowingthe underlying translation density.

  5. Quantification of smoothing requirement for 3D optic flow calculation of volumetric images

    DEFF Research Database (Denmark)

    Bab-Hadiashar, Alireza; Tennakoon, Ruwan B.; de Bruijne, Marleen

    2013-01-01

    Complexities of dynamic volumetric imaging challenge the available computer vision techniques on a number of different fronts. This paper examines the relationship between the estimation accuracy and required amount of smoothness for a general solution from a robust statistics perspective. We show...... that a (surprisingly) small amount of local smoothing is required to satisfy both the necessary and sufficient conditions for accurate optic flow estimation. This notion is called 'just enough' smoothing, and its proper implementation has a profound effect on the preservation of local information in processing 3D...... dynamic scans. To demonstrate the effect of 'just enough' smoothing, a robust 3D optic flow method with quantized local smoothing is presented, and the effect of local smoothing on the accuracy of motion estimation in dynamic lung CT images is examined using both synthetic and real image sequences...

  6. Tumor necrosis factor-alpha enhances mRNA expression and secretion of interleukin-6 in cultured human airway smooth muscle cells

    NARCIS (Netherlands)

    S. McKay (Sue); S.J. Hirst (Stuart); M. Bertrand-de Haas (Marion); J.C. de Jongste (Johan); H.C. Hoogsteden (Henk); P.R. Saxena (Pramod Ranjan); H.S. Sharma (Hari)

    2000-01-01

    textabstractAirway smooth muscle (ASM) is considered to be an end-target cell for the effects of mediators released during airway wall inflammation. Several reports suggest that activated ASM may be capable of generating various proinflammatory cytokines. We

  7. Measurement-induced decoherence and Gaussian smoothing of the Wigner distribution function

    International Nuclear Information System (INIS)

    Chun, Yong-Jin; Lee, Hai-Woong

    2003-01-01

    We study the problem of measurement-induced decoherence using the phase-space approach employing the Gaussian-smoothed Wigner distribution function. Our investigation is based on the notion that measurement-induced decoherence is represented by the transition from the Wigner distribution to the Gaussian-smoothed Wigner distribution with the widths of the smoothing function identified as measurement errors. We also compare the smoothed Wigner distribution with the corresponding distribution resulting from the classical analysis. The distributions we computed are the phase-space distributions for simple one-dimensional dynamical systems such as a particle in a square-well potential and a particle moving under the influence of a step potential, and the time-frequency distributions for high-harmonic radiation emitted from an atom irradiated by short, intense laser pulses

  8. Smooth-arm spiral galaxies: their properties and significance to cluster-galaxy evolution

    International Nuclear Information System (INIS)

    Wilkerson, M.S.

    1979-01-01

    In this dissertation a number of galaxies with optical appearances between those of normal, actively-star-forming spirals and SO galaxies have been examined. These so-called smooth-arm spiral galaxies exhibit spiral arms without any of the spiral tracers - H II regions, O-B star associations, dust - indicative of current star formation. Tests were made to find if, perhaps, these smooth-arm spirals could have, at one time, been normal, actively-star-forming spirals whose gas had been somehow removed; and that are currently transforming into SO galaxies. This scenario proceeds as (1) removal of gas, (2) gradual dying of disk density wave, (3) emergence of SO galaxy. If the dominant method of gas removal is ram-pressure stripping by a hot, intracluster medium, then smooth-arm spirals should occur primarily in x-ray clusters. Some major findings of this dissertation are as follows: (1) Smooth-arm spirals are redder than normal spirals of the same morphological type. Most smooth-arm spirals cannot be distinguished by color from SO galaxies. (2) A weak trend exists for smooth-arm spirals with stronger arms to be bluer than those with weaker arms; thus implying that the interval since gas removal has been shorter for the galaxies with stronger arms. (3) Smooth-arm spirals are deficient in neutral hydrogen - sometimes by an order of magnitude or, possibly, more

  9. Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation

    International Nuclear Information System (INIS)

    Fukuda, Kazuki; Matsumura, Takeshi; Senokuchi, Takafumi; Ishii, Norio; Kinoshita, Hiroyuki; Yamada, Sarie; Murakami, Saiko; Nakao, Saya; Motoshima, Hiroyuki; Kondo, Tatsuya; Kukidome, Daisuke; Kawasaki, Shuji; Kawada, Teruo; Nishikawa, Takeshi; Araki, Eiichi

    2015-01-01

    Highlights: • Statins induce PPARγ activation in vascular smooth muscle cells. • Statin-induced PPARγ activation is mediated by COX-2 expression. • Statins suppress cell migration and proliferation in vascular smooth muscle cells. • Statins inhibit LPS-induced inflammatory responses by PPARγ activation. • Fluvastatin suppress the progression of atherosclerosis and induces PPARγ activation in the aorta of apoE-deficient mice. - Abstract: The peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of lipid and glucose metabolism, and its activation is reported to suppress the progression of atherosclerosis. We have reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) activate PPARγ in macrophages. However, it is not yet known whether statins activate PPARγ in other vascular cells. In the present study, we investigated whether statins activate PPARγ in smooth muscle cells (SMCs) and endothelial cells (ECs) and thus mediate anti-atherosclerotic effects. Human aortic SMCs (HASMCs) and human umbilical vein ECs (HUVECs) were used in this study. Fluvastatin and pitavastatin activated PPARγ in HASMCs, but not in HUVECs. Statins induced cyclooxygenase-2 (COX-2) expression in HASMCs, but not in HUVECs. Moreover, treatment with COX-2-siRNA abrogated statin-mediated PPARγ activation in HASMCs. Statins suppressed migration and proliferation of HASMCs, and inhibited lipopolysaccharide-induced expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in HASMCs. These effects of statins were abrogated by treatment with PPARγ-siRNA. Treatment with statins suppressed atherosclerotic lesion formation in Apoe −/− mice. In addition, transcriptional activity of PPARγ and CD36 expression were increased, and the expression of MCP-1 and TNF-α was decreased, in the aorta of statin-treated Apoe −/− mice. In conclusion, statins mediate anti-atherogenic effects through PPAR

  10. Restoring a smooth function from its noisy integrals

    Science.gov (United States)

    Goulko, Olga; Prokof'ev, Nikolay; Svistunov, Boris

    2018-05-01

    Numerical (and experimental) data analysis often requires the restoration of a smooth function from a set of sampled integrals over finite bins. We present the bin hierarchy method that efficiently computes the maximally smooth function from the sampled integrals using essentially all the information contained in the data. We perform extensive tests with different classes of functions and levels of data quality, including Monte Carlo data suffering from a severe sign problem and physical data for the Green's function of the Fröhlich polaron.

  11. Development of human umbilical vein endothelial cell (HUVEC) and human umbilical vein smooth muscle cell (HUVSMC) branch/stem structures on hydrogel layers via biological laser printing (BioLP)

    International Nuclear Information System (INIS)

    Wu, P K; Ringeisen, B R

    2010-01-01

    Angiogenesis is one of the prerequisite steps for viable tissue formation. The ability to influence the direction and structure in the formation of a vascular system is crucial in engineering tissue. Using biological laser printing (BioLP), we fabricated branch/stem structures of human umbilical vein endothelial cells (HUVEC) and human umbilical vein smooth muscle cells (HUVSMC). The structure is simple as to mimic vascular networks in natural tissue but also allow cells to develop new, finer structures away from the stem and branches. Additionally, we printed co-culture structures by first depositing only HUVECs, followed by 24 h incubation to allow for adequate cell-cell communication and differentiation into lumina; these cell printed scaffold layers were then removed from incubation and inserted into the BioLP apparatus so that HUVSMCs could be directly deposited on top and around the previously printed HUVEC structures. The growth and differentiation of these co-culture structures was then compared to the growth of printed samples with either HUVECs or HUVSMCs alone. Lumen formation was found to closely mimic the original branch and stem structure. The beginning of a network structure is observed. HUVSMCs acted to limit HUVEC over-growth and migration when compared to printed HUVEC structures alone. HUVSMCs and HUVECS, when printed in close contact, appear to form cell-cell junctions around lumen-like structures. They demonstrate a symbiotic relationship which affects their development of phenotype when in close proximity of each other. Our results indicate that it is possible to direct the formation and growth of lumen and lumen network using BioLP.

  12. Cigarette Smoke and Estrogen Signaling in Human Airway Smooth Muscle

    Directory of Open Access Journals (Sweden)

    Venkatachalem Sathish

    2015-06-01

    Full Text Available Aims: Cigarette smoke (CS in active smokers and second-hand smoke exposure exacerbate respiratory disorders such as asthma and chronic bronchitis. While women are known to experience a more asthmatic response to CS than emphysema in men, there is limited information on the mechanisms of CS-induced airway dysfunction. We hypothesize that CS interferes with a normal (protective bronchodilatory role of estrogens, thus worsening airway contractility. Methods: We tested effects of cigarette smoke extract (CSE on 17β-estradiol (E2 signaling in enzymatically-dissociated bronchial airway smooth muscle (ASM obtained from lung samples of non-smoking female patients undergoing thoracic surgery. Results: In fura-2 loaded ASM cells, CSE increased intracellular calcium ([Ca2+]i responses to 10µM histamine. Acute exposure to physiological concentrations of E2 decreased [Ca2+]i responses. However, in 24h exposed CSE cells, although expression of estrogen receptors was increased, the effect of E2 on [Ca2+]i was blunted. Acute E2 exposure also decreased store-operated Ca2+ entry and inhibited stromal interaction molecule 1 (STIM1 phosphorylation: effects blunted by CSE. Acute exposure to E2 increased cAMP, but less so in 24h CSE-exposed cells. 24h CSE exposure increased S-nitrosylation of ERα. Furthermore, 24h CSE-exposed bronchial rings showed increased bronchoconstrictor agonist responses that were not reduced as effectively by E2 compared to non-CSE controls. Conclusion: These data suggest that CS induces dysregulation of estrogen signaling in ASM, which could contribute to increased airway contractility in women exposed to CS.

  13. Nonparenchymal cells cultivated from explants of fibrotic liver resemble endothelial and smooth muscle cells from blood vessel walls

    International Nuclear Information System (INIS)

    Voss, B.; Rauterberg, J.; Pott, G.; Brehmer, U.; Allam, S.; Lehmann, R.; von Bassewitz, D.B.

    1982-01-01

    Tissue specimens from human fibrotic liver obtained by needle biopsy were cultured. Two cell types emerged from the tissue explants. From their morphology and biosynthetic products they resembled smooth muscle cells and endothelial cells from blood vessel walls. In the endothelial cells, factor VIII-associated protein was demonstrated by indirect immunofluorescence. Synthesis of collagen types I and III, basement membrane collagen types IV and V, and fibronectin by both cell types was observed by immunofluorescence microscopy. Homogeneous cultures of smooth muscle cells were observed in subcultures. After incubation with [ 14 C]glycine, collagen was isolated and characterized by CM cellulose chromatography, and consisted mainly of types I and III. These data suggest involvement of mesenchymal cells in hepatic fibrosis; they presumably originate from blood vessel or sinusoidal walls

  14. Adaptive Smoothed Finite Elements (ASFEM) for history dependent material models

    International Nuclear Information System (INIS)

    Quak, W.; Boogaard, A. H. van den

    2011-01-01

    A successful simulation of a bulk forming process with finite elements can be difficult due to distortion of the finite elements. Nodal smoothed Finite Elements (NSFEM) are an interesting option for such a process since they show good distortion insensitivity and moreover have locking-free behavior and good computational efficiency. In this paper a method is proposed which takes advantage of the nodally smoothed field. This method, named adaptive smoothed finite elements (ASFEM), revises the mesh for every step of a simulation without mapping the history dependent material parameters. In this paper an updated-Lagrangian implementation is presented. Several examples are given to illustrate the method and to show its properties.

  15. Heparin modulates human intestinal smooth muscle (HISM) cell proliferation and matrix production

    International Nuclear Information System (INIS)

    Graham, M.; Perr, H.; Drucker, D.E.; Diegelmann, R.F.

    1986-01-01

    (HISM) cell proliferation and collagen production may play a role in the pathogenesis of intestinal stricture in Crohn's disease. The present studies were performed to evaluate the effects of heparin, a known modulator of vascular smooth muscle cells, on HISM cell proliferation and collagen production. Heparin (100 μg/ml) was added daily to HISM cell cultures for cell proliferation studies and for 24 hours at various time points during culture for collagen synthesis studies. Collagen synthesis was determined by the uptake of 3 H proline into collagenase-sensitive protein. Heparin completely inhibited cell proliferation for 7 days, after which cell numbers increased but at a slower rate than controls. Cells released from heparin inhibition demonstrated catch-up growth to control levels. Collagen production was significantly inhibited by 24 hours exposure to heparin but only at those times during culture when collagen synthesis was maximal (8 to 12 days). Non-collagen protein synthesis was inhibited by heparin at all time points during culture. Heparin through its modulation of HISM cells may play an important role in the control of the extracellular matrix of the intestinal wall

  16. Fetuin-A and albumin alter cytotoxic effects of calcium phosphate nanoparticles on human vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Yana Dautova

    Full Text Available Calcification is a detrimental process in vascular ageing and in diseases such as atherosclerosis and arthritis. In particular, small calcium phosphate (CaP crystal deposits are associated with inflammation and atherosclerotic plaque de-stabilisation. We previously reported that CaP particles caused human vascular smooth muscle cell (VSMC death and that serum reduced the toxic effects of the particles. Here, we found that the serum proteins fetuin-A and albumin (≥ 1 µM reduced intracellular Ca2+ elevations and cell death in VSMCs in response to CaP particles. In addition, CaP particles functionalised with fetuin-A, but not albumin, were less toxic than naked CaP particles. Electron microscopic studies revealed that CaP particles were internalised in different ways; via macropinocytosis, membrane invagination or plasma membrane damage, which occurred within 10 minutes of exposure to particles. However, cell death did not occur until approximately 30 minutes, suggesting that plasma membrane repair and survival mechanisms were activated. In the presence of fetuin-A, CaP particle-induced damage was inhibited and CaP/plasma membrane interactions and particle uptake were delayed. Fetuin-A also reduced dissolution of CaP particles under acidic conditions, which may contribute to its cytoprotective effects after CaP particle exposure to VSMCs. These studies are particularly relevant to the calcification observed in blood vessels in patients with kidney disease, where circulating levels of fetuin-A and albumin are low, and in pathological situations where CaP crystal formation outweighs calcification-inhibitory mechanisms.

  17. Efference copy failure during smooth pursuit eye movements in schizophrenia.

    Science.gov (United States)

    Spering, Miriam; Dias, Elisa C; Sanchez, Jamie L; Schütz, Alexander C; Javitt, Daniel C

    2013-07-17

    Abnormal smooth pursuit eye movements in patients with schizophrenia are often considered a consequence of impaired motion perception. Here we used a novel motion prediction task to assess the effects of abnormal pursuit on perception in human patients. Schizophrenia patients (n = 15) and healthy controls (n = 16) judged whether a briefly presented moving target ("ball") would hit/miss a stationary vertical line segment ("goal"). To relate prediction performance and pursuit directly, we manipulated eye movements: in half of the trials, observers smoothly tracked the ball; in the other half, they fixated on the goal. Strict quality criteria ensured that pursuit was initiated and that fixation was maintained. Controls were significantly better in trajectory prediction during pursuit than during fixation, their performance increased with presentation duration, and their pursuit gain and perceptual judgments were correlated. Such perceptual benefits during pursuit may be due to the use of extraretinal motion information estimated from an efference copy signal. With an overall lower performance in pursuit and perception, patients showed no such pursuit advantage and no correlation between pursuit gain and perception. Although patients' pursuit showed normal improvement with longer duration, their prediction performance failed to benefit from duration increases. This dissociation indicates relatively intact early visual motion processing, but a failure to use efference copy information. Impaired efference function in the sensory system may represent a general deficit in schizophrenia and thus contribute to symptoms and functional outcome impairments associated with the disorder.

  18. Smooth random change point models.

    Science.gov (United States)

    van den Hout, Ardo; Muniz-Terrera, Graciela; Matthews, Fiona E

    2011-03-15

    Change point models are used to describe processes over time that show a change in direction. An example of such a process is cognitive ability, where a decline a few years before death is sometimes observed. A broken-stick model consists of two linear parts and a breakpoint where the two lines intersect. Alternatively, models can be formulated that imply a smooth change between the two linear parts. Change point models can be extended by adding random effects to account for variability between subjects. A new smooth change point model is introduced and examples are presented that show how change point models can be estimated using functions in R for mixed-effects models. The Bayesian inference using WinBUGS is also discussed. The methods are illustrated using data from a population-based longitudinal study of ageing, the Cambridge City over 75 Cohort Study. The aim is to identify how many years before death individuals experience a change in the rate of decline of their cognitive ability. Copyright © 2010 John Wiley & Sons, Ltd.

  19. Smooth muscle myosin light chain kinase efficiently phosphorylates serine 15 of cardiac myosin regulatory light chain

    International Nuclear Information System (INIS)

    Josephson, Matthew P.; Sikkink, Laura A.; Penheiter, Alan R.; Burghardt, Thomas P.; Ajtai, Katalin

    2011-01-01

    Highlights: ► Cardiac myosin regulatory light chain (MYL2) is phosphorylated at S15. ► Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase. ► It is a widely believed that MYL2 is a poor substrate for smMLCK. ► In fact, smMLCK efficiently and rapidly phosphorylates S15 in MYL2. ► Phosphorylation kinetics measured by novel fluorescence method without radioactivity. -- Abstract: Specific phosphorylation of the human ventricular cardiac myosin regulatory light chain (MYL2) modifies the protein at S15. This modification affects MYL2 secondary structure and modulates the Ca 2+ sensitivity of contraction in cardiac tissue. Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase prevalent in uterus and present in other contracting tissues including cardiac muscle. The recombinant 130 kDa (short) smMLCK phosphorylated S15 in MYL2 in vitro. Specific modification of S15 was verified using the direct detection of the phospho group on S15 with mass spectrometry. SmMLCK also specifically phosphorylated myosin regulatory light chain S15 in porcine ventricular myosin and chicken gizzard smooth muscle myosin (S20 in smooth muscle) but failed to phosphorylate the myosin regulatory light chain in rabbit skeletal myosin. Phosphorylation kinetics, measured using a novel fluorescence method eliminating the use of radioactive isotopes, indicates similar Michaelis–Menten V max and K M for regulatory light chain S15 phosphorylation rates in MYL2, porcine ventricular myosin, and chicken gizzard myosin. These data demonstrate that smMLCK is a specific and efficient kinase for the in vitro phosphorylation of MYL2, cardiac, and smooth muscle myosin. Whether smMLCK plays a role in cardiac muscle regulation or response to a disease causing stimulus is unclear but it should be considered a potentially significant kinase in cardiac tissue on the basis of its specificity, kinetics, and tissue expression.

  20. Smooth muscle myosin light chain kinase efficiently phosphorylates serine 15 of cardiac myosin regulatory light chain

    Energy Technology Data Exchange (ETDEWEB)

    Josephson, Matthew P.; Sikkink, Laura A. [Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 (United States); Penheiter, Alan R. [Molecular Medicine Program, Mayo Clinic, Rochester, MN 55905 (United States); Burghardt, Thomas P., E-mail: burghardt@mayo.edu [Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 (United States); Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905 (United States); Ajtai, Katalin [Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 (United States)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Cardiac myosin regulatory light chain (MYL2) is phosphorylated at S15. Black-Right-Pointing-Pointer Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase. Black-Right-Pointing-Pointer It is a widely believed that MYL2 is a poor substrate for smMLCK. Black-Right-Pointing-Pointer In fact, smMLCK efficiently and rapidly phosphorylates S15 in MYL2. Black-Right-Pointing-Pointer Phosphorylation kinetics measured by novel fluorescence method without radioactivity. -- Abstract: Specific phosphorylation of the human ventricular cardiac myosin regulatory light chain (MYL2) modifies the protein at S15. This modification affects MYL2 secondary structure and modulates the Ca{sup 2+} sensitivity of contraction in cardiac tissue. Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase prevalent in uterus and present in other contracting tissues including cardiac muscle. The recombinant 130 kDa (short) smMLCK phosphorylated S15 in MYL2 in vitro. Specific modification of S15 was verified using the direct detection of the phospho group on S15 with mass spectrometry. SmMLCK also specifically phosphorylated myosin regulatory light chain S15 in porcine ventricular myosin and chicken gizzard smooth muscle myosin (S20 in smooth muscle) but failed to phosphorylate the myosin regulatory light chain in rabbit skeletal myosin. Phosphorylation kinetics, measured using a novel fluorescence method eliminating the use of radioactive isotopes, indicates similar Michaelis-Menten V{sub max} and K{sub M} for regulatory light chain S15 phosphorylation rates in MYL2, porcine ventricular myosin, and chicken gizzard myosin. These data demonstrate that smMLCK is a specific and efficient kinase for the in vitro phosphorylation of MYL2, cardiac, and smooth muscle myosin. Whether smMLCK plays a role in cardiac muscle regulation or response to a disease causing stimulus is unclear but it should be considered a potentially significant

  1. Regularization by fractional filter methods and data smoothing

    International Nuclear Information System (INIS)

    Klann, E; Ramlau, R

    2008-01-01

    This paper is concerned with the regularization of linear ill-posed problems by a combination of data smoothing and fractional filter methods. For the data smoothing, a wavelet shrinkage denoising is applied to the noisy data with known error level δ. For the reconstruction, an approximation to the solution of the operator equation is computed from the data estimate by fractional filter methods. These fractional methods are based on the classical Tikhonov and Landweber method, but avoid, at least partially, the well-known drawback of oversmoothing. Convergence rates as well as numerical examples are presented

  2. Non-linear second-order periodic systems with non-smooth potential

    Indian Academy of Sciences (India)

    In this paper we study second order non-linear periodic systems driven by the ordinary vector -Laplacian with a non-smooth, locally Lipschitz potential function. Our approach is variational and it is based on the non-smooth critical point theory. We prove existence and multiplicity results under general growth conditions on ...

  3. Non-linear second-order periodic systems with non-smooth potential

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    Abstract. In this paper we study second order non-linear periodic systems driven by the ordinary vector p-Laplacian with a non-smooth, locally Lipschitz potential function. Our approach is variational and it is based on the non-smooth critical point theory. We prove existence and multiplicity results under general growth ...

  4. Poster - 52: Smoothing constraints in Modulated Photon Radiotherapy (XMRT) fluence map optimization

    International Nuclear Information System (INIS)

    McGeachy, Philip; Villarreal-Barajas, Jose Eduardo; Zinchenko, Yuriy; Khan, Rao

    2016-01-01

    Purpose: Modulated Photon Radiotherapy (XMRT), which simultaneously optimizes photon beamlet energy (6 and 18 MV) and fluence, has recently shown dosimetric improvement in comparison to conventional IMRT. That said, the degree of smoothness of resulting fluence maps (FMs) has yet to be investigated and could impact the deliverability of XMRT. This study looks at investigating FM smoothness and imposing smoothing constraint in the fluence map optimization. Methods: Smoothing constraints were modeled in the XMRT algorithm with the sum of positive gradient (SPG) technique. XMRT solutions, with and without SPG constraints, were generated for a clinical prostate scan using standard dosimetric prescriptions, constraints, and a seven coplanar beam arrangement. The smoothness, with and without SPG constraints, was assessed by looking at the absolute and relative maximum SPG scores for each fluence map. Dose volume histograms were utilized when evaluating impact on the dose distribution. Results: Imposing SPG constraints reduced the absolute and relative maximum SPG values by factors of up to 5 and 2, respectively, when compared with their non-SPG constrained counterparts. This leads to a more seamless conversion of FMS to their respective MLC sequences. This improved smoothness resulted in an increase to organ at risk (OAR) dose, however the increase is not clinically significant. Conclusions: For a clinical prostate case, there was a noticeable improvement in the smoothness of the XMRT FMs when SPG constraints were applied with a minor increase in dose to OARs. This increase in OAR dose is not clinically meaningful.

  5. Poster - 52: Smoothing constraints in Modulated Photon Radiotherapy (XMRT) fluence map optimization

    Energy Technology Data Exchange (ETDEWEB)

    McGeachy, Philip; Villarreal-Barajas, Jose Eduardo; Zinchenko, Yuriy; Khan, Rao [Department of Medical Physics, CancerCare Manitoba, Winnipeg, MB, CAN, Department of Physics and Astronomy, University of Calgary, Calgary, AB, CAN, Department of Mathematics and Statistics, University of Calgary, Calgary, AB, CAN, Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO (United States)

    2016-08-15

    Purpose: Modulated Photon Radiotherapy (XMRT), which simultaneously optimizes photon beamlet energy (6 and 18 MV) and fluence, has recently shown dosimetric improvement in comparison to conventional IMRT. That said, the degree of smoothness of resulting fluence maps (FMs) has yet to be investigated and could impact the deliverability of XMRT. This study looks at investigating FM smoothness and imposing smoothing constraint in the fluence map optimization. Methods: Smoothing constraints were modeled in the XMRT algorithm with the sum of positive gradient (SPG) technique. XMRT solutions, with and without SPG constraints, were generated for a clinical prostate scan using standard dosimetric prescriptions, constraints, and a seven coplanar beam arrangement. The smoothness, with and without SPG constraints, was assessed by looking at the absolute and relative maximum SPG scores for each fluence map. Dose volume histograms were utilized when evaluating impact on the dose distribution. Results: Imposing SPG constraints reduced the absolute and relative maximum SPG values by factors of up to 5 and 2, respectively, when compared with their non-SPG constrained counterparts. This leads to a more seamless conversion of FMS to their respective MLC sequences. This improved smoothness resulted in an increase to organ at risk (OAR) dose, however the increase is not clinically significant. Conclusions: For a clinical prostate case, there was a noticeable improvement in the smoothness of the XMRT FMs when SPG constraints were applied with a minor increase in dose to OARs. This increase in OAR dose is not clinically meaningful.

  6. Hypoxia Enhances Differentiation of Adipose Tissue-Derived Stem Cells toward the Smooth Muscle Phenotype

    Directory of Open Access Journals (Sweden)

    Fang Wang

    2018-02-01

    Full Text Available Smooth muscle differentiated adipose tissue-derived stem cells are a valuable resource for regeneration of gastrointestinal tissues, such as the gut and sphincters. Hypoxia has been shown to promote adipose tissue-derived stem cells proliferation and maintenance of pluripotency, but the influence of hypoxia on their smooth myogenic differentiation remains unexplored. This study investigated the phenotype and contractility of adipose-derived stem cells differentiated toward the smooth myogenic lineage under hypoxic conditions. Oxygen concentrations of 2%, 5%, 10%, and 20% were used during differentiation of adipose tissue-derived stem cells. Real time reverse transcription polymerase chain reaction and immunofluorescence staining were used to detect the expression of smooth muscle cells-specific markers, including early marker smooth muscle alpha actin, middle markers calponin, caldesmon, and late marker smooth muscle myosin heavy chain. The specific contractile properties of cells were verified with both a single cell contraction assay and a gel contraction assay. Five percent oxygen concentration significantly increased the expression levels of α-smooth muscle actin, calponin, and myosin heavy chain in adipose-derived stem cell cultures after 2 weeks of induction (p < 0.01. Cells differentiated in 5% oxygen conditions showed greater contraction effect (p < 0.01. Hypoxia influences differentiation of smooth muscle cells from adipose stem cells and 5% oxygen was the optimal condition to generate smooth muscle cells that contract from adipose stem cells.

  7. Validation of CMIP5 multimodel ensembles through the smoothness of climate variables

    KAUST Repository

    Lee, Myoungji

    2015-05-14

    Smoothness is an important characteristic of a spatial process that measures local variability. If climate model outputs are realistic, then not only the values at each grid pixel but also the relative variation over nearby pixels should represent the true climate. We estimate the smoothness of long-term averages for land surface temperature anomalies in the Coupled Model Intercomparison Project Phase 5 (CMIP5), and compare them by climate regions and seasons. We also compare the estimated smoothness of the climate outputs in CMIP5 with those of reanalysis data. The estimation is done through the composite likelihood approach for locally self-similar processes. The composite likelihood that we consider is a product of conditional likelihoods of neighbouring observations. We find that the smoothness of the surface temperature anomalies in CMIP5 depends primarily on the modelling institution and on the climate region. The seasonal difference in the smoothness is generally small, except for some climate regions where the average temperature is extremely high or low.

  8. Analysis of elastic-plastic problems using edge-based smoothed finite element method

    International Nuclear Information System (INIS)

    Cui, X.Y.; Liu, G.R.; Li, G.Y.; Zhang, G.Y.; Sun, G.Y.

    2009-01-01

    In this paper, an edge-based smoothed finite element method (ES-FEM) is formulated for stress field determination of elastic-plastic problems using triangular meshes, in which smoothing domains associated with the edges of the triangles are used for smoothing operations to improve the accuracy and the convergence rate of the method. The smoothed Galerkin weak form is adopted to obtain the discretized system equations, and the numerical integration becomes a simple summation over the edge-based smoothing domains. The pseudo-elastic method is employed for the determination of stress field and Hencky's total deformation theory is used to define effective elastic material parameters, which are treated as field variables and considered as functions of the final state of stress fields. The effective elastic material parameters are then obtained in an iterative manner based on the strain controlled projection method from the uniaxial material curve. Some numerical examples are investigated and excellent results have been obtained demonstrating the effectivity of the present method.

  9. Smoothing and projecting age-specific probabilities of death by TOPALS

    Directory of Open Access Journals (Sweden)

    Joop de Beer

    2012-10-01

    Full Text Available BACKGROUND TOPALS is a new relational model for smoothing and projecting age schedules. The model is operationally simple, flexible, and transparent. OBJECTIVE This article demonstrates how TOPALS can be used for both smoothing and projecting age-specific mortality for 26 European countries and compares the results of TOPALS with those of other smoothing and projection methods. METHODS TOPALS uses a linear spline to describe the ratios between the age-specific death probabilities of a given country and a standard age schedule. For smoothing purposes I use the average of death probabilities over 15 Western European countries as standard, whereas for projection purposes I use an age schedule of 'best practice' mortality. A partial adjustment model projects how quickly the death probabilities move in the direction of the best-practice level of mortality. RESULTS On average, TOPALS performs better than the Heligman-Pollard model and the Brass relational method in smoothing mortality age schedules. TOPALS can produce projections that are similar to those of the Lee-Carter method, but can easily be used to produce alternative scenarios as well. This article presents three projections of life expectancy at birth for the year 2060 for 26 European countries. The Baseline scenario assumes a continuation of the past trend in each country, the Convergence scenario assumes that there is a common trend across European countries, and the Acceleration scenario assumes that the future decline of death probabilities will exceed that in the past. The Baseline scenario projects that average European life expectancy at birth will increase to 80 years for men and 87 years for women in 2060, whereas the Acceleration scenario projects an increase to 90 and 93 years respectively. CONCLUSIONS TOPALS is a useful new tool for demographers for both smoothing age schedules and making scenarios.

  10. A note on the Akivis algebra of a smooth hyporeductive loop

    International Nuclear Information System (INIS)

    Issa, A.N.

    2002-05-01

    Using the fundamental tensors of a smooth loop and the differential geometric characterization of smooth hyporeductive loops, the Akivis operations of a local smooth hyporeductive loop are expressed through the two binary and the one ternary operations of the hyporeductive triple algebra (h.t.a.) associated with the given hyporeductive loop. Those Akivis operations are also given in terms of Lie brackets of a Lie algebra of vector fields with the hyporeductive decomposition which generalizes the reductive decomposition of Lie algebras. A nontrivial real two-dimensional h.t.a. is presented. (author)

  11. Log canonical thresholds of smooth Fano threefolds

    International Nuclear Information System (INIS)

    Cheltsov, Ivan A; Shramov, Konstantin A

    2008-01-01

    The complex singularity exponent is a local invariant of a holomorphic function determined by the integrability of fractional powers of the function. The log canonical thresholds of effective Q-divisors on normal algebraic varieties are algebraic counterparts of complex singularity exponents. For a Fano variety, these invariants have global analogues. In the former case, it is the so-called α-invariant of Tian; in the latter case, it is the global log canonical threshold of the Fano variety, which is the infimum of log canonical thresholds of all effective Q-divisors numerically equivalent to the anticanonical divisor. An appendix to this paper contains a proof that the global log canonical threshold of a smooth Fano variety coincides with its α-invariant of Tian. The purpose of the paper is to compute the global log canonical thresholds of smooth Fano threefolds (altogether, there are 105 deformation families of such threefolds). The global log canonical thresholds are computed for every smooth threefold in 64 deformation families, and the global log canonical thresholds are computed for a general threefold in 20 deformation families. Some bounds for the global log canonical thresholds are computed for 14 deformation families. Appendix A is due to J.-P. Demailly.

  12. Transformation-invariant and nonparametric monotone smooth estimation of ROC curves.

    Science.gov (United States)

    Du, Pang; Tang, Liansheng

    2009-01-30

    When a new diagnostic test is developed, it is of interest to evaluate its accuracy in distinguishing diseased subjects from non-diseased subjects. The accuracy of the test is often evaluated by receiver operating characteristic (ROC) curves. Smooth ROC estimates are often preferable for continuous test results when the underlying ROC curves are in fact continuous. Nonparametric and parametric methods have been proposed by various authors to obtain smooth ROC curve estimates. However, there are certain drawbacks with the existing methods. Parametric methods need specific model assumptions. Nonparametric methods do not always satisfy the inherent properties of the ROC curves, such as monotonicity and transformation invariance. In this paper we propose a monotone spline approach to obtain smooth monotone ROC curves. Our method ensures important inherent properties of the underlying ROC curves, which include monotonicity, transformation invariance, and boundary constraints. We compare the finite sample performance of the newly proposed ROC method with other ROC smoothing methods in large-scale simulation studies. We illustrate our method through a real life example. Copyright (c) 2008 John Wiley & Sons, Ltd.

  13. Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells

    Science.gov (United States)

    Martín, Pedro; Enrique, Nicolás; Palomo, Ana R. Roldán; Rebolledo, Alejandro; Milesi, Veronica

    2012-01-01

    Bupivacaine is a local anesthetic compound belonging to the amino amide group. Its anesthetic effect is commonly related to its inhibitory effect on voltage-gated sodium channels. However, several studies have shown that this drug can also inhibit voltage-operated K+ channels by a different blocking mechanism. This could explain the observed contractile effects of bupivacaine on blood vessels. Up to now, there were no previous reports in the literature about bupivacaine effects on large conductance voltage- and Ca2+-activated K+ channels (BKCa). Using the patch-clamp technique, it is shown that bupivacaine inhibits single-channel and whole-cell K+ currents carried by BKCa channels in smooth muscle cells isolated from human umbilical artery (HUA). At the single-channel level bupivacaine produced, in a concentration- and voltage-dependent manner (IC50 324 µM at +80 mV), a reduction of single-channel current amplitude and induced a flickery mode of the open channel state. Bupivacaine (300 µM) can also block whole-cell K+ currents (~45% blockage) in which, under our working conditions, BKCa is the main component. This study presents a new inhibitory effect of bupivacaine on an ion channel involved in different cell functions. Hence, the inhibitory effect of bupivacaine on BKCa channel activity could affect different physiological functions where these channels are involved. Since bupivacaine is commonly used during labor and delivery, its effects on umbilical arteries, where this channel is highly expressed, should be taken into account. PMID:22688134

  14. Angiotensin II upregulates the expression of placental growth factor in human vascular endothelial cells and smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Guo Yingqiang

    2010-05-01

    Full Text Available Abstract Background Atherosclerosis is now recognized as a chronic inflammatory disease. Angiotensin II (Ang II is a critical factor in inflammatory responses, which promotes the pathogenesis of atherosclerosis. Placental growth factor (PlGF is a member of the vascular endothelial growth factor (VEGF family cytokines and is associated with inflammatory progress of atherosclerosis. However, the potential link between PlGF and Ang II has not been investigated. In the current study, whether Ang II could regulate PlGF expression, and the effect of PlGF on cell proliferation, was investigated in human vascular endothelial cells (VECs and smooth muscle cells (VSMCs. Results In growth-arrested human VECs and VSMCs, Ang II induced PlGF mRNA expression after 4 hour treatment, and peaked at 24 hours. 10-6 mol/L Ang II increased PlGF protein production after 8 hour treatment, and peaked at 24 hours. Stimulation with Ang II also induced mRNA expression of VEGF receptor-1 and -2(VEGFR-1 and -2 in these cells. The Ang II type I receptor (AT1R antagonist blocked Ang II-induced PlGF gene expression and protein production. Several intracellular signals elicited by Ang II were involved in PlGF synthesis, including activation of protein kinase C, extracellular signal-regulated kinase 1/2 (ERK1/2 and PI3-kinase. A neutralizing antibody against PlGF partially inhibited the Ang II-induced proliferation of VECs and VSMCs. However, this antibody showed little effect on the basal proliferation in these cells, whereas blocking antibody of VEGF could suppress both basal and Ang II-induced proliferation in VECs and VSMCs. Conclusion Our results showed for the first time that Ang II could induce the gene expression and protein production of PlGF in VECs and VSMCs, which might play an important role in the pathogenesis of vascular inflammation and atherosclerosis.

  15. Adropin Contributes to Anti-Atherosclerosis by Suppressing Monocyte-Endothelial Cell Adhesion and Smooth Muscle Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Kengo Sato

    2018-04-01

    Full Text Available Adropin, a peptide hormone expressed in liver and brain, is known to improve insulin resistance and endothelial dysfunction. Serum levels of adropin are negatively associated with the severity of coronary artery disease. However, it remains unknown whether adropin could modulate atherogenesis. We assessed the effects of adropin on inflammatory molecule expression and human THP1 monocyte adhesion in human umbilical vein endothelial cells (HUVECs, foam cell formation in THP1 monocyte-derived macrophages, and the migration and proliferation of human aortic smooth muscle cells (HASMCs in vitro and atherogenesis in Apoe−/− mice in vivo. Adropin was expressed in THP1 monocytes, their derived macrophages, HASMCs, and HUVECs. Adropin suppressed tumor necrosis factor α-induced THP1 monocyte adhesion to HUVECs, which was associated with vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 downregulation in HUVECs. Adropin shifted the phenotype to anti-inflammatory M2 rather than pro-inflammatory M1 via peroxisome proliferator-activated receptor γ upregulation during monocyte differentiation into macrophages. Adropin had no significant effects on oxidized low-density lipoprotein-induced foam cell formation in macrophages. In HASMCs, adropin suppressed the migration and proliferation without inducing apoptosis via ERK1/2 and Bax downregulation and phosphoinositide 3-kinase/Akt/Bcl2 upregulation. Chronic administration of adropin to Apoe−/− mice attenuated the development of atherosclerotic lesions in the aorta, with reduced the intra-plaque monocyte/macrophage infiltration and smooth muscle cell content. Thus, adropin could serve as a novel therapeutic target in atherosclerosis and related diseases.

  16. Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts

    International Nuclear Information System (INIS)

    Wang Zhirong; Chen Yan; Labinskyy, Nazar; Hsieh Tzechen; Ungvari, Zoltan; Wu, Joseph M.

    2006-01-01

    Epidemiologic studies suggest that low to moderate consumption of red wine is inversely associated with the risk of coronary heart disease; the protection is in part attributed to grape-derived polyphenols, notably trans-resveratrol, present in red wine. It is not clear whether the cardioprotective effects of resveratrol can be reproduced by standardized grape extracts (SGE). In the present studies, we determined, using cultured human aortic smooth muscle cells (HASMC), growth and specific gene responses to resveratrol and SGE provided by the California Table Grape Commission. Suppression of HASMC proliferation by resveratrol was accompanied by a dose-dependent increase in the expression of tumor suppressor gene p53 and heat shock protein HSP27. Using resveratrol affinity chromatography and biochemical fractionation procedures, we showed by immunoblot analysis that treatment of HASMC with resveratrol increased the expression of quinone reductase I and II, and also altered their subcellular distribution. Growth of HASMC was significantly inhibited by 70% ethanolic SGE; however, gene expression patterns in various cellular compartments elicited in response to SGE were substantially different from those observed in resveratrol-treated cells. Further, SGE also differed from resveratrol in not being able to induce relaxation of rat carotid arterial rings. These results indicate that distinct mechanisms are involved in the regulation of HASMC growth and gene expression by SGE and resveratrol

  17. TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells

    International Nuclear Information System (INIS)

    Patel, Devang N.; Bailey, Steven R.; Gresham, John K.; Schuchman, David B.; Shelhamer, James H.; Goldstein, Barry J.; Foxwell, Brian M.; Stemerman, Michael B.; Maranchie, Jodi K.; Valente, Anthony J.; Mummidi, Srinivas; Chandrasekar, Bysani

    2006-01-01

    CXCL16 is a transmembrane non-ELR CXC chemokine that signals via CXCR6 to induce aortic smooth muscle cell (ASMC) proliferation. While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known. Here, we demonstrate that LPS upregulates CXCR6 mRNA, protein, and surface expression in human ASMC. Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-κB (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression. Using dominant negative expression vectors and siRNA interference, we demonstrate that LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways. Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS-mediated AP-1-dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA. Finally, CXCR6 knockdown inhibited CXCL16-induced ASMC proliferation. These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis

  18. Smooth homogeneous structures in operator theory

    CERN Document Server

    Beltita, Daniel

    2005-01-01

    Geometric ideas and techniques play an important role in operator theory and the theory of operator algebras. Smooth Homogeneous Structures in Operator Theory builds the background needed to understand this circle of ideas and reports on recent developments in this fruitful field of research. Requiring only a moderate familiarity with functional analysis and general topology, the author begins with an introduction to infinite dimensional Lie theory with emphasis on the relationship between Lie groups and Lie algebras. A detailed examination of smooth homogeneous spaces follows. This study is illustrated by familiar examples from operator theory and develops methods that allow endowing such spaces with structures of complex manifolds. The final section of the book explores equivariant monotone operators and Kähler structures. It examines certain symmetry properties of abstract reproducing kernels and arrives at a very general version of the construction of restricted Grassmann manifolds from the theory of loo...

  19. Nicotinamide Phosphoribosyltransferase in Smooth Muscle Cells Maintains Genome Integrity, Resists Aortic Medial Degeneration, and Is Suppressed in Human Thoracic Aortic Aneurysm Disease.

    Science.gov (United States)

    Watson, Alanna; Nong, Zengxuan; Yin, Hao; O'Neil, Caroline; Fox, Stephanie; Balint, Brittany; Guo, Linrui; Leo, Oberdan; Chu, Michael W A; Gros, Robert; Pickering, J Geoffrey

    2017-06-09

    The thoracic aortic wall can degenerate over time with catastrophic consequences. Vascular smooth muscle cells (SMCs) can resist and repair artery damage, but their capacities decline with age and stress. Recently, cellular production of nicotinamide adenine dinucleotide (NAD + ) via nicotinamide phosphoribosyltransferase (Nampt) has emerged as a mediator of cell vitality. However, a role for Nampt in aortic SMCs in vivo is unknown. To determine whether a Nampt-NAD + control system exists within the aortic media and is required for aortic health. Ascending aortas from patients with dilated aortopathy were immunostained for NAMPT, revealing an inverse relationship between SMC NAMPT content and aortic diameter. To determine whether a Nampt-NAD + control system in SMCs impacts aortic integrity, mice with Nampt -deficient SMCs were generated. SMC- Nampt knockout mice were viable but with mildly dilated aortas that had a 43% reduction in NAD + in the media. Infusion of angiotensin II led to aortic medial hemorrhage and dissection. SMCs were not apoptotic but displayed senescence associated-ß-galactosidase activity and upregulated p16, indicating premature senescence. Furthermore, there was evidence for oxidized DNA lesions, double-strand DNA strand breaks, and pronounced susceptibility to single-strand breakage. This was linked to suppressed poly(ADP-ribose) polymerase-1 activity and was reversible on resupplying NAD + with nicotinamide riboside. Remarkably, we discovered unrepaired DNA strand breaks in SMCs within the human ascending aorta, which were specifically enriched in SMCs with low NAMPT. NAMPT promoter analysis revealed CpG hypermethylation within the dilated human thoracic aorta and in SMCs cultured from these tissues, which inversely correlated with NAMPT expression. The aortic media depends on an intrinsic NAD + fueling system to protect against DNA damage and premature SMC senescence, with relevance to human thoracic aortopathy. © 2017 American Heart

  20. Intelligent PV Power Smoothing Control Using Probabilistic Fuzzy Neural Network with Asymmetric Membership Function

    Directory of Open Access Journals (Sweden)

    Faa-Jeng Lin

    2017-01-01

    Full Text Available An intelligent PV power smoothing control using probabilistic fuzzy neural network with asymmetric membership function (PFNN-AMF is proposed in this study. First, a photovoltaic (PV power plant with a battery energy storage system (BESS is introduced. The BESS consisted of a bidirectional DC/AC 3-phase inverter and LiFePO4 batteries. Then, the difference of the actual PV power and smoothed power is supplied by the BESS. Moreover, the network structure of the PFNN-AMF and its online learning algorithms are described in detail. Furthermore, the three-phase output currents of the PV power plant are converted to the dq-axis current components. The resulted q-axis current is the input of the PFNN-AMF power smoothing control, and the output is a smoothing PV power curve to achieve the effect of PV power smoothing. Comparing to the other smoothing methods, a minimum energy capacity of the BESS with a small fluctuation of the grid power can be achieved by the PV power smoothing control using PFNN-AMF. In addition, a personal computer- (PC- based PV power plant emulator and BESS are built for the experimentation. From the experimental results of various irradiance variation conditions, the effectiveness of the proposed intelligent PV power smoothing control can be verified.

  1. Mercury levels in the Smooth Hammerhead Shark Sphyrna zygaena (Carcharhiniformes: Sphyrnidae from Northern Peru

    Directory of Open Access Journals (Sweden)

    Adriana Gonzalez-Pestana

    2017-12-01

    Full Text Available The smooth hammerhead shark Sphyrna zygaena (Linnaeus, 1758 is one of the elasmobranch species most used for human consumption in Peru. However, the level of mercury in hammerhead muscle tissue is unknown. This study assessed the level of mercury found in the muscle of hammerhead sharks and its relation with human health. Moreover, we evaluated the relationship between shark body size and mercury levels. We analyzed 27 muscle samples of neonates and juveniles captured in northern Peru. Mercury concentrations varied between 0.13 and 0.86 mg kg-1 wet weight. Moreover, we found a negative and significant relationship between shark body size and mercury levels. This study represents the first evaluation of mercury levels of sharks in Peru. Although the values found do not exceed levels recommended by the World Health Organization (< 1 mg kg-1, we recommend expanding this study to include other size classes of sharks as well as other marine resources used for human consumption.

  2. CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression

    Directory of Open Access Journals (Sweden)

    Ming-Horng Tsai

    2017-08-01

    Full Text Available Ang II has been involved in the pathogenesis of cardiovascular diseases, and matrix metalloproteinase-9 (MMP-9 induced migration of human aortic smooth muscle cells (HASMCs is the most common and basic pathological feature. Carbon monoxide (CO, a byproduct of heme breakdown by heme oxygenase, exerts anti-inflammatory effects in various tissues and organ systems. In the present study, we aimed to investigate the effects and underlying mechanisms of carbon monoxide releasing molecule-2 (CORM-2 on Ang II-induced MMP-9 expression and cell migration of HASMCs. Ang II significantly up-regulated MMP-9 expression and cell migration of HASMCs, which was inhibited by transfection with siRNA of p47phox, Nox2, Nox4, p65, angiotensin II type 1 receptor (AT1R and pretreatment with the inhibitors of NADPH oxidase, ROS, and NF-κB. In addition, Ang II also induced NADPH oxidase/ROS generation and p47phox translocation from the cytosol to the membrane. Moreover, Ang II-induced oxidative stress and MMP-9-dependent cell migration were inhibited by pretreatment with CORM-2. Finally, we observed that Ang II induced IL-6 release in HASMCs via AT1R, but not AT2R, which could further caused MMP-9 secretion and cell migration. Pretreatment with CORM-2 reduced Ang II-induced IL-6 release. In conclusion, CORM-2 inhibits Ang II-induced HASMCs migration through inactivation of suppression of NADPH oxidase/ROS generation, NF-κB inactivation and IL-6/MMP-9 expression. Thus, application of CO, especially CORM-2, is a potential countermeasure to reverse the pathological changes of various cardiovascular diseases. Further effects aimed at identifying novel antioxidant and anti-inflammatory substances protective for heart and blood vessels that targeting CO and establishment of well-designed in vivo models properly evaluating the efficacy of these agents are needed. Keywords: Angiotensin II, Carbon monoxide, Human aortic smooth muscle cell, Inflammation, Matrix metallopeptidase

  3. Guiding the orientation of smooth muscle cells on random and aligned polyurethane/collagen nanofibers.

    Science.gov (United States)

    Jia, Lin; Prabhakaran, Molamma P; Qin, Xiaohong; Ramakrishna, Seeram

    2014-09-01

    Fabricating scaffolds that can simulate the architecture and functionality of native extracellular matrix is a huge challenge in vascular tissue engineering. Various kinds of materials are engineered via nano-technological approaches to meet the current challenges in vascular tissue regeneration. During this study, nanofibers from pure polyurethane and hybrid polyurethane/collagen in two different morphologies (random and aligned) and in three different ratios of polyurethane:collagen (75:25; 50:50; 25:75) are fabricated by electrospinning. The fiber diameters of the nanofibrous scaffolds are in the range of 174-453 nm and 145-419 for random and aligned fibers, respectively, where they closely mimic the nanoscale dimensions of native extracellular matrix. The aligned polyurethane/collagen nanofibers expressed anisotropic wettability with mechanical properties which is suitable for regeneration of the artery. After 12 days of human aortic smooth muscle cells culture on different scaffolds, the proliferation of smooth muscle cells on hybrid polyurethane/collagen (3:1) nanofibers was 173% and 212% higher than on pure polyurethane scaffolds for random and aligned scaffolds, respectively. The results of cell morphology and protein staining showed that the aligned polyurethane/collagen (3:1) scaffold promote smooth muscle cells alignment through contact guidance, while the random polyurethane/collagen (3:1) also guided cell orientation most probably due to the inherent biochemical composition. Our studies demonstrate the potential of aligned and random polyurethane/collagen (3:1) as promising substrates for vascular tissue regeneration. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  4. Biomimetics of human movement: functional or aesthetic?

    International Nuclear Information System (INIS)

    Harris, Christopher M

    2009-01-01

    How should robotic or prosthetic arms be programmed to move? Copying human smooth movements is popular in synthetic systems, but what does this really achieve? We cannot address these biomimetic issues without a deep understanding of why natural movements are so stereotyped. In this article, we distinguish between 'functional' and 'aesthetic' biomimetics. Functional biomimetics requires insight into the problem that nature has solved and recognition that a similar problem exists in the synthetic system. In aesthetic biomimetics, nature is copied for its own sake and no insight is needed. We examine the popular minimum jerk (MJ) model that has often been used to generate smooth human-like point-to-point movements in synthetic arms. The MJ model was originally justified as maximizing 'smoothness'; however, it is also the limiting optimal trajectory for a wide range of cost functions for brief movements, including the minimum variance (MV) model, where smoothness is a by-product of optimizing the speed-accuracy trade-off imposed by proportional noise (PN: signal-dependent noise with the standard deviation proportional to mean). PN is unlikely to be dominant in synthetic systems, and the control objectives of natural movements (speed and accuracy) would not be optimized in synthetic systems by human-like movements. Thus, employing MJ or MV controllers in robotic arms is just aesthetic biomimetics. For prosthetic arms, the goal is aesthetic by definition, but it is still crucial to recognize that MV trajectories and PN are deeply embedded in the human motor system. Thus, PN arises at the neural level, as a recruitment strategy of motor units and probably optimizes motor neuron noise. Human reaching is under continuous adaptive control. For prosthetic devices that do not have this natural architecture, natural plasticity would drive the system towards unnatural movements. We propose that a truly neuromorphic system with parallel force generators (muscle fibres) and noisy

  5. Low density lipoprotein uptake by an endothelial-smooth muscle cell bilayer

    International Nuclear Information System (INIS)

    Alexander, J.J.; Miguel, R.; Graham, D.

    1991-01-01

    To study the interaction of endothelial and smooth muscle cells, and the means by which such interaction may affect lipid permeability of the arterial wall, cell bilayers were established by use of a transwell culture system. After confluent growth of both cell types had been achieved, iodine 125 bound to low-density lipoprotein (10 ng protein/ml) was added to the media of the upper well. After a 3-hour incubation period, the iodine 125-bound low-density lipoprotein content of the upper and lower media demonstrated an impedance to lipoprotein movement across the endothelial cell monolayer as compared to the bare porous polycarbonate filter of the transwell (p less than 10(-6)). The presence of smooth muscle cells in the bottom well significantly enhanced the permeability of the endothelial cell layer (p less than 10(-60)). This effect remained unchanged over a 9-day time course. Membrane binding and cellular uptake of low-density lipoprotein by endothelial cells was not altered by smooth muscle cells, indicating that this change in permeability could not be easily attributed to changes in receptor-mediated transport or transcytosis. Membrane binding (p less than 0.02) and cellular uptake (p less than 10(-6)) of low-density lipoprotein by smooth muscle cells in the bilayer, when adjusted for counts available in the smooth muscle cell media, were both reduced in the early incubation period as compared to isolated smooth muscle cells. The disproportionate reduction in uptake as compared to binding would suggest that this was not entirely a receptor-dependent process

  6. The smooth entropy formalism for von Neumann algebras

    International Nuclear Information System (INIS)

    Berta, Mario; Furrer, Fabian; Scholz, Volkher B.

    2016-01-01

    We discuss information-theoretic concepts on infinite-dimensional quantum systems. In particular, we lift the smooth entropy formalism as introduced by Renner and collaborators for finite-dimensional systems to von Neumann algebras. For the smooth conditional min- and max-entropy, we recover similar characterizing properties and information-theoretic operational interpretations as in the finite-dimensional case. We generalize the entropic uncertainty relation with quantum side information of Tomamichel and Renner and discuss applications to quantum cryptography. In particular, we prove the possibility to perform privacy amplification and classical data compression with quantum side information modeled by a von Neumann algebra

  7. Chain rules for smooth min-and max-entropies

    DEFF Research Database (Denmark)

    Vitanov, Alexande; Dupont-Dupuis, Fréderic; Tomamichel, Marco

    2013-01-01

    The chain rule for the Shannon and von Neumann en- tropy, which relates the total entropy of a system to the entropies of its parts, is of central importance to information theory. Here, we consider the chain rule for the more general smooth min- and max-entropies, used in one-shot in formation...... theory. For these en- tropy measures, the chain rule no longer holds as an equality. How- ever, the standard chain rule for the von Neum ann entropy is re- trieved asymptotically when evaluating the smooth entropies for many identical and independently distributed states....

  8. The smooth entropy formalism for von Neumann algebras

    Energy Technology Data Exchange (ETDEWEB)

    Berta, Mario, E-mail: berta@caltech.edu [Institute for Quantum Information and Matter, California Institute of Technology, Pasadena, California 91125 (United States); Furrer, Fabian, E-mail: furrer@eve.phys.s.u-tokyo.ac.jp [Department of Physics, Graduate School of Science, University of Tokyo, Tokyo, Japan and Institute for Theoretical Physics, Leibniz University Hanover, Hanover (Germany); Scholz, Volkher B., E-mail: scholz@phys.ethz.ch [Institute for Theoretical Physics, ETH Zurich, Zurich (Switzerland)

    2016-01-15

    We discuss information-theoretic concepts on infinite-dimensional quantum systems. In particular, we lift the smooth entropy formalism as introduced by Renner and collaborators for finite-dimensional systems to von Neumann algebras. For the smooth conditional min- and max-entropy, we recover similar characterizing properties and information-theoretic operational interpretations as in the finite-dimensional case. We generalize the entropic uncertainty relation with quantum side information of Tomamichel and Renner and discuss applications to quantum cryptography. In particular, we prove the possibility to perform privacy amplification and classical data compression with quantum side information modeled by a von Neumann algebra.

  9. Smoothing type buffer memory device

    International Nuclear Information System (INIS)

    Podorozhnyj, D.M.; Yashin, I.V.

    1990-01-01

    The layout of the micropower 4-bit smoothing type buffer memory device allowing one to record without counting the sequence of input randomly distributed pulses in multi-channel devices with serial poll, is given. The power spent by a memory cell for one binary digit recording is not greater than 0.15 mW, the device dead time is 10 mus

  10. Weak Measurement and Quantum Smoothing of a Superconducting Qubit

    Science.gov (United States)

    Tan, Dian

    In quantum mechanics, the measurement outcome of an observable in a quantum system is intrinsically random, yielding a probability distribution. The state of the quantum system can be described by a density matrix rho(t), which depends on the information accumulated until time t, and represents our knowledge about the system. The density matrix rho(t) gives probabilities for the outcomes of measurements at time t. Further probing of the quantum system allows us to refine our prediction in hindsight. In this thesis, we experimentally examine a quantum smoothing theory in a superconducting qubit by introducing an auxiliary matrix E(t) which is conditioned on information obtained from time t to a final time T. With the complete information before and after time t, the pair of matrices [rho(t), E(t)] can be used to make smoothed predictions for the measurement outcome at time t. We apply the quantum smoothing theory in the case of continuous weak measurement unveiling the retrodicted quantum trajectories and weak values. In the case of strong projective measurement, while the density matrix rho(t) with only diagonal elements in a given basis |n〉 may be treated as a classical mixture, we demonstrate a failure of this classical mixture description in determining the smoothed probabilities for the measurement outcome at time t with both diagonal rho(t) and diagonal E(t). We study the correlations between quantum states and weak measurement signals and examine aspects of the time symmetry of continuous quantum measurement. We also extend our study of quantum smoothing theory to the case of resonance fluorescence of a superconducting qubit with homodyne measurement and observe some interesting effects such as the modification of the excited state probabilities, weak values, and evolution of the predicted and retrodicted trajectories.

  11. Adaptive quantization-parameter clip scheme for smooth quality in H.264/AVC.

    Science.gov (United States)

    Hu, Sudeng; Wang, Hanli; Kwong, Sam

    2012-04-01

    In this paper, we investigate the issues over the smooth quality and the smooth bit rate during rate control (RC) in H.264/AVC. An adaptive quantization-parameter (Q(p)) clip scheme is proposed to optimize the quality smoothness while keeping the bit-rate fluctuation at an acceptable level. First, the frame complexity variation is studied by defining a complexity ratio between two nearby frames. Second, the range of the generated bits is analyzed to prevent the encoder buffer from overflow and underflow. Third, based on the safe range of the generated bits, an optimal Q(p) clip range is developed to reduce the quality fluctuation. Experimental results demonstrate that the proposed Q(p) clip scheme can achieve excellent performance in quality smoothness and buffer regulation.

  12. Effects of drugs and ionic variations on contractions of rat smooth ...

    African Journals Online (AJOL)

    The result of this suggests that as membrane depolarisation increases contraction in Rat Vas Deferens smooth muscle declined, while Verapamil and Nifedipine were more sensitive in blocking K+ than Ach and NA induced contractions. Keywords: Smooth muscle, Ileum, Stomach strip, Vas deferens, Contractions, Rat.

  13. EMMPRIN (CD147) Expression in Smooth Muscle Tumors of the Uterus.

    Science.gov (United States)

    Kefeli, Mehmet; Yildiz, Levent; Gun, Seda; Ozen, Fatma Z; Karagoz, Filiz

    2016-01-01

    Smooth muscle tumors of the uterus are the most common mesenchymal tumors of the gynecologic tract. The vast majority of these are benign leiomyomas that present no diagnostic difficulty. Because some benign smooth muscle tumors may degenerate and uncommon variants exist, the diagnosis can be challenging in some cases. The goal of this research was to investigate EMMPRIN expression in leiomyomas, leiomyoma variants, and leiomyosarcomas (LMS) to determine whether it has a potential role in differential diagnosis. EMMPRIN expression was investigated with immunohistochemistry in 103 uterine smooth muscle tumors, which included 19 usual leiomyomas, 52 leiomyoma variants, and 32 LMS. They were evaluated on the basis of staining extent, intensity, and also their combined score, and the groups were compared. EMMPRIN expression was present in 3 of 19 (15.7%) usual leiomyomas, 23 of 52 (44.3%) leiomyoma variants, and 28 of 32 (87.5%) LMS. There were statistically significant differences in staining extent and intensity, and also for their combined scores, between the LMS and benign groups. Although uterine smooth muscle tumors are usually diagnosed easily with conventional diagnostic criteria, the differentiation of LMS from some variants of leiomyoma can be challenging based soley on morphology. EMMPRIN may be a valuable immunohistochemical marker for differentiating LMS from benign smooth muscle tumors in problematic cases.

  14. Smooth Maps of a Foliated Manifold in a Symplectic Manifold

    Indian Academy of Sciences (India)

    Let be a smooth manifold with a regular foliation F and a 2-form which induces closed forms on the leaves of F in the leaf topology. A smooth map f : ( M , F ) ⟶ ( N , ) in a symplectic manifold ( N , ) is called a foliated symplectic immersion if restricts to an immersion on each leaf of the foliation and further, the ...

  15. Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth

    International Nuclear Information System (INIS)

    Patecki, Margret; Schaewen, Markus von; Tkachuk, Sergey; Jerke, Uwe; Dietz, Rainer; Dumler, Inna; Kusch, Angelika

    2007-01-01

    The urokinase (uPA)/uPA receptor (uPAR) system plays a role in the response of the vessel wall to injury, presumably by modulating vascular smooth muscle cell (VSMC) functional behaviour. The Jak/Stat signaling pathway has been implicated to mediate the uPA/uPAR-directed cell migration and proliferation in VSMC. We have therefore investigated the underlying molecular mechanisms, which remained not completely understood. In particular, we aimed at identification of the kinase involved in the signaling cascade leading to Stat1 phosphorylation by uPA and its impact on VSMC growth. We performed expression in VSMC of kinase-deficient mutant forms of the Janus kinases Jak1 and Tyk2 and used different cell culture models imitating the response to vascular injury. We provide evidence that Tyk2, but not Jak1, mediates uPA-induced Stat1 phosphorylation and VSMC growth inhibition and suggest a novel function for Tyk2 as an important modulator of the uPA-directed VSMC functional behaviour at the place of injury

  16. A Smooth Tour Construction Approach for a Mobile Robot with Kinematic Constraints

    Directory of Open Access Journals (Sweden)

    Ahmet Yazici

    2013-10-01

    Full Text Available Mobile robots are increasingly used for service-like applications in which the service points are known and the mobile robot starts from a starting location, visits all the service points requested and returns to the starting location. The tour construction problem in these applications can be treated as a Travelling Salesman Problem (TSP. Classical tour construction algorithms that are proposed for the TSP find tours do not consider robot kinematic constraints. These tours may have sharp turns at some service points. When a mobile robot follows such a tour, it stops, turns and speeds up again. Therefore, the robots waste a considerable amount of power and time. In these cases, tour smoothing can be used to overcome this problem. However, smoothing an existing tour may result in unnecessarily long tours. In this study, a Smooth Tour Construction (STC approach is proposed for mobile robots with kinematic constraints. The STC approach considers tour construction and tour smoothing concurrently. The logic behind the tour construction part of the approach is based on the Savings Algorithm (SA. The tour smoothing is based on Dubins' arc-line approach. Experiments are conducted for P3-DX robots in a laboratory environment. Comparisons are also drawn with various tour smoothing algorithms in simulation environments to demonstrate the effectiveness of the proposed STC approach.

  17. Dense-body aggregates as plastic structures supporting tension in smooth muscle cells.

    Science.gov (United States)

    Zhang, Jie; Herrera, Ana M; Paré, Peter D; Seow, Chun Y

    2010-11-01

    The wall of hollow organs of vertebrates is a unique structure able to generate active tension and maintain a nearly constant passive stiffness over a large volume range. These properties are predominantly attributable to the smooth muscle cells that line the organ wall. Although smooth muscle is known to possess plasticity (i.e., the ability to adapt to large changes in cell length through structural remodeling of contractile apparatus and cytoskeleton), the detailed structural basis for the plasticity is largely unknown. Dense bodies, one of the most prominent structures in smooth muscle cells, have been regarded as the anchoring sites for actin filaments, similar to the Z-disks in striated muscle. Here, we show that the dense bodies and intermediate filaments formed cable-like structures inside airway smooth muscle cells and were able to adjust the cable length according to cell length and tension. Stretching the muscle cell bundle in the relaxed state caused the cables to straighten, indicating that these intracellular structures were connected to the extracellular matrix and could support passive tension. These plastic structures may be responsible for the ability of smooth muscle to maintain a nearly constant tensile stiffness over a large length range. The finding suggests that the structural plasticity of hollow organs may originate from the dense-body cables within the smooth muscle cells.

  18. Finishing aeronautical planetary herringbone gear wheels in container vibrating smoothing machine

    Directory of Open Access Journals (Sweden)

    Jacek MICHALSKI

    2015-12-01

    Full Text Available The paper presents the technological process of abrasive-chemical machining wheel bearing surface of the cylindrical herringbone gears planetary gear in vibrating container smoothing machine according to Isotropic Finishing ISF® technology of the REM Chemicals Inc. company. Gear wheels are made of stainless Pyrowear 53 and subjected to carburizing, hardening, cold working and low tempering. The change in value of deviation indicators for the kinematic accuracy, smoothness and geometric structure of the machined surfaces of the gear teeth after smoothing compared with the contoured grinding were analyzed. The findings are different a characteristic performance on the surface of the tooth side along the outline, especially with a higher value at the head of the tooths. This creates a need for appropriate modification of the lateral surface of the teeth in the process of contoured grinding. The results of the mechanical strength of the samples gear wheel after the smoothing process and evaluating the hydrogen embrittlement are presented.

  19. Smooth Nb surfaces fabricated by buffered electropolishing

    International Nuclear Information System (INIS)

    Wu, Andy T.; Mammosser, John; Phillips, Larry; Delayen, Jean; Reece, Charles; Wilkerson, Amy; Smith, David; Ike, Robert

    2007-01-01

    It was demonstrated that smooth Nb surfaces could be obtained through buffered electropolishing (BEP) employing an electrolyte consisting of lactic, sulfuric, and hydrofluoric acids. Parameters that control the polishing process were optimized to achieve a smooth surface finish. The polishing rate of BEP was determined to be 0.646 μm/min which was much higher than 0.381 μm/min achieved by the conventional electropolishing (EP) process widely used in the superconducting radio frequency (SRF) community. Root mean square measurements using a 3D profilometer revealed that Nb surfaces treated by BEP were an order of magnitude smoother than those treated by the optimized EP process. The chemical composition of the Nb surfaces after BEP was analyzed by static and dynamic secondary ion mass spectrometry (SIMS) systems. SIMS results implied that the surface oxide structure of Nb might be more complicated than what usually believed and could be inhomogeneous. Preliminary results of BEP on Nb SRF single cell cavities and half-cells were reported. It was shown that smooth and bright surfaces could be obtained in 1800 s when the electric field inside a SRF cavity was uniform during a BEP process. This study showed that BEP is a promising technique for surface treatment on Nb SRF cavities to be used in particle accelerators

  20. Signature-tagged mutagenesis screening revealed a novel smooth-to-rough transition determinant of Salmonella enterica serovar Enteritidis.

    Science.gov (United States)

    Jiao, Yang; Guo, Rongxian; Tang, Peipei; Kang, Xilong; Yin, Junlei; Wu, Kaiyue; Geng, Shizhong; Li, Qiuchun; Sun, Jun; Xu, Xiulong; Zhou, Xiaohui; Gan, Junji; Jiao, Xinan; Liu, Xiufan; Pan, Zhiming

    2017-03-03

    Salmonella enterica serovar Enteritidis (S. Enteritidis) has emerged as one of the most important food-borne pathogens for humans. Lipopolysaccharide (LPS), as a component of the outer membrane, is responsible for the virulence and smooth-to-rough transition in S. Enteritidis. In this study, we screened S. Enteritidis signature-tagged transposon mutant library using monoclonal antibody against somatic O 9 antigen (O 9 MAb) and O 9 factor rabbit antiserum to identify novel genes that are involved in smooth-to-rough transition. A total of 480 mutants were screened and one mutant with transposon insertion in rfbG gene had smooth-to-rough transition phenotype. In order to verify the role of rfbG gene, an rfbG insertion or deletion mutant was constructed using λ-Red recombination system. Phenotypic and biological analysis revealed that rfbG insertion or deletion mutants were similar to the wild-type strain in growth rate and biochemical properties, but the swimming motility was reduced. SE Slide Agglutination test and ELISA test showed that rfbG mutants do not stimulate animals to produce agglutinating antibody. In addition, the half-lethal dose (LD 50 ) of the rfbG deletion mutant strain was 10 6.6 -fold higher than that of the parent strain in a mouse model when injected intraperitoneally. These data indicate that the rfbG gene is involved in smooth-to-rough transition, swimming motility and virulence of S. Enteritidis. Furthermore, somatic O-antigen antibody-based approach to screen signature-tagged transposon mutants is feasible to clarify LPS biosynthesis and to find suitable markers in DIVA-vaccine research.

  1. Extracellular matrix collagen alters cell proliferation and cell cycle progression of human uterine leiomyoma smooth muscle cells.

    Science.gov (United States)

    Koohestani, Faezeh; Braundmeier, Andrea G; Mahdian, Arash; Seo, Jane; Bi, JiaJia; Nowak, Romana A

    2013-01-01

    Uterine leiomyomas (ULs) are benign tumors occurring in the majority of reproductive aged women. Despite the high prevalence of these tumors, little is known about their etiology. A hallmark of ULs is the excessive deposition of extracellular matrix (ECM), primarily collagens. Collagens are known to modulate cell behavior and function singularly or through interactions with integrins and growth factor-mediated mitogenic pathways. To better understand the pathogenesis of ULs and the role of ECM collagens in their growth, we investigated the interaction of leiomyoma smooth muscle cells (LSMCs) with two different forms of collagen, non-polymerized collagen (monomeric) and polymerized collagen (fibrillar), in the absence or presence of platelet-derived growth factor (PDGF), an abundant growth factor in ULs. Primary cultures of human LSMCS from symptomatic patients were grown on these two different collagen matrices and their morphology, cytoskeletal organization, cellular proliferation, and signaling pathways were evaluated. Our results showed that LSMCs had distinct morphologies on the different collagen matrices and their basal as well as PDGF-stimulated proliferation varied on these matrices. These differences in proliferation were accompanied by changes in cell cycle progression and p21, an inhibitory cell cycle protein. In addition we found alterations in the phosphorylation of focal adhesion kinase, cytoskeletal reorganization, and activation of the mitogen activated protein kinase (MAPK) signaling pathway. In conclusion, our results demonstrate a direct effect of ECM on the proliferation of LSMCs through interplay between the collagen matrix and the PDGF-stimulated MAPK pathway. In addition, these findings will pave the way for identifying novel therapeutic approaches for ULs that target ECM proteins and their signaling pathways in ULs.

  2. Parametric inference for stochastic differential equations: a smooth and match approach

    NARCIS (Netherlands)

    Gugushvili, S.; Spreij, P.

    2012-01-01

    We study the problem of parameter estimation for a univariate discretely observed ergodic diffusion process given as a solution to a stochastic differential equation. The estimation procedure we propose consists of two steps. In the first step, which is referred to as a smoothing step, we smooth the

  3. The small GTPase Rac1 is required for smooth muscle contraction

    DEFF Research Database (Denmark)

    Rahman, Awahan; Davis, Benjamin; Lövdahl, Cecilia

    2014-01-01

    The role of the small GTP-binding protein Rac1 in smooth muscle contraction was examined using small molecule inhibitors (EHT1864, NSC23766) and a novel smooth muscle-specific, conditional, Rac1 knockout mouse strain. EHT1864, which affects nucleotide binding and inhibits Rac1 activity, concentra...

  4. Multiple predictor smoothing methods for sensitivity analysis: Example results

    International Nuclear Information System (INIS)

    Storlie, Curtis B.; Helton, Jon C.

    2008-01-01

    The use of multiple predictor smoothing methods in sampling-based sensitivity analyses of complex models is investigated. Specifically, sensitivity analysis procedures based on smoothing methods employing the stepwise application of the following nonparametric regression techniques are described in the first part of this presentation: (i) locally weighted regression (LOESS), (ii) additive models, (iii) projection pursuit regression, and (iv) recursive partitioning regression. In this, the second and concluding part of the presentation, the indicated procedures are illustrated with both simple test problems and results from a performance assessment for a radioactive waste disposal facility (i.e., the Waste Isolation Pilot Plant). As shown by the example illustrations, the use of smoothing procedures based on nonparametric regression techniques can yield more informative sensitivity analysis results than can be obtained with more traditional sensitivity analysis procedures based on linear regression, rank regression or quadratic regression when nonlinear relationships between model inputs and model predictions are present

  5. Border-Collision Bifurcations and Chaotic Oscillations in a Piecewise-Smooth Dynamical System

    DEFF Research Database (Denmark)

    Zhusubaliyev, Z.T.; Soukhoterin, E.A.; Mosekilde, Erik

    2002-01-01

    Many problems of engineering and applied science result in the consideration of piecewise-smooth dynamical systems. Examples are relay and pulse-width control systems, impact oscillators, power converters, and various electronic circuits with piecewise-smooth characteristics. The subject...... of investigation in the present paper is the dynamical model of a constant voltage converter which represents a three-dimensional piecewise-smooth system of nonautonomous differential equations. A specific type of phenomena that arise in the dynamics of piecewise-smooth systems are the so-called border......-collision bifurcations. The paper contains a detailed analysis of this type of bifurcational transition in the dynamics of the voltage converter, in particular, the merging and subsequent disappearance of cycles of different types, change of solution type, and period-doubling, -tripling, -quadrupling and -quintupling...

  6. Smooth maps of a foliated manifold in a symplectic manifold

    Indian Academy of Sciences (India)

    Abstract. Let M be a smooth manifold with a regular foliation F and a 2-form ω which induces closed forms on the leaves of F in the leaf topology. A smooth map f : (M, F) −→ (N,σ) in a symplectic manifold (N,σ) is called a foliated symplectic immersion if f restricts to an immersion on each leaf of the foliation and further, the.

  7. Identification and characterization of novel smoothelin isoforms in vascular smooth muscle.

    Science.gov (United States)

    Krämer, J; Quensel, C; Meding, J; Cardoso, M C; Leonhardt, H

    2001-01-01

    Smoothelin is a cytoskeletal protein specifically expressed in differentiated smooth muscle cells and has been shown to colocalize with smooth muscle alpha actin. In addition to the small smoothelin isoform of 59 kD, we recently identified a large smoothelin isoform of 117 kD. The aim of this study was to identify and characterize novel smoothelin isoforms. The genomic structure and sequence of the smoothelin gene were determined by genomic PCR, RT-PCR and DNA sequencing. Comparison of the cDNA and genomic sequences shows that the small smoothelin isoform is generated by transcription initiation 10 kb downstream of the start site of the large isoform. In addition to the known smoothelin cDNA (c1 isoform) we identified two novel cDNA variants (c2 and c3 isoform) that are generated by alternative splicing within a region, which shows similarity to the spectrin family of F-actin cross-linking proteins. Visceral organs express the c1 form, while the c2 form prevails in well-vascularized tissue as analyzed by RT-PCR. We then generated specific antibodies against the major smoothelin isoforms and could show by Western blotting and immunohistochemistry that the large isoform is specifically expressed in vascular smooth muscle cells, while the small isoform is abundant in visceral smooth muscle. These results strongly suggest that the smoothelin gene contains a vascular and a visceral smooth muscle promoter. The cell-type-specific expression of smoothelin isoforms that are associated with actin filaments may play a role in the modulation of the contractile properties of different smooth muscle cell types. Copyright 2001 S. Karger AG, Basel

  8. Purification and partial characterization of glycosaminoglycans and proteoglycans from cultured rabbit smooth muscle cells

    International Nuclear Information System (INIS)

    Sabatino, R.D.

    1985-01-01

    Glycosaminoglycans synthesized by cultured rabbit smooth muscle cells were isolated after incorporation of [ 3 H]-glucosamine into glycosaminoglycans in the presence or absence of 10% fetal bovine serum. Glycosaminoglycans were quantitated by two-dimensional electrophoresis after proteolytic digestion of the cell layers and media. The results show that the presence of serum has no effect on the chondroitin sulfate, heparan sulfate and dermatan sulfate content of the cell layers. The incorporation of [ 3 H]-glucosamine into hyaluronic acid of the cell layers was three times higher in the presence of serum. In the medium , the quantity of hyaluronic was two times higher in the presence of serum while the other glycosaminoglycans remained unchanged. The incorporation of [ 3 H]-glucosamine into hyaluronic acid was unaffected by the presence of serum. Specific proteoglycans were isolated from medium after with [ 35 S]-sulfate and [ 3 H]-serine by isopycnic ultracentrifugation and chromatography on Sepharose CL-4B and DEAE-cellulose. Preparations contained a chondroitin sulfate proteoglycan, a condroitin sulfate-dermatan sulfate proteoglycan and a heparan sulfate proteoglycan. Glycosaminoglycans and proteoglycans synthesized by rabbit aorta smooth muscle cells are similar to those from human aorta

  9. Tungstate-Targeting of BKαβ1 Channels Tunes ERK Phosphorylation and Cell Proliferation in Human Vascular Smooth Muscle

    OpenAIRE

    López López, José Ramón; Fernández Mariño, Ana Isabel; Cidad, Pilar; Zafra, Delia; Nocito, Laura; Domínguez, Jorge; Oliván Viguera, Aida; Köhler, Ralf; Pérez García, María Teresa; Valverde, Miguel Ángel; Guinovart, Joan J.; Fernández Fernández, José Manuel

    2015-01-01

    Producción Científica Despite the substantial knowledge on the antidiabetic, antiobesity and antihypertensive actions of tungstate, information on its primary target/s is scarce. Tungstate activates both the ERK1/2 pathway and the vascular voltage- and Ca2+-dependent large-conductance BKαβ1 potassium channel, which modulates vascular smooth muscle cell (VSMC) proliferation and function, respectively. Here, we have assessed the possible involvement of BKαβ1 channels in the tungstate-induced...

  10. A Non-smooth Newton Method for Multibody Dynamics

    International Nuclear Information System (INIS)

    Erleben, K.; Ortiz, R.

    2008-01-01

    In this paper we deal with the simulation of rigid bodies. Rigid body dynamics have become very important for simulating rigid body motion in interactive applications, such as computer games or virtual reality. We present a novel way of computing contact forces using a Newton method. The contact problem is reformulated as a system of non-linear and non-smooth equations, and we solve this system using a non-smooth version of Newton's method. One of the main contribution of this paper is the reformulation of the complementarity problems, used to model impacts, as a system of equations that can be solved using traditional methods.

  11. A Smoothed Finite Element-Based Elasticity Model for Soft Bodies

    Directory of Open Access Journals (Sweden)

    Juan Zhang

    2017-01-01

    Full Text Available One of the major challenges in mesh-based deformation simulation in computer graphics is to deal with mesh distortion. In this paper, we present a novel mesh-insensitive and softer method for simulating deformable solid bodies under the assumptions of linear elastic mechanics. A face-based strain smoothing method is adopted to alleviate mesh distortion instead of the traditional spatial adaptive smoothing method. Then, we propose a way to combine the strain smoothing method and the corotational method. With this approach, the amplitude and frequency of transient displacements are slightly affected by the distorted mesh. Realistic simulation results are generated under large rotation using a linear elasticity model without adding significant complexity or computational cost to the standard corotational FEM. Meanwhile, softening effect is a by-product of our method.

  12. Trajectories of Smooth: The Multidimensionality of Spatial Relations and Autism Spectrum

    Science.gov (United States)

    Reddington, Sarah; Price, Deborah

    2017-01-01

    This paper examines how two men with autism spectrum (AS) experience educational spaces having attended public school in Nova Scotia, Canada. Smooth and striated space is mobilised as the main conceptual framework to account for the men's affectivities when experiencing the educational terrain. The central aim when applying smooth and striated…

  13. Eye features in three Danish patients with multisystemic smooth muscle dysfunction syndrome

    DEFF Research Database (Denmark)

    Moller, Hans Ulrik; Fledelius, Hans C; Milewicz, Dianna M

    2012-01-01

    A de novo mutation of the ACTA2 gene encoding the smooth muscle cell α-actin has been established in patients with multisystemic smooth muscle dysfunction syndrome associated with patent ductus arteriosus and mydriasis present at birth....

  14. Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells.

    Science.gov (United States)

    Ross, Jeffrey J; Hong, Zhigang; Willenbring, Ben; Zeng, Lepeng; Isenberg, Brett; Lee, Eu Han; Reyes, Morayma; Keirstead, Susan A; Weir, E Kenneth; Tranquillo, Robert T; Verfaillie, Catherine M

    2006-12-01

    Smooth muscle formation and function are critical in development and postnatal life. Hence, studies aimed at better understanding SMC differentiation are of great importance. Here, we report that multipotent adult progenitor cells (MAPCs) isolated from rat, murine, porcine, and human bone marrow demonstrate the potential to differentiate into cells with an SMC-like phenotype and function. TGF-beta1 alone or combined with PDGF-BB in serum-free medium induces a temporally correct expression of transcripts and proteins consistent with smooth muscle development. Furthermore, SMCs derived from MAPCs (MAPC-SMCs) demonstrated functional L-type calcium channels. MAPC-SMCs entrapped in fibrin vascular molds became circumferentially aligned and generated force in response to KCl, the L-type channel opener FPL64176, or the SMC agonists 5-HT and ET-1, and exhibited complete relaxation in response to the Rho-kinase inhibitor Y-27632. Cyclic distention (5% circumferential strain) for 3 weeks increased responses by 2- to 3-fold, consistent with what occurred in neonatal SMCs. These results provide evidence that MAPC-SMCs are phenotypically and functionally similar to neonatal SMCs and that the in vitro MAPC-SMC differentiation system may be an ideal model for the study of SMC development. Moreover, MAPC-SMCs may lend themselves to tissue engineering applications.

  15. EVALUATION OF THE FUNCTIONAL PROPERTIES OF HUMAN ENDOTHELIAL AND SMOOTH MUSCLE CELLS AFTER SEEDING ON THE SURFACE OF NATURAL AND SYNTHETIC MATERIALS

    Directory of Open Access Journals (Sweden)

    Sh. B. Saaya

    2016-01-01

    Full Text Available At present, vascular surgery using small diameter synthetic grafts is associated with a higher incidence of complications (thrombosis, restenosis, intimal hyperplasia than in operations using autologous vessels. However, the occurrence of concomitant pathology, reoperations and multifocal vascular disease limit the use of autologous vein and arteries. The important factor providing a long-term patency is the presence of vascular cells, which produce biologically active substance and provide mechanical properties. Aim. Selection of the optimal scaffold for creating cell-seeded tissue-engineering vessels. Materials and methods. Endothelial (EC and smooth muscle cells (SMC derived from human myocardium were seeded on different surfaces: decellularized homoarteriа, хenopericardium, polytetrafl uoroethylene (PTFE, polyethylene terephthalate (PET, polycaprolactone (PCL and polylactide-co-glycolide (PLGA. Results. Synthetic biodegradable materials polycaprolactone and polylactide-co-glycolide provide cell adhesion. The cells cultured on the polycaprolactone and polylactide-coglycolide scaffolds retain their functional properties: viability and proliferative properties, maintain specifi c endothelial antigens and synthesis of extracellular matrix. Conclusion. Synthetic biodegradable polycaprolactone and polylactide-co-glycolide electrospun scaffolds can be used for creation of cell-fi lled vascular prostheses. 

  16. Trajectory generation algorithm for smooth movement of a hybrid-type robot Rocker-Pillar

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Seung Min; Choi, Dong Kyu; Kim, Jong Won [School of Mechanical and Aerospace Engineering, Seoul National University, Seoul (Korea, Republic of); Kim, Hwa Soo [Dept. of Mechanical System Engineering, Kyonggi University, Suwon (Korea, Republic of)

    2016-11-15

    While traveling on rough terrain, smooth movement of a mobile robot plays an important role in carrying out the given tasks successfully. This paper describes the trajectory generation algorithm for smooth movement of hybrid-type mobile robot Rocker-Pillar by adjusting the angular velocity of its caterpillar as well as each wheel velocity in such a manner to minimize a proper index for smoothness. To this end, a new Smoothness index (SI) is first suggested to evaluate the smoothness of movement of Rocker-Pillar. Then, the trajectory generation algorithm is proposed to reduce the undesired oscillations of its Center of mass (CoM). The experiment are performed to examine the movement of Rocker-Pillar climbing up the step whose height is twice larger than its wheel radius. It is verified that the resulting SI is improved by more than 40 % so that the movement of Rocker-Pillar becomes much smoother by the proposed trajectory algorithm.

  17. Did you smooth your well logs the right way for seismic interpretation?

    International Nuclear Information System (INIS)

    Duchesne, Mathieu J; Gaillot, Philippe

    2011-01-01

    Correlations between physical properties and seismic reflection data are useful to determine the geological nature of seismic reflections and the lateral extent of geological strata. The difference in resolution between well logs and seismic data is a major hurdle faced by seismic interpreters when tying both data sets. In general, log data have a resolution of at least two orders of magnitude greater than seismic data. Smoothing physical property logs improves correlation at the seismic scale. Three different approaches were used and compared to smooth a density log: binomial filtering, seismic wavelet filtering and discrete wavelet transform (DWT) filtering. Regression plots between the density logs and the acoustic impedance show that the data smoothed with the DWT is the only method that preserves the original relationship between the raw density data and the acoustic impedance. Smoothed logs were then used to generate synthetic seismograms that were tied to seismic data at the borehole site. Best ties were achieved using the synthetic seismogram computed with the density log processed with the DWT. The good performance of the DWT is explained by its adaptive multi-scale characteristic which preserved significant local changes of density on the high-resolution data series that were also pictured at the seismic scale. Since synthetic seismograms are generated using smoothed logs, the choice of the smoothing method impacts on the quality of seismic-to-well ties. This ultimately can have economical implications during hydrocarbon exploration or exploitation phases

  18. Smoothness in Banach spaces. Selected problems

    Czech Academy of Sciences Publication Activity Database

    Fabian, Marián; Montesinos, V.; Zizler, Václav

    2006-01-01

    Roč. 100, č. 2 (2006), s. 101-125 ISSN 1578-7303 R&D Projects: GA ČR(CZ) GA201/04/0090; GA AV ČR(CZ) IAA100190610 Institutional research plan: CEZ:AV0Z10190503 Keywords : smooth norm * renorming * weakly compactly generated space Subject RIV: BA - General Mathematics

  19. Ion bombardment induced smoothing of amorphous metallic surfaces: Experiments versus computer simulations

    International Nuclear Information System (INIS)

    Vauth, Sebastian; Mayr, S. G.

    2008-01-01

    Smoothing of rough amorphous metallic surfaces by bombardment with heavy ions in the low keV regime is investigated by a combined experimental-simulational study. Vapor deposited rough amorphous Zr 65 Al 7.5 Cu 27.5 films are the basis for systematic in situ scanning tunneling microscopy measurements on the smoothing reaction due to 3 keV Kr + ion bombardment. The experimental results are directly compared to the predictions of a multiscale simulation approach, which incorporates stochastic rate equations of the Langevin type in combination with previously reported classical molecular dynamics simulations [Phys. Rev. B 75, 224107 (2007)] to model surface smoothing across length and time scales. The combined approach of experiments and simulations clearly corroborates a key role of ion induced viscous flow and ballistic effects in low keV heavy ion induced smoothing of amorphous metallic surfaces at ambient temperatures

  20. Detection of small human cerebral cortical lesions with MRI under different levels of Gaussian smoothing: applications in epilepsy

    Science.gov (United States)

    Cantor-Rivera, Diego; Goubran, Maged; Kraguljac, Alan; Bartha, Robert; Peters, Terry

    2010-03-01

    The main objective of this study was to assess the effect of smoothing filter selection in Voxel-Based Morphometry studies on structural T1-weighted magnetic resonance images. Gaussian filters of 4 mm, 8 mm or 10 mm Full Width at High Maximum are commonly used, based on the assumption that the filter size should be at least twice the voxel size to obtain robust statistical results. The hypothesis of the presented work was that the selection of the smoothing filter influenced the detectability of small lesions in the brain. Mesial Temporal Sclerosis associated to Epilepsy was used as the case to demonstrate this effect. Twenty T1-weighted MRIs from the BrainWeb database were selected. A small phantom lesion was placed in the amygdala, hippocampus, or parahippocampal gyrus of ten of the images. Subsequently the images were registered to the ICBM/MNI space. After grey matter segmentation, a T-test was carried out to compare each image containing a phantom lesion with the rest of the images in the set. For each lesion the T-test was repeated with different Gaussian filter sizes. Voxel-Based Morphometry detected some of the phantom lesions. Of the three parameters considered: location,size, and intensity; it was shown that location is the dominant factor for the detection of the lesions.

  1. Smoothing by spectral dispersion using random phase modulation for inertial confinement fusion

    International Nuclear Information System (INIS)

    Rothenberg, J.E.

    1995-01-01

    Numerical simulations of beam smoothing using random phase modulation and grating dispersion are presented. Spatial spectra of the target illumination show that significantly improved smoothing at low spatial frequency is achieved while maintaining uniform intensity in the laser amplifier

  2. Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Kazuki [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Senokuchi, Takafumi; Ishii, Norio; Kinoshita, Hiroyuki; Yamada, Sarie; Murakami, Saiko [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Nakao, Saya [Department of Environmental & Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto (Japan); Motoshima, Hiroyuki; Kondo, Tatsuya; Kukidome, Daisuke; Kawasaki, Shuji [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Kawada, Teruo [Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto (Japan); Nishikawa, Takeshi; Araki, Eiichi [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan)

    2015-01-30

    Highlights: • Statins induce PPARγ activation in vascular smooth muscle cells. • Statin-induced PPARγ activation is mediated by COX-2 expression. • Statins suppress cell migration and proliferation in vascular smooth muscle cells. • Statins inhibit LPS-induced inflammatory responses by PPARγ activation. • Fluvastatin suppress the progression of atherosclerosis and induces PPARγ activation in the aorta of apoE-deficient mice. - Abstract: The peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of lipid and glucose metabolism, and its activation is reported to suppress the progression of atherosclerosis. We have reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) activate PPARγ in macrophages. However, it is not yet known whether statins activate PPARγ in other vascular cells. In the present study, we investigated whether statins activate PPARγ in smooth muscle cells (SMCs) and endothelial cells (ECs) and thus mediate anti-atherosclerotic effects. Human aortic SMCs (HASMCs) and human umbilical vein ECs (HUVECs) were used in this study. Fluvastatin and pitavastatin activated PPARγ in HASMCs, but not in HUVECs. Statins induced cyclooxygenase-2 (COX-2) expression in HASMCs, but not in HUVECs. Moreover, treatment with COX-2-siRNA abrogated statin-mediated PPARγ activation in HASMCs. Statins suppressed migration and proliferation of HASMCs, and inhibited lipopolysaccharide-induced expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in HASMCs. These effects of statins were abrogated by treatment with PPARγ-siRNA. Treatment with statins suppressed atherosclerotic lesion formation in Apoe{sup −/−} mice. In addition, transcriptional activity of PPARγ and CD36 expression were increased, and the expression of MCP-1 and TNF-α was decreased, in the aorta of statin-treated Apoe{sup −/−} mice. In conclusion, statins mediate anti-atherogenic effects

  3. Reverse mode Na+/Ca2+ exchange mediated by STIM1 contributes to Ca2+ influx in airway smooth muscle following agonist stimulation

    Directory of Open Access Journals (Sweden)

    Fox Jane

    2010-12-01

    Full Text Available Abstract Background Agonist stimulation of airway smooth muscle (ASM results in IP3 mediated Ca2+ release from the sarcoplasmic reticulum followed by the activation of store operated and receptor operated non-selective cation channels. Activation of these non-selective channels also results in a Na+ influx. This localised increase in Na+ levels can potentially switch the Na+/Ca2+ exchanger into reverse mode and so result in a further influx of Ca2+. The aim of this study was to characterise the expression and physiological function of the Na+/Ca2+ exchanger in cultured human bronchial smooth muscle cells and determine its contribution to agonist induced Ca2+ influx into these cells. Methods The expression profile of NCX (which encodes the Na+/Ca2+ exchanger homologues in cultured human bronchial smooth muscle cells was determined by reverse transcriptase PCR. The functional activity of reverse mode NCX was investigated using a combination of whole cell patch clamp, intracellular Ca2+ measurements and porcine airway contractile analyses. KB-R7943 (an antagonist for reverse mode NCX and target specific siRNA were utilised as tools to inhibit NCX function. Results NCX1 protein was detected in cultured human bronchial smooth muscle cells (HBSMC cells and NCX1.3 was the only mRNA transcript variant detected. A combination of intracellular Na+ loading and addition of extracellular Ca2+ induced an outwardly rectifying current which was augmented following stimulation with histamine. This outwardly rectifying current was inhibited by 10 μM KB-R7943 (an antagonist of reverse mode NCX1 and was reduced in cells incubated with siRNA against NCX1. Interestingly, this outwardly rectifying current was also inhibited following knockdown of STIM1, suggesting for the first time a link between store operated cation entry and NCX1 activation. In addition, 10 μM KB-R7943 inhibited agonist induced changes in cytosolic Ca2+ and induced relaxation of porcine

  4. Implementation of mobile ip smooth handoff in wireless networks

    International Nuclear Information System (INIS)

    Kayastha, M.; Chowdhry, B.S.; Memon, A.R.

    2002-01-01

    This paper describes implementation of mobile IP services in two separate wireless LANs based on IEEE 802.11b standards, located in two distant buildings of a university campus. The purpose of the project was to achieve smooth hand-off when a mobile node moves between the two LANs. During our experimentation we have identified some of the limitation of IEEE 802.11b that affects mobile 1P smooth hand off. We have also proposed an algorithm to solve this problem when the mobility is within a limited number of separate wireless LANs. (author)

  5. Hydrostatic pressure and muscarinic receptors are involved in the release of inflammatory cytokines in human bladder smooth muscle cells.

    Science.gov (United States)

    Liang, Zhou; Xin, Wei; Qiang, Liu; Xiang, Cai; Bang-Hua, Liao; Jin, Yang; De-Yi, Luo; Hong, Li; Kun-Jie, Wang

    2017-06-01

    Abnormal intravesical pressure results in a series of pathological changes. We investigated the effects of hydrostatic pressure and muscarinic receptors on the release of inflammatory cytokines in rat and human bladder smooth muscle cells (HBSMCs). Animal model of bladder outlet obstruction was induced by urethra ligation. HBSMCs were subjected to elevated hydrostatic pressure and/or acetylcholine (Ach). Macrophage infiltration in the bladder wall was determined by immunohistochemical staining. The expression of inflammatory genes was measured by RT-PCR, ELISA and immunofluorescence. In obstructed bladder, inflammatory genes and macrophage infiltration were remarkably induced. When HBSMCs were subjected to 200-300 cm H 2 O pressure for 2-24 h in vitro, the expressions of IL-6 and RANTES were significantly increased. Hydrostatic pressure promoted the protein levels of phospho-NFκB p65 and phospho-ERK1/2 as well as muscarinic receptors. Moreover, NFκB or ERK1/2 inhibitors suppressed pressure-induced inflammatory genes mRNA. When cells were treated with 1 μM acetylcholine for 6 h, a significant increase in IL-6 mRNA expression was detected. Acetylcholine also enhanced pressure-induced phospho-NFκB p65 and IL-6 protein expression. Additionally, pressure-induced IL-6 was partially suppressed by muscarinic receptors antagonists. Hydrostatic pressure and muscarinic receptors were involved in the secretion of inflammatory cytokines in HBSMCs, indicating a pro-inflammatory effect of the two factors in the pathological process of BOO. © 2016 Wiley Periodicals, Inc.

  6. Smoothed Spectra, Ogives, and Error Estimates for Atmospheric Turbulence Data

    Science.gov (United States)

    Dias, Nelson Luís

    2018-01-01

    A systematic evaluation is conducted of the smoothed spectrum, which is a spectral estimate obtained by averaging over a window of contiguous frequencies. The technique is extended to the ogive, as well as to the cross-spectrum. It is shown that, combined with existing variance estimates for the periodogram, the variance—and therefore the random error—associated with these estimates can be calculated in a straightforward way. The smoothed spectra and ogives are biased estimates; with simple power-law analytical models, correction procedures are devised, as well as a global constraint that enforces Parseval's identity. Several new results are thus obtained: (1) The analytical variance estimates compare well with the sample variance calculated for the Bartlett spectrum and the variance of the inertial subrange of the cospectrum is shown to be relatively much larger than that of the spectrum. (2) Ogives and spectra estimates with reduced bias are calculated. (3) The bias of the smoothed spectrum and ogive is shown to be negligible at the higher frequencies. (4) The ogives and spectra thus calculated have better frequency resolution than the Bartlett spectrum, with (5) gradually increasing variance and relative error towards the low frequencies. (6) Power-law identification and extraction of the rate of dissipation of turbulence kinetic energy are possible directly from the ogive. (7) The smoothed cross-spectrum is a valid inner product and therefore an acceptable candidate for coherence and spectral correlation coefficient estimation by means of the Cauchy-Schwarz inequality. The quadrature, phase function, coherence function and spectral correlation function obtained from the smoothed spectral estimates compare well with the classical ones derived from the Bartlett spectrum.

  7. Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung

    International Nuclear Information System (INIS)

    Mak, J.C.; Barnes, P.J.

    1990-01-01

    Muscarinic receptor subtypes have been localized in human and guinea pig lung sections by an autoradiographic technique, using [3H](-)quinuclidinyl benzilate [( 3H]QNB) and selective muscarinic antagonists. [3H]QNB was incubated with tissue sections for 90 min at 25 degrees C, and nonspecific binding was determined by incubating adjacent serial sections in the presence of 1 microM atropine. Binding to lung sections had the characterization expected for muscarinic receptors. Autoradiography revealed that muscarinic receptors were widely distributed in human lung, with dense labeling over submucosal glands and airway ganglia, and moderate labeling over nerves in intrapulmonary bronchi and of airway smooth muscle of large and small airways. In addition, alveolar walls were uniformly labeled. In guinea pig lung, labeling of airway smooth muscle was similar, but in contrast to human airways, epithelium was labeled but alveolar walls were not. The muscarinic receptors of human airway smooth muscle from large to small airways were entirely of the M3-subtype, whereas in guinea pig airway smooth muscle, the majority were the M3-subtype with a very small population of the M2-subtype present. In human bronchial submucosal glands, M1- and M3-subtypes appeared to coexist in the proportions of 36 and 64%, respectively. In human alveolar walls the muscarinic receptors were entirely of the M1-subtype, which is absent from the guinea pig lung. No M2-receptors were demonstrated in human lung. The localization of M1-receptors was confirmed by direct labeling with [3H]pirenzepine. With the exception of the alveolar walls in human lung, the localization of muscarinic receptor subtypes on structures in the lung is consistent with known functional studies

  8. Local smoothness for global optical flow

    DEFF Research Database (Denmark)

    Rakêt, Lars Lau

    2012-01-01

    by this technique and work on local-global optical flow we propose a simple method for fusing optical flow estimates of different smoothness by evaluating interpolation quality locally by means of L1 block match on the corresponding set of gradient images. We illustrate the method in a setting where optical flows...

  9. Influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery.

    Science.gov (United States)

    Bermúdez, Beatriz; López, Sergio; Pacheco, Yolanda M; Villar, José; Muriana, Francisco J G; Hoheisel, Jöerg D; Bauer, Andrea; Abia, Rocío

    2008-07-15

    Postprandial triglyceride-rich lipoproteins (TRL) have a direct effect on vascular smooth muscle cells (SMC) and they increase the risk of atherogenesis. Here, we have tested the hypothesis that the different fatty acid composition of TRL is capable of differentially modifying gene expression in human coronary artery SMC (CASMC). In addition, the effect of TRL on cell proliferation and transcription factor activation was also evaluated. TRL were prepared from plasma of healthy volunteers after the ingestion of meals enriched in refined olive oil (ROO), butter or a mixture of vegetable and fish oils (VEFO). We use cDNA microarrays to determine the genes differentially expressed in TRL-treated CASMC. Correspondence cluster analysis demonstrated that TRL-butter, -ROO and -VEFO provoked different transcriptional profiles in CASMC. Sixty-six genes were regulated by TRL-butter, 55 by -ROO, and 47 by -VEFO. The data revealed that TRL-butter predominantly activated genes involved in the regulation of cell proliferation and inflammation. Likewise, TRL-VEFO induced the expression of genes implicated in inflammation, while TRL-ROO promoted a less atherogenic gene profile. The pathophysiological contribution of TRL to the development of atherosclerosis and the stability of atherosclerotic plaques may depend on the fatty acid composition of TRL. Our findings suggest a role for macrophage-inhibiting cytokine-1 (MIC-1) in coronary artery cardiovascular events.

  10. Turbulence Intensity and the Friction Factor for Smooth- and Rough-Wall Pipe Flow

    OpenAIRE

    Nils T. Basse

    2017-01-01

    Turbulence intensity profiles are compared for smooth- and rough-wall pipe flow measurements made in the Princeton Superpipe. The profile development in the transition from hydraulically smooth to fully rough flow displays a propagating sequence from the pipe wall towards the pipe axis. The scaling of turbulence intensity with Reynolds number shows that the smooth- and rough wall level deviates with increasing Reynolds number. We quantify the correspondence between turbulence intensity and th...

  11. A Meshfree Cell-based Smoothed Point Interpolation Method for Solid Mechanics Problems

    International Nuclear Information System (INIS)

    Zhang Guiyong; Liu Guirong

    2010-01-01

    In the framework of a weakened weak (W 2 ) formulation using a generalized gradient smoothing operation, this paper introduces a novel meshfree cell-based smoothed point interpolation method (CS-PIM) for solid mechanics problems. The W 2 formulation seeks solutions from a normed G space which includes both continuous and discontinuous functions and allows the use of much more types of methods to create shape functions for numerical methods. When PIM shape functions are used, the functions constructed are in general not continuous over the entire problem domain and hence are not compatible. Such an interpolation is not in a traditional H 1 space, but in a G 1 space. By introducing the generalized gradient smoothing operation properly, the requirement on function is now further weakened upon the already weakened requirement for functions in a H 1 space and G 1 space can be viewed as a space of functions with weakened weak (W 2 ) requirement on continuity. The cell-based smoothed point interpolation method (CS-PIM) is formulated based on the W 2 formulation, in which displacement field is approximated using the PIM shape functions, which possess the Kronecker delta property facilitating the enforcement of essential boundary conditions [3]. The gradient (strain) field is constructed by the generalized gradient smoothing operation within the cell-based smoothing domains, which are exactly the triangular background cells. A W 2 formulation of generalized smoothed Galerkin (GS-Galerkin) weak form is used to derive the discretized system equations. It was found that the CS-PIM possesses the following attractive properties: (1) It is very easy to implement and works well with the simplest linear triangular mesh without introducing additional degrees of freedom; (2) it is at least linearly conforming; (3) this method is temporally stable and works well for dynamic analysis; (4) it possesses a close-to-exact stiffness, which is much softer than the overly-stiff FEM model and

  12. Suppression of stochastic pulsation in laser-plasma interaction by smoothing methods

    International Nuclear Information System (INIS)

    Hora, H.; Aydin, M.

    1992-01-01

    The control of the very complex behavior of a plasma with laser interaction by smoothing with induced spatial incoherence or other methods was related to improving the lateral uniformity of the irradiation. While this is important, it is shown from numerical hydrodynamic studies that the very strong temporal pulsation (stuttering) will mostly be suppressed by these smoothing methods too

  13. From depolarization-dependent contractions in gastrointestinal smooth muscle to aortic pulse-synchronized contractions

    Directory of Open Access Journals (Sweden)

    Marion SB

    2014-03-01

    Full Text Available Sarah B Marion, Allen W MangelRTI Health Solutions, Research Triangle Park, NC, USAAbstract: For decades, it was believed that the diameter of gastrointestinal smooth muscle cells is sufficiently narrow, and that the diffusion of calcium across the plasma membrane is sufficient, to support contractile activity. Thus, depolarization-triggered release of intracellular calcium was not believed to be operative in gastrointestinal smooth muscle. However, after the incubation of muscle segments in solutions devoid of calcium and containing the calcium chelator ethylene glycol tetraacetic acid, an alternative electrical event occurred that was distinct from normal slow waves and spikes. Subsequently, it was demonstrated in gastrointestinal smooth muscle segments that membrane depolarization associated with this alternative electrical event triggered rhythmic contractions by release of intracellular calcium. Although this concept of depolarization-triggered calcium release was iconoclastic, it has now been demonstrated in multiple gastrointestinal smooth muscle preparations. On the basis of these observations, we investigated whether a rhythmic electrical and mechanical event would occur in aortic smooth muscle under the same calcium-free conditions. The incubation of aortic segments in a solution with no added calcium plus ethylene glycol tetraacetic acid induced a fast electrical event without corresponding tension changes. On the basis of the frequency of these fast electrical events, we pursued, contrary to what has been established dogma for more than three centuries, the question of whether the smooth muscle wall of the aorta undergoes rhythmic activation during the cardiac cycle. As with depolarization-triggered contractile activity in gastrointestinal smooth muscle, it was “well known” that rhythmic activation of the aorta does not occur in synchrony with the heartbeat. In a series of experiments, however, it was demonstrated that rhythmic

  14. Ensemble Kalman filtering with one-step-ahead smoothing

    KAUST Repository

    Raboudi, Naila F.

    2018-01-11

    The ensemble Kalman filter (EnKF) is widely used for sequential data assimilation. It operates as a succession of forecast and analysis steps. In realistic large-scale applications, EnKFs are implemented with small ensembles and poorly known model error statistics. This limits their representativeness of the background error covariances and, thus, their performance. This work explores the efficiency of the one-step-ahead (OSA) smoothing formulation of the Bayesian filtering problem to enhance the data assimilation performance of EnKFs. Filtering with OSA smoothing introduces an updated step with future observations, conditioning the ensemble sampling with more information. This should provide an improved background ensemble in the analysis step, which may help to mitigate the suboptimal character of EnKF-based methods. Here, the authors demonstrate the efficiency of a stochastic EnKF with OSA smoothing for state estimation. They then introduce a deterministic-like EnKF-OSA based on the singular evolutive interpolated ensemble Kalman (SEIK) filter. The authors show that the proposed SEIK-OSA outperforms both SEIK, as it efficiently exploits the data twice, and the stochastic EnKF-OSA, as it avoids observational error undersampling. They present extensive assimilation results from numerical experiments conducted with the Lorenz-96 model to demonstrate SEIK-OSA’s capabilities.

  15. Exchange rate smoothing in Hungary

    OpenAIRE

    Karádi, Péter

    2005-01-01

    The paper proposes a structural empirical model capable of examining exchange rate smoothing in the small, open economy of Hungary. The framework assumes the existence of an unobserved and changing implicit exchange rate target. The central bank is assumed to use interest rate policy to obtain this preferred rate in the medium term, while market participants are assumed to form rational expectations about this target and influence exchange rates accordingly. The paper applies unobserved varia...

  16. Technique for smoothing free-flight oscillation data.

    CSIR Research Space (South Africa)

    Beyers, ME

    1975-01-01

    Full Text Available A technique based on superposition of tricyclic solutions has been proposed for smoothing free-flight angular motion. When incorporated into a conventional tricyclic data reduction program, the method is convenient to use and does not require a...

  17. Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-α and dexamethasone

    Directory of Open Access Journals (Sweden)

    Walseth Timothy F

    2008-03-01

    Full Text Available Abstract Background CD38 is expressed in human airway smooth muscle (HASM cells, regulates intracellular calcium, and its expression is augmented by tumor necrosis factor alpha (TNF-α. CD38 has a role in airway hyperresponsiveness, a hallmark of asthma, since deficient mice develop attenuated airway hyperresponsiveness compared to wild-type mice following intranasal challenges with cytokines such as IL-13 and TNF-α. Regulation of CD38 expression in HASM cells involves the transcription factor NF-κB, and glucocorticoids inhibit this expression through NF-κB-dependent and -independent mechanisms. In this study, we determined whether the transcriptional regulation of CD38 expression in HASM cells involves response elements within the promoter region of this gene. Methods We cloned a putative 3 kb promoter fragment of the human cd38 gene into pGL3 basic vector in front of a luciferase reporter gene. Sequence analysis of the putative cd38 promoter region revealed one NF-κB and several AP-1 and glucocorticoid response element (GRE motifs. HASM cells were transfected with the 3 kb promoter, a 1.8 kb truncated promoter that lacks the NF-κB and some of the AP-1 sites, or the promoter with mutations of the NF-κB and/or AP-1 sites. Using the electrophoretic mobility shift assays, we determined the binding of nuclear proteins to oligonucleotides encoding the putative cd38 NF-κB, AP-1, and GRE sites, and the specificity of this binding was confirmed by gel supershift analysis with appropriate antibodies. Results TNF-α induced a two-fold activation of the 3 kb promoter following its transfection into HASM cells. In cells transfected with the 1.8 kb promoter or promoter constructs lacking NF-κB and/or AP-1 sites or in the presence of dexamethasone, there was no induction in the presence of TNF-α. The binding of nuclear proteins to oligonucleotides encoding the putative cd38 NF-κB site and some of the six AP-1 sites was increased by TNF-α, and to

  18. Discrete wavelet transform: a tool in smoothing kinematic data.

    Science.gov (United States)

    Ismail, A R; Asfour, S S

    1999-03-01

    Motion analysis systems typically introduce noise to the displacement data recorded. Butterworth digital filters have been used to smooth the displacement data in order to obtain smoothed velocities and accelerations. However, this technique does not yield satisfactory results, especially when dealing with complex kinematic motions that occupy the low- and high-frequency bands. The use of the discrete wavelet transform, as an alternative to digital filters, is presented in this paper. The transform passes the original signal through two complementary low- and high-pass FIR filters and decomposes the signal into an approximation function and a detail function. Further decomposition of the signal results in transforming the signal into a hierarchy set of orthogonal approximation and detail functions. A reverse process is employed to perfectly reconstruct the signal (inverse transform) back from its approximation and detail functions. The discrete wavelet transform was applied to the displacement data recorded by Pezzack et al., 1977. The smoothed displacement data were twice differentiated and compared to Pezzack et al.'s acceleration data in order to choose the most appropriate filter coefficients and decomposition level on the basis of maximizing the percentage of retained energy (PRE) and minimizing the root mean square error (RMSE). Daubechies wavelet of the fourth order (Db4) at the second decomposition level showed better results than both the biorthogonal and Coiflet wavelets (PRE = 97.5%, RMSE = 4.7 rad s-2). The Db4 wavelet was then used to compress complex displacement data obtained from a noisy mathematically generated function. Results clearly indicate superiority of this new smoothing approach over traditional filters.

  19. Smoothing the payoff for efficient computation of Basket option prices

    KAUST Repository

    Bayer, Christian

    2017-07-22

    We consider the problem of pricing basket options in a multivariate Black–Scholes or Variance-Gamma model. From a numerical point of view, pricing such options corresponds to moderate and high-dimensional numerical integration problems with non-smooth integrands. Due to this lack of regularity, higher order numerical integration techniques may not be directly available, requiring the use of methods like Monte Carlo specifically designed to work for non-regular problems. We propose to use the inherent smoothing property of the density of the underlying in the above models to mollify the payoff function by means of an exact conditional expectation. The resulting conditional expectation is unbiased and yields a smooth integrand, which is amenable to the efficient use of adaptive sparse-grid cubature. Numerical examples indicate that the high-order method may perform orders of magnitude faster than Monte Carlo or Quasi Monte Carlo methods in dimensions up to 35.

  20. Multiple predictor smoothing methods for sensitivity analysis: Description of techniques

    International Nuclear Information System (INIS)

    Storlie, Curtis B.; Helton, Jon C.

    2008-01-01

    The use of multiple predictor smoothing methods in sampling-based sensitivity analyses of complex models is investigated. Specifically, sensitivity analysis procedures based on smoothing methods employing the stepwise application of the following nonparametric regression techniques are described: (i) locally weighted regression (LOESS), (ii) additive models, (iii) projection pursuit regression, and (iv) recursive partitioning regression. Then, in the second and concluding part of this presentation, the indicated procedures are illustrated with both simple test problems and results from a performance assessment for a radioactive waste disposal facility (i.e., the Waste Isolation Pilot Plant). As shown by the example illustrations, the use of smoothing procedures based on nonparametric regression techniques can yield more informative sensitivity analysis results than can be obtained with more traditional sensitivity analysis procedures based on linear regression, rank regression or quadratic regression when nonlinear relationships between model inputs and model predictions are present

  1. PAF-receptor is preferentially expressed in a distinct synthetic phenotype of smooth muscle cells cloned from human internal thoracic artery: Functional implications in cell migration

    International Nuclear Information System (INIS)

    Stengel, Dominique; O'Neil, Caroline; Brocheriou, Isabelle; Karabina, Sonia-Athina; Durand, Herve; Caplice, Noel M.; Pickering, J. Geoffrey; Ninio, Ewa

    2006-01-01

    Platelet-activating-Factor (PAF) and its structural analogues formed upon low density lipoprotein oxidation are involved in atherosclerotic plaque formation and may signal through PAF-receptor (PAF-R) expressed in human macrophages and in certain smooth muscle cells (SMCs) in the media, but rarely in the intima of human plaques. Our aim was to determine which SMC phenotype expresses PAF-R and whether this receptor is functional in cell migration. Circulating SMC progenitors and two phenotypically distinct clones of proliferative, epithelioid phenotype vs contractile, spindle-shaped SMCs from the media of adult internal thoracic artery were studied for the presence of PAF-receptor (PAF-R). The levels of specific mRNA were obtained by reverse transcription/real-time PCR, the protein expression was deduced from immunohistochemistry staining, and the functional transmigration assay was performed by Boyden chamber-type chemotaxis assay. Only SMCs of spindle-shape and synthetic phenotype expressed both mRNA and PAF-R protein and in the functional test migrated at low concentrations of PAF. Two unrelated, specific PAF-R antagonists inhibited PAF-induced migration, but did not modify the migration initiated by PDGF. The presence of functional PAF-R in arterial spindle-shaped SMCs of synthetic phenotype may be important for their migration from the media into the intima and atherosclerotic plaques formation

  2. A simple smoothness indicator for the WENO scheme with adaptive order

    Science.gov (United States)

    Huang, Cong; Chen, Li Li

    2018-01-01

    The fifth order WENO scheme with adaptive order is competent for solving hyperbolic conservation laws, its reconstruction is a convex combination of a fifth order linear reconstruction and three third order linear reconstructions. Note that, on uniform mesh, the computational cost of smoothness indicator for fifth order linear reconstruction is comparable with the sum of ones for three third order linear reconstructions, thus it is too heavy; on non-uniform mesh, the explicit form of smoothness indicator for fifth order linear reconstruction is difficult to be obtained, and its computational cost is much heavier than the one on uniform mesh. In order to overcome these problems, a simple smoothness indicator for fifth order linear reconstruction is proposed in this paper.

  3. Fragmented esophageal smooth muscle contraction segments on high resolution manometry: a marker of esophageal hypomotility.

    Science.gov (United States)

    Porter, R F; Kumar, N; Drapekin, J E; Gyawali, C P

    2012-08-01

    Esophageal peristalsis consists of a chain of contracting striated and smooth muscle segments on high resolution manometry (HRM). We compared smooth muscle contraction segments in symptomatic subjects with reflux disease to healthy controls. High resolution manometry Clouse plots were analyzed in 110 subjects with reflux disease (50 ± 1.4 years, 51.5% women) and 15 controls (27 ± 2.1 years, 60.0% women). Using the 30 mmHg isobaric contour tool, sequences were designated fragmented if either smooth muscle contraction segment was absent or if the two smooth muscle segments were separated by a pressure trough, and failed if both smooth muscle contraction segments were absent. The discriminative value of contraction segment analysis was assessed. A total of 1115 swallows were analyzed (reflux group: 965, controls: 150). Reflux subjects had lower peak and averaged contraction amplitudes compared with controls (P value to HRM analysis. Specifically, fragmented smooth muscle contraction segments may be a marker of esophageal hypomotility. © 2012 Blackwell Publishing Ltd.

  4. Adaptive Smoothing in fMRI Data Processing Neural Networks

    DEFF Research Database (Denmark)

    Vilamala, Albert; Madsen, Kristoffer Hougaard; Hansen, Lars Kai

    2017-01-01

    in isolation. With the advent of new tools for deep learning, recent work has proposed to turn these pipelines into end-to-end learning networks. This change of paradigm offers new avenues to improvement as it allows for a global optimisation. The current work aims at benefitting from this paradigm shift...... by defining a smoothing step as a layer in these networks able to adaptively modulate the degree of smoothing required by each brain volume to better accomplish a given data analysis task. The viability is evaluated on real fMRI data where subjects did alternate between left and right finger tapping tasks....

  5. Smooth germanium nanowires prepared by a hydrothermal deposition process

    Energy Technology Data Exchange (ETDEWEB)

    Pei, L.Z., E-mail: lzpei1977@163.com [School of Materials Science and Engineering, Institute of Molecular Engineering and Applied Chemistry, Key Laboratory of Materials Science and Processing of Anhui Province, Anhui University of Technology, Ma' anshan, Anhui 243002 (China); Zhao, H.S. [School of Materials Science and Engineering, Institute of Molecular Engineering and Applied Chemistry, Key Laboratory of Materials Science and Processing of Anhui Province, Anhui University of Technology, Ma' anshan, Anhui 243002 (China); Tan, W. [Henkel Huawei Electronics Co. Ltd., Lian' yungang, Jiangsu 222006 (China); Yu, H.Y. [School of Materials Science and Engineering, Institute of Molecular Engineering and Applied Chemistry, Key Laboratory of Materials Science and Processing of Anhui Province, Anhui University of Technology, Ma' anshan, Anhui 243002 (China); Chen, Y.W. [Department of Materials Science, Fudan University, Shanghai 200433 (China); Fan, C.G. [School of Materials Science and Engineering, Institute of Molecular Engineering and Applied Chemistry, Key Laboratory of Materials Science and Processing of Anhui Province, Anhui University of Technology, Ma' anshan, Anhui 243002 (China); Zhang, Qian-Feng, E-mail: zhangqf@ahut.edu.cn [School of Materials Science and Engineering, Institute of Molecular Engineering and Applied Chemistry, Key Laboratory of Materials Science and Processing of Anhui Province, Anhui University of Technology, Ma' anshan, Anhui 243002 (China)

    2009-11-15

    Smooth germanium nanowires were prepared using Ge and GeO{sub 2} as the starting materials and Cu sheet as the substrate by a simple hydrothermal deposition process. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterizations show that the germanium nanowires are smooth and straight with uniform diameter of about 150 nm in average and tens of micrometers in length. X-ray diffraction (XRD) and Raman spectrum of the germanium nanowires display that the germanium nanowires are mainly composed of cubic diamond phase. PL spectrum shows a strong blue light emission at 441 nm. The growth mechanism is also discussed.

  6. Smooth germanium nanowires prepared by a hydrothermal deposition process

    International Nuclear Information System (INIS)

    Pei, L.Z.; Zhao, H.S.; Tan, W.; Yu, H.Y.; Chen, Y.W.; Fan, C.G.; Zhang, Qian-Feng

    2009-01-01

    Smooth germanium nanowires were prepared using Ge and GeO 2 as the starting materials and Cu sheet as the substrate by a simple hydrothermal deposition process. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterizations show that the germanium nanowires are smooth and straight with uniform diameter of about 150 nm in average and tens of micrometers in length. X-ray diffraction (XRD) and Raman spectrum of the germanium nanowires display that the germanium nanowires are mainly composed of cubic diamond phase. PL spectrum shows a strong blue light emission at 441 nm. The growth mechanism is also discussed.

  7. CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation

    Directory of Open Access Journals (Sweden)

    Capra Valérie

    2006-03-01

    Full Text Available Abstract Background Cysteine-containing leukotrienes (cysteinyl-LTs are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other inflammatory conditions. In particular, cysteinyl-LTs exert a variety of effects with relevance to the aetiology of asthma such as smooth muscle contraction, eosinophil recruitment, increased microvascular permeability, enhanced mucus secretion and decreased mucus transport and, finally, airway smooth muscle cells (ASMC proliferation. We used human ASMC (HASMC to identify the signal transduction pathway(s of the leukotriene D4 (LTD4-induced DNA synthesis. Methods Proliferation of primary HASMC was measured by [3H]thymidine incorporation. Phosphorylation of EGF receptor (EGF-R and ERK1/2 was assessed with a polyclonal anti-EGF-R or anti-phosphoERKl/2 monoclonal antibody. A Ras pull-down assay kit was used to evaluate Ras activation. The production of reactive oxygen species (ROS was estimated by measuring dichlorodihydrofluorescein (DCF oxidation. Results We demonstrate that in HASMC LTD4-stimulated thymidine incorporation and potentiation of EGF-induced mitogenic signaling mostly depends upon EGF-R transactivation through the stimulation of CysLT1-R. Accordingly, we found that LTD4 stimulation was able to trigger the increase of Ras-GTP and, in turn, to activate ERK1/2. We show here that EGF-R transactivation was sensitive to pertussis toxin (PTX and phosphoinositide 3-kinase (PI3K inhibitors and that it occurred independently from Src activity, despite the observation of a strong impairment of LTD4-induced DNA synthesis following Src inhibition. More interestingly, CysLT1-R stimulation increased the production of ROS and N-acetylcysteine (NAC abolished LTD4-induced EGF-R phosphorylation and thymidine incorporation. Conclusion Collectively, our data demonstrate that in HASMC LTD4 stimulation of a Gi/o coupled CysLT1-R triggers the transactivation of the EGF

  8. Role of retinal slip in the prediction of target motion during smooth and saccadic pursuit.

    Science.gov (United States)

    de Brouwer, S; Missal, M; Lefèvre, P

    2001-08-01

    Visual tracking of moving targets requires the combination of smooth pursuit eye movements with catch-up saccades. In primates, catch-up saccades usually take place only during pursuit initiation because pursuit gain is close to unity. This contrasts with the lower and more variable gain of smooth pursuit in cats, where smooth eye movements are intermingled with catch-up saccades during steady-state pursuit. In this paper, we studied in detail the role of retinal slip in the prediction of target motion during smooth and saccadic pursuit in the cat. We found that the typical pattern of pursuit in the cat was a combination of smooth eye movements with saccades. During smooth pursuit initiation, there was a correlation between peak eye acceleration and target velocity. During pursuit maintenance, eye velocity oscillated at approximately 3 Hz around a steady-state value. The average gain of smooth pursuit was approximately 0.5. Trained cats were able to continue pursuing in the absence of a visible target, suggesting a role of the prediction of future target motion in this species. The analysis of catch-up saccades showed that the smooth-pursuit motor command is added to the saccadic command during catch-up saccades and that both position error and retinal slip are taken into account in their programming. The influence of retinal slip on catch-up saccades showed that prediction about future target motion is used in the programming of catch-up saccades. Altogether, these results suggest that pursuit systems in primates and cats are qualitatively similar, with a lower average gain in the cat and that prediction affects both saccades and smooth eye movements during pursuit.

  9. Isolation and characterization of the inositol trisphosphate receptor from smooth muscle

    International Nuclear Information System (INIS)

    Chadwick, C.C.; Saito, A.; Fleischer, S.

    1990-01-01

    The release of Ca 2+ from internal stores is requisite to muscle contraction. In skeletal muscle and heart, the Ca 2+ release channels (ryanodine receptor) of sarcoplasmic reticulum, involved in excitation-contraction coupling, have recently been isolated and characterized. In smooth muscle, inositol 1,4,5-trisphosphate (IP 3 ) is believed to mobilize Ca 2+ from internal stores and thereby modulate contraction. The authors describe the isolation of an IP 3 receptor from smooth muscle. Bovine aorta smooth muscle microsomes were solubilized with 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate, and the IP 3 receptor was purified by sucrose gradient centrifugation and column chromatography with heparin-agarose and wheat germ agglutinin-agarose. The receptor is an oligomer of a single polypeptide with a M r of 224,000 as determined by SDS/PAGE. Negative-staining electron microscopy reveals that the receptor is a large pinwheel-like structure having surface dimensions of ∼250 x 250 angstrom with fourfold symmetry. The IP 3 receptor from smooth muscle is similar to the ryanodine receptor with regard to its large size and fourfold symmetry, albeit distinct with regard to appearance, protomer size, and ligand binding

  10. Defective Resensitization in Human Airway Smooth Muscle Cells Evokes β-Adrenergic Receptor Dysfunction in Severe Asthma.

    Directory of Open Access Journals (Sweden)

    Manveen K Gupta

    Full Text Available β2-adrenergic receptor (β2AR agonists (β2-agonist are the most commonly used therapy for acute relief in asthma, but chronic use of these bronchodilators paradoxically exacerbates airway hyper-responsiveness. Activation of βARs by β-agonist leads to desensitization (inactivation by phosphorylation through G-protein coupled receptor kinases (GRKs which mediate β-arrestin binding and βAR internalization. Resensitization occurs by dephosphorylation of the endosomal βARs which recycle back to the plasma membrane as agonist-ready receptors. To determine whether the loss in β-agonist response in asthma is due to altered βAR desensitization and/or resensitization, we used primary human airway smooth muscle cells (HASMCs isolated from the lungs of non-asthmatic and fatal-asthmatic subjects. Asthmatic HASMCs have diminished adenylyl cyclase activity and cAMP response to β-agonist as compared to non-asthmatic HASMCs. Confocal microscopy showed significant accumulation of phosphorylated β2ARs in asthmatic HASMCs. Systematic analysis of desensitization components including GRKs and β-arrestin showed no appreciable differences between asthmatic and non-asthmatic HASMCs. However, asthmatic HASMC showed significant increase in PI3Kγ activity and was associated with reduction in PP2A activity. Since reduction in PP2A activity could alter receptor resensitization, endosomal fractions were isolated to assess the agonist ready β2ARs as a measure of resensitization. Despite significant accumulation of β2ARs in the endosomes of asthmatic HASMCs, endosomal β2ARs cannot robustly activate adenylyl cyclase. Furthermore, endosomes from asthmatic HASMCs are associated with significant increase in PI3Kγ and reduced PP2A activity that inhibits β2AR resensitization. Our study shows that resensitization, a process considered to be a homeostasis maintaining passive process is inhibited in asthmatic HASMCs contributing to β2AR dysfunction which may underlie

  11. Endometrial stem cell differentiation into smooth muscle cell: a novel approach for bladder tissue engineering in women.

    Science.gov (United States)

    Shoae-Hassani, Alireza; Sharif, Shiva; Seifalian, Alexander M; Mortazavi-Tabatabaei, Seyed Abdolreza; Rezaie, Sassan; Verdi, Javad

    2013-10-01

    To investigate manufacturing smooth muscle cells (SMCs) for regenerative bladder reconstruction from differentiation of endometrial stem cells (EnSCs), as the recent discovery of EnSCs from the lining of women's uteri, opens up the possibility of using these cells for tissue engineering applications, such as building up natural tissue to repair prolapsed pelvic floors as well as building urinary bladder wall. Human EnSCs that were positive for cluster of differentiation 146 (CD146), CD105 and CD90 were isolated and cultured in Dulbecco's modified Eagle/F12 medium supplemented with myogenic growth factors. The myogenic factors included: transforming growth factor β, platelet-derived growth factor, hepatocyte growth factor and vascular endothelial growth factor. Differentiated SMCs on bioabsorbable polyethylene-glycol and collagen hydrogels were checked for SMC markers by real-time reverse-transcriptase polymerase chain reaction (RT-PCR), western blot (WB) and immunocytochemistry (ICC) analyses. Histology confirmed the growth of SMCs in the hydrogel matrices. The myogenic growth factors decreased the proliferation rate of EnSCs, but they differentiated the human EnSCs into SMCs more efficiently on hydrogel matrices and expressed specific SMC markers including α-smooth muscle actin, desmin, vinculin and calponin in RT-PCR, WB and ICC experiments. The survival rate of cultures on the hydrogel-coated matrices was significantly higher than uncoated cultures. Human EnSCs were successfully differentiated into SMCs, using hydrogels as scaffold. EnSCs may be used for autologous bladder wall regeneration without any immunological complications in women. Currently work is in progress using bioabsorbable nanocomposite materials as EnSC scaffolds for developing urinary bladder wall tissue. © 2013 The Authors. BJU International © 2013 BJU International.

  12. Smooth controllability of infinite-dimensional quantum-mechanical systems

    International Nuclear Information System (INIS)

    Wu, Re-Bing; Tarn, Tzyh-Jong; Li, Chun-Wen

    2006-01-01

    Manipulation of infinite-dimensional quantum systems is important to controlling complex quantum dynamics with many practical physical and chemical backgrounds. In this paper, a general investigation is casted to the controllability problem of quantum systems evolving on infinite-dimensional manifolds. Recognizing that such problems are related with infinite-dimensional controllability algebras, we introduce an algebraic mathematical framework to describe quantum control systems possessing such controllability algebras. Then we present the concept of smooth controllability on infinite-dimensional manifolds, and draw the main result on approximate strong smooth controllability. This is a nontrivial extension of the existing controllability results based on the analysis over finite-dimensional vector spaces to analysis over infinite-dimensional manifolds. It also opens up many interesting problems for future studies

  13. Advanced haptic sensor for measuring human skin conditions

    Science.gov (United States)

    Tsuchimi, Daisuke; Okuyama, Takeshi; Tanaka, Mami

    2010-01-01

    This paper is concerned with the development of a tactile sensor using PVDF (Polyvinylidene Fluoride) film as a sensory receptor of the sensor to evaluate softness, smoothness, and stickiness of human skin. Tactile sense is the most important sense in the sensation receptor of the human body along with eyesight, and we can examine skin condition quickly using these sense. But, its subjectivity and ambiguity make it difficult to quantify skin conditions. Therefore, development of measurement device which can evaluate skin conditions easily and objectively is demanded by dermatologists, cosmetic industries, and so on. In this paper, an advanced haptic sensor system that can measure multiple information of skin condition in various parts of human body is developed. The applications of the sensor system to evaluate softness, smoothness, and stickiness of skin are investigated through two experiments.

  14. Regulation of collagen biosynthesis in cultured bovine aortic smooth muscle cells

    International Nuclear Information System (INIS)

    Stepp, M.A.

    1986-01-01

    Aortic smooth muscles cells have been implicated in the etiology of lesions which occur in atherosclerosis and hypertension. Both diseases involve proliferation of smooth muscle cells and accumulation of excessive amounts of extracellular matrix proteins, including collagen type I and type III produced by the smooth muscle cells. To better understand the sites of regulation of collagen biosynthesis and to correlate these with the growth rate of the cells, cultured bovine aortic smooth muscle cells were studied as a function of the number of days (3 to 14) in second passage. Cells grew rapidly up to day 6 when confluence was reached. The total incorporation of [ 3 H]-proline into proteins was highest at day 3 and decreased to a constant level after the cultures reached confluence. In contrast, collagen protein production was lowest before confluence and continued to increase over the entire time course of the experiments. cDNA clones for the α1 and α2 chains of type I and the α1 chain of type III collagen were used to quantitate the steady state level of collagen mRNAs. RNA was tested in a cell-free translation system. Changes in the translational activity of collagen mRNAs parallelled the observed increases in collagen protein production. Thus, at later time points, collagen mRNAs are more active in directing synthesis of preprocollagens, even though less collagen mRNA is present. The conclusion is that the site of regulation of the expression of collagen genes is a function of the growth rate of cultured smooth muscle cells

  15. A three-dimensional cell-based smoothed finite element method for elasto-plasticity

    International Nuclear Information System (INIS)

    Lee, Kye Hyung; Im, Se Yong; Lim, Jae Hyuk; Sohn, Dong Woo

    2015-01-01

    This work is concerned with a three-dimensional cell-based smoothed finite element method for application to elastic-plastic analysis. The formulation of smoothed finite elements is extended to cover elastic-plastic deformations beyond the classical linear theory of elasticity, which has been the major application domain of smoothed finite elements. The finite strain deformations are treated with the aid of the formulation based on the hyperelastic constitutive equation. The volumetric locking originating from the nearly incompressible behavior of elastic-plastic deformations is remedied by relaxing the volumetric strain through the mean value. The comparison with the conventional finite elements demonstrates the effectiveness and accuracy of the present approach.

  16. A three-dimensional cell-based smoothed finite element method for elasto-plasticity

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kye Hyung; Im, Se Yong [KAIST, Daejeon (Korea, Republic of); Lim, Jae Hyuk [KARI, Daejeon (Korea, Republic of); Sohn, Dong Woo [Korea Maritime and Ocean University, Busan (Korea, Republic of)

    2015-02-15

    This work is concerned with a three-dimensional cell-based smoothed finite element method for application to elastic-plastic analysis. The formulation of smoothed finite elements is extended to cover elastic-plastic deformations beyond the classical linear theory of elasticity, which has been the major application domain of smoothed finite elements. The finite strain deformations are treated with the aid of the formulation based on the hyperelastic constitutive equation. The volumetric locking originating from the nearly incompressible behavior of elastic-plastic deformations is remedied by relaxing the volumetric strain through the mean value. The comparison with the conventional finite elements demonstrates the effectiveness and accuracy of the present approach.

  17. On the Significance of Demand and Inventory Smoothing Interventions in Supply Chain

    NARCIS (Netherlands)

    Cannella, S.; Ciancimino, E.; Ashayeri, J.

    2010-01-01

    The aim of this paper is to quantify the benefit of demand and inventory smoothing in contrasting the extreme volatility and impetuous alteration of the market produced by the current economic recession. To do so we model a traditional supply chain and we test five settings of order smoothing under

  18. Urodynamics in a community-dwelling population of females 80 years or older: which motive? Which diagnosis?

    Directory of Open Access Journals (Sweden)

    Françoise A. Valentini

    2010-04-01

    Full Text Available PURPOSE: To determine why community-dwelling women aged 80 years or over were referred for urodynamic evaluation despite their advanced age and which urodynamic diagnosis was made. MATERIALS AND METHODS: One hundred consecutive females (80-93 years were referred to our urodynamics outpatient clinic for evaluation of lower urinary tract symptoms (LUTS between 2005 and 2008. Clinical evaluation comprised of a previous history of LUTS, previous medical history of neurological disease or dementia, pelvic floor dysfunction or prior pelvic surgery. Exclusion criteria were complete retention and severe dementia involving failure to understand simple instructions. Assessed items were results of uroflows (free flow and intubated flow, cystometry and urethral pressure profilometry, and final urodynamic diagnosis. RESULTS: The main complaint evoked by the patients was incontinence (65.0% of which 61.5% was "complicated" and urgency was reported by 70.0%. Interpretable free flow at arrival was very low (44.0%. Prevalence of detrusor overactivity was high, found in 45 patients of whom 16 had detrusor hyperactivity with impaired detrusor contractility. Detrusor overactivity and urgency were strongly associated (p = 0.004. Twenty-five patients had intrinsic sphincteric deficiency alone and 15 detrusor underactivity. CONCLUSION: In this particular community-dwelling with an elderly female population, urodynamics is easily feasible. Incontinence, mainly "complicated" is the more frequent complaint and urgency the more frequent symptom. Urodynamic diagnosis underlines the high incidence of detrusor overactivity as well as impaired detrusor function.

  19. Weak-noise limit of a piecewise-smooth stochastic differential equation.

    Science.gov (United States)

    Chen, Yaming; Baule, Adrian; Touchette, Hugo; Just, Wolfram

    2013-11-01

    We investigate the validity and accuracy of weak-noise (saddle-point or instanton) approximations for piecewise-smooth stochastic differential equations (SDEs), taking as an illustrative example a piecewise-constant SDE, which serves as a simple model of Brownian motion with solid friction. For this model, we show that the weak-noise approximation of the path integral correctly reproduces the known propagator of the SDE at lowest order in the noise power, as well as the main features of the exact propagator with higher-order corrections, provided the singularity of the path integral associated with the nonsmooth SDE is treated with some heuristics. We also show that, as in the case of smooth SDEs, the deterministic paths of the noiseless system correctly describe the behavior of the nonsmooth SDE in the low-noise limit. Finally, we consider a smooth regularization of the piecewise-constant SDE and study to what extent this regularization can rectify some of the problems encountered when dealing with discontinuous drifts and singularities in SDEs.

  20. Inlet effect induced ''upstream'' critical heat flux in smooth tubes

    International Nuclear Information System (INIS)

    Kitto, J.B. Jr.

    1986-01-01

    An unusual form of ''upstream'' critical heat flux (CHF) has been observed and directly linked to the inlet flow pattern during an experimental study of high pressure (17 - 20 MPa) water flowing through a vertical 38.1 mm ID smooth bore tube with uniform axial and nonuniform circumferential heating. These upstream CHF data were characterized by temperature excursions which initially occurred at a relatively fixed axial location in the middle of the test section while the outlet and inlet heated lengths experienced no change. A rifled tube inlet flow conditioner could be substituted for a smooth tube section to generate the desired swirling inlet flow pattern. The upstream CHF data were found to match data from a uniformly heated smooth bore tube when the comparison was made using the peak local heat flux. The mechanism proposed to account for the upstream CHF observations involves the destructive interference between the decaying swirl flow and the secondary circumferential liquid flow field resulting from the one-sided heating

  1. Phytochemical uptake following human consumption of Montmorency tart cherry (L. Prunus cerasus) and influence of phenolic acids on vascular smooth muscle cells in vitro.

    Science.gov (United States)

    Keane, Karen M; Bell, Phillip G; Lodge, John K; Constantinou, Costas L; Jenkinson, Sarah E; Bass, Rosemary; Howatson, Glyn

    2016-06-01

    To investigate the phytochemical uptake following human consumption of Montmorency tart cherry (L. Prunus cerasus) and influence of selected phenolic acids on vascular smooth muscle cells in vitro. In a randomised, double-blinded, crossover design, 12 healthy males consumed either 30 or 60 mL of Montmorency tart cherry concentrate. Following analysis of the juice composition, venous blood samples were taken before and 1, 2, 3, 5 and 8 h post-consumption of the beverage. In addition to examining some aspects of the concentrate contents, plasma concentrations of protocatechuic acid (PCA), vanillic acid (VA) and chlorogenic (CHL) acid were analysed by reversed-phase high-performance liquid chromatography (HPLC) with diode array for quantitation and mass spectrometry detection (LCMS) for qualitative purposes. Vascular smooth muscle cell migration and proliferation were also assessed in vitro. Both the 30 and 60 mL doses of Montmorency cherry concentrate contained high amounts of total phenolics (71.37 ± 0.11; 142.73 ± 0.22 mg/L) and total anthocyanins (62.47 ± 0.31; 31.24 ± 0.16 mg/L), as well as large quantities of CHL (0.205 ± 0.24; 0.410 ± 0.48 mg/L) and VA (0.253 ± 0.84; 0.506 ± 1.68 mg/L). HPLC/LCMS identified two dihydroxybenzoic acids (PCA and VA) in plasma following MC concentrate consumption. Both compounds were most abundant 1-2 h post-initial ingestion with traces detectable at 8 h post-ingestion. Cell migration was significantly influenced by the combination of PCA and VA, but not in isolation. There was no effect of the compounds on cell proliferation. These data show new information that phenolic compounds thought to exert vasoactive properties are bioavailable in vivo following MC consumption and subsequently can influence cell behaviour. These data may be useful for the design and interpretation of intervention studies investigating the health effects of Montmorency cherries.

  2. Nonparametric estimation of age-specific reference percentile curves with radial smoothing.

    Science.gov (United States)

    Wan, Xiaohai; Qu, Yongming; Huang, Yao; Zhang, Xiao; Song, Hanping; Jiang, Honghua

    2012-01-01

    Reference percentile curves represent the covariate-dependent distribution of a quantitative measurement and are often used to summarize and monitor dynamic processes such as human growth. We propose a new nonparametric method based on a radial smoothing (RS) technique to estimate age-specific reference percentile curves assuming the underlying distribution is relatively close to normal. We compared the RS method with both the LMS and the generalized additive models for location, scale and shape (GAMLSS) methods using simulated data and found that our method has smaller estimation error than the two existing methods. We also applied the new method to analyze height growth data from children being followed in a clinical observational study of growth hormone treatment, and compared the growth curves between those with growth disorders and the general population. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Suspension system vibration analysis with regard to variable type ability to smooth road irregularities

    Science.gov (United States)

    Rykov, S. P.; Rykova, O. A.; Koval, V. S.; Makhno, D. E.; Fedotov, K. V.

    2018-03-01

    The paper aims to analyze vibrations of the dynamic system equivalent of the suspension system with regard to tyre ability to smooth road irregularities. The research is based on static dynamics for linear systems of automated control, methods of correlation, spectral and numerical analysis. Input of new data on the smoothing effect of the pneumatic tyre reflecting changes of a contact area between the wheel and road under vibrations of the suspension makes the system non-linear which requires using numerical analysis methods. Taking into account the variable smoothing ability of the tyre when calculating suspension vibrations, one can approximate calculation and experimental results and improve the constant smoothing ability of the tyre.

  4. A nonlinear wavelet method for data smoothing of low-level gamma-ray spectra

    International Nuclear Information System (INIS)

    Gang Xiao; Li Deng; Benai Zhang; Jianshi Zhu

    2004-01-01

    A nonlinear wavelet method was designed for smoothing low-level gamma-ray spectra. The spectra of a 60 Co graduated radioactive source and a mixed soil sample were smoothed respectively according to this method and a 5 point smoothing method. The FWHM of 1,332 keV peak of 60 Co source and the absolute activities of 238 U of soil sample were calculated. The results show that the nonlinear wavelet method is better than the traditional method, with less loss of spectral peak and a more complete reduction of statistical fluctuation. (author)

  5. Do we need to know more about the effects of hormones on lower urinary tract dysfunction? ICI-RS 2014.

    Science.gov (United States)

    Hanna-Mitchell, Ann T; Robinson, Dudley; Cardozo, Linda; Everaert, Karel; Petkov, Georgi V

    2016-02-01

    This review article reflects the presentations and subsequent discussions during a think tank at the 5th International Consultation on Incontinence Research Society's annual meeting, held in Bristol, UK (September 22-24, 2014). It reviews the current state of knowledge on the role of hormones in lower urinary tract dysfunction (LUTD) and overactive bladder (OAB) and in particular: highlights some specific basic research findings from discussion participants; reviews future research topics; and discusses potential new therapeutic opportunities for LUTD and OAB. The role of the large conductance voltage- and Ca(2+) -activated K(+) (BK) channels, as novel therapeutic targets for OAB was discussed, in particular as recent studies on human detrusor smooth muscle suggest that estradiol exerts a direct non-genomic activation of the BK channels. Recent developments on the roles of sex hormones on diuresis, as well as the roles of melatonin and vitamin D on LUTD were also discussed. It was concluded that further basic science and translational studies are needed to better understand hormonal regulatory mechanisms of the lower urinary tract and the implications for novel treatment options for LUTD and OAB. © 2016 Wiley Periodicals, Inc.

  6. The Koch curve as a smooth manifold

    International Nuclear Information System (INIS)

    Epstein, Marcelo; Sniatycki, Jedrzej

    2008-01-01

    We show that there exists a homeomorphism between the closed interval [0,1] is contained in R and the Koch curve endowed with the subset topology of R 2 . We use this homeomorphism to endow the Koch curve with the structure of a smooth manifold with boundary

  7. An adaptive method for γ spectra smoothing

    International Nuclear Information System (INIS)

    Xiao Gang; Zhou Chunlin; Li Tiantuo; Han Feng; Di Yuming

    2001-01-01

    Adaptive wavelet method and multinomial fitting gliding method are used for smoothing γ spectra, respectively, and then FWHM of 1332 keV peak of 60 Co and activities of 238 U standard specimen are calculated. Calculated results show that adaptive wavelet method is better than the other

  8. Snap evaporation of droplets on smooth topographies.

    Science.gov (United States)

    Wells, Gary G; Ruiz-Gutiérrez, Élfego; Le Lirzin, Youen; Nourry, Anthony; Orme, Bethany V; Pradas, Marc; Ledesma-Aguilar, Rodrigo

    2018-04-11

    Droplet evaporation on solid surfaces is important in many applications including printing, micro-patterning and cooling. While seemingly simple, the configuration of evaporating droplets on solids is difficult to predict and control. This is because evaporation typically proceeds as a "stick-slip" sequence-a combination of pinning and de-pinning events dominated by static friction or "pinning", caused by microscopic surface roughness. Here we show how smooth, pinning-free, solid surfaces of non-planar topography promote a different process called snap evaporation. During snap evaporation a droplet follows a reproducible sequence of configurations, consisting of a quasi-static phase-change controlled by mass diffusion interrupted by out-of-equilibrium snaps. Snaps are triggered by bifurcations of the equilibrium droplet shape mediated by the underlying non-planar solid. Because the evolution of droplets during snap evaporation is controlled by a smooth topography, and not by surface roughness, our ideas can inspire programmable surfaces that manage liquids in heat- and mass-transfer applications.

  9. Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

    Science.gov (United States)

    Liu, Dong-Hai; Huang, Xu; Guo, Xin; Meng, Xiang-Min; Wu, Yi-Song; Lu, Hong-Li; Zhang, Chun-Mei; Kim, Young-chul; Xu, Wen-Xie

    2014-01-01

    Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV) was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV) to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

  10. Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

    International Nuclear Information System (INIS)

    Pei, Qing-Mei; Jiang, Ping; Yang, Min; Qian, Xue-Jiao; Liu, Jiang-Bo; Kim, Sung-Ho

    2016-01-01

    Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation

  11. Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Qing-Mei, E-mail: 34713316@qq.com [Department of Radiology, Tianjin Hospital of Integrated Traditional Chinese and Western Medicine, Tianjin (China); Jiang, Ping, E-mail: jiangping@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Yang, Min, E-mail: YangMin@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Qian, Xue-Jiao, E-mail: qianxuejiao@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Liu, Jiang-Bo, E-mail: LJB1984@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Kim, Sung-Ho, E-mail: chenghao0726@hotmail.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China)

    2016-10-01

    Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation

  12. An α-smooth muscle actin (acta2/αsma zebrafish transgenic line marking vascular mural cells and visceral smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Thomas R Whitesell

    Full Text Available Mural cells of the vascular system include vascular smooth muscle cells (SMCs and pericytes whose role is to stabilize and/or provide contractility to blood vessels. One of the earliest markers of mural cell development in vertebrates is α smooth muscle actin (acta2; αsma, which is expressed by pericytes and SMCs. In vivo models of vascular mural cell development in zebrafish are currently lacking, therefore we developed two transgenic zebrafish lines driving expression of GFP or mCherry in acta2-expressing cells. These transgenic fish were used to trace the live development of mural cells in embryonic and larval transgenic zebrafish. acta2:EGFP transgenic animals show expression that largely mirrors native acta2 expression, with early pan-muscle expression starting at 24 hpf in the heart muscle, followed by skeletal and visceral muscle. At 3.5 dpf, expression in the bulbus arteriosus and ventral aorta marks the first expression in vascular smooth muscle. Over the next 10 days of development, the number of acta2:EGFP positive cells and the number of types of blood vessels associated with mural cells increases. Interestingly, the mural cells are not motile and remain in the same position once they express the acta2:EGFP transgene. Taken together, our data suggests that zebrafish mural cells develop relatively late, and have little mobility once they associate with vessels.

  13. Opportunities to Target Specific Contractile Abnormalities with Smooth Muscle Protein Kinase Inhibitors

    Directory of Open Access Journals (Sweden)

    Annegret Ulke-Lemée

    2010-05-01

    Full Text Available Smooth muscle is a major component of most hollow organ systems (e.g., airways, vasculature, bladder and gut/gastrointestine; therefore, the coordinated regulation of contraction is a key property of smooth muscle. When smooth muscle functions normally, it contributes to general health and wellness, but its dysfunction is associated with morbidity and mortality. Rho-associated protein kinase (ROCK is central to calcium-independent, actomyosin-mediated contractile force generation in the vasculature, thereby playing a role in smooth muscle contraction, cell motility and adhesion. Recent evidence supports an important role for ROCK in the increased vasoconstriction and remodeling observed in various models of hypertension. This review will provide a commentary on the development of specific ROCK inhibitors and their clinical application. Fasudil will be discussed as an example of bench-to-bedside development of a clinical therapeutic that is used to treat conditions of vascular hypercontractility. Due to the wide spectrum of biological processes regulated by ROCK, many additional clinical indications might also benefit from ROCK inhibition. Apart from the importance of ROCK in smooth muscle contraction, a variety of other protein kinases are known to play similar roles in regulating contractile force. The zipper-interacting protein kinase (ZIPK and integrin-linked kinase (ILK are two well-described regulators of contraction. The relative contribution of each kinase to contraction depends on the muscle bed as well as hormonal and neuronal stimulation. Unfortunately, specific inhibitors for ZIPK and ILK are still in the development phase, but the success of fasudil suggests that inhibitors for these other kinases may also have valuable clinical applications. Notably, the directed inhibition of ZIPK with a pseudosubstrate molecule shows unexpected effects on the contractility of gastrointestinal smooth muscle.

  14. Patent ductus arteriosus in mice with smooth muscle-specific Jag1 deletion

    Science.gov (United States)

    Feng, Xuesong; Krebs, Luke T.; Gridley, Thomas

    2010-01-01

    The ductus arteriosus is an arterial vessel that shunts blood flow away from the lungs during fetal life, but normally occludes after birth to establish the adult circulation pattern. Failure of the ductus arteriosus to close after birth is termed patent ductus arteriosus and is one of the most common congenital heart defects. Mice with smooth muscle cell-specific deletion of Jag1, which encodes a Notch ligand, die postnatally from patent ductus arteriosus. These mice exhibit defects in contractile smooth muscle cell differentiation in the vascular wall of the ductus arteriosus and adjacent descending aorta. These defects arise through an inability to propagate the JAG1-Notch signal via lateral induction throughout the width of the vascular wall. Both heterotypic endothelial smooth muscle cell interactions and homotypic vascular smooth muscle cell interactions are required for normal patterning and differentiation of the ductus arteriosus and adjacent descending aorta. This new model for a common congenital heart defect provides novel insights into the genetic programs that underlie ductus arteriosus development and closure. PMID:21068062

  15. Data driven smooth tests for composite hypotheses

    NARCIS (Netherlands)

    Inglot, Tadeusz; Kallenberg, Wilbert C.M.; Ledwina, Teresa

    1997-01-01

    The classical problem of testing goodness-of-fit of a parametric family is reconsidered. A new test for this problem is proposed and investigated. The new test statistic is a combination of the smooth test statistic and Schwarz's selection rule. More precisely, as the sample size increases, an

  16. Interval Forecast for Smooth Transition Autoregressive Model ...

    African Journals Online (AJOL)

    In this paper, we propose a simple method for constructing interval forecast for smooth transition autoregressive (STAR) model. This interval forecast is based on bootstrapping the residual error of the estimated STAR model for each forecast horizon and computing various Akaike information criterion (AIC) function. This new ...

  17. Ensemble Kalman filtering with one-step-ahead smoothing

    KAUST Repository

    Raboudi, Naila F.; Ait-El-Fquih, Boujemaa; Hoteit, Ibrahim

    2018-01-01

    error statistics. This limits their representativeness of the background error covariances and, thus, their performance. This work explores the efficiency of the one-step-ahead (OSA) smoothing formulation of the Bayesian filtering problem to enhance

  18. GRADSPH: A parallel smoothed particle hydrodynamics code for self-gravitating astrophysical fluid dynamics

    NARCIS (Netherlands)

    Vanaverbeke, S.; Keppens, R.; Poedts, S.; Boffin, H.

    2009-01-01

    We describe the algorithms implemented in the first version of GRADSPH, a parallel, tree-based, smoothed particle hydrodynamics code for simulating self-gravitating astrophysical systems written in FORTRAN 90. The paper presents details on the implementation of the Smoothed Particle Hydro (SPH)

  19. Regulation of GPCR-mediated smooth muscle contraction : implications for asthma and pulmonary hypertension

    NARCIS (Netherlands)

    Wright, D B; Tripathi, S; Sikarwar, A; Santosh, K T; Perez-Zoghbi, J; Ojo, O O; Irechukwu, N; Ward, J P T; Schaafsma, D

    Contractile G-protein-coupled receptors (GPCRs) have emerged as key regulators of smooth muscle contraction, both under healthy and diseased conditions. This brief review will discuss some key topics and novel insights regarding GPCR-mediated airway and vascular smooth muscle contraction as

  20. A Smooth Transition Logit Model of the Effects of Deregulation in the Electricity Market

    DEFF Research Database (Denmark)

    Hurn, A.S.; Silvennoinen, Annastiina; Teräsvirta, Timo

    We consider a nonlinear vector model called the logistic vector smooth transition autoregressive model. The bivariate single-transition vector smooth transition regression model of Camacho (2004) is generalised to a multivariate and multitransition one. A modelling strategy consisting of specific......We consider a nonlinear vector model called the logistic vector smooth transition autoregressive model. The bivariate single-transition vector smooth transition regression model of Camacho (2004) is generalised to a multivariate and multitransition one. A modelling strategy consisting...... of specification, including testing linearity, estimation and evaluation of these models is constructed. Nonlinear least squares estimation of the parameters of the model is discussed. Evaluation by misspecification tests is carried out using tests derived in a companion paper. The use of the modelling strategy...