WorldWideScience

Sample records for node sinusoidal endothelial

  1. The Relationship between fenestrations, sieve plates and rafts in liver sinusoidal endothelial cells.

    Directory of Open Access Journals (Sweden)

    Dmitri Svistounov

    Full Text Available Fenestrations are transcellular pores in endothelial cells that facilitate transfer of substrates between blood and the extravascular compartment. In order to understand the regulation and formation of fenestrations, the relationship between membrane rafts and fenestrations was investigated in liver sinusoidal endothelial cells where fenestrations are grouped into sieve plates. Three dimensional structured illumination microscopy, scanning electron microscopy, internal reflectance fluorescence microscopy and two-photon fluorescence microscopy were used to study liver sinusoidal endothelial cells isolated from mice. There was an inverse distribution between sieve plates and membrane rafts visualized by structured illumination microscopy and the fluorescent raft stain, Bodipy FL C5 ganglioside GM1. 7-ketocholesterol and/or cytochalasin D increased both fenestrations and lipid-disordered membrane, while Triton X-100 decreased both fenestrations and lipid-disordered membrane. The effects of cytochalasin D on fenestrations were abrogated by co-administration of Triton X-100, suggesting that actin disruption increases fenestrations by its effects on membrane rafts. Vascular endothelial growth factor (VEGF depleted lipid-ordered membrane and increased fenestrations. The results are consistent with a sieve-raft interaction, where fenestrations form in non-raft lipid-disordered regions of endothelial cells once the membrane-stabilizing effects of actin cytoskeleton and membrane rafts are diminished.

  2. Dietary macronutrients and the aging liver sinusoidal endothelial cell.

    Science.gov (United States)

    Cogger, Victoria Carroll; Mohamad, Mashani; Solon-Biet, Samantha Marie; Senior, Alistair M; Warren, Alessandra; O'Reilly, Jennifer Nicole; Tung, Bui Thanh; Svistounov, Dmitri; McMahon, Aisling Clare; Fraser, Robin; Raubenheimer, David; Holmes, Andrew J; Simpson, Stephen James; Le Couteur, David George

    2016-05-01

    Fenestrations are pores within the liver sinusoidal endothelial cells (LSECs) that line the sinusoids of the highly vascularized liver. Fenestrations facilitate the transfer of substrates between blood and hepatocytes. With pseudocapillarization of the hepatic sinusoid in old age, there is a loss of fenestrations. LSECs are uniquely exposed to gut-derived dietary and microbial substrates delivered by the portal circulation to the liver. Here we studied the effect of 25 diets varying in content of macronutrients and energy on LSEC fenestrations using the Geometric Framework method in a large cohort of mice aged 15 mo. Macronutrient distribution rather than total food or energy intake was associated with changes in fenestrations. Porosity and frequency were inversely associated with dietary fat intake, while fenestration diameter was inversely associated with protein or carbohydrate intake. Fenestrations were also linked to diet-induced changes in gut microbiome, with increased fenestrations associated with higher abundance of Firmicutes and reduced abundance of Bacteroidetes Diet-induced changes in levels of several fatty acids (C16:0, C19:0, and C20:4) were also significantly inversely associated with fenestrations, suggesting a link between dietary fat and modulation of lipid rafts in the LSECs. Diet influences fenestrations and these data reflect both the key role of the LSECs in clearing gut-derived molecules from the vascular circulation and the impact these molecules have on LSEC morphology. Copyright © 2016 the American Physiological Society.

  3. Liver sinusoidal endothelial cells induce immunosuppressive IL-10-producing Th1 cells via the Notch pathway

    NARCIS (Netherlands)

    Neumann, Katrin; Rudolph, Christine; Neumann, Christian; Janke, Marko; Amsen, Derk; Scheffold, Alexander

    2015-01-01

    Under homeostasis, liver sinusoidal endothelial cells (LSECs) shift intrahepatic T-cell responses towards tolerance. However, the role of LSECs in the regulation of T-cell-induced liver inflammation is less clear. Here, we studied the capacity of LSECs to modulate pro-inflammatory Th1-cell

  4. Tolerogenic properties of lymphatic endothelial cells are controlled by the lymph node microenvironment.

    Directory of Open Access Journals (Sweden)

    Jarish N Cohen

    Full Text Available Peripheral self-tolerance eliminates lymphocytes specific for tissue-specific antigens not encountered in the thymus. Recently, we demonstrated that lymphatic endothelial cells in mice directly express peripheral tissue antigens, including tyrosinase, and induce deletion of specific CD8 T cells via Programmed Death Ligand-1 (PD-L1. Here, we demonstrate that high-level expression of peripheral tissue antigens and PD-L1 is confined to lymphatic endothelial cells in lymph nodes, as opposed to tissue (diaphragm and colon lymphatics. Lymphatic endothelial cells in the lymph node medullary sinus express the highest levels of peripheral tissue antigens and PD-L1, and are the only subpopulation that expresses tyrosinase epitope. The representation of lymphatic endothelial cells in the medullary sinus expressing high-level PD-L1, which is necessary for normal CD8 T cell deletion kinetics, is controlled by lymphotoxin-β receptor signaling and B cells. Lymphatic endothelial cells from neonatal mice do not express high-level PD-L1 or present tyrosinase epitope. This work uncovers a critical role for the lymph node microenvironment in endowing lymphatic endothelial cells with potent tolerogenic properties.

  5. 3D hepatic cultures simultaneously maintain primary hepatocyte and liver sinusoidal endothelial cell phenotypes.

    Directory of Open Access Journals (Sweden)

    Yeonhee Kim

    Full Text Available Developing in vitro engineered hepatic tissues that exhibit stable phenotype is a major challenge in the field of hepatic tissue engineering. However, the rapid dedifferentiation of hepatic parenchymal (hepatocytes and non-parenchymal (liver sinusoidal endothelial, LSEC cell types when removed from their natural environment in vivo remains a major obstacle. The primary goal of this study was to demonstrate that hepatic cells cultured in layered architectures could preserve or potentially enhance liver-specific behavior of both cell types. Primary rat hepatocytes and rat LSECs (rLSECs were cultured in a layered three-dimensional (3D configuration. The cell layers were separated by a chitosan-hyaluronic acid polyelectrolyte multilayer (PEM, which served to mimic the Space of Disse. Hepatocytes and rLSECs exhibited several key phenotypic characteristics over a twelve day culture period. Immunostaining for the sinusoidal endothelial 1 antibody (SE-1 demonstrated that rLSECs cultured in the 3D hepatic model maintained this unique feature over twelve days. In contrast, rLSECs cultured in monolayers lost their phenotype within three days. The unique stratified structure of the 3D culture resulted in enhanced heterotypic cell-cell interactions, which led to improvements in hepatocyte functions. Albumin production increased three to six fold in the rLSEC-PEM-Hepatocyte cultures. Only rLSEC-PEM-Hepatocyte cultures exhibited increasing CYP1A1/2 and CYP3A activity. Well-defined bile canaliculi were observed only in the rLSEC-PEM-Hepatocyte cultures. Together, these data suggest that rLSEC-PEM-Hepatocyte cultures are highly suitable models to monitor the transformation of toxins in the liver and their transport out of this organ. In summary, these results indicate that the layered rLSEC-PEM-hepatocyte model, which recapitulates key features of hepatic sinusoids, is a potentially powerful medium for obtaining comprehensive knowledge on liver metabolism

  6. Cytotoxicity of pyrrolizidine alkaloid in human hepatic parenchymal and sinusoidal endothelial cells: Firm evidence for the reactive metabolites mediated pyrrolizidine alkaloid-induced hepatotoxicity.

    Science.gov (United States)

    Yang, Mengbi; Ruan, Jianqing; Fu, Peter P; Lin, Ge

    2016-01-05

    Pyrrolizidine alkaloids (PAs) widely distribute in plants and can cause hepatic sinusoidal obstruction syndrome (HSOS), which typically presents as a primary sinusoidal endothelial cell damage. It is well-recognized that after ingestion, PAs undergo hepatic cytochromes P450 (CYPs)-mediated metabolic activation to generate dehydropyrrolizidine alkaloids (DHPAs), which are hydrolyzed to dehydroretronecine (DHR). DHPAs and DHR are reactive metabolites having same core pyrrole moiety, and can bind proteins to form pyrrole-protein adducts, which are believed as the primary cause for PA-induced HSOS. However, to date, the direct evidences supporting the toxicity of DHPAs and DHR in the liver, in particular in the sinusoidal endothelial cells, are lacking. Using human hepatic sinusoidal endothelial cells (HSEC) and HepG2 (representing hepatic parenchymal cells), cells that lack CYPs activity, this study determined the direct cytotoxicity of dehydromonocrotaline, a representative DHPA, and DHR, but no cytotoxicity of the intact PA (monocrotaline) in both cell lines, confirming that reactive metabolites mediate PA intoxication. Comparing with HepG2, HSEC had significantly lower basal glutathione (GSH) level, and was significantly more susceptible to the reactive metabolites with severer GSH depletion and pyrrole-protein adducts formation. The toxic potency of two reactive metabolites was also compared. DHPA was more reactive than DHR, leading to severer toxicity. In conclusion, our results unambiguously provided the first direct evidence for the critical role of DHPA and DHR in the reactive metabolites-mediated PA-induced hepatotoxicity, which occurs predominantly in HSEC due to severe GSH depletion and the significant formation of pyrrole-protein adducts in HSEC. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Upregulation of miR21 and repression of Grhl3 by leptin mediates sinusoidal endothelial injury in experimental nonalcoholic steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Sahar Pourhoseini

    Full Text Available Sinusoidal endothelial dysfunction (SED has been found to be an early event in nonalcoholic steatohepatitis (NASH progression but the molecular mechanisms underlying its causation remains elusive. We hypothesized that adipokine leptin worsens sinusoidal injury by decreasing functionally active nitric oxide synthase 3 (NOS3 via miR21. Using rodent models of NASH, and transgenic mice lacking leptin and leptin receptor, results showed that hyperleptinemia caused a 4-5 fold upregulation of hepatic miR21 as assessed by qRTPCR. The upregulation of miR21 led to a time-dependent repression of its target protein Grhl3 levels as shown by western blot analyses. NOS3-p/NOS3 ratio which is controlled by Grhl3 was significantly decreased in NASH models. SED markers ICAM-1, VEGFR-2, and E-selectin as assessed by immunofluorescence microscopy were significantly up regulated in the progressive phases of NASH. Lack of leptin or its receptor in vivo, reversed the upregulation of miR21 and restored the levels of Grhl3 and NOS3-p/NOS3 ratio coupled with decreased SED dysfunction markers. Interestingly, leptin supplementation in mice lacking leptin, significantly enhanced miR21 levels, decreased Grhl3 repression and NOS3 phosphorylation. Leptin supplementation in isolated primary endothelial cells, Kupffer cells and stellate cells showed increased mir21 expression in stellate cells while sinusoidal injury was significantly higher in all cell types. Finally miR21 KO mice showed increased NOS3-p/NOS3 ratio and reversed SED markers in the rodent models of NASH. The experimental results described here show a close association of leptin-induced miR21 in aiding sinusoidal injury in NASH.

  8. Fibronectin Extra Domain A Promotes Liver Sinusoid Repair following Hepatectomy.

    Directory of Open Access Journals (Sweden)

    Bridget Sackey-Aboagye

    Full Text Available Liver sinusoidal endothelial cells (LSECs are the main endothelial cells in the liver and are important for maintaining liver homeostasis as well as responding to injury. LSECs express cellular fibronectin containing the alternatively spliced extra domain A (EIIIA-cFN and increase expression of this isoform after liver injury, although its function is not well understood. Here, we examined the role of EIIIA-cFN in liver regeneration following partial hepatectomy. We carried out two-thirds partial hepatectomies in mice lacking EIIIA-cFN and in their wild type littermates, studied liver endothelial cell adhesion on decellularized, EIIIA-cFN-containing matrices and investigated the role of cellular fibronectins in liver endothelial cell tubulogenesis. We found that liver weight recovery following hepatectomy was significantly delayed and that sinusoidal repair was impaired in EIIIA-cFN null mice, especially females, as was the lipid accumulation typical of the post-hepatectomy liver. In vitro, we found that liver endothelial cells were more adhesive to cell-deposited matrices containing the EIIIA domain and that cellular fibronectin enhanced tubulogenesis and vascular cord formation. The integrin α9β1, which specifically binds EIIIA-cFN, promoted tubulogenesis and adhesion of liver endothelial cells to EIIIA-cFN. Our findings identify a role for EIIIA-cFN in liver regeneration and tubulogenesis. We suggest that sinusoidal repair is enhanced by increased LSEC adhesion, which is mediated by EIIIA-cFN.

  9. Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient uPA mice.

    Directory of Open Access Journals (Sweden)

    Marina E Fomin

    Full Text Available Liver sinusoidal endothelial cells (LSECs form a semi-permeable barrier between parenchymal hepatocytes and the blood. LSECs participate in liver metabolism, clearance of pathological agents, immunological responses, architectural maintenance of the liver and synthesis of growth factors and cytokines. LSECs also play an important role in coagulation through the synthesis of Factor VIII (FVIII. Herein, we phenotypically define human LSECs isolated from fetal liver using flow cytometry and immunofluorescence microscopy. Isolated LSECs were cultured and shown to express endothelial markers and markers specific for the LSEC lineage. LSECs were also shown to engraft the liver when human fetal liver cells were transplanted into immunodeficient mice with liver specific expression of the urokinase-type plasminogen activator (uPA transgene (uPA-NOG mice. Engrafted cells expressed human Factor VIII at levels approaching those found in human plasma. We also demonstrate engraftment of adult LSECs, as well as hepatocytes, transplanted into uPA-NOG mice. We propose that overexpression of uPA provides beneficial conditions for LSEC engraftment due to elevated expression of the angiogenic cytokine, vascular endothelial growth factor. This work provides a detailed characterization of human midgestation LSECs, thereby providing the means for their purification and culture based on their expression of CD14 and CD32 as well as a lack of CD45 expression. The uPA-NOG mouse is shown to be a permissive host for human LSECs and adult hepatocytes, but not fetal hepatoblasts. Thus, these mice provide a useful model system to study these cell types in vivo. Demonstration of human FVIII production by transplanted LSECs encourages further pursuit of LSEC transplantation as a cellular therapy for the treatment of hemophilia A.

  10. Unique cell type-specific junctional complexes in vascular endothelium of human and rat liver sinusoids.

    Directory of Open Access Journals (Sweden)

    Cyrill Géraud

    Full Text Available Liver sinusoidal endothelium is strategically positioned to control access of fluids, macromolecules and cells to the liver parenchyma and to serve clearance functions upstream of the hepatocytes. While clearance of macromolecular debris from the peripheral blood is performed by liver sinusoidal endothelial cells (LSECs using a delicate endocytic receptor system featuring stabilin-1 and -2, the mannose receptor and CD32b, vascular permeability and cell trafficking are controlled by transcellular pores, i.e. the fenestrae, and by intercellular junctional complexes. In contrast to blood vascular and lymphatic endothelial cells in other organs, the junctional complexes of LSECs have not yet been consistently characterized in molecular terms. In a comprehensive analysis, we here show that LSECs express the typical proteins found in endothelial adherens junctions (AJ, i.e. VE-cadherin as well as α-, β-, p120-catenin and plakoglobin. Tight junction (TJ transmembrane proteins typical of endothelial cells, i.e. claudin-5 and occludin, were not expressed by rat LSECs while heterogenous immunreactivity for claudin-5 was detected in human LSECs. In contrast, junctional molecules preferentially associating with TJ such as JAM-A, B and C and zonula occludens proteins ZO-1 and ZO-2 were readily detected in LSECs. Remarkably, among the JAMs JAM-C was considerably over-expressed in LSECs as compared to lung microvascular endothelial cells. In conclusion, we show here that LSECs form a special kind of mixed-type intercellular junctions characterized by co-occurrence of endothelial AJ proteins, and of ZO-1 and -2, and JAMs. The distinct molecular architecture of the intercellular junctional complexes of LSECs corroborates previous ultrastructural findings and provides the molecular basis for further analyses of the endothelial barrier function of liver sinusoids under pathologic conditions ranging from hepatic inflammation to formation of liver metastasis.

  11. TRAIL enhances paracetamol-induced liver sinusoidal endothelial cell death in a Bim- and Bid-dependent manner

    Science.gov (United States)

    Badmann, A; Langsch, S; Keogh, A; Brunner, T; Kaufmann, T; Corazza, N

    2012-01-01

    Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic alterations. Although hepatocytes represent the main target of the cytotoxic effect of paracetamol overdose, perturbations within the endothelium involving morphological changes of liver sinusoidal endothelial cells (LSECs) have also been described in paracetamol-induced liver disease. Recently, we have shown that paracetamol-induced liver damage is synergistically enhanced by the TRAIL signaling pathway. As LSECs are constantly exposed to activated immune cells expressing death ligands, including TRAIL, we investigated the effect of TRAIL on paracetamol-induced LSEC death. We here demonstrate for the first time that TRAIL strongly enhances paracetamol-mediated LSEC death with typical features of apoptosis. Inhibition of caspases using specific inhibitors resulted in a strong reduction of cell death. TRAIL appears to enhance paracetamol-induced LSEC death via the activation of the pro-apoptotic BH3-only proteins Bid and Bim, which initiate the mitochondrial apoptotic pathway. Taken together this study shows that the liver endothelial layer, mainly LSECs, represent a direct target of the cytotoxic effect of paracetamol and that activation of TRAIL receptor synergistically enhances paracetamol-induced LSEC death via the mitochondrial apoptotic pathway. TRAIL-mediated acceleration of paracetamol-induced cell death may thus contribute to the pathogenesis of paracetamol-induced liver damage. PMID:23254290

  12. Regorafenib suppresses sinusoidal obstruction syndrome in rats.

    Science.gov (United States)

    Okuno, Masayuki; Hatano, Etsuro; Nakamura, Kojiro; Miyagawa-Hayashino, Aya; Kasai, Yosuke; Nishio, Takahiro; Seo, Satoru; Taura, Kojiro; Uemoto, Shinji

    2015-02-01

    Sinusoidal obstruction syndrome (SOS), a form of drug-induced liver injury related to oxaliplatin treatment, is associated with postoperative morbidity after hepatectomy. This study aimed to examine the impact of regorafenib, the first small-molecule kinase inhibitor to show efficacy against metastatic colorectal cancer, on a rat model of SOS. Rats with monocrotaline (MCT)-induced SOS were divided into two groups according to treatment with either regorafenib (6 mg/kg) or vehicle alone, which were administered at 12 and 36 h, respectively, before MCT administration. Histopathologic examination and serum biochemistry tests were performed 48 h after MCT administration. Sinusoidal endothelial cells were evaluated by immunohistochemistry and electron microscopy. To examine whether regorafenib preserved remnant liver function, a 30% hepatectomy was performed in each group. The rats in the vehicle group displayed typical SOS features, whereas these features were suppressed in the regorafenib group. The total SOS scores were significantly lower in the regorafenib group than in the vehicle group. Immunohistochemistry and electron microscopy showed that regorafenib had a protective effect on sinusoidal endothelial cells. The postoperative survival rate after 7 d was significantly better in the regorafenib group than that in the vehicle group (26.7% versus 6.7%, P Regorafenib reduced the phosphorylation of extracellular signal-regulated kinase, which induced matrix metalloproteinase-9 (MMP-9) activation and decreased the activity of MMP-9, one of the crucial mediators of SOS development. Regorafenib suppressed MCT-induced SOS, concomitant with attenuating extracellular signal-regulated kinase phosphorylation, and MMP-9 activation, suggesting that regorafenib may be a favorable agent for use in combination with oxaliplatin-based chemotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2 mediated regeneration of sinusoidal endothelial cells

    Science.gov (United States)

    Hooper, Andrea T.; Butler, Jason M.; Nolan, Daniel J; Kranz, Andrea; Iida, Kaoruko; Kobayashi, Mariko; Kopp, Hans-Georg; Shido, Koji; Petit, Isabelle; Yanger, Kilangsungla; James, Daylon; Witte, Larry; Zhu, Zhenping; Wu, Yan; Pytowski, Bronislaw; Rosenwaks, Zev; Mittal, Vivek; Sato, Thomas N.; Rafii, Shahin

    2011-01-01

    SUMMARY The phenotypic attributes and molecular determinants for the regeneration of bone marrow (BM) sinusoidal endothelial cells (SECs) and their contribution to hematopoiesis are unknown. We show that after myelosuppression VEGFR2 activation promotes reassembly of regressed SECs, reconstituting hematopoietic stem and progenitor cells (HSPCs). VEGFR2 and VEGFR3 expression are restricted to BM vasculature, demarcating a continuous network of VEGFR2+VEGFR3+Sca1− SECs and VEGFR2+VEGFR3−Sca1+ arterioles. While chemotherapy (5FU) and sublethal irradiation (650 rad) induce minor SEC regression, lethal irradiation (950 rad) induces severe regression of SECs requiring BM transplantation (BMT) for regeneration. Conditional deletion of VEGFR2 in adult mice blocks regeneration of SECs in sublethally irradiated animals, preventing hematopoietic reconstitution. Inhibition of VEGFR2 signaling in lethally irradiated wild type mice rescued with BMT severely impairs SEC reconstruction, preventing engraftment and reconstitution of HSPCs. Therefore, activation of VEGFR2 is critical for regeneration of VEGFR3+Sca1− SECs that are essential for engraftment and restoration of HSPCs and hematopoiesis. PMID:19265665

  14. Arachidonic acid metabolites and endothelial dysfunction of portal hypertension.

    Science.gov (United States)

    Sacerdoti, David; Pesce, Paola; Di Pascoli, Marco; Brocco, Silvia; Cecchetto, Lara; Bolognesi, Massimo

    2015-07-01

    Increased resistance to portal flow and increased portal inflow due to mesenteric vasodilatation represent the main factors causing portal hypertension in cirrhosis. Endothelial cell dysfunction, defined as an imbalance between the synthesis, release, and effect of endothelial mediators of vascular tone, inflammation, thrombosis, and angiogenesis, plays a major role in the increase of resistance in portal circulation, in the decrease in the mesenteric one, in the development of collateral circulation. Reduced response to vasodilators in liver sinusoids and increased response in the mesenteric arterioles, and, viceversa, increased response to vasoconstrictors in the portal-sinusoidal circulation and decreased response in the mesenteric arterioles are also relevant to the pathophysiology of portal hypertension. Arachidonic acid (AA) metabolites through the three pathways, cyclooxygenase (COX), lipoxygenase, and cytochrome P450 monooxygenase and epoxygenase, are involved in endothelial dysfunction of portal hypertension. Increased thromboxane-A2 production by liver sinusoidal endothelial cells (LSECs) via increased COX-1 activity/expression, increased leukotriens, increased epoxyeicosatrienoic acids (EETs) (dilators of the peripheral arterial circulation, but vasoconstrictors of the portal-sinusoidal circulation), represent a major component in the increased portal resistance, in the decreased portal response to vasodilators and in the hyper-response to vasoconstrictors. Increased prostacyclin (PGI2) via COX-1 and COX-2 overexpression, and increased EETs/heme-oxygenase-1/K channels/gap junctions (endothelial derived hyperpolarizing factor system) play a major role in mesenteric vasodilatation, hyporeactivity to vasoconstrictors, and hyper-response to vasodilators. EETs, mediators of liver regeneration after hepatectomy and of angiogenesis, may play a role in the development of regenerative nodules and collateral circulation, through stimulation of vascular endothelial

  15. An optimized method for mouse liver sinusoidal endothelial cell isolation

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, Jeremy, E-mail: jeremy.meyer@hcuge.ch [Division of Digestive and Transplantation Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211 Genève 14 (Switzerland); Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206 Genève (Switzerland); Lacotte, Stéphanie, E-mail: stephanie.lacotte@unige.ch [Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206 Genève (Switzerland); Morel, Philippe, E-mail: philippe.morel@hcuge.ch [Division of Digestive and Transplantation Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211 Genève 14 (Switzerland); Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206 Genève (Switzerland); Gonelle-Gispert, Carmen, E-mail: carmen.gonelle@unige.ch [Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206 Genève (Switzerland); Bühler, Léo, E-mail: leo.buhler@hcuge.ch [Division of Digestive and Transplantation Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211 Genève 14 (Switzerland); Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206 Genève (Switzerland)

    2016-12-10

    The objective of the present study was to develop an accurate and reproducible method for liver sinusoidal endothelial cell (LSEC) isolation in mice. Non-parenchymal cells were isolated using a modified two-step collagenase digestion combined with Optiprep density gradient centrifugation. LSEC were further purified using two prevalent methods, short-term selective adherence and CD146+ magnetic-activated cell sorting (MACS), and compared in terms of cell yield, viability and purity to our purification technique using CD11b cell depletion combined with long-term selective adherence. LSEC purification using our technique allowed to obtain 7.07±3.80 million LSEC per liver, while CD146+ MACS and short-term selective adherence yielded 2.94±1.28 and 0.99±0.66 million LSEC, respectively. Purity of the final cell preparation reached 95.10±2.58% when using our method. In contrast, CD146+ MACS and short-term selective adherence gave purities of 86.75±3.26% and 47.95±9.82%, respectively. Similarly, contamination by non-LSEC was the lowest when purification was performed using our technique, with a proportion of contaminating macrophages of only 1.87±0.77%. Further, isolated cells analysed by scanning electron microscopy presented typical LSEC fenestrations organized in sieve plates, demonstrating that the technique allowed to isolate bona fide LSEC. In conclusion, we described a reliable and reproducible technique for the isolation of high yields of pure LSEC in mice. This protocol provides an efficient method to prepare LSEC for studying their biological functions. - Highlights: • This protocol provides an efficient method to prepare primary mouse LSEC for studying their biological functions. • The liver cell dispersion step was improved by performing a retrograde cannulation of the liver. • The cell yield and the purity obtained were higher than comparative techniques in mice. • Contaminating macrophages were removed by introducing a CD11b- magnetic

  16. An optimized method for mouse liver sinusoidal endothelial cell isolation

    International Nuclear Information System (INIS)

    Meyer, Jeremy; Lacotte, Stéphanie; Morel, Philippe; Gonelle-Gispert, Carmen; Bühler, Léo

    2016-01-01

    The objective of the present study was to develop an accurate and reproducible method for liver sinusoidal endothelial cell (LSEC) isolation in mice. Non-parenchymal cells were isolated using a modified two-step collagenase digestion combined with Optiprep density gradient centrifugation. LSEC were further purified using two prevalent methods, short-term selective adherence and CD146+ magnetic-activated cell sorting (MACS), and compared in terms of cell yield, viability and purity to our purification technique using CD11b cell depletion combined with long-term selective adherence. LSEC purification using our technique allowed to obtain 7.07±3.80 million LSEC per liver, while CD146+ MACS and short-term selective adherence yielded 2.94±1.28 and 0.99±0.66 million LSEC, respectively. Purity of the final cell preparation reached 95.10±2.58% when using our method. In contrast, CD146+ MACS and short-term selective adherence gave purities of 86.75±3.26% and 47.95±9.82%, respectively. Similarly, contamination by non-LSEC was the lowest when purification was performed using our technique, with a proportion of contaminating macrophages of only 1.87±0.77%. Further, isolated cells analysed by scanning electron microscopy presented typical LSEC fenestrations organized in sieve plates, demonstrating that the technique allowed to isolate bona fide LSEC. In conclusion, we described a reliable and reproducible technique for the isolation of high yields of pure LSEC in mice. This protocol provides an efficient method to prepare LSEC for studying their biological functions. - Highlights: • This protocol provides an efficient method to prepare primary mouse LSEC for studying their biological functions. • The liver cell dispersion step was improved by performing a retrograde cannulation of the liver. • The cell yield and the purity obtained were higher than comparative techniques in mice. • Contaminating macrophages were removed by introducing a CD11b- magnetic

  17. "Artificial micro organs"--a microfluidic device for dielectrophoretic assembly of liver sinusoids.

    Science.gov (United States)

    Schütte, Julia; Hagmeyer, Britta; Holzner, Felix; Kubon, Massimo; Werner, Simon; Freudigmann, Christian; Benz, Karin; Böttger, Jan; Gebhardt, Rolf; Becker, Holger; Stelzle, Martin

    2011-06-01

    In order to study possible toxic side effects of potential drug compounds in vitro a reliable test system is needed. Predicting liver toxicity presents a major challenge of particular importance as liver cells grown in a cell culture suffer from a rapid loss of their liver specific functions. Therefore we are developing a new microfluidic test system for liver toxicity. This test system is based on an organ-like liver 3D co-culture of hepatocytes and endothelial cells. We devised a microfluidic chip featuring cell culture chambers with integrated electrodes for the assembly of liver sinusoids by dielectrophoresis. Fluid channels enable an organ-like perfusion with culture media and test compounds. Different chamber designs were studied and optimized with regard to dielectrophoretic force distribution, hydrodynamic flow profile, and cell trapping rate using numeric simulations. Based on simulation results a microchip was injection-moulded from COP. This chip allowed the assembly of viable hepatocytes and endothelial cells in a sinusoid-like fashion.

  18. Scavenger receptor-mediated endocytosis by sinusoidal cells in rat bone marrow

    International Nuclear Information System (INIS)

    Geoffroy, J.S.

    1987-01-01

    Endocytosis of serum albumin by sinusoidal endothelial cells in rat bone marrow was investigated initially at the ultrastructural level with subsequent biochemical investigation of the specificity mediating this event. Bovine serum albumin adsorbed to 20nm colloidal gold particles (AuBSA) was chosen as the electron microscopic probe. Morphological data strongly suggested that a receptor was involved in uptake of AuBSA. Confirmation of receptor involvement in the uptake of AuBSA by marrow sinusoidal endothelial cells was achieved utilizing an in situ isolated hind limb perfusion protocol in conjunction with unlabeled, radiolabeled, and radio-/colloidal gold labeled probes. The major findings of competition and saturation experiments were: (1) endocytosis of AuBSA was mediated by a receptor for modified/treated serum albumin; (2) endocytosis of formaldehyde-treated serum albumin was mediated by a binding site which may be the same or closely related to the site responsible for the uptake of AuBSA; and (3) endocytosis of native untreated albumin was not mediated by receptor and probably represents fluid-phase pinocitosis

  19. Sinusoidal obstruction syndrome (SOS): A light and electron microscopy study in human liver.

    Science.gov (United States)

    Vreuls, C P H; Driessen, A; Olde Damink, S W M; Koek, G H; Duimel, H; van den Broek, M A J; Dejong, C H C; Braet, F; Wisse, E

    2016-05-01

    Oxaliplatin is an important chemotherapeutic agent, used in the treatment of hepatic colorectal metastases, and known to induce the sinusoidal obstruction syndrome (SOS). Pathophysiological knowledge concerning SOS is based on a rat model. Therefore, the aim was to perform a comprehensive study of the features of human SOS, using both light microscopy (LM) and electron microscopy (EM). Included were all patients of whom wedge liver biopsies were collected during a partial hepatectomy for colorectal liver metastases, in a 4-year period. The wedge biopsy were perfusion fixated and processed for LM and EM. The SOS lesions were selected by LM and details were studied using EM. Material was available of 30 patients, of whom 28 patients received neo-adjuvant oxaliplatin. Eighteen (64%) of the 28 patients showed SOS lesions, based on microscopy. The lesions consisted of sinusoidal endothelial cell detachment from the space of Disse on EM. In the enlarged space of Disse a variable amount of erythrocytes were located. Sinusoidal endothelial cell detachment was present in human SOS, accompanied by enlargement of the space of Disse and erythrocytes in this area. These findings, originally described in a rat model, were now for the first time confirmed in human livers under clinically relevant settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Hepatitis C virus core protein induces dysfunction of liver sinusoidal endothelial cell by down-regulation of silent information regulator 1.

    Science.gov (United States)

    Sun, Li-Jie; Yu, Jian-Wu; Shi, Yu-Guang; Zhang, Xiao-Yu; Shu, Meng-Ni; Chen, Mo-Yang

    2018-05-01

    Hepatic fibrosis is a frequent feature of chronic hepatitis C virus (HCV) infection. Some evidence has suggested the potential role of silent information regulator 1 (SIRT1) in organ fibrosis. The aim of this study was to investigate the effect of HCV core protein on expression of SIRT1 of liver sinusoidal endothelial cell (LSEC) and function of LSEC. LSECs were co-cultured with HepG2 cells or HepG2 cells expressing HCV core protein and LSECs cultured alone were used as controls. After co-culture, the activity and expression levels of mRNA and protein of SIRT1 in LSEC were detected by a SIRT1 fluorometric assay kit, real time-PCR (RT-PCR), Western blot, respectively. The levels of adiponectin receptor 2 (AdipoR2), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were measured by Western blot. Cluster of differentiation 31 (CD31), CD14, and von Willebrand factor (vWf) of LSECs was performed by flow cytometry. The level of reactive oxygen species (ROS) was assayed. Malondialdehyde (MDA), superoxide dismutase (SOD), adiponectin, nitric oxide (NO), and endothelin-1 (ET-1) levels in the co-culture supernatant were measured. The co-culture supernatant was then used to cultivate LX-2 cells. The levels of α-smooth muscle actin (ASMA) and transforming growth factor-β1 (TGF-β1) protein in LX-2 cells were measured by Western blot. Compared with LSEC co-cultured with HepG2 cells group, in LSEC co-cultured with HepG2-core cells group, the activity and expression level of mRNA and protein of SIRT1 reduced; the level of adiponectin reduced and the expression level of AdipoR2 protein decreased; ROS levels increased; the expression level of eNOS, VEGF protein decreased; and the expression level of CD14 decreased; the expression level of vWf and CD31 increased; NO and SOD levels decreased; whereas ET-1 and MDA levels increased; the levels of ASMA and TGF-β1 protein in LX-2 cells increased. SIRT1 activator improved the above-mentioned changes

  1. Intravascular Immune Surveillance by CXCR6+ NKT Cells Patrolling Liver Sinusoids

    Directory of Open Access Journals (Sweden)

    Geissmann Frederic

    2005-01-01

    Full Text Available We examined the in vivo behavior of liver natural killer T cells (NKT cells by intravital fluorescence microscopic imaging of mice in which a green fluorescent protein cDNA was used to replace the gene encoding the chemokine receptor CXCR6. NKT cells, which account for most CXCR6+ cells in liver, were found to crawl within hepatic sinusoids at 10-20 µm/min and to stop upon T cell antigen receptor activation. CXCR6-deficient mice exhibited a selective and severe reduction of CD1d-reactive NKT cells in the liver and decreased susceptibility to T-cell-dependent hepatitis. CXCL16, the cell surface ligand for CXCR6, is expressed on sinusoidal endothelial cells, and CXCR6 deficiency resulted in reduced survival, but not in altered speed or pattern of patrolling of NKT cells. Thus, NKT cells patrol liver sinusoids to provide intravascular immune surveillance, and CXCR6 contributes to liver-based immune responses by regulating their abundance.

  2. Efficiency enhancement of a self-propelled pitching profile using non-sinusoidal trajectories

    Science.gov (United States)

    Mekadem, M.; Chihani, E.; Oualli, H.; Hanchi, S.; Bouabdallah, A.; Gad-El-Hak, M.

    2017-11-01

    A symmetrical profile is subjected to non-sinusoidal pitching motion. The airfoil has a chord length c = 0.006 m and a semi-circular leading edge with a diameter of D = 0.001 m. The extrados and intrados are two straight lines that intersect at a tapered trailing edge, and the pitching pivot point is positioned at the leading edge. The pitching frequency is in the range of 1 based upon the maximum profile thickness D varies in the range of 35 <= Re <= 210 , which matches insect's Reynolds numbers. The foil movement is executed using the dynamic mesh technique and a user defined function (UDF). The adopted mesh has 70,445 nodes with 5,1960 quadrilateral cells. The results are in good agreement with prior experiments, and, compared to sinusoidal oscillations, show that non-sinusoidal flapping trajectories lead to advancing velocity increase of 550%. Additionally, if improved propulsive efficiency is sought, non-sinusoidal flapping lead to better thrust.

  3. Efficient uptake of blood-borne BK and JC polyomavirus-like particles in endothelial cells of liver sinusoids and renal vasa recta.

    Directory of Open Access Journals (Sweden)

    Jaione Simon-Santamaria

    Full Text Available Liver sinusoidal endothelial cells (LSECs are specialized scavenger cells that mediate high-capacity clearance of soluble waste macromolecules and colloid material, including blood-borne adenovirus. To explore if LSECs function as a sink for other viruses in blood, we studied the fate of virus-like particles (VLPs of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like complete virions, VLPs specifically bind to receptors and enter cells, but unlike complete virions, they cannot replicate. 125I-labeled VLPs were used to assess blood decay, organ-, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and -cytochemistry. BK- and JC-VLPs rapidly distributed to liver, with lesser uptake in kidney and spleen. Liver uptake was predominantly in LSECs. Blood half-life (∼1 min, and tissue distribution of JC-VLPs and two JC-VLP-mutants (L55F and S269F that lack sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. Liver uptake was not mediated by scavenger receptors. In spleen, the VLPs localized to the red pulp marginal zone reticuloendothelium, and in kidney to the endothelial lining of vasa recta segments, and the transitional epithelium of renal pelvis. Most VLP-positive vessels in renal medulla did not express PV-1/Meca 32, suggesting location to the non-fenestrated part of vasa recta. The endothelial cells of these vessels also efficiently endocytosed a scavenger receptor ligand, formaldehyde-denatured albumin, suggesting high endocytic activity compared to other renal endothelia. We conclude that LSECs very effectively cleared a large fraction of blood-borne BK- and JC-VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. In addition, we report the novel finding that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed

  4. Distribution of Porcine Haemal Nodes and Morphological Variations in the Haemal Nodes of Cattle and West African Dwarf Goats

    Directory of Open Access Journals (Sweden)

    Anietie Francis UDOUMOH

    2016-12-01

    Full Text Available Apparently healthy, non-lactating, non-gravid adult large white pigs (15, adult cattle (10 and adult West African Dwarf (WAD goats of either genders were used to investigate the morphology of haemal nodes using gross anatomical and histological techniques. The results demonstrated that the haemal nodes of pigs occurred in the thoracic, abdominal and pelvic regions along the course of blood vessels. The ranges of the longest diameters of the dark brown organs were 6.1 – 30.3 cm in pigs, 4.1 – 18.7 cm in cattle and 2.7 – 8.2 cm in WAD goats. Bovine haemal nodes showed cortical and medullary parenchymal areas, with the cortex demonstrating primary and secondary lymphoid follicles in a circumferential fashion. The medulla showed blood filled medullary sinusoids and medullary cords. In WAD goat, the reticular cells and smooth muscle cells of the capsule were oriented in different directions and the subcapsular, cortical and medullary sinusoids exhibited erythrocytes in pockets. In conclusion, the present study has provided information on the distribution of haemal nodes in pigs as well as other unique morphological features of cattle and WAD goat haemal nodes that could aid their identification and suggest their roles in the body.

  5. Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

    Science.gov (United States)

    Fan, Cathy Q.; Crawford, James M.

    2014-01-01

    Hepatic sinusoidal obstruction syndrome (SOS) is an obliterative venulitis of the terminal hepatic venules, which in its more severe forms imparts a high risk of mortality. SOS, also known as veno-occlusive disease (VOD), occurs as a result of cytoreductive therapy prior to hematopoietic stem cell transplantation (HSCT), following oxaliplatin-containing adjuvant or neoadjuvant chemotherapy for colorectal carcinoma metastatic to the liver and treated by partial hepatectomy, in patients taking pyrrolizidine alkaloid-containing herbal remedies, and in other particular settings such as the autosomal recessive condition of veno-occlusive disease with immunodeficiency (VODI). A central pathogenic event is toxic destruction of hepatic sinusoidal endothelial cells (SEC), with sloughing and downstream occlusion of terminal hepatic venules. Contributing factors are SEC glutathione depletion, nitric oxide depletion, increased intrahepatic expression of matrix metalloproteinases and vascular endothelial growth factor (VEGF), and activation of clotting factors. The clinical presentation of SOS includes jaundice, development of right upper-quadrant pain and tender hepatomegaly, ascites, and unexplained weight gain. Owing to the potentially critical condition of these patients, transjugular biopsy may be the preferred route for liver biopsy to exclude other potential causes of liver dysfunction and to establish a diagnosis of SOS. Treatment includes rigorous fluid management so as to avoid excessive fluid overload while avoiding too rapid diuresis or pericentesis, potential use of pharmaceutics such as defibrotide, coagulolytic agents, or methylprednisolone, and liver transplantation. Proposed strategies for prevention and prophylaxis include reduced-intensity conditioning radiation for HSCT, treatment with ursodeoxycholic acid, and inclusion of bevacizumab with oxaliplatin-based chemotherapeutic regimes. While significant progress has been made in understanding the pathogenesis

  6. Liver sinusoidal endothelial cells induce immunosuppressive IL-10-producing Th1 cells via the Notch pathway.

    Science.gov (United States)

    Neumann, Katrin; Rudolph, Christine; Neumann, Christian; Janke, Marko; Amsen, Derk; Scheffold, Alexander

    2015-07-01

    Under homeostasis, liver sinusoidal endothelial cells (LSECs) shift intrahepatic T-cell responses towards tolerance. However, the role of LSECs in the regulation of T-cell-induced liver inflammation is less clear. Here, we studied the capacity of LSECs to modulate pro-inflammatory Th1-cell differentiation in mice. Using in vitro co-culture systems and subsequent cytokine analysis, we showed that LSECs induced high amounts of the anti-inflammatory cytokine IL-10 in developing Th1 cells. These LSEC-stimulated Th1 cells had no pro-inflammatory capacity in vivo but instead actively suppressed an inflammatory Th1-cell-induced delayed-type hypersensitivity reaction. Blockage of IL-10 signaling in vivo inhibited immunosuppressive activity of LSEC-stimulated Th1 cells. We identified the Notch pathway as a mechanism how LSECs trigger IL-10 expression in Th1 cells. LSECs expressed high levels of the Delta-like and Jagged family of Notch ligands and induced expression of the Notch target genes hes-1 and deltex-1 in Th1 cells. Blockade of Notch signaling selectively inhibited IL-10 induction in Th1 cells by LSECs. Our findings suggest that LSEC-induced IL-10 expression in Th1 cells via the Notch pathway may contribute to the control of hepatic inflammatory immune responses by induction of a self-regulatory mechanism in pro-inflammatory Th1 cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Decrease of PECAM-1-gene-expression induced by proinflammatory cytokines IFN-γ and IFN-α is reversed by TGF-β in sinusoidal endothelial cells and hepatic mononuclear phagocytes

    Directory of Open Access Journals (Sweden)

    Ramadori Giuliano

    2008-05-01

    Full Text Available Abstract Background and aim The mechanisms of transmigration of inflammatory cells through the sinusoids are still poorly understood. This study aims to identify in vitro conditions (cytokine treatment which may allow a better understanding of the changes in PECAM (platelet endothelial cell adhesion molecule-1-gene-expression observed in vivo. Methods and results In this study we show by immunohistochemistry, that there is an accumulation of ICAM-1 (intercellular cell adhesion molecule-1 and ED1 positive cells in necrotic areas of livers of CCl4-treated rats, whereas there are few PECAM-1 positive cells observable. After the administration of CCl4, we could detect an early rise of levels of IFN-γ followed by an enhanced TGF-β protein level. As shown by Northern blot analysis and surface protein expression analysed by flow cytometry, IFN-γ-treatment decreased PECAM-1-gene-expression in isolated SECs (sinusoidal endothelial cells and mononuclear phagocytes (MNPs in parallel with an increase in ICAM-1-gene-expression in a dose and time dependent manner. In contrast, TGF-β-treatment increased PECAM-1-expression. Additional administration of IFN-γ to CCl4-treated rats and observations in IFN-γ-/- mice confirmed the effect of IFN-γ on PECAM-1 and ICAM-1-expression observed in vitro and increased the number of ED1-expressing cells 12 h after administration of the toxin. Conclusion The early decrease of PECAM-1-expression and the parallel increase of ICAM-1-expression following CCl4-treatment is induced by elevated levels of IFN-γ in livers and may facilitate adhesion and transmigration of inflammatory cells. The up-regulation of PECAM-1-expression in SECs and MNPs after TGF-β-treatment suggests the involvement of PECAM-1 during the recovery after liver damage.

  8. Endothelial dysfunction in the regulation of portal hypertension

    Science.gov (United States)

    Iwakiri, Yasuko

    2013-01-01

    Portal hypertension is caused by an increased intrahepatic resistance, a major consequence of cirrhosis. Endothelial dysfunction in liver sinusoidal endothelial cells (LSECs) decreases the production of vasodilators, such as nitric oxide (NO) and favors vasoconstriction. This contributes to an increased vascular resistance in the intrahepatic/sinusoidal microcirculation. Portal hypertension, once developed, causes endothelial cell (EC) dysfunction in the extrahepatic, i.e. splanchnic and systemic, circulation. Unlike LSEC dysfunction, EC dysfunction in the splanchnic and systemic circulation overproduces vasodilator molecules, leading to arterial vasodilatation. In addition, portal hypertension leads to the formation of portosystemic collateral vessels. Both arterial vasodilatation and portosystemic collateral vessel formation exacerbate portal hypertension by increasing the blood flow through the portal vein. Pathologic consequences, such as esophageal varices and ascites, result. While the sequence of pathological vascular events in cirrhosis and portal hypertension have been elucidated, the underlying cellular and molecular mechanisms causing EC dysfunctions are not yet fully understood. This review article summarizes the current cellular and molecular studies on EC dysfunctions found during the development of cirrhosis and portal hypertension with a focus on intra- and extrahepatic circulation. The article ends by discussing future directions of study for EC dysfunctions. PMID:21745318

  9. A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.

    Science.gov (United States)

    Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Córdoba, Bernat; Bosch, Anna; Calvo, Maria; Rodrigo-Torres, Daniel; Sancho-Bru, Pau; Mira, Aurea; Jiménez, Wladimiro; Morales-Ruiz, Manuel

    2017-11-01

    Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl 4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl 4 -treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-β1 (TGF-β1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P livers correlated with a significant decrease in liver fibrosis ( P livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization. NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-β1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization. Copyright © 2017 the American

  10. Mesenchymal stem cell-conditioned medium prevents radiation-induced liver injury by inhibiting inflammation and protecting sinusoidal endothelial cells

    International Nuclear Information System (INIS)

    Chen Yixing; Zeng Zhaochong; Sun Jing; Huang Yan; Zhang Zhenyu; Zeng Haiying

    2015-01-01

    Current management of radiation-induced liver injury is limited. Sinusoidal endothelial cell (SEC) apoptosis and inflammation are considered to be initiating events in hepatic damage. We hypothesized that mesenchymal stem cells (MSCs) possess anti-apoptotic and anti-inflammatory actions during hepatic irradiation, acting via paracrine mechanisms. This study aims to examine whether MSC-derived bioactive components are protective against radiation-induced liver injury in rats. MSC-conditioned medium (MSC-CM) was generated from rat bone marrow–derived MSCs. The effect of MSC-CM on the viability of irradiated SECs was examined by flow cytometric analysis. Activation of the Akt and ERK pathways was analyzed by western blot. MSC-CM was also delivered to Sprague–Dawley rats immediately before receiving liver irradiation, followed by testing for pathological features, changes in serum hyaluronic acid, ALT, and inflammatory cytokine levels, and liver cell apoptosis. MSC-CM enhanced the viability of irradiated SECs in vitro and induced Akt and ERK phosphorylation in these cells. Infusion of MSC-CM immediately before liver irradiation provided a significant anti-apoptotic effect on SECs and improved the histopathological features of injury in the irradiated liver. MSC-CM also reduced the secretion and expression of inflammatory cytokines and increased the expression of anti-inflammatory cytokines. MSC-derived bioactive components could be a novel therapeutic approach for treating radiation-induced liver injury. (author)

  11. CD147 promotes liver fibrosis progression via VEGF-A/VEGFR2 signalling-mediated cross-talk between hepatocytes and sinusoidal endothelial cells.

    Science.gov (United States)

    Yan, Zhaoyong; Qu, Kai; Zhang, Jing; Huang, Qichao; Qu, Ping; Xu, Xinsen; Yuan, Peng; Huang, Xiaojun; Shao, Yongping; Liu, Chang; Zhang, Hongxin; Xing, Jinliang

    2015-10-01

    Although previous evidence indicates close involvement of CD147 in the pathogenesis of liver fibrosis, the underlying molecular mechanisms and its therapeutic value remain largely unknown. In the present study, we investigated the biological roles of CD147 in liver fibrosis and assessed its therapeutic value as a target molecule in the CCl4-induced liver fibrosis mouse model. We found that CD147 was highly expressed in both hepatocytes and SECs (sinusoidal endothelial cells) in fibrotic liver tissues. Additionally, it was significantly associated with the fibrosis stage. TGF-β1 (transforming growth factor β1) was found to be mainly responsible for the up-regulation of CD147. Bioinformatic and experimental data suggest a functional link between CD147 expression and VEGF-A (vascular endothelial growth factor A)/VEGR-2 (VEGF receptor 2) signalling-mediated angiogenesis in fibrotic liver tissues. Furthermore, we observed that the CD147-induced activation of the PI3K (phosphoinositide 3-kinase)/Akt signalling pathway promotes the production of VEGF-A in hepatocytes and expression of VEGFR-2 in SECs, which was found to enhance the angiogenic capability of SECs. Finally, our data indicate that blocking of CD147 using an mAb (monoclonal antibody) attenuated liver fibrosis progression via inhibition of VEGF-A/VEGFR-2 signalling and subsequent amelioration of microvascular abnormality in the CCl4-induced mouse model. Our findings suggest a novel functional mechanism that CD147 may promote liver fibrosis progression via inducing the VEGF-A/VEGFR-2 signalling pathway-mediated cross-talk between hepatocytes and SECs. New strategies based on the intervention of CD147 can be expected for prevention of liver fibrosis. © 2015 Authors; published by Portland Press Limited.

  12. A transgenic model for conditional induction and rescue of portal hypertension reveals a role of VEGF-mediated regulation of sinusoidal fenestrations.

    Directory of Open Access Journals (Sweden)

    Dalit May

    Full Text Available Portal hypertension (PH is a common complication and a leading cause of death in patients with chronic liver diseases. PH is underlined by structural and functional derangement of liver sinusoid vessels and its fenestrated endothelium. Because in most clinical settings PH is accompanied by parenchymal injury, it has been difficult to determine the precise role of microvascular perturbations in causing PH. Reasoning that Vascular Endothelial Growth Factor (VEGF is required to maintain functional integrity of the hepatic microcirculation, we developed a transgenic mouse system for a liver-specific-, reversible VEGF inhibition. The system is based on conditional induction and de-induction of a VEGF decoy receptor that sequesters VEGF and preclude signaling. VEGF blockade results in sinusoidal endothelial cells (SECs fenestrations closure and in accumulation and transformation of the normally quiescent hepatic stellate cells, i.e. provoking the two processes underlying sinusoidal capillarization. Importantly, sinusoidal capillarization was sufficient to cause PH and its typical sequela, ascites, splenomegaly and venous collateralization without inflicting parenchymal damage or fibrosis. Remarkably, these dramatic phenotypes were fully reversed within few days from lifting-off VEGF blockade and resultant re-opening of SECs' fenestrations. This study not only uncovered an indispensible role for VEGF in maintaining structure and function of mature SECs, but also highlights the vasculo-centric nature of PH pathogenesis. Unprecedented ability to rescue PH and its secondary manifestations via manipulating a single vascular factor may also be harnessed for examining the potential utility of de-capillarization treatment modalities.

  13. Defibrotide Stimulates Angiogenesis and Protects Endothelial Cells from Calcineurin Inhibitor-Induced Apoptosis via Upregulation of AKT/Bcl-xL.

    Science.gov (United States)

    Wang, Xiangmin; Pan, Bin; Hashimoto, Yuko; Ohkawara, Hiroshi; Xu, Kailin; Zeng, Lingyu; Ikezoe, Takayuki

    2018-01-01

    Sinusoidal obstruction syndrome is a life-threatening complication that can occur after haematopoietic stem cell transplantation. Defibrotide (DF) has been approved for the treatment of individuals with severe sinusoidal obstruction syndrome following haematopoietic stem cell transplantation in the European Union and the United States. However, the precise mechanisms by which DF protects endothelial cells remain to be elucidated. In this study, we found that DF stimulated angiogenesis in vitro and in vivo as assessed by vascular tube formation, scratch-wound repair and Matrigel plug assays. These effects were associated with an activation of pro-survival signalling pathways, including AKT (protein kinase B), ERK (extracellular signal-regulated kinases) and p38. More importantly, DF alleviated calcineurin inhibitor-induced growth inhibition and apoptosis of human umbilical vein endothelial cells and human hepatic sinusoidal endothelial cells in parallel with upregulation of anti-apoptotic protein B-cell lymphoma-extra-large (Bcl-xL), which was mediated by AKT (protein kinase B). Notably, these effects were abrogated when Bcl-xL was depleted by small interfering RNA (ribonucleic acid). In addition, DF counteracted calcineurin inhibitor-induced activation of nuclear factor-κB and Janus kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) signalling and production of cytokines in vascular endothelial cell-derived EA.hy926 cells. Taken together, DF has pro-angiogenic, anti-apoptotic and anti-inflammatory effects on endothelial cells. DF is a potentially useful agent to prevent the development of, and treat individuals with, endothelial cell injury-related complications after haematopoietic stem cell transplantation. Schattauer GmbH Stuttgart.

  14. [Defibrotide therapy for patients with sinusoidal obstruction syndrome after hematopoietic stem cell transplantation].

    Science.gov (United States)

    Yakushijin, Kimikazu; Okamura, Atsuo; Ono, Kanako; Kawano, Yuko; Kawano, Hiroki; Funakoshi, Yohei; Kawamori, Yuriko; Nishikawa, Shinichiro; Minagawa, Kentaro; Sada, Akiko; Shimoyama, Manabu; Yamamoto, Katsuya; Katayama, Yoshio; Matsui, Toshimitsu

    2009-01-01

    Sinusoidal obstruction syndrome (SOS) is one of the life-threatening complications caused by endothelial damage to the hepatic sinusoids after hematopoietic stem cell transplantation. However, a satisfactory treatment for SOS has not yet been established. Defibrotide has anti-thrombotic, anti-ischemic, anti-inflammatory, and thrombolytic properties without systemic anticoagulant effects. We treated eight post-transplant SOS patients with defibrotide. Three patients responded to the therapy and the initial response was observed within a week. In addition to the improvement of liver function, rapid recovery of response to diuretic drugs followed by the improvement of renal function was observed. All of the five patients with respiratory dysfunction died despite administration of defibrotide, suggesting that early treatment might lead to better outcomes. There were no severe adverse effects directly due to defibrotide administration. Defibrotide seems to be a promising treatment for SOS, and the initiation of a clinical study in Japan would be important.

  15. Sinusoidal Representation of Acoustic Signals

    Science.gov (United States)

    Honda, Masaaki

    Sinusoidal representation of acoustic signals has been an important tool in speech and music processing like signal analysis, synthesis and time scale or pitch modifications. It can be applicable to arbitrary signals, which is an important advantage over other signal representations like physical modeling of acoustic signals. In sinusoidal representation, acoustic signals are composed as sums of sinusoid (sine wave) with different amplitudes, frequencies and phases, which is based on the timedependent short-time Fourier transform (STFT). This article describes the principles of acoustic signal analysis/synthesis based on a sinusoid representation with focus on sine waves with rapidly varying frequency.

  16. Construction of a liver sinusoid based on the laminar flow on chip and self-assembly of endothelial cells.

    Science.gov (United States)

    Mi, Shengli; Yi, Xiaoman; Du, Zhichang; Xu, Yuanyuan; Sun, Wei

    2018-02-20

    The liver is one of the main metabolic organs, and nearly all ingested drugs will be metabolized by the liver. Only a small fraction of drugs are able to come onto the market during drug development, and hepatic toxicity is a major cause for drug failure. Since drug development is costly in both time and materials, an in vitro liver model that can accelerate bioreactions in the liver and reduce drug consumption is imperative in the pharmaceutical industry. The liver on a chip is an ideal alternative for its controllable environment and tiny size, which means constructing a more biomimetic model, reducing material consumption as well as promoting drug diffusion and reaction. In this study, taking advantage of the laminar flow on chips and using natural degradable gel rat tail Collagen-I, we constructed a liver sinusoid on a chip. By synchronously injecting two kinds of cell-laden collagen, HepG2-laden collagen and HUVEC-laden collagen, we formed two collagen layers with a clear borderline. By controlling the HUVEC density and injection of growth factors, HUVECs in collagen formed a monolayer through self-assembly. Thus, a liver sinusoid on a chip was achieved in a more biomimetic environment with a more controllable and uniform distribution of discrete HUVECs. Viability, album secretion and urea synthesis of the live sinusoid on a chip were analysed on days 3, 5 and 7 after collagen injection with acetaminophen treatment at 0 (control), 10 and 20 mM. The results indicated that our liver sinusoid on a chip was able to maintain bioactivity and function for at least 7 d and was beneficial for hepatotoxic drug screening.

  17. Mapping the distinctive populations of lymphatic endothelial cells in different zones of human lymph nodes.

    Directory of Open Access Journals (Sweden)

    Saem Mul Park

    Full Text Available The lymphatic sinuses in human lymph nodes (LNs are crucial to LN function yet their structure remains poorly defined. Much of our current knowledge of lymphatic sinuses derives from rodent models, however human LNs differ substantially in their sinus structure, most notably due to the presence of trabeculae and trabecular lymphatic sinuses that rodent LNs lack. Lymphatic sinuses are bounded and traversed by lymphatic endothelial cells (LECs. A better understanding of LECs in human LNs is likely to improve our understanding of the regulation of cell trafficking within LNs, now an important therapeutic target, as well as disease processes that involve lymphatic sinuses. We therefore sought to map all the LECs within human LNs using multicolor immunofluorescence microscopy to visualize the distribution of a range of putative markers. PROX1 was the only marker that uniquely identified the LECs lining and traversing all the sinuses in human LNs. In contrast, LYVE1 and STAB2 were only expressed by LECs in the paracortical and medullary sinuses in the vast majority of LNs studied, whilst the subcapsular and trabecular sinuses lacked these molecules. These data highlight the existence of at least two distinctive populations of LECs within human LNs. Of the other LEC markers, we confirmed VEGFR3 was not specific for LECs, and CD144 and CD31 stained both LECs and blood vascular endothelial cells (BECs; in contrast, CD59 and CD105 stained BECs but not LECs. We also showed that antigen-presenting cells (APCs in the sinuses could be clearly distinguished from LECs by their expression of CD169, and their lack of expression of PROX1 and STAB2, or endothelial markers such as CD144. However, both LECs and sinus APCs were stained with DCN46, an antibody commonly used to detect CD209.

  18. New ways of looking at very small holes - using optical nanoscopy to visualize liver sinusoidal endothelial cell fenestrations

    Science.gov (United States)

    Øie, Cristina I.; Mönkemöller, Viola; Hübner, Wolfgang; Schüttpelz, Mark; Mao, Hong; Ahluwalia, Balpreet S.; Huser, Thomas R.; McCourt, Peter

    2018-02-01

    Super-resolution fluorescence microscopy, also known as nanoscopy, has provided us with a glimpse of future impacts on cell biology. Far-field optical nanoscopy allows, for the first time, the study of sub-cellular nanoscale biological structures in living cells, which in the past was limited to electron microscopy (EM) (in fixed/dehydrated) cells or tissues. Nanoscopy has particular utility in the study of "fenestrations" - phospholipid transmembrane nanopores of 50-150 nm in diameter through liver sinusoidal endothelial cells (LSECs) that facilitate the passage of plasma, but (usually) not blood cells, to and from the surrounding hepatocytes. Previously, these fenestrations were only discernible with EM, but now they can be visualized in fixed and living cells using structured illumination microscopy (SIM) and in fixed cells using single molecule localization microscopy (SMLM) techniques such as direct stochastic optical reconstruction microscopy. Importantly, both methods use wet samples, avoiding dehydration artifacts. The use of nanoscopy can be extended to the in vitro study of fenestration dynamics, to address questions such as the following: are they actually dynamic structures, and how do they respond to endogenous and exogenous agents? A logical further extension of these methodologies to liver research (including the liver endothelium) will be their application to liver tissue sections from animal models with different pathological manifestations and ultimately to patient biopsies. This review will cover the current state of the art of the use of nanoscopy in the study of liver endothelium and the liver in general. Potential future applications in cell biology and the clinical implications will be discussed.

  19. Amelioration of cirrhotic portal hypertension by targeted cyclooxygenase-1 siRNA delivery to liver sinusoidal endothelium with polyethylenimine grafted hyaluronic acid.

    Science.gov (United States)

    Lin, Liteng; Cai, Mingyue; Deng, Shaohui; Huang, Wensou; Huang, Jingjun; Huang, Xinghua; Huang, Mingsheng; Wang, Yong; Shuai, Xintao; Zhu, Kangshun

    2017-10-01

    Portal hypertension (PH), a leading cause of mortality in cirrhosis, lacks effective clinical therapeutic strategies. The increased thromboxane A 2 (TXA 2 ), derived primarily from the upregulation of cyclooxygenase-1 (COX-1) in cirrhotic liver sinusoidal endothelial cells (LSECs), is responsible for hepatic endothelial dysfunction and PH. Thus, blocking the COX-1 pathway in cirrhotic LSECs may benefit the treatment of PH. In this study, hyaluronate-graft-polyethylenimine (HA-PEI) was synthesized for the targeted delivery of COX-1 siRNA to LSECs. Compared to non-targeted PEI, HA-PEI mediated much more efficient siRNA delivery, which resulted in potent targeted gene silencing in LSECs. In vivo, HA-PEI notably increased the accumulation of siRNA along the sinusoidal lining of the liver, inhibited over-activation of the COX-1/TXA 2 pathway in LSECs, and successfully reduced portal pressure in cirrhotic mice. These results highlight the potential of HA-PEI complexed siRNA to serve as a LSECs-specific nanomedical system for effective gene therapy in PH. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Sinusoidal obstruction syndrome.

    Science.gov (United States)

    Valla, Dominique-Charles; Cazals-Hatem, Dominique

    2016-09-01

    Sinusoidal obstruction syndrome (SOS) is characterized by damage to small hepatic vessels affecting particularly sinusoidal endothelium. Damaged sinusoids can be associated with a partial or complete occlusion of small hepatic veins, hence the previous denomination of hepatic veno-occlusive disease (VOD). Exposure to certain exogenous toxins appears to be specific to this condition and is frequently included in its definition. Typical histopathological features of SOS in a liver biopsy specimen are presented in the text. The purpose of this article is to provide an overview on the different entities corresponding to this general definition. Such entities include: (i) liver disease related to pyrrolizidine alcaloids; (ii) liver injury related to conditioning for hematopoietic stem cell transplantation; (iii) vascular liver disease occurring in patients treated with chemotherapy for liver metastasis of colorectal cancer; and (iv) other liver diseases related to toxic agents. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Sinusoids theory and technological applications

    CERN Document Server

    Kythe, Prem K

    2014-01-01

    A Complete Treatment of Current Research Topics in Fourier Transforms and Sinusoids Sinusoids: Theory and Technological Applications explains how sinusoids and Fourier transforms are used in a variety of application areas, including signal processing, GPS, optics, x-ray crystallography, radioastronomy, poetry and music as sound waves, and the medical sciences. With more than 200 illustrations, the book discusses electromagnetic force and sychrotron radiation comprising all kinds of waves, including gamma rays, x-rays, UV rays, visible light rays, infrared, microwaves, and radio waves. It also covers topics of common interest, such as quasars, pulsars, the Big Bang theory, Olbers' paradox, black holes, Mars mission, and SETI.The book begins by describing sinusoids-which are periodic sine or cosine functions-using well-known examples from wave theory, including traveling and standing waves, continuous musical rhythms, and the human liver. It next discusses the Fourier series and transform in both continuous and...

  2. Targeted Delivery of Immunomodulators to Lymph Nodes

    Directory of Open Access Journals (Sweden)

    Jamil Azzi

    2016-05-01

    Full Text Available Active-targeted delivery to lymph nodes represents a major advance toward more effective treatment of immune-mediated disease. The MECA79 antibody recognizes peripheral node addressin molecules expressed by high endothelial venules of lymph nodes. By mimicking lymphocyte trafficking to the lymph nodes, we have engineered MECA79-coated microparticles containing an immunosuppressive medication, tacrolimus. Following intravenous administration, MECA79-bearing particles showed marked accumulation in the draining lymph nodes of transplanted animals. Using an allograft heart transplant model, we show that targeted lymph node delivery of microparticles containing tacrolimus can prolong heart allograft survival with negligible changes in tacrolimus serum level. Using MECA79 conjugation, we have demonstrated targeted delivery of tacrolimus to the lymph nodes following systemic administration, with the capacity for immune modulation in vivo.

  3. The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction.

    Science.gov (United States)

    Schwabl, Philipp; Hambruch, Eva; Seeland, Berit A; Hayden, Hubert; Wagner, Michael; Garnys, Lukas; Strobel, Bastian; Schubert, Tim-Lukas; Riedl, Florian; Mitteregger, Dieter; Burnet, Michael; Starlinger, Patrick; Oberhuber, Georg; Deuschle, Ulrich; Rohr-Udilova, Nataliya; Podesser, Bruno K; Peck-Radosavljevic, Markus; Reiberger, Thomas; Kremoser, Claus; Trauner, Michael

    2017-04-01

    Steroidal farnesoid X receptor (FXR) agonists demonstrated potent anti-fibrotic activities and lowered portal hypertension in experimental models. The impact of the novel non-steroidal and selective FXR agonist PX20606 on portal hypertension and fibrosis was explored in this study. In experimental models of non-cirrhotic (partial portal vein ligation, PPVL, 7days) and cirrhotic (carbon tetrachloride, CCl 4 , 14weeks) portal hypertension, PX20606 (PX,10mg/kg) or the steroidal FXR agonist obeticholic acid (OCA,10mg/kg) were gavaged. We then measured portal pressure, intrahepatic vascular resistance, liver fibrosis and bacterial translocation. PX decreased portal pressure in non-cirrhotic PPVL (12.6±1.7 vs. 10.4±1.1mmHg; p=0.020) and cirrhotic CCl 4 (15.2±0.5 vs. 11.8±0.4mmHg; p=0.001) rats. In PPVL animals, we observed less bacterial translocation (-36%; p=0.041), a decrease in lipopolysaccharide binding protein (-30%; p=0.024) and splanchnic tumour necrosis factor α levels (-39%; p=0.044) after PX treatment. In CCl 4 rats, PX decreased fibrotic Sirius Red area (-43%; p=0.005), hepatic hydroxyproline (-66%; pportal pressure (-14%; p=0.041) by restoring endothelial function, 14week PX therapy additionally inhibited sinusoidal remodelling and decreased portal pressure to a greater extent (-22%; p=0.001). In human liver sinusoidal endothelial cells, PX increased eNOS and DDAH expression. The non-steroidal FXR agonist PX20606 ameliorates portal hypertension by reducing liver fibrosis, vascular remodelling and sinusoidal dysfunction. The novel drug PX20606 activates the bile acid receptor FXR and shows beneficial effects in experimental liver cirrhosis: In the liver, it reduces scarring and inflammation, and also widens blood vessels. Thus, PX20606 leads to an improved blood flow through the liver and decreases hypertension of the portal vein. Additionally, PX20606 improves the altered intestinal barrier and decreases bacterial migration from the gut. Copyright

  4. Kruppel-like factor 2 inhibit the angiogenesis of cultured human liver sinusoidal endothelial cells through the ERK1/2 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Xiao-Qing, E-mail: zeng.xiaoqing@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Li, Na, E-mail: Linala.2009@163.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Pan, Du-Yi, E-mail: lasikesmi@hotmail.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Miao, Qing, E-mail: sadsadvenus@163.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Ma, Gui-Fen, E-mail: ma.guifen@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Liu, Yi-Mei, E-mail: liuyimei1988@163.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Tseng, Yu-Jen, E-mail: dianatseng14@gmail.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Li, Feng, E-mail: li.feng2@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Xu, Li-Li, E-mail: xu.lili3@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Chen, Shi-Yao, E-mail: chen.shiyao@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Institute of Endoscopic Research of Zhongshan Hospital, Fudan University, Shanghai (China)

    2015-09-04

    Kruppel-like factor 2 (KLF2) is a crucial anti-angiogenic factor. However, its precise role in hepatic angiogenesis induced by liver sinusoidal endothelial cells (LSECs) remain unclear. This study was aimed to evaluate the effect of KLF2 on angiogenesis of LSECs and to explore the corresponding mechanism. Cultured human LSECs were infected with different lentiviruses to overexpress or suppress KLF2 expression. The CCK-8 assay, transwell migration assay and tube formation test, were used to investigate the roles of KLF2 in the proliferation, migration and vessel tube formation of LSECs, respectively. The expression and phosphorylation of ERK1/2 were detected by western blot. We discovered that the up-regulation of KLF2 expression dramatically inhibited proliferation, migration and tube formation in treated LSECs. Correspondingly, down-regulation of KLF2 expression significantly promoted proliferation, migration and tube formation in treated LSECs. Additionally, KLF2 inhibited the phosphorylation of ERK1/2 pathway, followed by the function of KLF2 in the angiogenesis of LSECs disrupted. In conclusion, KLF2 suppressed the angiogenesis of LSECs through inhibition of cell proliferation, migration, and vessel tube formation. These functions of KLF2 may be mediated through the ERK1/2 signaling pathway. - Highlights: • Overexpression of KLF2 inhibits the proliferation and migration of LSECs. • Overexpression of KLF2 inhibits the angiogenesis of LSECs. • ERK1/2 signaling pathway involved in the anti-angiogenic process of KLF2 on LSECs.

  5. Mathematical Models of the Sinusoidal Screen Family

    Directory of Open Access Journals (Sweden)

    Tajana Koren

    2011-06-01

    Full Text Available In this paper we will define a family of sinusoidal screening elements and explore the possibilities of their application in graphic arts, securities printing and design solutions in photography and typography editing. For this purpose mathematical expressions of sinusoidal families were converted into a Postscript language. The introduction of a random variable results in a countless number of various mutations which cannot be repeated without knowing the programming code itself. The use of the family of screens in protection of securities is thus of great importance. Other possible application of modulated sinusoidal screens is related to the large format color printing. This paper will test the application of sinusoidal screens in vector graphics, pixel graphics and typography. The development of parameters in the sinusoidal screen element algorithms gives new forms defined within screening cells with strict requirements of coverage implementation. Individual solutions include stochastic algorithms, as well as the autonomy of screening forms in regard to multicolor printing channels.

  6. Single ICCII Sinusoidal Oscillators Employing Grounded Capacitors

    Directory of Open Access Journals (Sweden)

    J. W. Horng

    2011-09-01

    Full Text Available Two inverting second-generation current conveyors (ICCII based sinusoidal oscillators are presented. The first sinusoidal oscillator is composed of one ICCII, two grounded capacitors and two resistors. The oscillation condition and oscillation frequency can be orthogonally controllable. The second sinusoidal oscillator is composed of one ICCII, two grounded capacitors and three resistors. The oscillation condition and oscillation frequency can be independently controllable through different resistors.

  7. Noise upon the Sinusoids

    DEFF Research Database (Denmark)

    Jensen, Karl Kristoffer

    2005-01-01

    Sinusoids are used for making harmonic and other sounds. In order to having life in the sounds and adding a wide variety of noises, irregularities are inserted in the frequency and amplitudes. A simple and intuitive noise model is presented, consisting of a low-pass filtered noise, and having...... control for strength and bandwidth. The noise is added on the frequency and amplitudes of the sinusoids, and the resulting irregularity’s (jitter and shimmer) bandwidth is derived. This, together with an overview of investigation methods of the jitter and shimmer results in an analysis of the necessary...

  8. Parametric modeling for damped sinusoids from multiple channels

    DEFF Research Database (Denmark)

    Zhou, Zhenhua; So, Hing Cheung; Christensen, Mads Græsbøll

    2013-01-01

    frequencies and damping factors are then computed with the multi-channel weighted linear prediction method. The estimated sinusoidal poles are then matched to each channel according to the extreme value theory of distribution of random fields. Simulations are performed to show the performance advantages......The problem of parametric modeling for noisy damped sinusoidal signals from multiple channels is addressed. Utilizing the shift invariance property of the signal subspace, the number of distinct sinusoidal poles in the multiple channels is first determined. With the estimated number, the distinct...... of the proposed multi-channel sinusoidal modeling methodology compared with existing methods....

  9. Transplantation of endothelial progenitor cells ameliorates vascular dysfunction and portal hypertension in carbon tetrachloride-induced rat liver cirrhotic model.

    Science.gov (United States)

    Sakamoto, Masaharu; Nakamura, Toru; Torimura, Takuji; Iwamoto, Hideki; Masuda, Hiroshi; Koga, Hironori; Abe, Mitsuhiko; Hashimoto, Osamu; Ueno, Takato; Sata, Michio

    2013-01-01

    In cirrhosis, sinusoidal endothelial cell injury results in increased endothelin-1 (ET-1) and decreased nitric oxide synthase (NOS) activity, leading to portal hypertension. However, the effects of transplanted endothelial progenitor cells (EPCs) on the cirrhotic liver have not yet been clarified. We investigated whether EPC transplantation reduces portal hypertension. Cirrhotic rats were created by the administration of carbon tetrachloride (CCl(4) ) twice weekly for 10 weeks. From week 7, rat bone marrow-derived EPCs were injected via the tail vein in this model once a week for 4 weeks. Endothelial NOS (eNOS), vascular endothelial growth factor (VEGF) and caveolin expressions were examined by Western blots. Hepatic tissue ET-1 was measured by a radioimmunoassay (RIA). Portal venous pressure, mean aortic pressure, and hepatic blood flow were measured. Endothelial progenitor cell transplantation reduced liver fibrosis, α-smooth muscle actin-positive cells, caveolin expression, ET-1 concentration and portal venous pressure. EPC transplantation increased hepatic blood flow, protein levels of eNOS and VEGF. Immunohistochemical analyses of eNOS and isolectin B4 demonstrated that the livers of EPC-transplanted animals had markedly increased vascular density, suggesting reconstitution of sinusoidal blood vessels with endothelium. Transplantation of EPCs ameliorates vascular dysfunction and portal hypertension, suggesting this treatment may provide a new approach in the therapy of portal hypertension with liver cirrhosis. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  10. Defibrotide sodium for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome.

    Science.gov (United States)

    Richardson, Paul G; Triplett, Brandon M; Ho, Vincent T; Chao, Nelson; Dignan, Fiona L; Maglio, Michelle; Mohty, Mohamad

    2018-02-01

    Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is an unpredictable condition associated with endothelial-cell damage due to conditioning for hematopoietic stem-cell transplantation (HSCT) or chemotherapy without HSCT. Mortality in patients with VOD/SOS and multi-organ dysfunction (MOD) may be >80%. Areas covered: Defibrotide is the only approved drug for the treatment of severe hepatic VOD/SOS after HSCT in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction in the United States. Its efficacy in patients with VOD/SOS with MOD post-HSCT was demonstrated in a clinical-trial program that included a historically controlled treatment study, a phase 2 trial, and a large T-IND expanded-access program that also included patients without MOD and who received chemotherapy without HSCT. Expert commentary: Defibrotide appears to protect endothelial cells and restore the thrombolytic-fibrinolytic balance. It addresses a significant clinical need and has demonstrated favorable Day +100 survival and overall adverse-event rates that seem similar to control groups receiving supportive care alone. Currently, defibrotide is under investigation for the prevention of VOD/SOS in high-risk pediatric and adult patients.

  11. Sinusoidal masks for single channel speech separation

    DEFF Research Database (Denmark)

    Mowlaee, Pejman; Christensen, Mads Græsbøll; Jensen, Søren Holdt

    2010-01-01

    In this paper we present a new approach for binary and soft masks used in single-channel speech separation. We present a novel approach called the sinusoidal mask (binary mask and Wiener filter) in a sinusoidal space. Theoretical analysis is presented for the proposed method, and we show...... that the proposed method is able to minimize the target speech distortion while suppressing the crosstalk to a predetermined threshold. It is observed that compared to the STFTbased masks, the proposed sinusoidal masks improve the separation performance in terms of objective measures (SSNR and PESQ) and are mostly...

  12. Amplitude Modulated Sinusoidal Signal Decomposition for Audio Coding

    DEFF Research Database (Denmark)

    Christensen, M. G.; Jacobson, A.; Andersen, S. V.

    2006-01-01

    In this paper, we present a decomposition for sinusoidal coding of audio, based on an amplitude modulation of sinusoids via a linear combination of arbitrary basis vectors. The proposed method, which incorporates a perceptual distortion measure, is based on a relaxation of a nonlinear least......-squares minimization. Rate-distortion curves and listening tests show that, compared to a constant-amplitude sinusoidal coder, the proposed decomposition offers perceptually significant improvements in critical transient signals....

  13. Identification of a carbohydrate-based endothelial ligand for a lymphocyte homing receptor

    International Nuclear Information System (INIS)

    Imai, Y.; Singer, M.S.; Fennie, C.; Lasky, L.A.; Rosen, S.D.

    1991-01-01

    Lymphocyte attachment to high endothelial venules within lymph nodes is mediated by the peripheral lymph node homing receptor (pnHR), originally defined on mouse lymphocytes by the MEL-14 mAb. The pnHR is a calcium-dependent lectin-like receptor, a member of the LEC-CAM family of adhesion proteins. Here, using a soluble recombinant form of the homing receptor, we have identified an endothelial ligand for the pnHR as an ∼ 50-kD sulfated, fucosylated, and sialylated glycoprotein, which we designate Sgp50 (sulfated glycoprotein of 50 kD). Recombinant receptor binding to this lymph node-specific glycoprotein requires calcium and is inhibitable by specific carbohydrates and by MEL-14 mAb. Sialylation of the component is required for binding. Additionally, the glycoprotein is precipitated by MECA-79, an adhesion-blocking mAb reactive with lymph node HEV. A related glycoprotein of ∼ 90 kD (designated as Sgp90) is also identified

  14. HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P1) promotes regeneration and suppresses fibrosis in the liver

    DEFF Research Database (Denmark)

    Ding, Bi-Sen; Liu, Catherine H; Sun, Yue

    2016-01-01

    Regeneration of hepatic sinusoidal vasculature is essential for non-fibrotic liver regrowth and restoration of its metabolic capacity. However, little is known about how this specialized vascular niche is regenerated. Here we show that activation of endothelial sphingosine-1-phosphate receptor-1 ...

  15. Placental extract ameliorates non-alcoholic steatohepatitis (NASH by exerting protective effects on endothelial cells

    Directory of Open Access Journals (Sweden)

    Akihiro Yamauchi

    2017-09-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE. In both the HPE and control groups, fibrosis was seen in regions adjacent to the sinusoids, but the fibrosis was less pronounced in the HPE-treated mice. Levels of TNF-α and MMP9 expression were also significantly reduced in HPE-treated mice, and oxidative stress was suppressed in the perivascular region. In addition, HPE dose-dependently increased survival of cultured endothelial cells exposed to 100 μM H2O2, and it upregulated expression of eNOS and the anti-apoptotic factors bcl-2 and bcl-xL. From these observations, we conclude that HPE ameliorates NASH-associated pathologies by suppressing inflammation, oxidative stress and fibrosis. These beneficially effects of HPE are in part attributable to its protective effects on liver sinusoidal endothelial cells. HPE could thus be an attractive therapeutic candidate with which to suppress progression from simple fatty liver to NASH.

  16. Compressed Domain Packet Loss Concealment of Sinusoidally Coded Speech

    DEFF Research Database (Denmark)

    Rødbro, Christoffer A.; Christensen, Mads Græsbøll; Andersen, Søren Vang

    2003-01-01

    We consider the problem of packet loss concealment for voice over IP (VoIP). The speech signal is compressed at the transmitter using a sinusoidal coding scheme working at 8 kbit/s. At the receiver, packet loss concealment is carried out working directly on the quantized sinusoidal parameters......, based on time-scaling of the packets surrounding the missing ones. Subjective listening tests show promising results indicating the potential of sinusoidal speech coding for VoIP....

  17. Sensorless optimal sinusoidal brushless direct current for hard disk drives

    Science.gov (United States)

    Soh, C. S.; Bi, C.

    2009-04-01

    Initiated by the availability of digital signal processors and emergence of new applications, market demands for permanent magnet synchronous motors have been surging. As its back-emf is sinusoidal, the drive current should also be sinusoidal for reducing the torque ripple. However, in applications like hard disk drives, brushless direct current (BLDC) drive is adopted instead of sinusoidal drive for simplification. The adoption, however, comes at the expense of increased harmonics, losses, torque pulsations, and acoustics. In this paper, we propose a sensorless optimal sinusoidal BLDC drive. First and foremost, the derivation for an optimal sinusoidal drive is presented, and a power angle control scheme is proposed to achieve an optimal sinusoidal BLDC. The scheme maintains linear relationship between the motor speed and drive voltage. In an attempt to execute the sensorless drive, an innovative power angle measurement scheme is devised, which takes advantage of the freewheeling diodes and measures the power angle through the detection of diode voltage drops. The objectives as laid out will be presented and discussed in this paper, supported by derivations, simulations, and experimental results. The proposed scheme is straightforward, brings about the benefits of sensorless sinusoidal drive, negates the need for current sensors by utilizing the freewheeling diodes, and does not incur additional cost.

  18. Sinusoidal Analysis-Synthesis of Audio Using Perceptual Criteria

    Science.gov (United States)

    Painter, Ted; Spanias, Andreas

    2003-12-01

    This paper presents a new method for the selection of sinusoidal components for use in compact representations of narrowband audio. The method consists of ranking and selecting the most perceptually relevant sinusoids. The idea behind the method is to maximize the matching between the auditory excitation pattern associated with the original signal and the corresponding auditory excitation pattern associated with the modeled signal that is being represented by a small set of sinusoidal parameters. The proposed component-selection methodology is shown to outperform the maximum signal-to-mask ratio selection strategy in terms of subjective quality.

  19. Deep-etched sinusoidal polarizing beam splitter grating.

    Science.gov (United States)

    Feng, Jijun; Zhou, Changhe; Cao, Hongchao; Lv, Peng

    2010-04-01

    A sinusoidal-shaped fused-silica grating as a highly efficient polarizing beam splitter (PBS) is investigated based on the simplified modal method. The grating structure depends mainly on the ratio of groove depth to grating period and the ratio of incident wavelength to grating period. These ratios can be used as a guideline for the grating design at different wavelengths. A sinusoidal-groove PBS grating is designed at a wavelength of 1310 nm under Littrow mounting, and the transmitted TM and TE polarized waves are mainly diffracted into the zeroth order and the -1st order, respectively. The grating profile is optimized by using rigorous coupled-wave analysis. The designed PBS grating is highly efficient (>95.98%) over the O-band wavelength range (1260-1360 nm) for both TE and TM polarizations. The sinusoidal grating can exhibit higher diffraction efficiency, larger extinction ratio, and less reflection loss than the rectangular-groove PBS grating. By applying wet etching technology on the rectangular grating, which was manufactured by holographic recording and inductively coupled plasma etching technology, the sinusoidal grating can be approximately fabricated. Experimental results are in agreement with theoretical values.

  20. Variable Dimension Trellis-Coded Quantization of Sinusoidal Parameters

    DEFF Research Database (Denmark)

    Larsen, Morten Holm; Christensen, Mads G.; Jensen, Søren Holdt

    2008-01-01

    In this letter, we propose joint quantization of the parameters of a set of sinusoids based on the theory of trellis-coded quantization. A particular advantage of this approach is that it allows for joint quantization of a variable number of sinusoids, which is particularly relevant in variable...

  1. Estimating Aquifer Properties Using Sinusoidal Pumping Tests

    Science.gov (United States)

    Rasmussen, T. C.; Haborak, K. G.; Young, M. H.

    2001-12-01

    We develop the theoretical and applied framework for using sinusoidal pumping tests to estimate aquifer properties for confined, leaky, and partially penetrating conditions. The framework 1) derives analytical solutions for three boundary conditions suitable for many practical applications, 2) validates the analytical solutions against a finite element model, 3) establishes a protocol for conducting sinusoidal pumping tests, and 4) estimates aquifer hydraulic parameters based on the analytical solutions. The analytical solutions to sinusoidal stimuli in radial coordinates are derived for boundary value problems that are analogous to the Theis (1935) confined aquifer solution, the Hantush and Jacob (1955) leaky aquifer solution, and the Hantush (1964) partially penetrated confined aquifer solution. The analytical solutions compare favorably to a finite-element solution of a simulated flow domain, except in the region immediately adjacent to the pumping well where the implicit assumption of zero borehole radius is violated. The procedure is demonstrated in one unconfined and two confined aquifer units near the General Separations Area at the Savannah River Site, a federal nuclear facility located in South Carolina. Aquifer hydraulic parameters estimated using this framework provide independent confirmation of parameters obtained from conventional aquifer tests. The sinusoidal approach also resulted in the elimination of investigation-derived wastes.

  2. Encryption in Chaotic Systems with Sinusoidal Excitations

    Directory of Open Access Journals (Sweden)

    G. Obregón-Pulido

    2014-01-01

    Full Text Available In this contribution an encryption method using a chaotic oscillator, excited by “n” sinusoidal signals, is presented. The chaotic oscillator is excited by a sum of “n” sinusoidal signals and a message. The objective is to encrypt such a message using the chaotic behavior and transmit it, and, as the chaotic system is perturbed by the sinusoidal signal, the transmission security could be increased due to the effect of such a perturbation. The procedure is based on the regulation theory and consider that the receiver knows the frequencies of the perturbing signal, with this considerations the algorithm estimates the excitation in such a way that the receiver can cancel out the perturbation and all the undesirable dynamics in order to produce only the message. In this way we consider that the security level is increased.

  3. Bottomside sinusoidal irregularities in the equatorial F region

    Science.gov (United States)

    Valladares, C. E.; Hanson, W. B.; Mcclure, J. P.; Cragin, B. L.

    1983-01-01

    By using the Ogo 6 satellite, McClure and Hanson (1973) have discovered sinusoidal irregularities in the equatorial F region ion number density. In the present investigation, a description is provided of the properties of a distinct category of sinusoidal irregularities found in equatorial data from the AE-C and AE-E satellites. The observed scale sizes vary from about 300 m to 3 km in the direction perpendicular to B, overlapping with and extending the range observed by using Ogo 6. Attention is given to low and high resolution data, a comparison with Huancayo ionograms, the confinement of 'bottomside sinusoidal' (BSS) irregularities essentially to the bottomside of the F layer, spectral characteristics, and BSS, scintillation, and ionosonde observations.

  4. HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P1) promotes regeneration and suppresses fibrosis in the liver.

    Science.gov (United States)

    Ding, Bi-Sen; Liu, Catherine H; Sun, Yue; Chen, Yutian; Swendeman, Steven L; Jung, Bongnam; Chavez, Deebly; Cao, Zhongwei; Christoffersen, Christina; Nielsen, Lars Bo; Schwab, Susan R; Rafii, Shahin; Hla, Timothy

    2016-12-22

    Regeneration of hepatic sinusoidal vasculature is essential for non-fibrotic liver regrowth and restoration of its metabolic capacity. However, little is known about how this specialized vascular niche is regenerated. Here we show that activation of endothelial sphingosine-1-phosphate receptor-1 (S1P 1 ) by its natural ligand bound to HDL (HDL-S1P) induces liver regeneration and curtails fibrosis. In mice lacking HDL-S1P, liver regeneration after partial hepatectomy was impeded and associated with aberrant vascular remodeling, thrombosis and peri-sinusoidal fibrosis. Notably, this "maladaptive repair" phenotype was recapitulated in mice that lack S1P 1 in the endothelium. Reciprocally, enhanced plasma levels of HDL-S1P or administration of SEW2871, a pharmacological agonist specific for S1P 1 enhanced regeneration of metabolically functional vasculature and alleviated fibrosis in mouse chronic injury and cholestasis models. This study shows that natural and pharmacological ligands modulate endothelial S1P 1 to stimulate liver regeneration and inhibit fibrosis, suggesting that activation of this pathway may be a novel therapeutic strategy for liver fibrosis.

  5. Adaptive Feedforward Cancellation of Sinusoidal Disturbances in Superconducting RF Cavities

    CERN Document Server

    Kandil, T H; Hartung, W; Khalil, H; Popielarski, J; Vincent, J; York, R C

    2004-01-01

    A control method, known as adaptive feedforward cancellation (AFC) is applied to damp sinusoidal disturbances due to microphonics in superconducting RF (SRF) cavities. AFC provides a method for damping internal, and external sinusoidal disturbances with known frequencies. It is preferred over other schemes because it uses rudimentary information about the frequency response at the disturbance frequencies, without the necessity of knowing an analytic model (transfer function) of the system. It estimates the magnitude and phase of the sinusoidal disturbance inputs and generates a control signal to cancel their effect. AFC, along with a frequency estimation process, is shown to be very successful in the cancellation of sinusoidal signals from different sources. The results of this research may significantly reduce the power requirements and increase the stability for lightly loaded continuous-wave SRF systems.

  6. Sinusoidal oscillators and waveform generators using modern electronic circuit building blocks

    CERN Document Server

    Senani, Raj; Singh, V K; Sharma, R K

    2016-01-01

    This book serves as a single-source reference to sinusoidal oscillators and waveform generators, using classical as well as a variety of modern electronic circuit building blocks. It provides a state-of-the-art review of a large variety of sinusoidal oscillators and waveform generators and includes a catalogue of over 600 configurations of oscillators and waveform generators, describing their relevant design details and salient performance features/limitations. The authors discuss a number of interesting, open research problems and include a comprehensive collection of over 1500 references on oscillators and non-sinusoidal waveform generators/relaxation oscillators. Offers readers a single-source reference to everything connected to sinusoidal oscillators and waveform generators, using classical as well as modern electronic circuit building blocks; Provides a state-of-the-art review of a large variety of sinusoidal oscillators and waveform generators; Includes a catalog of over 600 configurations of oscillato...

  7. Long live the liver: immunohistochemical and stereological study of hepatocytes, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells of male and female rats throughout ageing.

    Science.gov (United States)

    Marcos, Ricardo; Correia-Gomes, Carla

    2016-12-01

    Male/female differences in enzyme activity and gene expression in the liver are known to be attenuated with ageing. Nevertheless, the effect of ageing on liver structure and quantitative cell morphology remains unknown. Male and female Wistar rats aged 2, 6, 12 and 18 months were examined by means of stereological techniques and immunohistochemical tagging of hepatocytes (HEP), liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC) and hepatic stellate cells (HSC) in order to assess the total number and number per gram of these cells throughout life. The mean cell volume of HEP and HSC, the lobular position and the collagen content of the liver were also evaluated with stereological techniques. The number per gram of HSC was similar for both genders and was maintained throughout ageing. The mean volume of HSC was also conserved but differences in the cell body and lobular location were observed. Statistically significant gender differences in HEP were noted in young rats (females had smaller and more binucleated HEP) but were attenuated with ageing. The same occurred for KC and LSEC, since the higher number per gram in young females disappeared in older animals. Liver collagen increased with ageing but only in males. Thus, the numbers of these four cell types are related throughout ageing, with well-defined cell ratios. The shape and lobular position of HSC change with ageing in both males and females. Gender dimorphism in HEP, KC and LSEC of young rat liver disappears with ageing.

  8. A Cell Culture Platform to Maintain Long-term Phenotype of Primary Human Hepatocytes and Endothelial Cells.

    Science.gov (United States)

    Ware, Brenton R; Durham, Mitchell J; Monckton, Chase P; Khetani, Salman R

    2018-03-01

    Modeling interactions between primary human hepatocytes (PHHs) and primary human liver sinusoidal endothelial cells (LSECs) in vitro can help elucidate human-specific mechanisms underlying liver physiology/disease and drug responses; however, existing hepatocyte/endothelial coculture models are suboptimal because of their use of rodent cells, cancerous cell lines, and/or nonliver endothelial cells. Hence, we sought to develop a platform that could maintain the long-term phenotype of PHHs and primary human LSECs. Primary human LSECs or human umbilical vein endothelial cells as the nonliver control were cocultivated with micropatterned PHH colonies (to control homotypic interactions) followed by an assessment of PHH morphology and functions (albumin and urea secretion, and cytochrome P-450 2A6 and 3A4 enzyme activities) over 3 weeks. Endothelial phenotype was assessed via gene expression patterns and scanning electron microscopy to visualize fenestrations. Hepatic responses in PHH/endothelial cocultures were benchmarked against responses in previously developed PHH/3T3-J2 fibroblast cocultures. Finally, PHH/fibroblast/endothelial cell tricultures were created and characterized as described previously. LSECs, but not human umbilical vein endothelial cells, induced PHH albumin secretion for ∼11 days; however, neither endothelial cell type could maintain PHH morphology and functions to the same magnitude/longevity as the fibroblasts. In contrast, both PHHs and endothelial cells displayed stable phenotype for 3 weeks in PHH/fibroblast/endothelial cell tricultures; furthermore, layered tricultures in which PHHs and endothelial cells were separated by a protein gel to mimic the space of Disse displayed similar functional levels as the coplanar tricultures. PHH/fibroblast/endothelial tricultures constitute a robust platform to elucidate reciprocal interactions between PHHs and endothelial cells in physiology, disease, and after drug exposure.

  9. Endothelial Plasmalemma Vesicle Associated Protein regulates the homeostasis of splenic immature B cell and B1 B cells

    Science.gov (United States)

    Elgueta, Raul; Tse, Dan; Deharvengt, Sophie J.; Luciano, Marcus R.; Carriere, Catherine; Noelle, Randolph J.; Stan, Radu V.

    2016-01-01

    Plasmalemma vesicle associated protein (Plvap) is an endothelial protein with roles in endothelial diaphragm formation and maintenance of basal vascular permeability. At the same time Plvap has roles in immunity by facilitating leukocyte diapedesis at inflammatory sites and controlling peripheral lymph node morphogenesis and the entry of soluble antigens into lymph node conduits. Based on its postulated role in diapedesis, we have investigated the role of Plvap in hematopoiesis and show that deletion of Plvap results in a dramatic decrease of IgM+IgDlo B cells in both the spleen and peritoneal cavity. Tissue specific deletion of Plvap demonstrates that the defect is B cell extrinsic, as B cell and pan hematopoietic Plvap deletion has no effect on IgM+IgDlo B cell numbers. Endothelial specific deletion of Plvap in the embryo or at adult stage recapitulates the full Plvap knockout phenotype whereas endothelial specific reconstitution of Plvap under the Chd5 promoter rescues the IgM+IgDlo B cell phenotype. Taken together, these results show that Plvap expression in endothelial cells is important in the maintenance of IgM+ B cells in the spleen and peritoneal cavity. PMID:27742829

  10. CNNs for sinusoidal signal recognition in hearing rehabilitation

    Science.gov (United States)

    Carnimeo, Leonarda; Giaquinto, Antonio

    2003-04-01

    In this paper, a contribution is given to provide a tool to the recognition of sinusoidal signals with a particular reference to the field of pediatric hearing rehabilitation. To this purpose, a synthesis technique previously developed by the authors' is used to design a Cellular Neural Network for an Associative Memory able to compare submitted discrete-time sinusoidal signals with memorized ones. A robustness analysis of the synthesized associative memory is also developed both for noisy inputs and for parameter variations. Simulation results are then reported to illustrate the performances of the designed network.

  11. Cosmology and the Sinusoidal Potential

    Science.gov (United States)

    Bartlett, David F.

    2006-06-01

    The nature of dark matter (and dark energy) remains a mystery. An alternative is being explored by several scientists: changing Newton's (and Einstein's) field equations. The sinusoidal potential is the latest attempt[1]. Here the gravitational law is alternately attractive and repulsive:φ = -GM cos(kor)/r, where λo=2π/ko = 1/20 of the distance from the sun to the center of the Milky Way. The proposal accommodates several structural features of the Milky Way including, paradoxically, its spiral shape and flat rotation curve. The sinusoidal potential's unique feature is strong galactic tidal forces (dg/dr). These may explain why the new planetoid Sedna is securely between the Kuiper Belt and the Oort cloud and why distant comets are more influenced by galactic tides that are in the r, rather than the z-direction.At this meeting I discuss the consequences of the sinusoidal potential for cosmology. Here the alternation of attraction and repulsion gives (i) an open universe, and (ii) gravitational lensing which is usually weak, but occasionally very strong. An open universe is one that, asymptotically, has a size R which varies directly as time t. The open universe conflicts both with the old Einstein-deSitter model (R α t2/3} and the new accelerating one. The evidence for an accelerating universe decisively rejects the Einstein-deSitter model. The rejection of an open (or empty) universe is less secure. This rejection is influenced by the different ways the groups studying the brightness of supernovae use the HST. Surprising additional inputs include neutrino masses, the equivalence principle, LSB galaxies, and "over-luminous" Sn1a. I thank Mostafa Jon Dadras and Patrick Motl for early help and John Cumalat for continual support. [1] D.F. Bartlett, "Analogies between electricity and gravity", Metrologia 41, S115-S124 (2004).

  12. Endothelial Plasmalemma Vesicle-Associated Protein Regulates the Homeostasis of Splenic Immature B Cells and B-1 B Cells.

    Science.gov (United States)

    Elgueta, Raul; Tse, Dan; Deharvengt, Sophie J; Luciano, Marcus R; Carriere, Catherine; Noelle, Randolph J; Stan, Radu V

    2016-11-15

    Plasmalemma vesicle-associated protein (Plvap) is an endothelial protein with roles in endothelial diaphragm formation and maintenance of basal vascular permeability. At the same time, Plvap has roles in immunity by facilitating leukocyte diapedesis at inflammatory sites and controlling peripheral lymph node morphogenesis and the entry of soluble Ags into lymph node conduits. Based on its postulated role in diapedesis, we have investigated the role of Plvap in hematopoiesis and show that deletion of Plvap results in a dramatic decrease of IgM + IgD lo B cells in both the spleen and the peritoneal cavity. Tissue-specific deletion of Plvap demonstrates that the defect is B cell extrinsic, because B cell and pan-hematopoietic Plvap deletion has no effect on IgM + IgD lo B cell numbers. Endothelial-specific deletion of Plvap in the embryo or at adult stage recapitulates the full Plvap knockout phenotype, whereas endothelial-specific reconstitution of Plvap under the Chd5 promoter rescues the IgM + IgD lo B cell phenotype. Taken together, these results show that Plvap expression in endothelial cells is important in the maintenance of IgM + B cells in the spleen and peritoneal cavity. Copyright © 2016 by The American Association of Immunologists, Inc.

  13. Converter for Measurement of non-sinusoidal current peak value

    DEFF Research Database (Denmark)

    Butvin, P.; Nielsen, Otto V; Brauer, Peter

    1997-01-01

    A linear-response toroid with core wound of rapidly quenched soft magnetic metallic ribbon and fitted with two windings is used to enable correct measurement of mean peak value of non-sinusoidal and not noise-free alternating current.......A linear-response toroid with core wound of rapidly quenched soft magnetic metallic ribbon and fitted with two windings is used to enable correct measurement of mean peak value of non-sinusoidal and not noise-free alternating current....

  14. STUDIES ON ENDOTHELIAL REACTIONS

    Science.gov (United States)

    Foot, Nathan Chandler

    1923-01-01

    operative. On the other hand, there may be an increase in the phagocytic activity of the endothelium of the sinusoids which might take up more bacteria under these changed conditions. Several investigators have claimed, recently, that there is an increased activity of the liver endothelium following splenectomy, their experiments being directed chiefly toward determining the fate of the erythrocytes. Pearce (1918) in reporting the effects of experimental splenectomy in dogs, states that there are definite compensatory changes in the lymph nodes, in the form of an increased proliferation of endothelial phagocytes, and that the stellate cells of the liver sinusoids often show a similar compensatory increase in number. In both cases the cells are, apparently, formed in situ rather than transported to the organs. He says: ‘Such findings suggest the development of a compensatory function on the part of the lymph-nodes and possibly the liver,’ and suggests that, in times of stress ‘the stellate cells of the liver thus assume, in part at least, the function of destroying red blood-corpuscles by phagocytosis.’ Incidentally, he presents an excellent discussion of the history and subject of splenectomy. Motohashi (1922) reports a great increase in the hemophagic power of the hepatic endothelium and an increase in the number of endothelial elements, after some 45 days following splenectomy in rabbits. Nishikawa and Takagi (1922) have observed similar phenomena with white rats, the Kupffer cells taking up erythrocytes in large numbers in splenectomized animals, whereas controls never show similar propensities on the part of these cells. It may be that different substances cause different reactions on the part of the hepatic endothelium. Contributory Experiment.—A side experiment was performed with five rabbits, two splenectomized and three controls, into which uniform doses of pneumococci were injected intravenously. They all died of septicemia after a few days. The results

  15. Computationally Efficient Amplitude Modulated Sinusoidal Audio Coding using Frequency-Domain Linear Prediction

    DEFF Research Database (Denmark)

    Christensen, M. G.; Jensen, Søren Holdt

    2006-01-01

    A method for amplitude modulated sinusoidal audio coding is presented that has low complexity and low delay. This is based on a subband processing system, where, in each subband, the signal is modeled as an amplitude modulated sum of sinusoids. The envelopes are estimated using frequency......-domain linear prediction and the prediction coefficients are quantized. As a proof of concept, we evaluate different configurations in a subjective listening test, and this shows that the proposed method offers significant improvements in sinusoidal coding. Furthermore, the properties of the frequency...

  16. 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

  17. Full-Band Quasi-Harmonic Analysis and Synthesis of Musical Instrument Sounds with Adaptive Sinusoids

    Directory of Open Access Journals (Sweden)

    Marcelo Caetano

    2016-05-01

    Full Text Available Sinusoids are widely used to represent the oscillatory modes of musical instrument sounds in both analysis and synthesis. However, musical instrument sounds feature transients and instrumental noise that are poorly modeled with quasi-stationary sinusoids, requiring spectral decomposition and further dedicated modeling. In this work, we propose a full-band representation that fits sinusoids across the entire spectrum. We use the extended adaptive Quasi-Harmonic Model (eaQHM to iteratively estimate amplitude- and frequency-modulated (AM–FM sinusoids able to capture challenging features such as sharp attacks, transients, and instrumental noise. We use the signal-to-reconstruction-error ratio (SRER as the objective measure for the analysis and synthesis of 89 musical instrument sounds from different instrumental families. We compare against quasi-stationary sinusoids and exponentially damped sinusoids. First, we show that the SRER increases with adaptation in eaQHM. Then, we show that full-band modeling with eaQHM captures partials at the higher frequency end of the spectrum that are neglected by spectral decomposition. Finally, we demonstrate that a frame size equal to three periods of the fundamental frequency results in the highest SRER with AM–FM sinusoids from eaQHM. A listening test confirmed that the musical instrument sounds resynthesized from full-band analysis with eaQHM are virtually perceptually indistinguishable from the original recordings.

  18. Inverse modelling and pulsating torque minimization of salient pole non-sinusoidal synchronous machines

    Energy Technology Data Exchange (ETDEWEB)

    Ait-gougam, Y.; Ibtiouen, R.; Touhami, O. [Laboratoire de Recherche en Electrotechnique, Ecole Nationale Polytechnique, BP 182, El-Harrach 16200 (Algeria); Louis, J.-P.; Gabsi, M. [Systemes et Applications des Technologies de l' Information et de l' Energie (SATIE), CNRS UMR 8029, Ecole Normale Superieure de Cachan, 61 Avenue du President Wilson, 94235 Cachan Cedex (France)

    2008-01-15

    Sinusoidal motor's mathematical models are usually obtained using classical d-q transformation in the case of salient pole synchronous motors having sinusoidal field distribution. In this paper, a new inverse modelling for synchronous motors is presented. This modelling is derived from the properties of constant torque curves in the Concordia's reference frame. It takes into account the non-sinusoidal field distribution; EMF, self and mutual inductances having non-sinusoidal variations with respect to the angular rotor position. Both copper losses and torque ripples are minimized by adapted currents waveforms calculated from this model. Experimental evaluation was carried out on a DSP-controlled PMSM drive platform. Test results obtained demonstrate the effectiveness of the proposed method in reducing torque ripple. (author)

  19. Electronically Tunable Quadrature Sinusoidal Oscillator with Equal Output Amplitudes during Frequency Tuning Process

    Directory of Open Access Journals (Sweden)

    Den Satipar

    2017-01-01

    Full Text Available A new configuration of voltage-mode quadrature sinusoidal oscillator is proposed. The proposed oscillator employs two voltage differencing current conveyors (VDCCs, two resistors, and two grounded capacitors. In this design, the use of multiple/dual output terminal active building block is not required. The tuning of frequency of oscillation (FO can be done electronically by adjusting the bias current of active device without affecting condition of oscillation (CO. The electronic tuning can be done by controlling the bias current using a digital circuit. The amplitude of two sinusoidal outputs is equal when the frequency of oscillation is tuned. This makes the sinusoidal output voltages meet good total harmonic distortions (THD. Moreover, the proposed circuit can provide the sinusoidal output current with high impedance which is connected to external load or to another circuit without the use of buffer device. To confirm that the oscillator can generate the quadrature sinusoidal output signal, the experimental results using VDCC constructed from commercially available ICs are also included. The experimental results agree well with theoretical anticipation.

  20. A Perceptual Model for Sinusoidal Audio Coding Based on Spectral Integration

    Directory of Open Access Journals (Sweden)

    Jensen Søren Holdt

    2005-01-01

    Full Text Available Psychoacoustical models have been used extensively within audio coding applications over the past decades. Recently, parametric coding techniques have been applied to general audio and this has created the need for a psychoacoustical model that is specifically suited for sinusoidal modelling of audio signals. In this paper, we present a new perceptual model that predicts masked thresholds for sinusoidal distortions. The model relies on signal detection theory and incorporates more recent insights about spectral and temporal integration in auditory masking. As a consequence, the model is able to predict the distortion detectability. In fact, the distortion detectability defines a (perceptually relevant norm on the underlying signal space which is beneficial for optimisation algorithms such as rate-distortion optimisation or linear predictive coding. We evaluate the merits of the model by combining it with a sinusoidal extraction method and compare the results with those obtained with the ISO MPEG-1 Layer I-II recommended model. Listening tests show a clear preference for the new model. More specifically, the model presented here leads to a reduction of more than 20% in terms of number of sinusoids needed to represent signals at a given quality level.

  1. Unidirectional Motion of Vehicle on Sinusoidal Path

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 17; Issue 4. Unidirectional Motion of Vehicle on Sinusoidal Path: Can it Cause Illusory Forward and Backward Motion? Anuj Bhatnagar. Classroom Volume 17 Issue 4 April 2012 pp 387-392 ...

  2. Crashworthiness Analysis and Evaluation of Fuselage Section with Sub-floor Composite Sinusoidal Specimens

    Directory of Open Access Journals (Sweden)

    H.L. Mou

    Full Text Available Abstract Crashworthiness is one of the main concerns in civil aviation safety particularly with regard to the increasing ratio of carbon fiber reinforced plastic (CFRP in aircraft primary structures. In order to generate dates for model validations, the mechanical properties of T700/3234 were obtained by material performance tests, and energy-absorbing results were gained by quasi-static crushing tests of composite sinusoidal specimens. The correctness of composite material model and single-layer finite element model of composite sinusoidal specimens were verified based on the simulation results and test results that were in good agreement. A typical civil aircraft fuselage section with composite sinusoidal specimens under cargo floor was suggested. The crashworthiness of finite element model of fuselage section was assessed by simulating the vertical drop test subjected to 7 m/s impact velocity, and the influences of different thickness of sub-floor composite sinusoidal specimens on crashworthiness of fuselage section were also analyzed. The simulation results show that the established finite element model can accurately simulate the crushing process of composite sinusoidal specimens; the failure process of fuselage section is more stable, and the safety of occupants can be effectively improved because of the smaller peak accelerations that was limited to human tolerance, a critical thickness of sub-floor composite sinusoidal specimens can restrict the magnitude of acceleration peaks, which has certain reference values for enhancing crashworthiness capabilities of fuselage section and improving the survivability of passengers.

  3. Walking strategies of visually impaired people on trapezoidal- and sinusoidal-section tactile groundsurface indicators.

    Science.gov (United States)

    Ranavolo, A; Conte, C; Iavicoli, S; Serrao, M; Silvetti, A; Sandrini, G; Pierelli, F; Draicchio, F

    2011-03-01

    The visual system in walking serves to perceive feedback or feed-forward signals. Therefore, visually impaired persons (VIP) have biased motor control mechanisms. The use of leading indicators (LIs) and long canes helps to improve their walking efficiency. The aims of this study were to compare the walking efficiency of VIP on trapezoidal- and sinusoidal-section LIs using an optoelectronic motion analysis system. VIP displayed a significantly longer stance phase, a shorter swing phase and shorter step and stride lengths when they walked on the sinusoidal LI than when they walked on the trapezoidal LI. Compared with the trapezoidal LI, VIP walking on the sinusoidal LI displayed significantly lower joint ranges of motion. The centre of mass lateral displacement was wider for VIP walking on the sinusoidal LI than on the trapezoidal LI. Some significant differences were also found in sighted persons walking on both LIs. In conclusion, the trapezoidal shape enabled visually impaired subjects to walk more efficiently, whereas the sinusoidal shape caused dynamic balance problems. STATEMENT OF RELEVANCE: These findings suggest that VIP can walk more efficiently, with a lower risk of falls, on trapezoidal-section than on sinusoidal-section LIs. These results should be considered when choosing the most appropriate ground tactile surface indicators for widespread use.

  4. The sinusoidal lining cells in "normal" human liver. A scanning electron microscopic investigation

    DEFF Research Database (Denmark)

    Horn, T; Henriksen, Jens Henrik Sahl; Christoffersen, P

    1986-01-01

    The scanning electron microscopic was used to study the fenestrations of human liver sinusoids. Thirteen biopsies, where light microscopy and transmission electron microscopy revealed normal sinusoidal architecture, were investigated. The number of fenestrae was calculated in acinar zone 3...

  5. Investigation of Calibrating Force Transducer Using Sinusoidal Force

    International Nuclear Information System (INIS)

    Zhang Li; Wang Yu; Zhang Lizhe

    2010-01-01

    Sinusoidal force calibration method was studied several years before at Physikalisch-Technische Bundesanstalt (PTB). A similar dynamic force calibration system is developed at Changcheng Institute of Metrology and Measurement (CIMM). It uses electro-dynamic shakers to generate dynamic force in the range from 1 N to 20 kN, and heterodyne laser interferometers are used for acceleration measurement. The force transducer to be calibrated is mounted on the shaker, and a mass block is screwed on the top of force transducer, the sinusoidal forces realized by accelerated load masses are traceable to acceleration and mass according to the force definition. The methods of determining Spatial-dependent acceleration on mass block and measuring the end mass of force transducer in dynamic force calibration are discussed in this paper.

  6. Some New Results on the Estimation of Sinusoids in Noise

    DEFF Research Database (Denmark)

    Nielsen, Jesper Kjær

    2012-01-01

    This thesis is concerned with the problem of estimating sinusoidal parameters from noisy observations. This field of research is applicable to solving problems in a large number of areas such as music and speech processing, electrocardiography, seismology, radar and sonar processing, astronomy....... Third, an efficient algorithm for performing inference and interpolation in a dynamic sinusoidal model is proposed. This method is applied to packet-loss concealment, and listening tests indicate that the proposed algorithm can be used for this purpose. Fourth, the Capon filtering method for amplitude...

  7. An Adaptive Filter for the Removal of Drifting Sinusoidal Noise Without a Reference.

    Science.gov (United States)

    Kelly, John W; Siewiorek, Daniel P; Smailagic, Asim; Wang, Wei

    2016-01-01

    This paper presents a method for filtering sinusoidal noise with a variable bandwidth filter that is capable of tracking a sinusoid's drifting frequency. The method, which is based on the adaptive noise canceling (ANC) technique, will be referred to here as the adaptive sinusoid canceler (ASC). The ASC eliminates sinusoidal contamination by tracking its frequency and achieving a narrower bandwidth than typical notch filters. The detected frequency is used to digitally generate an internal reference instead of relying on an external one as ANC filters typically do. The filter's bandwidth adjusts to achieve faster and more accurate convergence. In this paper, the focus of the discussion and the data is physiological signals, specifically electrocorticographic (ECoG) neural data contaminated with power line noise, but the presented technique could be applicable to other recordings as well. On simulated data, the ASC was able to reliably track the noise's frequency, properly adjust its bandwidth, and outperform comparative methods including standard notch filters and an adaptive line enhancer. These results were reinforced by visual results obtained from real ECoG data. The ASC showed that it could be an effective method for increasing signal to noise ratio in the presence of drifting sinusoidal noise, which is of significant interest for biomedical applications.

  8. Influence of sinusoidal flow on the thermal and hydraulic performance of microchannel heat sink

    International Nuclear Information System (INIS)

    Om, N I; Gunnasegaran, P; Rajasegaran, S

    2013-01-01

    In this paper, the effect of sinusoidal flow on the thermal and hydraulic performance of microchannel heat sink (MCHS) is numerically investigated. This investigation covers Reynolds number in the range of 100 ≤ Re ≤ 1000 and pure water is used as a working fluid. The three-dimensional steady, laminar flow and heat transfer governing equations are solved using finite volume method (FVM). The water flow field and heat transfer performance inside the sinusoidal microchannels is simulated and the results are compared with the straight microchannels. The effect of using sinusoidal microchannels on temperature distribution, Nusselt number, friction factor and thermal resistance is presented in this paper. It is found that with same rectangular cross-section, sinusoidal microchannels have a better heat transfer performance compared to the straight microchannels.

  9. Involvement of the lysophosphatidic acid-generating enzyme autotaxin in lymphocyte-endothelial cell interactions.

    Science.gov (United States)

    Nakasaki, Tae; Tanaka, Toshiyuki; Okudaira, Shinichi; Hirosawa, Michi; Umemoto, Eiji; Otani, Kazuhiro; Jin, Soojung; Bai, Zhongbin; Hayasaka, Haruko; Fukui, Yoshinori; Aozasa, Katsuyuki; Fujita, Naoya; Tsuruo, Takashi; Ozono, Keiichi; Aoki, Junken; Miyasaka, Masayuki

    2008-11-01

    Autotaxin (ATX) is a secreted protein with lysophospholipase D activity that generates lysophosphatidic acid (LPA) from lysophosphatidylcholine. Here we report that functional ATX is selectively expressed in high endothelial venules (HEVs) of both lymph nodes and Peyer's patches. ATX expression was developmentally regulated and coincided with lymphocyte recruitment to the lymph nodes. In adults, ATX expression was independent of HEV-expressed chemokines such as CCL21 and CXCL13, innate immunity signals including those via TLR4 or MyD88, and of the extent of lymphocyte trafficking across the HEVs. ATX expression was induced in venules at sites of chronic inflammation. Receptors for the ATX enzyme product LPA were constitutively expressed in HEV endothelial cells (ECs). In vitro, LPA induced strong morphological changes in HEV ECs. Forced ATX expression caused cultured ECs to respond to lysophosphatidylcholine, up-regulating lymphocyte binding to the ECs in a LPA receptor-dependent manner under both static and flow conditions. Although in vivo depletion of circulating ATX did not affect lymphocyte trafficking into the lymph nodes, we surmise, based on the above data, that ATX expressed by HEVs acts on HEVs in situ to facilitate lymphocyte binding to ECs and that ATX in the general circulation does not play a major role in this process. Tissue-specific inactivation of ATX will verify this hypothesis in future studies of its mechanism of action.

  10. Model selection and comparison for independents sinusoids

    DEFF Research Database (Denmark)

    Nielsen, Jesper Kjær; Christensen, Mads Græsbøll; Jensen, Søren Holdt

    2014-01-01

    In the signal processing literature, many methods have been proposed for estimating the number of sinusoidal basis functions from a noisy data set. The most popular method is the asymptotic MAP criterion, which is sometimes also referred to as the BIC. In this paper, we extend and improve this me...

  11. Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

    Directory of Open Access Journals (Sweden)

    Jerzy Laudański

    2011-04-01

    Full Text Available The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69. Positive LVI was significantly correlated with lymph node metastasis (p < 0.001, tumor size (p < 0.001, histological grading (p = 0.017, tumor depth (p = 0.001, and stage (p < 0.001. Multivariate logistic analysis identified LVI (p = 0.036 as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04 and overall survival (p = 0.032 in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 90–97

  12. New Canonic Active RC Sinusoidal Oscillator Circuits Using Second-Generation Current Conveyors with Application as a Wide-Frequency Digitally Controlled Sinusoid Generator

    Directory of Open Access Journals (Sweden)

    Abhirup Lahiri

    2011-01-01

    Full Text Available This paper reports two new circuit topologies using second-generation current conveyors (CCIIs for realizing variable frequency sinusoidal oscillators with minimum passive components. The proposed topologies in this paper provide new realizations of resistance-controlled and capacitor-controlled variable frequency oscillators (VFOs using only four passive components. The first topology employs three CCIIs, while the second topology employs two CCIIs. The second topology provides an advantageous feature of frequency tuning through two grounded elements. Application of the proposed circuits as a wide-frequency range digitally controlled sinusoid generator is exhibited wherein the digital frequency control has been enabled by replacing both the capacitors by two identical variable binary capacitor banks tunable by means of the same binary code. SPICE simulations of the CMOS implementation of the oscillators using 0.35 μm TSMC CMOS technology parameters and bipolar implementation of the oscillators using process parameters for NR200N-2X (NPN and PR200N-2X (PNP of bipolar arrays ALA400-CBIC-R have validated their workability. One of the oscillators (with CMOS implementation is exemplified as a digitally controlled sinusoid generator with frequency generation from 25 kHz to 6.36 MHz, achieved by switching capacitors and with power consumption of 7 mW in the entire operating frequency range.

  13. Light scattering by sinusoidal surfaces: illumination windows and harmonics in standards.

    Science.gov (United States)

    Marx, E; Lettieri, T R; Vorburger, T V

    1995-03-01

    Sinusoidal surfaces can be used as material standards to help calibrate instruments that measure the angular distribution of the intensity of light scattered by arbitrary surfaces, because the power in the diffraction peaks varies over several orders of magnitude. The calculated power in the higher-order diffraction peaks from sinusoidal surfaces expressed in terms of Bessel functions is much smaller than the values determined from angular distributions that are measured or computed from measured profiles, both of which are determined mainly by the harmonic contents of the profile. The finite size of the illuminated area, represented by an illumination window, gives rise to a background that is much larger than the calculated power in the higher-order peaks. For a rectangular window of a size equal to an even number of periods of the sinusoid, a computation of the power distribution produces minima at or near the location of the diffraction angles for higher-order diffraction angles.

  14. DISPLAY OF PIXEL LOSS AND REPLICATION IN REPROJECTING RASTER DATA FROM THE SINUSOIDAL PROJECTION

    Science.gov (United States)

    Recent studies show the sinusoidal projection to be a superior planar projection for representing global raster datasets. This study uses the sinusoidal projection as a basis for evaluating pixel loss and replication in eight other planar map projections. The percent of pixels ...

  15. Dynamic Characteristics of Ventilatory and Gas Exchange during Sinusoidal Walking in Humans.

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Fukuoka

    Full Text Available Our present study investigated whether the ventilatory and gas exchange responses show different dynamics in response to sinusoidal change in cycle work rate or walking speed even if the metabolic demand was equivalent in both types of exercise. Locomotive parameters (stride length and step frequency, breath-by-breath ventilation (V̇E and gas exchange (CO2 output (V̇CO2 and O2 uptake (V̇O2 responses were measured in 10 healthy young participants. The speed of the treadmill was sinusoidally changed between 3 km·h-1 and 6 km·h-1 with various periods (from 10 to 1 min. The amplitude of locomotive parameters against sinusoidal variation showed a constant gain with a small phase shift, being independent of the oscillation periods. In marked contrast, when the periods of the speed oscillations were shortened, the amplitude of V̇E decreased sharply whereas the phase shift of V̇E increased. In comparing walking and cycling at the equivalent metabolic demand, the amplitude of V̇E during sinusoidal walking (SW was significantly greater than that during sinusoidal cycling (SC, and the phase shift became smaller. The steeper slope of linear regression for the V̇E amplitude ratio to V̇CO2 amplitude ratio was observed during SW than SC. These findings suggested that the greater amplitude and smaller phase shift of ventilatory dynamics were not equivalent between SW and SC even if the metabolic demand was equivalent between both exercises. Such phenomenon would be derived from central command in proportion to locomotor muscle recruitment (feedforward and muscle afferent feedback.

  16. Endothelial RIG-I activation impairs endothelial function

    International Nuclear Information System (INIS)

    Asdonk, Tobias; Motz, Inga; Werner, Nikos; Coch, Christoph; Barchet, Winfried; Hartmann, Gunther; Nickenig, Georg; Zimmer, Sebastian

    2012-01-01

    Highlights: ► RIG-I activation impairs endothelial function in vivo. ► RIG-I activation alters HCAEC biology in vitro. ► EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 μg of the RIG-ligand 3pRNA (RNA with triphosphate at the 5′end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  17. Unified design of sinusoidal-groove fused-silica grating.

    Science.gov (United States)

    Feng, Jijun; Zhou, Changhe; Cao, Hongchao; Lu, Peng

    2010-10-20

    A general design rule of deep-etched subwavelength sinusoidal-groove fused-silica grating as a highly efficient polarization-independent or polarization-selective device is studied based on the simplified modal method, which shows that the device structure depends little on the incident wavelength, but mainly on the ratio of groove depth to incident wavelength and the ratio of wavelength to grating period. These two ratios could be used as the design guidelines for wavelength-independent structure from deep ultraviolet to far infrared. The optimized grating profile with a different function as a polarizing beam splitter, a polarization-independent two-port beam splitter, or a polarization-independent grating with high efficiency of -1st order is obtained at a wavelength of 1064 nm, and verified by using the rigorous coupled-wave analysis. The performance of the sinusoidal grating is better than a conventional rectangular one, which could be useful for practical applications.

  18. Riding the Ferris Wheel: A Sinusoidal Model

    Science.gov (United States)

    Mittag, Kathleen Cage; Taylor, Sharon E.

    2011-01-01

    When thinking of models for sinusoidal waves, examples such as tides of the ocean, daily temperatures for one year in your town, light and sound waves, and certain types of motion are used. Many textbooks [1, p. 222] also present a "Ferris wheel description problem" for students to work. This activity takes the Ferris wheel problem out of the…

  19. Endothelial RIG-I activation impairs endothelial function

    Energy Technology Data Exchange (ETDEWEB)

    Asdonk, Tobias, E-mail: tobias.asdonk@ukb.uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Motz, Inga; Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Coch, Christoph; Barchet, Winfried; Hartmann, Gunther [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg; Zimmer, Sebastian [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  20. Comparison between the water activation effects by pulsed and sinusoidal helium plasma jets

    Science.gov (United States)

    Xu, Han; Liu, Dingxin; Xia, Wenjie; Chen, Chen; Wang, Weitao; Liu, Zhijie; Wang, Xiaohua; Kong, Michael G.

    2018-01-01

    Comparisons between pulsed and sinusoidal plasma jets have been extensively reported for the discharge characteristics and gaseous reactive species, but rarely for the aqueous reactive species in water solutions treated by the two types of plasma jets. This motivates us to compare the concentrations of aqueous reactive species induced by a pulsed and a sinusoidal plasma jet, since it is widely reported that these aqueous reactive species play a crucial role in various plasma biomedical applications. Experimental results show that the aqueous H2O2, OH/O2-, and O2-/ONOO- induced by the pulsed plasma jet have higher concentrations, and the proportional difference increases with the discharge power. However, the emission intensities of OH(A) and O(3p5P) are higher for the sinusoidal plasma jet, which may be attributed to its higher gas temperature since more water vapor could participate in the plasma. In addition, the efficiency of bacterial inactivation induced by the pulsed plasma jet is higher than that for the sinusoidal plasma jet, in accordance with the concentration relation of aqueous reactive species for the two types of plasma jets.

  1. Trans-sinusoidal maxillary distraction in three cleft patients.

    NARCIS (Netherlands)

    Wenghoefer, M.H.; Martini, M.; Nadjmi, N.; Schutyser, F.A.C.; Jagtman, A.K.; Bergé, S.J.

    2006-01-01

    The trans-sinusoidal maxillary distractor (TS-MD) was used to achieve maxillary advancement in three patients with repaired cleft lip and palate. After preoperative computer-aided planning of the distraction vectors, each TS-MD was bent on a stereolithographic model of the maxilla of the patient.

  2. Reproducible isolation of lymph node stromal cells reveals site-dependent differences in fibroblastic reticular cells.

    Science.gov (United States)

    Fletcher, Anne L; Malhotra, Deepali; Acton, Sophie E; Lukacs-Kornek, Veronika; Bellemare-Pelletier, Angelique; Curry, Mark; Armant, Myriam; Turley, Shannon J

    2011-01-01

    Within lymph nodes, non-hematopoietic stromal cells organize and interact with leukocytes in an immunologically important manner. In addition to organizing T and B cell segregation and expressing lymphocyte survival factors, several recent studies have shown that lymph node stromal cells shape the naïve T cell repertoire, expressing self-antigens which delete self-reactive T cells in a unique and non-redundant fashion. A fundamental role in peripheral tolerance, in addition to an otherwise extensive functional portfolio, necessitates closer study of lymph node stromal cell subsets using modern immunological techniques; however this has not routinely been possible in the field, due to difficulties reproducibly isolating these rare subsets. Techniques were therefore developed for successful ex vivo and in vitro manipulation and characterization of lymph node stroma. Here we discuss and validate these techniques in mice and humans, and apply them to address several unanswered questions regarding lymph node composition. We explored the steady-state stromal composition of lymph nodes isolated from mice and humans, and found that marginal reticular cells and lymphatic endothelial cells required lymphocytes for their normal maturation in mice. We also report alterations in the proportion and number of fibroblastic reticular cells (FRCs) between skin-draining and mesenteric lymph nodes. Similarly, transcriptional profiling of FRCs revealed changes in cytokine production from these sites. Together, these methods permit highly reproducible stromal cell isolation, sorting, and culture.

  3. Evoked responses to sinusoidally modulated sound in unanaesthetized dogs

    NARCIS (Netherlands)

    Tielen, A.M.; Kamp, A.; Lopes da Silva, F.H.; Reneau, J.P.; Storm van Leeuwen, W.

    1. 1. Responses evoked by sinusoidally amplitude-modulated sound in unanaesthetized dogs have been recorded from inferior colliculus and from auditory cortex structures by means of chronically indwelling stainless steel wire electrodes. 2. 2. Harmonic analysis of the average responses demonstrated

  4. Optimization for sinusoidal profiles in surface relief gratings ...

    Indian Academy of Sciences (India)

    2014-02-07

    Feb 7, 2014 ... filometry [7–9] and monitoring of surface self-diffusion of solids under ultrahigh vacuum conditions [10]. In the present work, recording parameters, i.e. exposure time and deve- lopment time for fabrication of such holographic gratings have been optimized to obtain nearly perfect sinusoidal profiles in the ...

  5. Asymptotic Theory of the Least Squares Estimators of Sinusoidal Signal

    National Research Council Canada - National Science Library

    Kundu, Debasis

    1997-01-01

    ... normality are derived for the sinusoidal signal under the assumption of normal error (Kundu; 1993) and under the assumptions of independent and identically distributed random variables in Kundu and Mitra...

  6. Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients.

    Science.gov (United States)

    Ko, Jennifer S; Prieto, Victor G; Elson, Paul J; Vilain, Ricardo E; Pulitzer, Melissa P; Scolyer, Richard A; Reynolds, Jordan P; Piliang, Melissa P; Ernstoff, Marc S; Gastman, Brian R; Billings, Steven D

    2016-02-01

    Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, PMerkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications.

  7. Dynamic performance of maximum power point tracking circuits using sinusoidal extremum seeking control for photovoltaic generation

    Science.gov (United States)

    Leyva, R.; Artillan, P.; Cabal, C.; Estibals, B.; Alonso, C.

    2011-04-01

    The article studies the dynamic performance of a family of maximum power point tracking circuits used for photovoltaic generation. It revisits the sinusoidal extremum seeking control (ESC) technique which can be considered as a particular subgroup of the Perturb and Observe algorithms. The sinusoidal ESC technique consists of adding a small sinusoidal disturbance to the input and processing the perturbed output to drive the operating point at its maximum. The output processing involves a synchronous multiplication and a filtering stage. The filter instance determines the dynamic performance of the MPPT based on sinusoidal ESC principle. The approach uses the well-known root-locus method to give insight about damping degree and settlement time of maximum-seeking waveforms. This article shows the transient waveforms in three different filter instances to illustrate the approach. Finally, an experimental prototype corroborates the dynamic analysis.

  8. Estimation of the second heart sound split using windowed sinusoidal models

    DEFF Research Database (Denmark)

    Sæderup, Rasmus Gundorf; Hoang, Poul; Winther, Simon

    2018-01-01

    to the potential overlap between A2 and P2. In this paper, a model-based approach is proposed where both A2 and P2 are modeled as windowed sinusoids with their sum forming the S2 signal. Estimation of the model parameters and the S2 split form a non-convex optimization problem, where a local minimum is obtained...... using a sequential optimization procedure. First, the window parameters are found as the solution to a regularized least squares problem. Then, the frequencies and phases of the sinusoids are found by locating the maximal peaks of the heart signals’ frequency magnitudes, and using the corresponding...

  9. Sinusoidal modulation analysis for optical system MTF measurements.

    Science.gov (United States)

    Boone, J M; Yu, T; Seibert, J A

    1996-12-01

    The modulation transfer function (MTF) is a commonly used metric for defining the spatial resolution characteristics of imaging systems. While the MTF is defined in terms of how an imaging system demodulates the amplitude of a sinusoidal input, this approach has not been in general use to measure MTFs in the medical imaging community because producing sinusoidal x-ray patterns is technically difficult. However, for optical systems such as charge coupled devices (CCD), which are rapidly becoming a part of many medical digital imaging systems, the direct measurement of modulation at discrete spatial frequencies using a sinusoidal test pattern is practical. A commercially available optical test pattern containing spatial frequencies ranging from 0.375 cycles/mm to 80 cycles/mm was sued to determine the MRF of a CCD-based optical system. These results were compared with the angulated slit method of Fujita [H. Fujita, D. Tsia, T. Itoh, K. Doi, J. Morishita, K. Ueda, and A. Ohtsuka, "A simple method for determining the modulation transfer function in digital radiography," IEEE Trans. Medical Imaging 11, 34-39 (1992)]. The use of a semiautomated profiled iterated reconstruction technique (PIRT) is introduced, where the shift factor between successive pixel rows (due to angulation) is optimized iteratively by least-squares error analysis rather than by hand measurement of the slit angle. PIRT was used to find the slit angle for the Fujita technique and to find the sine-pattern angle for the sine-pattern technique. Computer simulation of PIRT for the case of the slit image (a line spread function) demonstrated that it produced a more accurate angle determination than "hand" measurement, and there is a significant difference between the errors in the two techniques (Wilcoxon Signed Rank Test, p < 0.001). The sine-pattern method and the Fujita slit method produced comparable MTF curves for the CCD camera evaluated.

  10. Ectopic expression of the calcium-binding protein parvalbumin in mouse liver endothelial cells

    DEFF Research Database (Denmark)

    Castillo, M B; Berchtold, M W; Rülicke, T

    1997-01-01

    To elucidate the physiological role of the Ca2+ binding protein parvalbumin, we have generated transgenic mice carrying the full-length complementary DNA (cDNA) of rat parvalbumin under the control of the heavy-metal inducible metallothionein IIA promoter. Immunohistochemical and biochemical...... methods have been used to detect the presence of ectopic parvalbumin expression in different tissues. Here we show the expression of parvalbumin in endothelial cells lining the liver sinusoids in situ and after isolation in vitro. The hemodynamic effects of endothelin 1, a peptide hormone mediating potent...... vasoconstriction via calcium signalling, were investigated in the mouse liver perfused in situ. Vasoconstriction, thought to be mediated by the Ito cell, was not affected in the transgenic animals, whereas microvascular exchange, probed with the multiple indicator dilution technique, was markedly decreased...

  11. Increased sinusoidal volume and solute extraction during retrograde liver perfusion

    International Nuclear Information System (INIS)

    Bass, N.M.; Manning, J.A.; Weisiger, R.A.

    1989-01-01

    Retrograde isolated liver perfusion has been used to probe acinar functional heterogeneity, but the hemodynamic effects of backward flow have not been characterized. In this study, extraction of a long-chain fatty acid derivative, 12-N-methyl-7-nitrobenzo-2-oxa-1,3-diazol-amino stearate (12-NBDS), was greater during retrograde than during anterograde perfusion of isolated rat liver. To determine whether hemodynamic differences between anterograde and retrograde perfused livers could account for this finding, the hepatic extracellular space was measured for both directions of flow by means of [ 14 C]sucrose washout during perfusion as well as by direct measurement of [ 14 C]sucrose entrapped during perfusion. A three- to fourfold enlargement of the total hepatic extracellular space was found during retrograde perfusion by both approaches. Examination of perfusion-fixed livers by light microscopy and morphometry revealed that marked distension of the sinusoids occurred during retrograde perfusion and that this accounts for the observed increase in the [ 14 C]sucrose space. These findings support the hypothesis that maximum resistance to perfusate flow in the isolated perfused rat liver is located at the presinusoidal level. In addition, increased transit time of perfusate through the liver and greater sinusoidal surface area resulting from sinusoidal distension may account for the higher extraction of 12-NBDS and possibly other compounds by retrograde perfused liver

  12. BPM Offset Determination by Sinusoidal Quadrupole K-modulation

    CERN Document Server

    Baer, T; Wenninger, J

    2011-01-01

    To ensure an adequate orbit steering that maximizes the machine aperture, a good knowledge of the BPM measurement offsets is crucial. During this MD, a sinusoidal k-modulation of individually powered quadrupoles was performed to determine the offsets of the nearby BPMs. An accuracy of 10µm for the determination of the absolute beam position is reached.

  13. Analysis of Passive Mixing in a Serpentine Microchannel with Sinusoidal Side Walls

    Directory of Open Access Journals (Sweden)

    Muhammad Usman Javaid

    2017-12-01

    Full Text Available Sample mixing is difficult in microfluidic devices because of laminar flow. Micromixers are designed to ensure the optimal use of miniaturized devices. The present study aims to design a chaotic-advection-based passive micromixer with enhanced mixing efficiency. A serpentine-shaped microchannel with sinusoidal side walls was designed, and three cases, with amplitude to wavelength (A/λ ratios of 0.1, 0.15, and 0.2 were investigated. Numerical simulations were conducted using the Navier–Stokes equations, to determine the flow field. The flow was then coupled with the convection–diffusion equation to obtain the species concentration distribution. The mixing performance of sinusoidal walled channels was compared with that of a simple serpentine channel for Reynolds numbers ranging from 0.1 to 50. Secondary flows were observed at high Reynolds numbers that mixed the fluid streams. These flows were dominant in the proposed sinusoidal walled channels, thereby showing better mixing performance than the simple serpentine channel at similar or less mixing cost. Higher mixing efficiency was obtained by increasing the A/λ ratio.

  14. Band structure and optical properties of sinusoidal superlattices: ZnSe1-xTex

    International Nuclear Information System (INIS)

    Yang, G.; Lee, S.; Furdyna, J. K.

    2000-01-01

    This paper examines the band structure and optical selection rules in superlattices with a sinusoidal potential profile. The analysis is motivated by the recent successful fabrication of high quality ZnSe 1-x Te x superlattices in which the composition x varies sinusoidally along the growth direction. Although the band alignment in the ZnSe 1-x Te x sinusoidal superlattices is staggered (type II), they exhibit unexpectedly strong photoluminescence, thus suggesting interesting optical behavior. The band structure of such sinusoidal superlattices is formulated in terms of the nearly-free-electron (NFE) approximation, in which the superlattice potential is treated as a perturbation. The resulting band structure is unique, characterized by a single minigap separating two wide, free-electron-like subbands for both electrons and holes. Interband selection rules are derived for optical transitions involving conduction and valence-band states at the superlattice Brillouin-zone center, and at the zone edge. A number of transitions are predicted due to wave-function mixing of different subband states. It should be noted that the zone-center and zone-edge transitions are especially easy to distinguish in these superlattices because of the large width of the respective subbands. The results of the NFE approximation are shown to hold surprisingly well over a wide range of parameters, particularly when the period of the superlattice is short. (c) 2000 The American Physical Society

  15. Biphase sinusoidal oscillator based on negative resistor.

    Science.gov (United States)

    Bayard, Jean

    2010-06-01

    This paper describes a biphase sinusoidal generator which provides two signals: v(ref)=V(M) sin(omegat) and v(out)=V(M) sin(omegat+DeltaPhi), where DeltaPhi is in the range 0, pi/2 or -pi/2, 0 and is not dependent on the frequency value. It is based on a negative resistor and it requires very few components. SPICE simulations and measurements on an experimental setup confirm the theoretical analysis.

  16. The two dynamical states in sinusoidal potentials: An analog simulation experiment

    Science.gov (United States)

    Sawkmie, Ivan Skhem; Mahato, Mangal C.

    2018-04-01

    The phenomenon of stochastic resonance (SR) is usually found to occur theoretically as well as experimentally in bi-stable systems [1]. Recently, it was numerically shown that SR is found to occur in underdamped (friction coefficient γ) sinusoidal potentials also. The occurrence of SR is explained in terms of two competing dynamical states of trajectories as a response to the external periodic drive. We setup an analog simulation experiment similar to the analog simulation work done earlier to study stochastic nonlinear dynamics [2], to verify the existence of the two dynamical states and to investigate the occurrence of SR in sinusoidal potentials obtained earlier [3]. We discuss our experimental setup and the results obtained in detail.

  17. Reproducible isolation of lymph node stromal cells reveals site-dependent differences in fibroblastic reticular cells

    Directory of Open Access Journals (Sweden)

    Anne L Fletcher

    2011-09-01

    Full Text Available Within lymph nodes, non-hematopoietic stromal cells organize and interact with leukocytes in an immunologically important manner. In addition to organizing T and B cell segregation and expressing lymphocyte survival factors, several recent studies have shown that lymph node stromal cells shape the naïve T cell repertoire, expressing self-antigens which delete self-reactive T cells in a unique and non-redundant fashion. A fundamental role in peripheral tolerance, in addition to an otherwise extensive functional portfolio, necessitates closer study of lymph node stromal cell subsets using modern immunological techniques; however this has not routinely been possible in the field, due to difficulties reproducibly isolating these rare subsets. Techniques were therefore developed for successful ex vivo and in vitro manipulation and characterization of lymph node stroma. Here we discuss and validate these techniques in mice and humans, and apply them to address several unanswered questions regarding lymph node composition. We explored the steady-state stromal composition of lymph nodes isolated from mice and humans, and found that marginal reticular cells and lymphatic endothelial cells required lymphocytes for their normal maturation in mice. We also report alterations in the proportion and number of fibroblastic reticular cells (FRCs between skin-draining and mesenteric lymph nodes. Similarly, transcriptional profiling of FRCs revealed changes in cytokine production from these sites. Together, these methods permit highly reproducible stromal cell isolation, sorting, and culture.

  18. Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node.

    Science.gov (United States)

    Srinivasan, Swetha; Vannberg, Fredrik O; Dixon, J Brandon

    2016-04-18

    It is well documented that cells secrete exosomes, which can transfer biomolecules that impact recipient cells' functionality in a variety of physiologic and disease processes. The role of lymphatic drainage and transport of exosomes is as yet unknown, although the lymphatics play critical roles in immunity and exosomes are in the ideal size-range for lymphatic transport. Through in vivo near-infrared (NIR) imaging we have shown that exosomes are rapidly transported within minutes from the periphery to the lymph node by lymphatics. Using an in vitro model of lymphatic uptake, we have shown that lymphatic endothelial cells actively enhanced lymphatic uptake and transport of exosomes to the luminal side of the vessel. Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow. Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake. Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

  19. New Results on Single-Channel Speech Separation Using Sinusoidal Modeling

    DEFF Research Database (Denmark)

    Mowlaee, Pejman; Christensen, Mads Græsbøll; Jensen, Søren Holdt

    2011-01-01

    We present new results on single-channel speech separation and suggest a new separation approach to improve the speech quality of separated signals from an observed mix- ture. The key idea is to derive a mixture estimator based on sinusoidal parameters. The proposed estimator is aimed at finding...... mixture estimator used in binary masks and the Wiener filtering approach, it is observed that the proposed method achieves an acceptable perceptual speech quality with less cross- talk at different signal-to-signal ratios. Moreover, the method is independent of pitch estimates and reduces the computational...... complexity of the separation by replacing the short-time Fourier transform (STFT) feature vectors of high dimensionality with sinusoidal feature vectors. We report separation results for the proposed method and compare them with respect to other benchmark methods. The improvements made by applying...

  20. Differential Gene Expression of Primary Cultured Lymphatic and Blood Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Gregory M. Nelson

    2007-12-01

    Full Text Available Blood vascular endothelial cells (BECs and the developmentally related lymphatic endothelial cells (LECs create complementary, yet distinct vascular networks. Each endothelial cell type interacts with flowing fluid and circulating cells, yet each vascular system has evolved specialized gene expression programs and thus both cell types display different phenotypes. BECs and LECs express distinct genes that are unique to their specific vascular microenvironment. Tumors also take advantage of the molecules that are expressed in these vascular systems to enhance their metastatic potential. We completed transcriptome analyses on primary cultured LECs and BECs, where each comparative set was isolated from the same individual. Differences were resolved in the expression of several major categories, such as cell adhesion molecules (CAMs, cytokines, cytokine receptors. We have identified new molecules that are associated with BECs (e.g., claudin-9, CXCL11, neurexin-1, neurexin-2, the neuronal growth factor regulator-1 and LECs (e.g., claudin-7, CD58, hyaluronan and proteoglycan link protein 1 (HAPLN1, the poliovirus receptor-related 3 molecule that may lead to novel therapeutic treatments for diseases of lymphatic or blood vessels, including metastasis of cancer to lymph nodes or distant organs.

  1. Measurement of definite integral of sinusoidal signal absolute value third power using digital stochastic method

    Directory of Open Access Journals (Sweden)

    Beljić Željko

    2017-01-01

    Full Text Available In this paper a special case of digital stochastic measurement of the third power of definite integral of sinusoidal signal’s absolute value, using 2-bit AD converters is presented. This case of digital stochastic method had emerged from the need to measure power and energy of the wind. Power and energy are proportional to the third power of wind speed. Anemometer output signal is sinusoidal. Therefore an integral of the third power of sinusoidal signal is zero. Two approaches are proposed for the third power calculation of the wind speed signal. One approach is to use absolute value of sinusoidal signal (before AD conversion for which there is no need of multiplier hardware change. The second approach requires small multiplier hardware change, but input signal remains unchanged. For the second approach proposed minimal hardware change was made to calculate absolute value of the result after AD conversion. Simulations have confirmed theoretical analysis. Expected precision of wind energy measurement of proposed device is better than 0,00051% of full scale. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. TR32019

  2. Evaluation of Steel Shear Walls Behavior with Sinusoidal and Trapezoidal Corrugated Plates

    Directory of Open Access Journals (Sweden)

    Emad Hosseinpour

    2015-01-01

    Full Text Available Reinforcement of structures aims to control the input energy of unnatural and natural forces. In the past four decades, steel shear walls are utilized in huge constructions in some seismic countries such as Japan, United States, and Canada to lessen the risk of destructive forces. The steel shear walls are divided into two types: unstiffened and stiffened. In the former, a series of plates (sinusoidal and trapezoidal corrugated with light thickness are used that have the postbuckling field property under overall buckling. In the latter, steel profile belt series are employed as stiffeners with different arrangement: horizontal, vertical, or diagonal in one side or both sides of wall. In the unstiffened walls, increasing the thickness causes an increase in the wall capacity under large forces in tall structures. In the stiffened walls, joining the stiffeners to the wall is costly and time consuming. The ANSYS software was used to analyze the different models of unstiffened one-story steel walls with sinusoidal and trapezoidal corrugated plates under lateral load. The obtained results demonstrated that, in the walls with the same dimensions, the trapezoidal corrugated plates showed higher ductility and ultimate bearing compared to the sinusoidal corrugated plates.

  3. Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

    Science.gov (United States)

    Lerner, Thomas R.; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R.G.; Borel, Sophie; Diedrich, Collin R.; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M.; Wilkinson, Robert J.; Griffiths, Gareth; Gutierrez, Maximiliano G.

    2016-01-01

    In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID:26901813

  4. Removal of Stationary Sinusoidal Noise from Random Vibration Signals.

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Brian; Cap, Jerome S.

    2018-02-01

    In random vibration environments, sinusoidal line noise may appear in the vibration signal and can affect analysis of the resulting data. We studied two methods which remove stationary sine tones from random noise: a matrix inversion algorithm and a chirp-z transform algorithm. In addition, we developed new methods to determine the frequency of the tonal noise. The results show that both of the removal methods can eliminate sine tones in prefabricated random vibration data when the sine-to-random ratio is at least 0.25. For smaller ratios down to 0.02 only the matrix inversion technique can remove the tones, but the metrics to evaluate its effectiveness also degrade. We also found that using fast Fourier transforms best identified the tonal noise, and determined that band-pass-filtering the signals prior to the process improved sine removal. When applied to actual vibration test data, the methods were not as effective at removing harmonic tones, which we believe to be a result of mixed-phase sinusoidal noise.

  5. Using piecewise sinusoidal basis functions to blanket multiple wire segments

    CSIR Research Space (South Africa)

    Lysko, AA

    2009-06-01

    Full Text Available This paper discusses application of the piecewise sinusoidal (PWS) basis function (BF) over a chain of several wire segments, for example as a multiple domain basis function. The usage of PWS BF is compared to results based on the piecewise linear...

  6. Sinusoidal velaroidal shell – numerical modelling of the nonlinear ...

    African Journals Online (AJOL)

    The nonlinearity, applied to a sinusoidal velaroidal shell with the inner radius r0, the outer variables radii from 10m to 20m and the number of waves n=8, will give rise to the investigation of its nonlinear buckling resistance. The building material is a high-performant concrete. The investigation emphasizes more on the ...

  7. The phosphoinositide 3-kinase/Akt-signal pathway mediates proliferation and secretory function of hepatic sinusoidal endothelial cells in rats after partial hepatectomy

    International Nuclear Information System (INIS)

    Chen Ping; Zhang Lin; Ding Jiming; Zhu Jin; Li Ying; Duan Shigang; Yan Hongtao; Huan Yongwei; Dong Jiahong

    2006-01-01

    Objective: To investigate the role of AKT signaling pathway in hepatic sinusoidal endothelial cells (SECs) early after partial hepatectomy in rats and the regulatory mechanisms involved. Methods: The animal model of 70% hepatectomy was made. Hepatic SECs were isolated and cultured according to Braet et al.'s method with some modifications. The cultured hepatic SECs were divided into two groups: 70% partial hepatectomy groups and LY294002 group (LY). We observed the expressions of AKT and NF-κB in cultured hepatic SECs by Western blot, measured the levels of NO, NOs, IL-6, and HGF in the supernatants of hepatic SEC cultures and [ 3 H]thymidine incorporation, and analyzed cell cycle of cultured hepatic SECs by flow cytometer. The relationship of the Akt pathway with secretions and proliferation of hepatic SECs after partial hepatectomy was probed. Results: The levels of Akt protein expression increased significantly after partial hepatectomy in OG group and with a peak at 24 h post operation. Meanwhile, there was a markedly increase in phosphorylated Akt protein during 2-72 h after operation. But the expression and activity of Akt protein did not change significantly after partial hepatectomy in the LY group. So, partial hepatectomy can marked induce Akt expression and result in rapid and marked phosphorylation of Akt from 2 to 72 h thereafter. The changes of NF-κB expression in cultured hepatic SECs were similar to those of Akt expression after operation. The concentrations of HGF and IL-6 in the supernatants of cultured hepatic SECs were relatively low in the LY group, and were markedly increased after partial hepatectomy, with a peak at 24 h in the OG group. There were significant differences between the OG and LY groups at 6 and 24 h (P < 0.05). Both NO and NOS secretion was increased in the OG group compared to the LY group within 24 h after partial hepatectomy. But the secretion of NO and NOS was increased more markedly in the LY group than that in the OG

  8. Electric stimulation with sinusoids and white noise for neural prostheses

    Directory of Open Access Journals (Sweden)

    Daniel K Freeman

    2010-02-01

    Full Text Available We are investigating the use of novel stimulus waveforms in neural prostheses to determine whether they can provide more precise control over the temporal and spatial pattern of elicited activity as compared to conventional pulsatile stimulation. To study this, we measured the response of retinal ganglion cells to both sinusoidal and white noise waveforms. The use of cell-attached and whole cell patch clamp recordings allowed the responses to be observed without significant obstruction from the stimulus artifact. Electric stimulation with sinusoids elicited robust responses. White noise analysis was used to derive the linear kernel for the ganglion cell’s spiking response as well as for the underlying excitatory currents. These results suggest that in response to electric stimulation, presynaptic retinal neurons exhibit bandpass filtering characteristics with peak response that occur 25ms after onset. The experimental approach demonstrated here may be useful for studying the temporal response properties of other neurons in the CNS.

  9. Femtosecond laser cutting of endothelial grafts: comparison of endothelial and epithelial applanation.

    Science.gov (United States)

    Bernard, Aurélien; He, Zhiguo; Gauthier, Anne Sophie; Trone, Marie Caroline; Baubeau, Emmanuel; Forest, Fabien; Dumollard, Jean Marc; Peocʼh, Michel; Thuret, Gilles; Gain, Philippe

    2015-02-01

    Stromal surface quality of endothelial lamellae cut for endothelial keratoplasty with a femtosecond laser (FSL) with epithelial applanation remains disappointing. Applanation of the endothelial side of the cornea, mounted inverted on an artificial chamber, has therefore been proposed to improve cut quality. We compared lamellar quality after FSL cutting using epithelial versus endothelial applanation. Lamellae were cut with an FSL from organ-cultured corneas. After randomization, 7 were cut with epithelial applanation and 7 with endothelial applanation. Lamellae of 50-, 75-, and 100-μm thickness were targeted. Thickness was measured by optical coherence tomography before and immediately after cutting. Viable endothelial cell density was quantified immediately after cutting using triple labeling with Hoechst/ethidium/calcein-AM coupled with image analysis with ImageJ. The stromal surface was evaluated by 9 masked observers using semiquantitative scoring of scanning electronic microscopy images. Histology of 2 samples was also analyzed before lamellar detachment. Precision (difference in target/actual thickness) and thickness regularity [coefficient of variation (CV) of 10 measurements] were significantly better with endothelial applanation (precision: 18 μm; range, 10-30; CV: 11%; range, 8-12) than with epithelial applanation (precision: 84 μm; range, 54-107; P = 0.002; CV: 24%; range, 13-47; P = 0.001). Endothelial applanation provided thinner lamellae. However, viable endothelial cell density was significantly lower after endothelial applanation (1183 cells/mm2; range, 787-1725 versus 1688 cells/mm2; range, 1288-2025; P = 0.018). FSL cutting of endothelial lamellae using endothelial applanation provides thinner more regular grafts with more predictable thickness than with conventional epithelial applanation but strongly reduces the pool of viable endothelial cells.

  10. New Canonic Active RC Sinusoidal Oscillator Circuits Using Second-Generation Current Conveyors with Application as a Wide-Frequency Digitally Controlled Sinusoid Generator

    OpenAIRE

    Abhirup Lahiri

    2011-01-01

    This paper reports two new circuit topologies using second-generation current conveyors (CCIIs) for realizing variable frequency sinusoidal oscillators with minimum passive components. The proposed topologies in this paper provide new realizations of resistance-controlled and capacitor-controlled variable frequency oscillators (VFOs) using only four passive components. The first topology employs three CCIIs, while the second topology employs two CCIIs. The second topology provides an advantag...

  11. phylo-node: A molecular phylogenetic toolkit using Node.js.

    Science.gov (United States)

    O'Halloran, Damien M

    2017-01-01

    Node.js is an open-source and cross-platform environment that provides a JavaScript codebase for back-end server-side applications. JavaScript has been used to develop very fast and user-friendly front-end tools for bioinformatic and phylogenetic analyses. However, no such toolkits are available using Node.js to conduct comprehensive molecular phylogenetic analysis. To address this problem, I have developed, phylo-node, which was developed using Node.js and provides a stable and scalable toolkit that allows the user to perform diverse molecular and phylogenetic tasks. phylo-node can execute the analysis and process the resulting outputs from a suite of software options that provides tools for read processing and genome alignment, sequence retrieval, multiple sequence alignment, primer design, evolutionary modeling, and phylogeny reconstruction. Furthermore, phylo-node enables the user to deploy server dependent applications, and also provides simple integration and interoperation with other Node modules and languages using Node inheritance patterns, and a customized piping module to support the production of diverse pipelines. phylo-node is open-source and freely available to all users without sign-up or login requirements. All source code and user guidelines are openly available at the GitHub repository: https://github.com/dohalloran/phylo-node.

  12. Pelagic behaviour of reservoir fishes: sinusoidal swimming and associated behaviour

    OpenAIRE

    JAROLÍM, Oldřich

    2009-01-01

    Annotation Long-term fixed-location hydroacoustic study with uplooking transducer was performed during 2005 in Římov reservoir, Czech Republic. It dealt mainly with fish behaviour in the open water of reservoir, especially with sinusoidal swimming behaviour. The dependence of pelagic fish behaviour on environmental conditions was also studied.

  13. Stochastic analysis/synthesis using sinusoidal atoms

    DEFF Research Database (Denmark)

    Jensen, Kristoffer

    2008-01-01

    This work proposes a method for re-synthesizing music for use in perceptual experiments regarding structural changes and in music creation. Atoms are estimated from music audio, modelled in a stochastic model, and re-synthesized from the model pa- rameters. The atoms are found by splitting...... sinusoids into short segments, and modelled into amplitude and envelope shape, frequency, time and duration. A simple model for creating envelopes with percussive, sustained or crescendo shape is presented. Single variable and joint probability density functions are created from the atom parameters and used...... to re-create sounds with the same distribution of the atoms parameters. A novel method for visualization music, the musigram, permits a better understanding of the re- synthesized sounds....

  14. Vascular Endothelial Growth Factor and Angiopoietin-1 Stimulate Postnatal Hematopoiesis by Recruitment of Vasculogenic and Hematopoietic Stem Cells

    Science.gov (United States)

    Hattori, Koichi; Dias, Sergio; Heissig, Beate; Hackett, Neil R.; Lyden, David; Tateno, Masatoshi; Hicklin, Daniel J.; Zhu, Zhenping; Witte, Larry; Crystal, Ronald G.; Moore, Malcolm A.S.; Rafii, Shahin

    2001-01-01

    Tyrosine kinase receptors for angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) are expressed not only by endothelial cells but also by subsets of hematopoietic stem cells (HSCs). To further define their role in the regulation of postnatal hematopoiesis and vasculogenesis, VEGF and Ang-1 plasma levels were elevated by injecting recombinant protein or adenoviral vectors expressing soluble VEGF165, matrix-bound VEGF189, or Ang-1 into mice. VEGF165, but not VEGF189, induced a rapid mobilization of HSCs and VEGF receptor (VEGFR)2+ circulating endothelial precursor cells (CEPs). In contrast, Ang-1 induced delayed mobilization of CEPs and HSCs. Combined sustained elevation of Ang-1 and VEGF165 was associated with an induction of hematopoiesis and increased marrow cellularity followed by proliferation of capillaries and expansion of sinusoidal space. Concomitant to this vascular remodeling, there was a transient depletion of hematopoietic activity in the marrow, which was compensated by an increase in mobilization and recruitment of HSCs and CEPs to the spleen resulting in splenomegaly. Neutralizing monoclonal antibody to VEGFR2 completely inhibited VEGF165, but not Ang-1–induced mobilization and splenomegaly. These data suggest that temporal and regional activation of VEGF/VEGFR2 and Ang-1/Tie-2 signaling pathways are critical for mobilization and recruitment of HSCs and CEPs and may play a role in the physiology of postnatal angiogenesis and hematopoiesis. PMID:11342585

  15. Evidences of the ultrarapid delayed rectifier potassium current (IKur on pacemaker activity in sinoatrial and atrioventricular nodes of Rat

    Directory of Open Access Journals (Sweden)

    Mohammad reza Nikmaram

    2008-09-01

    Full Text Available Background: Sinoatrial node (SAN is the primary pacemaker of the heart. If the SAN activity fails in any way, then the atrioventricular node (AVN immediately starts to regulate the activities of the heart. The aim of this study was to assess the existence or non existence of ultrarapid delayed rectifier potassium current (Ikur and its role on pacemaker activity of two intact SAN and AVN of rat. Methods: The pacemaker activities of distinct intact SAN and AVN by two separate metal microelectrodes that contact the endothelial surface of nodes were recorded and cycle length (CL of action potential was measured. The recording was done before and during 50µM 4-Aminopyridine (4-AP as an Ikur blocker. Results: Compared to control condition, CL of action potentials of SAN and VAN preparations had increased by 17.60 +/-2.9% and 35.90 +/-2.9%, respectively (P<0.05. Conclusion: It is possible to conclude that the Ikur was present in AVN and SAN and the effect of 4-AP on CL of action potential nodes was significantly different.

  16. Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity.

    Science.gov (United States)

    Schäfer, Nicola; Lohmann, Christine; Winnik, Stephan; van Tits, Lambertus J; Miranda, Melroy X; Vergopoulos, Athanasios; Ruschitzka, Frank; Nussberger, Jürg; Berger, Stefan; Lüscher, Thomas F; Verrey, François; Matter, Christian M

    2013-12-01

    Aldosterone plays a crucial role in cardiovascular disease. 'Systemic' inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the 'endothelial' MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis. C57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high 'endogenous' aldosterone) and in 'exogenous' aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR. Obesity-induced endothelial dysfunction depends on the 'endothelial' MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications.

  17. A Perceptual Model for Sinusoidal Audio Coding Based on Spectral Integration

    NARCIS (Netherlands)

    Van de Par, S.; Kohlrausch, A.; Heusdens, R.; Jensen, J.; Holdt Jensen, S.

    2005-01-01

    Psychoacoustical models have been used extensively within audio coding applications over the past decades. Recently, parametric coding techniques have been applied to general audio and this has created the need for a psychoacoustical model that is specifically suited for sinusoidal modelling of

  18. A perceptual model for sinusoidal audio coding based on spectral integration

    NARCIS (Netherlands)

    Van de Par, S.; Kohlrauch, A.; Heusdens, R.; Jensen, J.; Jensen, S.H.

    2005-01-01

    Psychoacoustical models have been used extensively within audio coding applications over the past decades. Recently, parametric coding techniques have been applied to general audio and this has created the need for a psychoacoustical model that is specifically suited for sinusoidal modelling of

  19. Node cookbook

    CERN Document Server

    Clements, David Mark

    2014-01-01

    In Node Cookbook Second Edition, each chapter focuses on a different aspect of working with Node. Following a Cookbook structure, the recipes are written in an easy-to-understand language. Readers will find it easier to grasp even the complex recipes which are backed by lots of illustrations, tips, and hints.If you have some knowledge of JavaScript and want to build fast, efficient, scalable client-server solutions, then Node Cookbook Second Edition is for you. Knowledge of Node will be an advantage but is not required. Experienced users of Node will be able to improve their skills.

  20. Impact Testing and Simulation of a Sinusoid Foam Sandwich Energy Absorber

    Science.gov (United States)

    Jackson, Karen E.; Fasanella, Edwin L; Littell, Justin D.

    2015-01-01

    A sinusoidal-shaped foam sandwich energy absorber was developed and evaluated at NASA Langley Research Center through multi-level testing and simulation performed under the Transport Rotorcraft Airframe Crash Testbed (TRACT) research project. The energy absorber, designated the "sinusoid," consisted of hybrid carbon- Kevlar® plain weave fabric face sheets, two layers for each face sheet oriented at +/-45deg with respect to the vertical or crush direction, and a closed-cell ELFOAM(TradeMark) P200 polyisocyanurate (2.0-lb/ft3) foam core. The design goal for the energy absorber was to achieve an average floor-level acceleration of between 25- and 40-g during the full-scale crash test of a retrofitted CH-46E helicopter airframe, designated TRACT 2. Variations in the design were assessed through quasi-static and dynamic crush testing of component specimens. Once the design was finalized, a 5-ft-long subfloor beam was fabricated and retrofitted into a barrel section of a CH-46E helicopter. A vertical drop test of the barrel section was conducted onto concrete to evaluate the performance of the energy absorber prior to retrofit into TRACT 2. Finite element models were developed of all test articles and simulations were performed using LSDYNA ®, a commercial nonlinear explicit transient dynamic finite element code. Test analysis results are presented for the sinusoid foam sandwich energy absorber as comparisons of load-displacement and acceleration-time-history responses, as well as predicted and experimental structural deformations and progressive damage for each evaluation level (component testing through barrel section drop testing).

  1. [The role of endothelial cells and endothelial precursor cells in angiogenesis].

    Science.gov (United States)

    Poreba, Małgorzata; Usnarska-Zubkiewicz, Lidia; Kuliczkowski, Kazimierz

    2006-01-01

    Endothelium plays a key role in maintenance of vascular homeostasis in human organism. According to new data endothelial cells and hematopoietic cells have a common precursor in prenatal life--a hemangioblast, which explains the fact of sharing the same determinants on the surface of both type of cells. Circulating endothelial precursors were identified in adults and this suggests that hemangioblasts may be present not only during embriogenesis. In some clinical situations the increased numbers of endothelial cells and endothelial precursors were noted, and especially in patients with neoplastic diseases, which is probably the result of increased angiogenesis. Endothelial precursors are thought to be the promice for therapeutic purposes in future--to increase local angiogenesis.

  2. Allocating resources between network nodes for providing a network node function

    NARCIS (Netherlands)

    Strijkers, R.J.; Meulenhoff, P.J.

    2014-01-01

    The invention provides a method wherein a first network node advertises available resources that a second network node may use to offload network node functions transparently to the first network node. Examples of the first network node are a client device (e.g. PC, notebook, tablet, smart phone), a

  3. Electronically tunable RC sinusoidal oscillators

    International Nuclear Information System (INIS)

    Florescu, Valeriu

    2008-01-01

    This paper presents two types of active configurations for realizing electronically tunable RC sinusoidal oscillators. The type-1 network employs two grounded scaled resistances KR 1 and KR 2 , where K is scaling factor. The frequency of oscillation W 0 is controlled conveniently by adjusting K, since W 0 appears in the form W 0 =1/K √ R 1 C 1 R 2 C 2 . For realizing the scaled resistances, an active configuration is proposed, which realizes KR 1 =R 1 /(1+f(V B )), where f(V B ) denotes a function of a controlling voltage V B . Thus the frequency tuning can be effected by controlling a voltage V B . The type-2 oscillator uses two periodically switched conductances. It is shown that the tuning of oscillation frequency can be done by varying the pulse width-to-period ratio (t/T) of the periodically switched conductances. (author)

  4. Core losses of a permanent magnet synchronous motor with an amorphous stator core under inverter and sinusoidal excitations

    Science.gov (United States)

    Yao, Atsushi; Sugimoto, Takaya; Odawara, Shunya; Fujisaki, Keisuke

    2018-05-01

    We report core loss properties of permanent magnet synchronous motors (PMSM) with amorphous magnetic materials (AMM) core under inverter and sinusoidal excitations. To discuss the core loss properties of AMM core, a comparison with non-oriented (NO) core is also performed. In addition, based on both experiments and numerical simulations, we estimate higher (time and space) harmonic components of the core losses under inverter and sinusoidal excitations. The core losses of PMSM are reduced by about 59% using AMM stator core instead of NO core under sinusoidal excitation. We show that the average decrease obtained by using AMM instead of NO in the stator core is about 94% in time harmonic components.

  5. Core losses of a permanent magnet synchronous motor with an amorphous stator core under inverter and sinusoidal excitations

    Directory of Open Access Journals (Sweden)

    Atsushi Yao

    2018-05-01

    Full Text Available We report core loss properties of permanent magnet synchronous motors (PMSM with amorphous magnetic materials (AMM core under inverter and sinusoidal excitations. To discuss the core loss properties of AMM core, a comparison with non-oriented (NO core is also performed. In addition, based on both experiments and numerical simulations, we estimate higher (time and space harmonic components of the core losses under inverter and sinusoidal excitations. The core losses of PMSM are reduced by about 59% using AMM stator core instead of NO core under sinusoidal excitation. We show that the average decrease obtained by using AMM instead of NO in the stator core is about 94% in time harmonic components.

  6. What is going on between defibrotide and endothelial cells? Snapshots reveal the hot spots of their romance.

    Science.gov (United States)

    Palomo, Marta; Mir, Enrique; Rovira, Montse; Escolar, Ginés; Carreras, Enric; Diaz-Ricart, Maribel

    2016-03-31

    Defibrotide (DF) has received European Medicines Agency authorization to treat sinusoidal obstruction syndrome, an early complication after hematopoietic cell transplantation. DF has a recognized role as an endothelial protective agent, although its precise mechanism of action remains to be elucidated. The aim of the present study was to investigate the interaction of DF with endothelial cells (ECs). A human hepatic EC line was exposed to different DF concentrations, previously labeled. Using inhibitory assays and flow cytometry techniques along with confocal microscopy, we explored: DF-EC interaction, endocytic pathways, and internalization kinetics. Moreover, we evaluated the potential role of adenosine receptors in DF-EC interaction and if DF effects on endothelium were dependent of its internalization. Confocal microscopy showed interaction of DF with EC membranes followed by internalization, though DF did not reach the cell nucleus even after 24 hours. Flow cytometry revealed concentration, temperature, and time dependent uptake of DF in 2 EC models but not in other cell types. Moreover, inhibitory assays indicated that entrance of DF into ECs occurs primarily through macropinocytosis. Our experimental approach did not show any evidence of the involvement of adenosine receptors in DF-EC interaction. The antiinflammatory and antioxidant properties of DF seem to be caused by the interaction of the drug with the cell membrane. Our findings contribute to a better understanding of the precise mechanisms of action of DF as a therapeutic and potential preventive agent on the endothelial damage underlying different pathologic situations. © 2016 by The American Society of Hematology.

  7. Mapping surface properties of sinusoidal roughness standards by TPM

    International Nuclear Information System (INIS)

    Liu, X; Rubert, P

    2005-01-01

    We report our investigation on the surface properties of sinusoidal roughness standards made from pure electroformed nickel. Two specimens having a sinusoidal profile with nominal R a of 0.36 μm and a peak spacing of 25 μm are chosen for this investigation. One specimen is further treated with a hard protective coating of nickel-boron. The surface topography, friction, hardness and Young's modulus of the specimens were measured by a novel instrument, the multi-function Tribological Probe Microscope (TPM). The results show that hardness of these two specimens is 14.1 GPa for uncoated specimen and 25.7 GPa for the coated one, while the Young's modulus is 188 GPa and 225 GPa, respectively. The ramping force was set to 3mN for both the specimens and the effect of the tip penetration was investigated by comparing the topography measurements before and after hardness mapping. It has been found out that there is no significant change in the averaged profiles over the scanned area, which indicates the topography distortion seen in the multi-function mapping, is recoverable. Cross correlation between topography and its corresponding hardness/Young's modulus has been carried out and the result will be discussed in the paper

  8. Generation of sinusoidal fringes with a holographic phase grating and a phase-only spatial light modulator

    International Nuclear Information System (INIS)

    Berberova, Natalia; Stoykova, Elena; Sainov, Ventseslav

    2012-01-01

    A variety of pattern projection methods for the three-dimensional capture of objects is based on the generation of purely sinusoidal fringes. This is not an easy task, especially when a portable non-interferometric system for outdoor usage is required. The use of phase gratings with coherent illumination as a possible solution has the advantage of providing good stability and a large measurement volume. In this work, we analyze the quality of fringes projected with two sinusoidal phase gratings. The first grating is recorded on a silver-halide holographic plate by means of a Michelson interferometer. The spatial resolution of the silver-halide material used is greater than 6000 lines per millimeter, and the recorded grating is practically analogous to a smooth variation of the phase profile. The second grating is formed as a sinusoidal phase variation on a liquid crystal-on-silicon phase-only reflective display with a resolution of 1920×1080 pixels, a pixel pitch of 8 μm and 256 phase levels. The frequency content of the fringes projected with both gratings is analyzed and compared on the basis of the calculated Fresnel diffraction pattern, taking into account that the sinusoidal phase distribution in the case of a spatial light modulator is both sampled and quantized. Experimental fringe patterns projected using both gratings are also provided.

  9. Allocating resources between network nodes for providing a network node function

    OpenAIRE

    Strijkers, R.J.; Meulenhoff, P.J.

    2014-01-01

    The invention provides a method wherein a first network node advertises available resources that a second network node may use to offload network node functions transparently to the first network node. Examples of the first network node are a client device (e.g. PC, notebook, tablet, smart phone), a server (e.g. application server, a proxy server, cloud location, router). Examples of the second network node are an application server, a cloud location or a router. The available resources may b...

  10. Levitation performance of high-T{sub c} superconductor in sinusoidal guideway magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Liu, W. [Applied Superconductivity Laboratory, Southwest Jiaotong University, Chengdu 610031 (China)], E-mail: asclab@asclab.cn; Wang, J.S.; Jing, H.; Jiang, M.; Zheng, J.; Wang, S.Y. [Applied Superconductivity Laboratory, Southwest Jiaotong University, Chengdu 610031 (China)

    2008-12-01

    The vertical component of the Halbach array's magnetic field exhibits a sinusoid distribution because of the closed magnetic flux area between two neighbouring poles, so this field can be regarded as the sinusoidal magnetic field. This article mainly discusses the influence of the closed flux region on the levitation performance of the bulk high-temperature superconductor (HTS). Moreover, the levitation performance is compared between the closed and diverging region of magnetic flux. The experimental results can be analyzed by the magnetic circuit theory and the frozen-image model. The analysis indicates that the closed region of magnetic flux can influence the levitation performance of bulk HTS obviously and provide an extra useful guidance force. These conclusions are helpful to optimize the HTS Maglev system.

  11. THE RESONANT OVERVOLTAGE IN NON-SINUSOIDAL MODE OF MAIN ELECTRIC NETWORK

    Directory of Open Access Journals (Sweden)

    V. G. Kuznetsov

    2018-04-01

    Full Text Available Purpose. The resonant overvoltage arises in main electrical networks as a result of random coincidence of some parameters of circuit and its mode and it may exist for a relatively long time. Therefore, the traditional means of limitation of short duration commutation surges are not effective in this case. The study determines conditions of appearance and development of non-sinusoidal mode after switching idle autotransformer to the overhead line of extra high voltage. The purpose of the paper is to choice measures for prevention overvoltage, too. Methodology. The study has used the result of extra high voltage line testing, the methods of electric circuit theory and the simulation in the MATLAB & Simulink package. Results. The simulation model of the extra high voltage transmission line for the study of resonant non-sinusoidal overvoltage is developed. The conditions for the appearance of resonant circuits in the real power line are found and harmonic frequency in which overvoltage arises are obtained. The study proposes using the controlled switching device as a measure to prevent resonance surges and determines the appropriate settings. Originality. The expression for calculation of resonant length of extra high voltage line was derived. The special investigation of processes in the resonant circuit of the extra high voltage transmission line for higher harmonic components of voltage is carried out. The program of switching for control apparatus that prevents non-sinusoidal overvoltage has been developed at the first time. Practical value. The using of the proposed settings of controlled switchgear will prevent the occurrence of hazardous resonant surge on higher harmonic components of voltage.

  12. Node-pair reliability of network systems with small distances between adjacent nodes

    International Nuclear Information System (INIS)

    Malinowski, Jacek

    2007-01-01

    A new method for computing the node-pair reliability of network systems modeled by random graphs with nodes arranged in sequence is presented. It is based on a recursive algorithm using the 'sliding window' technique, the window being composed of several consecutive nodes. In a single step, the connectivity probabilities for all nodes included in the window are found. Subsequently, the window is moved one node forward. This process is repeated until, in the last step, the window reaches the terminal node. The connectivity probabilities found at that point are used to compute the node-pair reliability of the network system considered. The algorithm is designed especially for graphs with small distances between adjacent nodes, where the distance between two nodes is defined as the absolute value of the difference between the nodes' numbers. The maximal distance between any two adjacent nodes is denoted by Γ(G), where G symbolizes a random graph. If Γ(G)=2 then the method can be applied for directed as well as undirected graphs whose nodes and edges are subject to failure. This is important in view of the fact that many algorithms computing network reliability are designed for graphs with failure-prone edges and reliable nodes. If Γ(G)=3 then the method's applicability is limited to undirected graphs with reliable nodes. The main asset of the presented algorithms is their low numerical complexity-O(n), where n denotes the number of nodes

  13. Ageing monitoring in IGBT module under sinusoidal loading

    DEFF Research Database (Denmark)

    Ghimire, Pramod; Pedersen, Kristian Bonderup; Rannestad, Bjørn

    2015-01-01

    This paper presents monitoring of ageing in high power insulated gate bipolar transistor (IGBT) modules subjected to sinusoidal loading at nominal power level. On-state voltage for IGBT, diode, and rise in interconnection resistance are used as ageing parameters. These are measured in three...... different ways: calibration of power modules after 24 h of operation, offline characterization every 5 min of operation, and continuous measurement during normal converter operation. Four power modules are tested, which are cycled to different degradation levels by number of cycles, where one is tested...

  14. Hydraulic testing in granite using the sinusoidal variation of pressure

    International Nuclear Information System (INIS)

    Black, J.H.; Holmes, D.C.; Noy, D.J.

    1982-09-01

    Access to two boreholes at the Carwynnen test site in Cornwall enabled the trial of a number of innovative approaches to the hydrogeology of fractured crystalline rock. These methods ranged from the use of seisviewer data to measure the orientation of fractures to the use of the sinusoidal pressure technique to measure directional hydraulic diffusivity. The testing began with a short programme of site investigation consisting of borehole caliper and seisviewer logging followed by some single borehole hydraulic tests. The single borehole hydraulic testing was designed to assess whether the available boreholes and adjacent rock were suitable for testing using the sinusoidal method. The main testing methods were slug and pulse tests and were analysed using the fissured porous medium analysis proposed in Barker and Black (1983). Derived hydraulic conductivity (K) ranged from 2 x 10 -12 m/sec to 5 x 10 -7 m/sec with one near-surface zone of high K being perceived in both boreholes. The results were of the form which is typical of fractured rock and indicated a combination of high fracture frequency and permeable granite matrix. The results are described and discussed. (author)

  15. Calculation of the mean path length of the Epstein frame under non-sinusoidal excitations using the double Epstein method

    International Nuclear Information System (INIS)

    Marketos, Philip; Zurek, Stan; Moses, Anthony J.

    2008-01-01

    This paper discusses the effect of non-sinusoidal excitation on the mean path length of the Epstein frame. Two different steels, a non-oriented (NO) steel and a high-permeability grain-oriented (HGO) electrical steel have been tested under pure sinusoidal and non-sinusoidal excitations and the mean path length of the Epstein frame has been re-calculated. Results indicate that the actual mean path of the Epstein frame depends not only on the material permeability and anisotropy but also on the peak flux density and magnetising frequency. The amount of distortion of the excitation frequency also has an effect on the value of the actual mean path length of the Epstein frame

  16. Research on a new magnetic-field-modulated brushless double-rotor machine with sinusoidal-permeance modulating ring

    Directory of Open Access Journals (Sweden)

    Ping Zheng

    2017-05-01

    Full Text Available The magnetic-field-modulated brushless double-rotor machine (MFM-BDRM, composed of a stator, a modulating ring rotor, and a PM rotor, is a kind of power-split device for hybrid electric vehicles (HEVs. In this paper, a new MFM-BDRM with sinusoidal-permeance modulating ring named Sinusoidal-Permeance-Modulating-Ring Brushless Double-Rotor Machine (SPMR-BDRM is proposed to solve the problem of poor mechanical strength and large iron loss. The structure and the operating principle of the MFM-BDRM are introduced. The design principle of the sinusoidal-permeance modulating ring is analyzed and derived. The main idea of that is to minimize the harmonic permeance of air gap, thereby the harmonic magnetic fields can be restrained. There are comparisons between a MFM-BDRM with sinusoidal-permeance modulating ring and a same size MFM-BDRM with traditional modulating ring, including magnetic field distributions and electromagnetic performances. Most importantly, the iron losses are compared under six different conditions. The result indicates that the harmonic magnetic fields in the air gap are restrained; the electromagnetic torque and power factor are almost the same with same armature current; the torque ripples of the modulating ring rotor and the PM rotor are reduced; the stator loss is reduced by 13% at least and the PM loss is reduced by 20% at least compared with the same size traditional MFM-BDRM under the same operating conditions.

  17. Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node Metastasis

    Directory of Open Access Journals (Sweden)

    Aula Ammar

    2011-01-01

    Full Text Available Background: Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1 in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process. Methods: 148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC, CD209 (immature DC, iDC and CD68 (macrophage, M&phis;. in vitro expression of CLEVER-1 on lymphatic (LEC and blood endothelial cells (BEC was examined by flow cytometry. Results: in vitro results showed that although both endothelial cell types express CLEVER-1, surface expression was only evident on LEC. In tumour sections CLEVER-1 was expressed in blood vessels (BV, 61.4% of samples, lymphatic vessels (LV, 18.2% of samples and in M&phis;/DCs (82.4% of samples. However, only CLEVER-1 expression in LV was associated with LN metastasis (p = 0.027 and with M&phis; indices (p = 0.021. Although LV CLEVER-1 was associated with LN positivity there was no significant correlation with recurrence or overall survival, BV CLEVER-1 expression was, however, associated with increased risk of recurrence (p = 0.049. The density of inflammatory infiltrate correlated with CLEVER-1 expression in BV (p < 0.001 and LV (p = 0.004. Conclusions: The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. Its upregulation on LV, related surface expression, and association with LN metastasis suggest that it may be an important mediator of tumor cell metastasis to LN.

  18. Observation of Sinusoidal Voltage Behaviour in Silver Doped YBCO

    Science.gov (United States)

    Altinkok, Atilgan; Olutas, Murat; Kilic, Kivilcim; Kilic, Atilla

    The influence of bi-directional square wave (BSW) current was investigated on the evolution of the V - t curves at different periods (P) , temperatures and external magnetic fields. It was observed that slow transport relaxation measurements result in regular sinusoidal voltage oscillations which were discussed mainly in terms of the dynamic competition between pinning and depinning.The symmetry in the voltage oscillations was attributed to the elastic coupling between the flux lines and the pinning centers along grain boundaries and partly inside the grains. This case was also correlated to the equality between flux entry and exit along the YBCO/Ag sample during regular oscillations. It was shown that the voltage oscillations can be described well by an empirical expression V (t) sin(wt + φ) . We found that the phase angle φgenerally takes different values for the repetitive oscillations. Fast Fourier Transform analysis of the V - t oscillations showed that the oscillation period is comparable to that (PI) of the BSW current. This finding suggests a physical mechanism associated with charge density waves (CDWs), and, indeed, the weakly pinned flux line system in YBCO/Ag resembles the general behavior of CDWs. At certain values of PI, amplitude of BSW current, H and T, the YBCO/Ag sample behaves like a double-integrator, since it converts the BSW current to sinusoidal voltage oscillations in time.

  19. Endothelial-regenerating cells: an expanding universe.

    Science.gov (United States)

    Steinmetz, Martin; Nickenig, Georg; Werner, Nikos

    2010-03-01

    Atherosclerosis is the most common cause for cardiovascular diseases and is based on endothelial dysfunction. A growing body of evidence suggests the contribution of bone marrow-derived endothelial progenitor cells, monocytic cells, and mature endothelial cells to vessel formation and endothelial rejuvenation. To this day, various subsets of these endothelial-regenerating cells have been identified according to cellular origin, phenotype, and properties in vivo and in vitro. However, the definition and biology, especially of endothelial progenitor cells, is complex and under heavy debate. In this review, we focus on current definitions of endothelial progenitor cells, highlight the clinical relevance of endothelial-regenerating cells, and provide new insights into cell-cell interactions involved in endothelial cell rejuvenation.

  20. An experimental study on flow friction and heat transfer of water in sinusoidal wavy silicon microchannels

    Science.gov (United States)

    Huang, Houxue; Wu, Huiying; Zhang, Chi

    2018-05-01

    Sinusoidal wavy microchannels have been known as a more heat transfer efficient heat sink for the cooling of electronics than normal straight microchannels. However, the existing experimental study on wavy silicon microchannels with different phase differences are few. As a result of this, in this paper an experimental study has been conducted to investigate the single phase flow friction and heat transfer of de-ionized water in eight different sinusoidal wavy silicon microchannels (SWSMCs) and one straight silicon microchannel (SMC). The SWSMCs feature different phase differences (α  =  0 to π) and different relative wavy amplitudes (β  =  A/l  =  0.05 to 0.4), but the same average hydraulic diameters (D h  =  160 µm). It is found that both flow friction constant fRe and the Nusselt number depend on the phase difference and relative wavy amplitude. For sinusoidal wavy microchannels with a relative wavy amplitude (β  =  0.05), the Nusselt number increased noticeably with the phase difference for Re  >  250, but the effect was insignificant for Re  reducing the wavy wave length induced higher pressure drop and apparent friction constant fRe, while the Nusselt number increased with relative wavy amplitude for Re  >  300. The results indicate that the thermal resistances of sinusoidal wavy silicon microchannels were generally lower than that of straight silicon microchannels, and the thermal resistance decreased with the increase in relative wavy amplitude. The enhancement of thermal performance is attributed to the flow re-circulation occurring in the corrugation troughs and the secondary flows or Dean vortices introduced by curved channels. It is concluded that silicon sinusoidal wavy microchannels provide higher heat transfer rate albeit with a higher flow friction, making it a better choice for the cooling of high heat flux electronics.

  1. Iron Losses in Electrical Machines Due to Non Sinusoidal Alternating Fluxes

    DEFF Research Database (Denmark)

    Ritchie, Ewen; Walker, J.A.; Dorrell, D. G.

    2007-01-01

    This paper shows how the flux waveform in the core of an electrical machine can be vary non- sinusoidally which complicates the calculation of the iron loss in a machine. A set of tests are conducted on a steel sample using an Epstein square where harmonics are injected into the flux waveform which...... of a machine....

  2. Numerical analysis of beam with sinusoidally corrugated webs

    Science.gov (United States)

    Górecki, Marcin; Pieńko, Michał; Łagoda, GraŻyna

    2018-01-01

    The paper presents numerical tests results of the steel beam with sinusoidally corrugated web, which were performed in the Autodesk Algor Simulation Professional 2010. The analysis was preceded by laboratory tests including the beam's work under the influence of the four point bending as well as the study of material characteristics. Significant web's thickness and use of tools available in the software allowed to analyze the behavior of the plate girder as beam, and also to observe the occurrence of stresses in the characteristic element - the corrugated web. The stress distribution observed on the both web's surfaces was analyzed.

  3. Compact broadband polarization beam splitter using a symmetric directional coupler with sinusoidal bends.

    Science.gov (United States)

    Zhang, Fan; Yun, Han; Wang, Yun; Lu, Zeqin; Chrostowski, Lukas; Jaeger, Nicolas A F

    2017-01-15

    We design and demonstrate a compact broadband polarization beam splitter (PBS) using a symmetric directional coupler with sinusoidal bends on a silicon-on-insulator platform. The sinusoidal bends in our PBS suppress the power exchange between two parallel symmetric strip waveguides for the transverse-electric (TE) mode, while allowing for the maximum power transfer to the adjacent waveguide for the transverse-magnetic (TM) mode. Our PBS has a nominal coupler length of 8.55 μm, and it has an average extinction ratio (ER) of 12.0 dB for the TE mode, an average ER of 20.1 dB for the TM mode, an average polarization isolation (PI) of 20.6 dB for the through port, and an average PI of 11.5 dB for the cross port, all over a bandwidth of 100 nm.

  4. CMOS-based active RC sinusoidal oscillator with four-phase quadrature outputs and single-resistance-controlled (SRC) tuning laws

    OpenAIRE

    Lahiri, Abhirup; Herencsár, Norbert

    2012-01-01

    This paper proposes a very compact CMOS realization of active RC sinusoidal oscillator capable of generating four quadrature voltage outputs. The oscillator is based on the cascade of lossless and lossy integrators in loop. The governing laws for the condition of oscillation (CO) and the frequency of oscillation (FO) are single-resistance-controlled (SRC) and which allow independent FO tuning. Unlike previously reported SRC-based sinusoidal oscillators based on the active building block (ABB)...

  5. Modular sensor network node

    Science.gov (United States)

    Davis, Jesse Harper Zehring [Berkeley, CA; Stark, Jr., Douglas Paul; Kershaw, Christopher Patrick [Hayward, CA; Kyker, Ronald Dean [Livermore, CA

    2008-06-10

    A distributed wireless sensor network node is disclosed. The wireless sensor network node includes a plurality of sensor modules coupled to a system bus and configured to sense a parameter. The parameter may be an object, an event or any other parameter. The node collects data representative of the parameter. The node also includes a communication module coupled to the system bus and configured to allow the node to communicate with other nodes. The node also includes a processing module coupled to the system bus and adapted to receive the data from the sensor module and operable to analyze the data. The node also includes a power module connected to the system bus and operable to generate a regulated voltage.

  6. Propiedades de transporte de una superred de grafeno tipo sinusoidal

    Directory of Open Access Journals (Sweden)

    J. A. Briones-Torres

    2015-01-01

    Full Text Available En este trabajo usamos el método de la matriz de transferencia para estudiar el tunelamiento de los electrones de Dirac a través de superredes en grafeno. Consideramos una superred con potencial sinusoidal o polaridad invertida, para ello consideramos dos maneras de crearla, una por medio de sustratos mixtos junto con la aplicación de un campo perpendicular sobre el sustrato de Óxido de Silicio (SiO2, la otra por medio de potenciales alternados aplicados perpendicularmente sobre la sábana de grafeno. Calculamos las propiedades de transmisión, transporte y estructura electrónica, variando diferentes parámetros como ángulo de incidencia, anchos de pozos y barreras y diferente número de barreras. Se encontró (1 el importante papel que juega el efecto Klein en tales estructuras, (2 las propiedades de transmisión y transporte presentan cierta simetría respecto del origen de la energía, y (3 el carácter sinusoidal del sistema trae consigo una baja en el nivel de energía de las subbandas en el espectro de estados acotados, además las degenera y origina que la apertura-cierre de las minibandas sea en el mismo nivel de energía.

  7. Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248.

    Science.gov (United States)

    Bagley, Rebecca G; Rouleau, Cecile; St Martin, Thia; Boutin, Paula; Weber, William; Ruzek, Melanie; Honma, Nakayuki; Nacht, Mariana; Shankara, Srinivas; Kataoka, Shiro; Ishida, Isao; Roberts, Bruce L; Teicher, Beverly A

    2008-08-01

    Angiogenesis occurs during normal physiologic processes as well as under pathologic conditions such as tumor growth. Serial analysis of gene expression profiling revealed genes [tumor endothelial markers (TEM)] that are overexpressed in tumor endothelial cells compared with normal adult endothelial cells. Because blood vessel development of malignant tumors under certain conditions may include endothelial precursor cells (EPC) recruited from bone marrow, we investigated TEM expression in EPC. The expression of TEM1 or endosialin (CD248) and other TEM has been discovered in a population of vascular endothelial growth factor receptor 2+/CD31+/CD45-/VE-cadherin+ EPC derived from human CD133+/CD34+ cells. EPC share some properties with fully differentiated endothelial cells from normal tissue, yet reverse transcription-PCR and flow cytometry reveal that EPC express higher levels of endosialin at the molecular and protein levels. The elevated expression of endosialin in EPC versus mature endothelial cells suggests that endosialin is involved in the earlier stages of tumor angiogenesis. Anti-endosialin antibodies inhibited EPC migration and tube formation in vitro. In vivo, immunohistochemistry indicated that human EPC continued to express endosialin protein in a Matrigel plug angiogenesis assay established in nude mice. Anti-endosialin antibodies delivered systemically at 25 mg/kg were also able to inhibit circulating murine EPC in nude mice bearing s.c. SKNAS tumors. EPC and bone marrow-derived cells have been shown previously to incorporate into malignant blood vessels in some instances, yet they remain controversial in the field. The data presented here on endothelial genes that are up-regulated in tumor vasculature and in EPC support the hypothesis that the angiogenesis process in cancer can involve EPC.

  8. Galalctic Tides & the Sinusoidal Potential

    Science.gov (United States)

    Bartlett, David F.

    2011-05-01

    The sinusoidal potential is a nonNewtonian alternative to dark matter. Instead of φ = -GM/r we write φ = -(GM/r) cos kor, where ko= 2π/ λo and λo = Ro/20= 400 pc. Evidence for this choice for the "wavelength” λo has been given in one article and many previous meetings of the AAS & DDA. The solar system and nearby stars are trapped in a local groove of width Δr Quality (4 types) and semi-major axis aoriginal . For 10 of the 12 classes radial tides dominate Z-tides. The classic Oort cloud comets (1851-1996) have a particularly strong modulation with galactic longitude. This modulation is exactly in those directions where a radial tide would be important. The equally numerous recent Oort comets (1996-2008) show a different evidence for strong radial tides. The recent comets generally have much larger perihelion distances q than the classic ones. Here the evidence is that a radial tide is removing angular momentum from the orbit and thus bringing the perihelion closer to the earth and to observers.

  9. Highly enhanced avalanche probability using sinusoidally-gated silicon avalanche photodiode

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Shingo; Namekata, Naoto, E-mail: nnao@phys.cst.nihon-u.ac.jp; Inoue, Shuichiro [Institute of Quantum Science, Nihon University, 1-8-14 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8308 (Japan); Tsujino, Kenji [Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan)

    2014-01-27

    We report on visible light single photon detection using a sinusoidally-gated silicon avalanche photodiode. Detection efficiency of 70.6% was achieved at a wavelength of 520 nm when an electrically cooled silicon avalanche photodiode with a quantum efficiency of 72.4% was used, which implies that a photo-excited single charge carrier in a silicon avalanche photodiode can trigger a detectable avalanche (charge) signal with a probability of 97.6%.

  10. Adherence of murine lymphocytes to high endothelial venules in vitro and its radiation effect

    Energy Technology Data Exchange (ETDEWEB)

    Lixin, Liu; Zijun, Mao; Zhiwei, Yin [Suzhou Medical Coll., JS (China). Dept. of Pathophysiology

    1991-02-01

    Using the assay of specific adhesion of lymphocytes to high endothelial venules (HEV) on cryostat sections of mesenteric lymph nodes (MLN), the effects of different doses (0, 1, 2, 4, 8 Gy) of {sup 60}Co {gamma}-ray irradiation of murine MLN lymphocytes in vitro on adhesion to normal HEV was observed. The results showed that in the irradiated murine MLN lymphocytes the ability to adhere to HEV of normal MLN was reduced. Statistical significance was revealed at 2, 4, 8 Gy irradiations. This results suggests that irradiation can inhibit the specific recognition and adhesion of lymphocytes to HEV to a certain extent.

  11. Sentinel Node Biopsy Alone versus Completion Axillary Node Dissection in Node Positive Breast Cancer: Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Rachna Ram

    2014-01-01

    Full Text Available Introduction. There has been recent interest in validity of completion axillary node dissection after a positive sentinel node. This systematic review aims to ascertain if sentinel lymph node dissection alone was noninferior to axillary lymph node dissection for breast cancer patients who have a positive sentinel node. Method. A systematic review of the electronic databases Embase, MEDLINE, and Cochrane Register of Controlled Trials was carried out. Only randomised trials that had patients with positive sentinel node as the study sample were included in the meta-analysis using the reported hazard ratios with a fixed effect model. Results. Three randomised controlled trials and five retrospective studies were identified. The pooled effect for overall survival was HR 0.94, 95% CI [0.79, 1.19], and for disease free survival was HR 0.83, 95% CI [0.60, 1.14]. The reported rates for locoregional recurrence were similar in both groups. The surgical morbidity was found to be significantly more in patients who had underwent axillary dissection. Conclusion. Amongst patients with micrometastasis in the sentinel node, no further axillary dissection is necessary. For patients with macrometastasis in the sentinel node, it is reasonable to consider omitting axillary dissection to avoid the morbidity of the procedure.

  12. Representative Sinusoids for Hepatic Four-Scale Pharmacokinetics Simulations.

    Directory of Open Access Journals (Sweden)

    Lars Ole Schwen

    Full Text Available The mammalian liver plays a key role for metabolism and detoxification of xenobiotics in the body. The corresponding biochemical processes are typically subject to spatial variations at different length scales. Zonal enzyme expression along sinusoids leads to zonated metabolization already in the healthy state. Pathological states of the liver may involve liver cells affected in a zonated manner or heterogeneously across the whole organ. This spatial heterogeneity, however, cannot be described by most computational models which usually consider the liver as a homogeneous, well-stirred organ. The goal of this article is to present a methodology to extend whole-body pharmacokinetics models by a detailed liver model, combining different modeling approaches from the literature. This approach results in an integrated four-scale model, from single cells via sinusoids and the organ to the whole organism, capable of mechanistically representing metabolization inhomogeneity in livers at different spatial scales. Moreover, the model shows circulatory mixing effects due to a delayed recirculation through the surrounding organism. To show that this approach is generally applicable for different physiological processes, we show three applications as proofs of concept, covering a range of species, compounds, and diseased states: clearance of midazolam in steatotic human livers, clearance of caffeine in mouse livers regenerating from necrosis, and a parameter study on the impact of different cell entities on insulin uptake in mouse livers. The examples illustrate how variations only discernible at the local scale influence substance distribution in the plasma at the whole-body level. In particular, our results show that simultaneously considering variations at all relevant spatial scales may be necessary to understand their impact on observations at the organism scale.

  13. Plasma characteristics in non-sinusoidally excited CCP discharges

    Science.gov (United States)

    Lafleur, Trevor; Booth, Jean-Paul

    2012-10-01

    Using particle-in-cell (PIC) simulations we perform a characterization of the plasma response to positive pulse-type voltage excitations (with a repetition frequency of 13.56 MHz) in a geometrically symmetric CCP reactor (with a gap length of 2 cm) operated with argon (for pressures between 20-500 mTorr). Use of these non-sinusoidal waveforms generates an electrical asymmetry effect in the system, which necessitates the formation of a DC bias. This DC bias, together with the shape of the voltage waveforms used, produces a number of new phenomena that are not present in typical sinusoidal discharges: (1) the plasma density and ion flux can be increased as the pulse width is reduced, (2) a significant asymmetry in the ion fluxes to the powered and grounded electrodes develops as the pressure increases, (3) the average ion energy striking the grounded electrode remains low and approximately constant as the pulse width decreases, and (4) the sheath at the grounded electrode never fully collapses; electrons are no longer lost in sharp pulses, but escape essentially throughout the rf cycle. Effects (1) and (3) above offer the possibility for a new form of control in these types of discharges, where the ion flux can be increased while the ion energy on the grounded electrode can be kept small and essentially constant. This effect has recently been exploited to control the crystallinity of silicon thin films [1], where the low ion bombarding energy was found to improve the quality of films grown. [4pt] [1] Johnson E V, Pouliquen S, Delattre P A, and Booth J P, J. Non-Cryst. Solids 2012, in press.

  14. Controlling data transfers from an origin compute node to a target compute node

    Science.gov (United States)

    Archer, Charles J [Rochester, MN; Blocksome, Michael A [Rochester, MN; Ratterman, Joseph D [Rochester, MN; Smith, Brian E [Rochester, MN

    2011-06-21

    Methods, apparatus, and products are disclosed for controlling data transfers from an origin compute node to a target compute node that include: receiving, by an application messaging module on the target compute node, an indication of a data transfer from an origin compute node to the target compute node; and administering, by the application messaging module on the target compute node, the data transfer using one or more messaging primitives of a system messaging module in dependence upon the indication.

  15. The endothelial αENaC contributes to vascular endothelial function in vivo

    DEFF Research Database (Denmark)

    Tarjus, Antoine; Maase, Martina; Jeggle, Pia

    2017-01-01

    The Epithelial Sodium Channel (ENaC) is a key player in renal sodium homeostasis. The expression of α β γ ENaC subunits has also been described in the endothelium and vascular smooth muscle, suggesting a role in vascular function. We recently demonstrated that endothelial ENaC is involved in aldo......-mediated dilation. Our data suggest that endothelial αENaC contributes to vascular endothelial function in vivo....

  16. Influence of the Periodicity of Sinusoidal Boundary Condition on the Unsteady Mixed Convection within a Square Enclosure Using an Ag–Water Nanofluid

    Directory of Open Access Journals (Sweden)

    Azharul Karim

    2017-12-01

    Full Text Available A numerical study of the unsteady mixed convection heat transfer characteristics of an Ag–water nanofluid confined within a square shape lid-driven cavity has been carried out. The Galerkin weighted residual of the finite element method has been employed to investigate the effects of the periodicity of sinusoidal boundary condition for a wide range of Grashof numbers (Gr (105 to 107 with the parametric variation of sinusoidal even and odd frequency, N, from 1 to 6 at different instants (for τ = 0.1 and 1. It has been observed that both the Grashof number and the sinusoidal even and odd frequency have a significant influence on the streamlines and isotherms inside the cavity. The heat transfer rate enhanced by 90% from the heated surface as the Grashof number (Gr increased from 105 to 107 at sinusoidal frequency N = 1 and τ = 1.

  17. Protocol for multiple node network

    Science.gov (United States)

    Kirkham, Harold (Inventor)

    1995-01-01

    The invention is a multiple interconnected network of intelligent message-repeating remote nodes which employs an antibody recognition message termination process performed by all remote nodes and a remote node polling process performed by other nodes which are master units controlling remote nodes in respective zones of the network assigned to respective master nodes. Each remote node repeats only those messages originated in the local zone, to provide isolation among the master nodes.

  18. Lymph node hemophagocytosis in rickettsial diseases: a pathogenetic role for CD8 T lymphocytes in human monocytic ehrlichiosis (HME?

    Directory of Open Access Journals (Sweden)

    Dumler J Stephen

    2006-07-01

    Full Text Available Abstract Background Human monocytic ehrlichiosis (HME and Rocky Mountain spotted fever (RMSF are caused by Ehrlichia chaffeensis and Rickettsia rickettsii, respectively. The pathogenesis of RMSF relates to rickettsia-mediated vascular injury, but it is unclear in HME. Methods To study histopathologic responses in the lymphatic system for correlates of immune injury, lymph nodes from patients with HME (n = 6 and RMSF (n = 5 were examined. H&E-stained lymph node tissues were examined for five histopathologic features, including hemophagocytosis, cellularity, necrosis, and vascular congestion and edema. The relative proportions of CD68 macrophages, CD8 and CD4 T lymphocytes, and CD20 B lymphocytes were evaluated by immunohistochemical staining. Results Hemophagocytosis was similar in HME and RMSF, and was greater than in control cases (p = .015. Cellularity in HME was not different from controls, whereas RMSF lymph nodes were markedly less cellular (p E. chaffeensis-infected mononuclear phagocytes were infrequent compared to R. rickettsii-infected endothelial cells. More CD8 cells in lymph nodes were observed with HME (p Conclusion Hemophagocytosis, CD8 T cell expansion, and the paucity of infected cells in HME, suggest that E. chaffeensis infection leads to macrophage activation and immune-mediated injury.

  19. Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection.

    Science.gov (United States)

    van Rijk, Maartje C; Nieweg, Omgo E; Rutgers, Emiel J T; Oldenburg, Hester S A; Olmos, Renato Valdés; Hoefnagel, Cornelis A; Kroon, Bin B R

    2006-04-01

    Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.

  20. Automatic fringe enhancement with novel bidimensional sinusoids-assisted empirical mode decomposition.

    Science.gov (United States)

    Wang, Chenxing; Kemao, Qian; Da, Feipeng

    2017-10-02

    Fringe-based optical measurement techniques require reliable fringe analysis methods, where empirical mode decomposition (EMD) is an outstanding one due to its ability of analyzing complex signals and the merit of being data-driven. However, two challenging issues hinder the application of EMD in practical measurement. One is the tricky mode mixing problem (MMP), making the decomposed intrinsic mode functions (IMFs) have equivocal physical meaning; the other is the automatic and accurate extraction of the sinusoidal fringe from the IMFs when unpredictable and unavoidable background and noise exist in real measurements. Accordingly, in this paper, a novel bidimensional sinusoids-assisted EMD (BSEMD) is proposed to decompose a fringe pattern into mono-component bidimensional IMFs (BIMFs), with the MMP solved; properties of the resulted BIMFs are then analyzed to recognize and enhance the useful fringe component. The decomposition and the fringe recognition are integrated and the latter provides a feedback to the former, helping to automatically stop the decomposition to make the algorithm simpler and more reliable. A series of experiments show that the proposed method is accurate, efficient and robust to various fringe patterns even with poor quality, rendering it a potential tool for practical use.

  1. Catalase and superoxide dismutase conjugated with platelet-endothelial cell adhesion molecule antibody distinctly alleviate abnormal endothelial permeability caused by exogenous reactive oxygen species and vascular endothelial growth factor.

    Science.gov (United States)

    Han, Jingyan; Shuvaev, Vladimir V; Muzykantov, Vladimir R

    2011-07-01

    Reactive oxygen species (ROS) superoxide anion (O(2)()) and hydrogen peroxide (H(2)O(2)) produced by activated leukocytes and endothelial cells in sites of inflammation or ischemia cause endothelial barrier dysfunction that may lead to tissue edema. Antioxidant enzymes (AOEs) catalase and superoxide dismutase (SOD) conjugated with antibodies to platelet-endothelial cell adhesion molecule-1 (PECAM-1) specifically bind to endothelium, quench the corresponding ROS, and alleviate vascular oxidative stress and inflammation. In the present work, we studied the effects of anti-PECAM/catalase and anti-PECAM/SOD conjugates on the abnormal permeability manifested by transendothelial electrical resistance decline, increased fluorescein isothiocyanate-dextran influx, and redistribution of vascular endothelial-cadherin in human umbilical vein endothelial cell (HUVEC) monolayers. Anti-PECAM/catalase protected HUVEC monolayers against H(2)O(2)-induced endothelial barrier dysfunction. Polyethylene glycol-conjugated catalase exerted orders of magnitude lower endothelial uptake and no protective effect, similarly to IgG/catalase. Anti-PECAM/catalase, but not anti-PECAM/SOD, alleviated endothelial hyperpermeability caused by exposure to hypoxanthine/xanthine oxidase, implicating primarily H(2)O(2) in the disruption of the endothelial barrier in this model. Thrombin-induced endothelial permeability was not affected by treatment with anti-PECAM/AOEs or the NADPH oxidase inhibitor apocynin or overexpression of AOEs, indicating that the endogenous ROS play no key role in thrombin-mediated endothelial barrier dysfunction. In contrast, anti-PECAM/SOD, but not anti-PECAM/catalase, inhibited a vascular endothelial growth factor (VEGF)-induced increase in endothelial permeability, identifying a key role of endogenous O(2)() in the VEGF-mediated regulation of endothelial barrier function. Therefore, AOEs targeted to endothelial cells provide versatile molecular tools for testing the roles of

  2. Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles.

    Science.gov (United States)

    Jansen, Felix; Yang, Xiaoyan; Hoelscher, Marion; Cattelan, Arianna; Schmitz, Theresa; Proebsting, Sebastian; Wenzel, Daniela; Vosen, Sarah; Franklin, Bernardo S; Fleischmann, Bernd K; Nickenig, Georg; Werner, Nikos

    2013-10-29

    Repair of the endothelium after vascular injury is crucial for preserving endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of endothelial cell repair are largely unknown. We sought to investigate whether endothelial microparticles (EMPs), released from apoptotic endothelial cells (ECs), influence EC repair. Systemic treatment of mice with EMPs after electric denudation of the endothelium accelerated reendothelialization in vivo. In vitro experiments revealed that EMP uptake in ECs promotes EC migration and proliferation, both critical steps in endothelial repair. To dissect the underlying mechanisms, Taqman microRNA array was performed, and microRNA (miR)-126 was identified as the predominantly expressed miR in EMPs. The following experiments demonstrated that miR-126 was transported into recipient human coronary artery endothelial cells by EMPs and functionally regulated the target protein sprouty-related, EVH1 domain-containing protein 1 (SPRED1). Knockdown of miR-126 in EMPs abrogated EMP-mediated effects on human coronary artery endothelial cell migration and proliferation in vitro and reendothelialization in vivo. Interestingly, after simulating diabetic conditions, EMPs derived from glucose-treated ECs contained significantly lower amounts of miR-126 and showed reduced endothelial repair capacity in vitro and in vivo. Finally, expression analysis of miR-126 in circulating microparticles from 176 patients with stable coronary artery disease with and without diabetes mellitus revealed a significantly reduced miR-126 expression in circulating microparticles from diabetic patients. Endothelial microparticles promote vascular endothelial repair by delivering functional miR-126 into recipient cells. In pathological hyperglycemic conditions, EMP-mediated miR-126-induced EC repair is altered.

  3. Endothelial MMP14 is required for endothelial-dependent growth support of human airway basal cells

    Science.gov (United States)

    Ding, Bi-Sen; Gomi, Kazunori; Rafii, Shahin; Crystal, Ronald G.; Walters, Matthew S.

    2015-01-01

    ABSTRACT Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying non-epithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated signaling. Building on these findings, we found, by RNA sequencing analysis, that basal cells expressed multiple fibroblast growth factor (FGF) ligands (FGF2, FGF5, FGF11 and FGF13) and that only FGF2 and FGF5 were capable of functioning in a paracrine manner to activate classical FGF receptor (FGFR) signaling. Antibody-mediated blocking of FGFR1 during basal-cell–endothelial-cell co-culture significantly reduced the endothelial-cell-dependent basal cell growth. Stimulation of endothelial cells with basal-cell-derived growth factors induced endothelial cell expression of matrix metallopeptidase 14 (MMP14), and short hairpin RNA (shRNA)-mediated knockdown of endothelial cell MMP14 significantly reduced the endothelial-cell-dependent growth of basal cells. Overall, these data characterize a new growth-factor-mediated reciprocal ‘crosstalk’ between human airway basal cells and endothelial cells that regulates proliferation of basal cells. PMID:26116571

  4. Design of Helical Capacitance Sensor for Holdup Measurement in Two-Phase Stratified Flow: A Sinusoidal Function Approach

    Science.gov (United States)

    Lim, Lam Ghai; Pao, William K. S.; Hamid, Nor Hisham; Tang, Tong Boon

    2016-01-01

    A 360° twisted helical capacitance sensor was developed for holdup measurement in horizontal two-phase stratified flow. Instead of suppressing nonlinear response, the sensor was optimized in such a way that a ‘sine-like’ function was displayed on top of the linear function. This concept of design had been implemented and verified in both software and hardware. A good agreement was achieved between the finite element model of proposed design and the approximation model (pure sinusoidal function), with a maximum difference of ±1.2%. In addition, the design parameters of the sensor were analysed and investigated. It was found that the error in symmetry of the sinusoidal function could be minimized by adjusting the pitch of helix. The experiments of air-water and oil-water stratified flows were carried out and validated the sinusoidal relationship with a maximum difference of ±1.2% and ±1.3% for the range of water holdup from 0.15 to 0.85. The proposed design concept therefore may pose a promising alternative for the optimization of capacitance sensor design. PMID:27384567

  5. Design of Helical Capacitance Sensor for Holdup Measurement in Two-Phase Stratified Flow: A Sinusoidal Function Approach

    Directory of Open Access Journals (Sweden)

    Lam Ghai Lim

    2016-07-01

    Full Text Available A 360° twisted helical capacitance sensor was developed for holdup measurement in horizontal two-phase stratified flow. Instead of suppressing nonlinear response, the sensor was optimized in such a way that a ‘sine-like’ function was displayed on top of the linear function. This concept of design had been implemented and verified in both software and hardware. A good agreement was achieved between the finite element model of proposed design and the approximation model (pure sinusoidal function, with a maximum difference of ±1.2%. In addition, the design parameters of the sensor were analysed and investigated. It was found that the error in symmetry of the sinusoidal function could be minimized by adjusting the pitch of helix. The experiments of air-water and oil-water stratified flows were carried out and validated the sinusoidal relationship with a maximum difference of ±1.2% and ±1.3% for the range of water holdup from 0.15 to 0.85. The proposed design concept therefore may pose a promising alternative for the optimization of capacitance sensor design.

  6. Design of Helical Capacitance Sensor for Holdup Measurement in Two-Phase Stratified Flow: A Sinusoidal Function Approach.

    Science.gov (United States)

    Lim, Lam Ghai; Pao, William K S; Hamid, Nor Hisham; Tang, Tong Boon

    2016-07-04

    A 360° twisted helical capacitance sensor was developed for holdup measurement in horizontal two-phase stratified flow. Instead of suppressing nonlinear response, the sensor was optimized in such a way that a 'sine-like' function was displayed on top of the linear function. This concept of design had been implemented and verified in both software and hardware. A good agreement was achieved between the finite element model of proposed design and the approximation model (pure sinusoidal function), with a maximum difference of ±1.2%. In addition, the design parameters of the sensor were analysed and investigated. It was found that the error in symmetry of the sinusoidal function could be minimized by adjusting the pitch of helix. The experiments of air-water and oil-water stratified flows were carried out and validated the sinusoidal relationship with a maximum difference of ±1.2% and ±1.3% for the range of water holdup from 0.15 to 0.85. The proposed design concept therefore may pose a promising alternative for the optimization of capacitance sensor design.

  7. Vascular endothelial growth factor receptor-3 directly interacts with phosphatidylinositol 3-kinase to regulate lymphangiogenesis.

    Directory of Open Access Journals (Sweden)

    Sanja Coso

    Full Text Available BACKGROUND: Dysfunctional lymphatic vessel formation has been implicated in a number of pathological conditions including cancer metastasis, lymphedema, and impaired wound healing. The vascular endothelial growth factor (VEGF family is a major regulator of lymphatic endothelial cell (LEC function and lymphangiogenesis. Indeed, dissemination of malignant cells into the regional lymph nodes, a common occurrence in many cancers, is stimulated by VEGF family members. This effect is generally considered to be mediated via VEGFR-2 and VEGFR-3. However, the role of specific receptors and their downstream signaling pathways is not well understood. METHODS AND RESULTS: Here we delineate the VEGF-C/VEGF receptor (VEGFR-3 signaling pathway in LECs and show that VEGF-C induces activation of PI3K/Akt and MEK/Erk. Furthermore, activation of PI3K/Akt by VEGF-C/VEGFR-3 resulted in phosphorylation of P70S6K, eNOS, PLCγ1, and Erk1/2. Importantly, a direct interaction between PI3K and VEGFR-3 in LECs was demonstrated both in vitro and in clinical cancer specimens. This interaction was strongly associated with the presence of lymph node metastases in primary small cell carcinoma of the lung in clinical specimens. Blocking PI3K activity abolished VEGF-C-stimulated LEC tube formation and migration. CONCLUSIONS: Our findings demonstrate that specific VEGFR-3 signaling pathways are activated in LECs by VEGF-C. The importance of PI3K in VEGF-C/VEGFR-3-mediated lymphangiogenesis provides a potential therapeutic target for the inhibition of lymphatic metastasis.

  8. Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?

    Science.gov (United States)

    McCarthy, E M; Wilkinson, F L; Parker, B; Alexander, M Y

    2016-11-01

    Autoimmune rheumatic diseases are characterised by systemic inflammation and complex immunopathology, with an increased risk of cardiovascular disease, initiated by endothelial dysfunction in a chronic inflammatory environment. Endothelial microparticles (EMPs) are released into the circulation from activated endothelial cells and may therefore, reflect disease severity, vascular and endothelial dysfunction, that could influence disease pathogenesis via autocrine/paracrine signalling. The exact function of EMPs in rheumatic disease remains unknown, and this has initiated research to elucidate EMP composition and function, which may be determined by the mode of endothelial activation and the micro environment. To date, EMPs are thought to play a role in angiogenesis, thrombosis and inflammation by transferring specific proteins and microRNAs (miRs) to target cells. Here, we review the mechanisms underlying the generation and composition of EMPs and the clinical and experimental studies describing the involvement of EMPs in rheumatic diseases, since we have previously shown endothelial dysfunction and an elevated risk of cardiovascular disease are characteristics in systemic lupus erythematosus. We will also discuss the potential of EMPs as future biomarkers of cardiovascular risk in these diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. CFD study on NACA 4415 airfoil implementing spherical and sinusoidal Tubercle Leading Edge.

    Science.gov (United States)

    Aftab, S M A; Ahmad, K A

    2017-01-01

    The Humpback whale tubercles have been studied for more than a decade. Tubercle Leading Edge (TLE) effectively reduces the separation bubble size and helps in delaying stall. They are very effective in case of low Reynolds number flows. The current Computational Fluid Dynamics (CFD) study is on NACA 4415 airfoil, at a Reynolds number 120,000. Two TLE shapes are tested on NACA 4415 airfoil. The tubercle designs implemented on the airfoil are sinusoidal and spherical. A parametric study is also carried out considering three amplitudes (0.025c, 0.05c and 0.075c), the wavelength (0.25c) is fixed. Structured mesh is utilized to generate grid and Transition SST turbulence model is used to capture the flow physics. Results clearly show spherical tubercles outperform sinusoidal tubercles. Furthermore experimental study considering spherical TLE is carried out at Reynolds number 200,000. The experimental results show that spherical TLE improve performance compared to clean airfoil.

  10. CFD study on NACA 4415 airfoil implementing spherical and sinusoidal Tubercle Leading Edge.

    Directory of Open Access Journals (Sweden)

    S M A Aftab

    Full Text Available The Humpback whale tubercles have been studied for more than a decade. Tubercle Leading Edge (TLE effectively reduces the separation bubble size and helps in delaying stall. They are very effective in case of low Reynolds number flows. The current Computational Fluid Dynamics (CFD study is on NACA 4415 airfoil, at a Reynolds number 120,000. Two TLE shapes are tested on NACA 4415 airfoil. The tubercle designs implemented on the airfoil are sinusoidal and spherical. A parametric study is also carried out considering three amplitudes (0.025c, 0.05c and 0.075c, the wavelength (0.25c is fixed. Structured mesh is utilized to generate grid and Transition SST turbulence model is used to capture the flow physics. Results clearly show spherical tubercles outperform sinusoidal tubercles. Furthermore experimental study considering spherical TLE is carried out at Reynolds number 200,000. The experimental results show that spherical TLE improve performance compared to clean airfoil.

  11. Controlled generation of nonlinear resonances through sinusoidal lattice modes in Bose–Einstein condensate

    International Nuclear Information System (INIS)

    Das, Priyam; Panigrahi, Prasanta K

    2015-01-01

    We study Bose–Einstein condensate in the combined presence of time modulated optical lattice and harmonic trap in the mean-field approach. Through the self-similar method, we show the existence of sinusoidal lattice modes in this inhomogeneous system, commensurate with the lattice potential. A significant advantage of this system is wide tunability of the parameters through chirp management. The combined effect of the interaction, harmonic trap and lattice potential leads to the generation of nonlinear resonances, exactly where the matter wave changes its direction. When the harmonic trap is switched off, the BEC undergoes a nonlinear compression for the static optical lattice potential. For better understanding of chirp management and the nature of the sinusoidal excitation, we investigate the energy spectrum of the condensate, which clearly reveals the generation of nonlinear resonances in the appropriate regime. We have also identified a classical dynamical phase transition occurring in the system, where loss of superfluidity takes the superfluid phase to an insulating state. (paper)

  12. Stress singularities in a model of a wood disk under sinusoidal pressure

    Science.gov (United States)

    Jay A. Johnson; John C. Hermanson; Steven M. Cramer; Charles Amundson

    2005-01-01

    A thin, solid, circular wood disk, cut from the transverse plane of a tree stem, can be modeled as a cylindrically orthotropic elastic material. It is known that a stress singularity can occur at the center of a cylindrically orthotropic disk subjected to uniform pressure. If a solid cylindrically orthotropic disk is subjected to sinusoidal pressure distributions, then...

  13. Curcumin modulates endothelial permeability and monocyte transendothelial migration by affecting endothelial cell dynamics.

    Science.gov (United States)

    Monfoulet, Laurent-Emmanuel; Mercier, Sylvie; Bayle, Dominique; Tamaian, Radu; Barber-Chamoux, Nicolas; Morand, Christine; Milenkovic, Dragan

    2017-11-01

    Curcumin is a phenolic compound that exhibits beneficial properties for cardiometabolic health. We previously showed that curcumin reduced the infiltration of immune cells into the vascular wall and prevented atherosclerosis development in mice. This study aimed to investigate the effect of curcumin on monocyte adhesion and transendothelial migration (TEM) and to decipher the underlying mechanisms of these actions. Human umbilical vein endothelial cells (HUVECs) were exposed to curcumin (0.5-1μM) for 3h prior to their activation by Tumor Necrosis Factor alpha (TNF-α). Endothelial permeability, monocyte adhesion and transendothelial migration assays were conducted under static condition and shear stress that mimics blood flow. We further investigated the impact of curcumin on signaling pathways and on the expression of genes using macroarrays. Pre-exposure of endothelial cells to curcumin reduced monocyte adhesion and their transendothelial migration in both static and shear stress conditions. Curcumin also prevented changes in both endothelial permeability and the area of HUVECs when induced by TNF-α. We showed that curcumin modulated the expression of 15 genes involved in the control of cytoskeleton and endothelial junction dynamic. Finally, we showed that curcumin inhibited NF-κB signaling likely through an antagonist interplay with several kinases as suggested by molecular docking analysis. Our findings demonstrate the ability of curcumin to reduce monocyte TEM through a multimodal regulation of the endothelial cell dynamics with a potential benefit on the vascular endothelial function barrier. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Pattern of Colon Cancer Lymph Node Metastases in Patients Undergoing Central Mesocolic Lymph Node Excision

    DEFF Research Database (Denmark)

    Bertelsen, Claus A; Kirkegaard-Klitbo, Anders; Nielsen, Mingyuan

    2016-01-01

    BACKGROUND: Extended mesocolic lymph node dissection in colon cancer surgery seems to improve oncological outcome. A possible reason might be related to metastases in the central mesocolic lymph nodes. OBJECTIVE: The purpose of this study was to describe the pattern of mesocolic lymph node...... metastases, particularly in central lymph nodes, and the risk of skip, aberrant, and gastrocolic ligament metastases as the argument for performing extended lymph node dissection. DATA SOURCES: EMBASE and PubMed were searched using the terms colon or colorectal with sentinel node, lymph node mapping, or skip...... node; lymph node resection colon; and complete or total and mesocolic excision. STUDY SELECTION: Studies describing the risk of metastases in central, skip, aberrant, and gastrocolic ligament lymph node metastases from colon adenocarcinomas in 10 or more patients were included. No languages were...

  15. Nematic liquid crystals on sinusoidal channels: the zigzag instability.

    Science.gov (United States)

    Silvestre, Nuno M; Romero-Enrique, Jose M; Telo da Gama, Margarida M

    2017-01-11

    Substrates which are chemically or topographically patterned induce a variety of liquid crystal textures. The response of the liquid crystal to competing surface orientations, typical of patterned substrates, is determined by the anisotropy of the elastic constants and the interplay of the relevant lengths scales, such as the correlation length and the surface geometrical parameters. Transitions between different textures, usually with different symmetries, may occur under a wide range of conditions. We use the Landau-de Gennes free energy to investigate the texture of nematics in sinusoidal channels with parallel anchoring bounded by nematic-air interfaces that favour perpendicular (hometropic) anchoring. In micron size channels 5CB was observed to exhibit a non-trivial texture characterized by a disclination line, within the channel, which is broken into a zigzag pattern. Our calculations reveal that when the elastic anisotropy of the nematic does not favour twist distortions the defect is a straight disclination line that runs along the channel, which breaks into a zigzag pattern with a characteristic period, when the twist elastic constant becomes sufficiently small when compared to the splay and bend constants. The transition occurs through a twist instability that drives the defect line to rotate from its original position. The interplay between the energetically favourable twist distortions that induce the defect rotation and the liquid crystal anchoring at the surfaces leads to the zigzag pattern. We investigate in detail the dependence of the periodicity of the zigzag pattern on the geometrical parameters of the sinusoidal channels, which in line with the experimental results is found to be non-linear.

  16. Partial axillary lymph node dissection inferior to the intercostobrachial nerves complements sentinel node biopsy in patients with clinically node-negative breast cancer.

    Science.gov (United States)

    Li, Jianyi; Jia, Shi; Zhang, Wenhai; Qiu, Fang; Zhang, Yang; Gu, Xi; Xue, Jinqi

    2015-06-30

    The practice of breast cancer diagnosis and treatment in China varies to that in western developed countries. With the unavailability of radioactive tracer technique for sentinel lymph nodes biopsy (SLNB), using blue dye alone has been the only option in China. Also, the diagnosis of breast malignant tumor in most Chinese centres heavily relies on intraoperative instant frozen histology which is normally followed by sentinel lymph nodes mapping, SLNB and the potential breast and axillary operations in one consecutive session. This practice appears to cause a high false negative rate (FNR) for SLNB. The present study aimed to investigate the impact of the current practice in China on the accuracy of SLNB, and whether partial axillary lymph node dissection (PALND), dissection of lymph nodes inferior to the intercostobrachial nerve (ICBN), was a good complementary procedure following SLNB using blue dye. 289 patients with clinically node-negative breast cancer were identified and recruited. Tumorectomy, intraoperative instant frozen histological diagnosis, SLNB using methylene blue dye, and PALND or complete axillary node dissection (ALND) were performed in one consecutive operative session. The choice of SLNB only, SLNB followed by PALND or by ALND was based on the pre-determined protocol and preoperative choice by the patient. Clinical parameters were analyzed and survival analysis was performed. 37% patients with clinically negative nodes were found nodes positive. 59 patients with positive SLN underwent ALND, including 47 patients with up to two positive nodes which were all located inferior to the ICBN. 9 patients had failed SLNB and underwent PALND. Among them, 3 (33.3%) patients were found to have one metastatic node. 149 patients showed negative SLNB but chose PALND. Among them, 30 (20.1%), 14 (9.4) and 1 (0.7%) patients were found to have one, two and three metastatic node(s), respectively. PALND detected 48 (30.4%) patients who had either failed SLNB or

  17. Animal study on transplantation of human umbilical vein endothelial cells for corneal endothelial decompensation

    Directory of Open Access Journals (Sweden)

    Li Cui

    2014-06-01

    Full Text Available AIM: To explore the feasibility of culturing human umbilical vein endothelial cells(HUVECon acellular corneal stroma and performing the posterior lamellar endothelial keratoplasty(PLEKtreating corneal endothelial decompensation.METHODS: Thirty New-Zealand rabbits were divided into three groups randomly, 10 rabbits for experimental group, 10 for stroma group and 10 for control group. Corneal endothelial cells were removed to establish animal model of corneal endothelial failure. PLEK was performed on the rabbits of experimental group and stroma group, and nothing was transplantated onto the rabbits of control group with the deep layer excised only. Postoperative observation was taken for 3mo. The degree of corneal edema and central corneal thickness were recorded for statistical analysis.RESULTS: Corneas in experimental group were relieved in edema obviously compared with that in stroma group and the control group, and showed increased transparency 7d after the operation. The average density of endothelial cells was 2 026.4±129.3cells/mm2, and average central corneal thickness was 505.2±25.4μm in experimental group, while 1 535.6±114.5μm in stroma group and 1 493.5±70.2μm in control group 3mo after operation.CONCLUSION:We achieved preliminary success in our study that culturing HUVEC on acellular corneal stroma and performing PLEK for corneal endothelial decompensation. HUVEC transplanted could survive in vivo, and have normal biological function of keeping cornea transparent. This study provides a new idea and a new way clinically for the treatment of corneal endothelial diseases.

  18. Losses analysis of soft magnetic ring core under sinusoidal pulse width modulation (SPWM) and space vector pulse width modulation (SVPWM) excitations

    Science.gov (United States)

    Gao, Hezhe; Li, Yongjian; Wang, Shanming; Zhu, Jianguo; Yang, Qingxin; Zhang, Changgeng; Li, Jingsong

    2018-05-01

    Practical core losses in electrical machines differ significantly from those experimental results using the standardized measurement method, i.e. Epstein Frame method. In order to obtain a better approximation of the losses in an electrical machine, a simulation method considering sinusoidal pulse width modulation (SPWM) and space vector pulse width modulation (SVPWM) waveforms is proposed. The influence of the pulse width modulation (PWM) parameters on the harmonic components in SPWM and SVPWM is discussed by fast Fourier transform (FFT). Three-level SPWM and SVPWM are analyzed and compared both by simulation and experiment. The core losses of several ring samples magnetized by SPWM, SVPWM and sinusoidal alternating current (AC) are obtained. In addition, the temperature rise of the samples under SPWM, sinusoidal excitation are analyzed and compared.

  19. Diffraction Efficiency Testing of Sinusoidal and Blazed Off-Plane Reflection Gratings

    Science.gov (United States)

    Tutt, James H.; McEntaffer, Randall L.; Marlowe, Hannah; Miles, Drew M.; Peterson, Thomas J.; Deroo, Casey T.; Scholze, Frank; Laubis, Christian

    2016-09-01

    Reflection gratings in the off-plane mount have the potential to enhance the performance of future high resolution soft X-ray spectrometers. Diffraction efficiency can be optimized through the use of blazed grating facets, achieving high-throughput on one side of zero-order. This paper presents the results from a comparison between a grating with a sinusoidally grooved profile and two gratings that have been blazed. The results show that the blaze does increase throughput to one side of zero-order; however, the total throughput of the sinusoidal gratings is greater than the blazed gratings, suggesting the method of manufacturing the blazed gratings does not produce precise facets. The blazed gratings were also tested in their Littrow and anti-Littrow configurations to quantify diffraction efficiency sensitivity to rotations about the grating normal. Only a small difference in the energy at which efficiency is maximized between the Littrow and anti-Littrow configurations is seen with a small shift in peak efficiency towards higher energies in the anti-Littrow case. This is due to a decrease in the effective blaze angle in the anti-Littrow mounting. This is supported by PCGrate-SX V6.1 modeling carried out for each blazed grating which predicts similar response trends in the Littrow and anti-Littrow orientations.

  20. Endothelial dysfunction after non-cardiac surgery

    DEFF Research Database (Denmark)

    Søndergaard, E S; Fonnes, S; Gögenur, I

    2015-01-01

    was to systematically review the literature to evaluate the association between non-cardiac surgery and non-invasive markers of endothelial function. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane Library Database according to the PRISMA guidelines. Endothelial dysfunction was described only...... transplantation and vascular surgery respectively) had an improvement in endothelial dysfunction 1 month after surgery. CONCLUSION: Endothelial function changes in relation to surgery. Assessment of endothelial function by non-invasive measures has the potential to guide clinicians in the prevention or treatment...

  1. Driving and control strategies in alternative current machines of permanent magnet with non-sinusoidal flux; Estrategias de acionamento e controle em maquinas CA de ima permanente com fluxo nao senoidal

    Energy Technology Data Exchange (ETDEWEB)

    Monteiro, Jose Roberto Boffino de Almeida

    1997-07-01

    The aim of this work is to study and analyze the torque performance of brush less machines with non-sinusoidal distributed magnetic fluxes. The machine type considered is a surface mount permanent magnet brush less machine. Three mathematical models for the machine are considered: the per stator phase, the vectorial and the linear second order speed-voltage models. Machines with different stator windings are compared including the permanent magnet synchronous machines with sinusoidal distributed stator windings. The torque outputs of these machines are obtained considering two kinds of open loop driving systems: one with a six-pulse waveform and other with a sinusoidal waveform. Finally, a vectorial control is proposed for the non-sinusoidal machines. The torque ripple as well the overall performance of non-sinusoidal machines with vectorial control is compared to that of sinusoidal machines. (author)

  2. Mitochondria and Endothelial Function

    Science.gov (United States)

    Kluge, Matthew A.; Fetterman, Jessica L.; Vita, Joseph A.

    2013-01-01

    In contrast to their role in other cell types with higher energy demands, mitochondria in endothelial cells primarily function in signaling cellular responses to environmental cues. This article provides an overview of key aspects of mitochondrial biology in endothelial cells, including subcellular location, biogenesis, dynamics, autophagy, ROS production and signaling, calcium homeostasis, regulated cell death, and heme biosynthesis. In each section, we introduce key concepts and then review studies showing the importance of that mechanism to endothelial control of vasomotor tone, angiogenesis, and inflammatory activation. We particularly highlight the small number of clinical and translational studies that have investigated each mechanism in human subjects. Finally, we review interventions that target different aspects of mitochondrial function and their effects on endothelial function. The ultimate goal of such research is the identification of new approaches for therapy. The reviewed studies make it clear that mitochondria are important in endothelial physiology and pathophysiology. A great deal of work will be needed, however, before mitochondria-directed therapies are available for the prevention and treatment of cardiovascular disease. PMID:23580773

  3. Implementation of Multiple Host Nodes in Wireless Sensing Node Network System for Landslide Monitoring

    International Nuclear Information System (INIS)

    Bin Abas, Faizulsalihin; Takayama, Shigeru

    2015-01-01

    This paper proposes multiple host nodes in Wireless Sensing Node Network System (WSNNS) for landslide monitoring. As landslide disasters damage monitoring system easily, one major demand in landslide monitoring is the flexibility and robustness of the system to evaluate the current situation in the monitored area. For various reasons WSNNS can provide an important contribution to reach that aim. In this system, acceleration sensors and GPS are deployed in sensing nodes. Location information by GPS, enable the system to estimate network topology and enable the system to perceive the location in emergency by monitoring the node mode. Acceleration sensors deployment, capacitate this system to detect slow mass movement that can lead to landslide occurrence. Once deployed, sensing nodes self-organize into an autonomous wireless ad hoc network. The measurement parameter data from sensing nodes is transmitted to Host System via host node and ''Cloud'' System. The implementation of multiple host nodes in Local Sensing Node Network System (LSNNS), improve risk- management of the WSNNS for real-time monitoring of landslide disaster

  4. Implementation of Multiple Host Nodes in Wireless Sensing Node Network System for Landslide Monitoring

    Science.gov (United States)

    Abas, Faizulsalihin bin; Takayama, Shigeru

    2015-02-01

    This paper proposes multiple host nodes in Wireless Sensing Node Network System (WSNNS) for landslide monitoring. As landslide disasters damage monitoring system easily, one major demand in landslide monitoring is the flexibility and robustness of the system to evaluate the current situation in the monitored area. For various reasons WSNNS can provide an important contribution to reach that aim. In this system, acceleration sensors and GPS are deployed in sensing nodes. Location information by GPS, enable the system to estimate network topology and enable the system to perceive the location in emergency by monitoring the node mode. Acceleration sensors deployment, capacitate this system to detect slow mass movement that can lead to landslide occurrence. Once deployed, sensing nodes self-organize into an autonomous wireless ad hoc network. The measurement parameter data from sensing nodes is transmitted to Host System via host node and "Cloud" System. The implementation of multiple host nodes in Local Sensing Node Network System (LSNNS), improve risk- management of the WSNNS for real-time monitoring of landslide disaster.

  5. Interleukin-24 is correlated with differentiation and lymph node numbers in rectal cancer

    Science.gov (United States)

    Choi, Youngmin; Roh, Mee-Sook; Hong, Young-Seoub; Lee, Hyung-Sik; Hur, Won-Joo

    2011-01-01

    AIM: To assess the significance of interleukin (IL)-24 and vascular endothelial growth factor (VEGF) expression in lymph-node-positive rectal cancer. METHODS: Between 1998 and 2005, 90 rectal adenocarcinoma patients with lymph node involvement were enrolled. All patients received radical surgery and postoperative pelvic chemoradiotherapy of 50.4-54.0 Gy. Chemotherapy of 5-fluorouracil and leucovorin or levamisole was given intravenously during the first and last week of radiotherapy, and then monthly for about 6 mo. Expression of IL-24 and VEGF was evaluated by immunohistochemical staining of surgical specimens, and their relations with patient characteristics and survival were analyzed. The median follow-up of surviving patients was 73 mo (range: 52-122 mo). RESULTS: IL-24 expression was found in 81 out of 90 patients; 31 showed weak intensity and 50 showed strong intensity. VEGF expression was found in 64 out of 90 patients. Negative and weak intensities of IL-24 expression were classified as negative expression for analysis. IL-24 expression was significantly reduced in poorly differentiated tumors in comparison with well or moderately differentiated tumors (P = 0.004), N2b to earlier N stages (P = 0.016), and stage IIIc to stage IIIa or IIIb (P = 0.028). The number of involved lymph nodes was also significantly reduced in IL-24-positive patients in comparison with IL-24-negative ones.There was no correlation between VEGF expression and patient characteristics. Expression of IL-24 and VEGF was not correlated with survival, but N stage and stages were significantly correlated with survival. CONCLUSION: IL-24 expression was significantly correlated with histological differentiation, and inversely correlated with the degree of lymph node involvement in stage III rectal cancer. PMID:21448421

  6. Dynamically reassigning a connected node to a block of compute nodes for re-launching a failed job

    Science.gov (United States)

    Budnik, Thomas A [Rochester, MN; Knudson, Brant L [Rochester, MN; Megerian, Mark G [Rochester, MN; Miller, Samuel J [Rochester, MN; Stockdell, William M [Byron, MN

    2012-03-20

    Methods, systems, and products for dynamically reassigning a connected node to a block of compute nodes for re-launching a failed job that include: identifying that a job failed to execute on the block of compute nodes because connectivity failed between a compute node assigned as at least one of the connected nodes for the block of compute nodes and its supporting I/O node; and re-launching the job, including selecting an alternative connected node that is actively coupled for data communications with an active I/O node; and assigning the alternative connected node as the connected node for the block of compute nodes running the re-launched job.

  7. Realization of Electronically Tunable Current- Mode Multiphase Sinusoidal Oscillators Using CFTAs

    OpenAIRE

    Prungsak Uttaphut

    2012-01-01

    An implementation of current-mode multiphase sinusoidal oscillators is presented. Using CFTA-based lossy integrators, odd and odd/even phase systems can be realized with following advantages. The condition of oscillation and frequency of oscillation can be orthogonally tuned. The high output impedances facilitate easy driving an external load without additional current buffers. The proposed MSOs provide odd or even phase signals that are equally spaced in phase and equal amplitude. The circui...

  8. Value of irradiation of neck nodes metastases. Pt. 1. Treatment of palpable nodes

    International Nuclear Information System (INIS)

    Bujko, K.

    1993-01-01

    Medical records of 222 patients with neck nodes metastases from squamous cell carcinoma of supraglottic larynx, tonsil and base of tongue were analyzed. All cases were treated with definitive irradiation. 110 patients were treated with orthovoltage technique with total doses of 5000-6000 rads, 150-10 rads per fraction; 112 patients with Co-60 with total doses 6000-7000 rads, 180-230 rads per fraction. Local-regional control was achieved in 28% of cases. Failures in the neck nodes with primary tumor controlled, were recorded in 10% of patients. Failures in a primary tumor alone were observed in 26% of patients, in primary tumor and neck nodes in 36%. Radiocurability of primary tumor and involved neck nodes was similar. In cases with primary tumor controlled, the probability of eradication of neck nodes metastases is high, even in N3 stage patients. Residual neck nodes palpable 1 to 3 months after irradiation were unfavorable prognostic factor indicated 50% risk of neck recurrence. In patients with complete regression of primary and nodal disease, failure in neck nodes was recorded in 5% of cases. The role of surgery following irradiation in patients with cervical nodes metastases is discussed. (author)

  9. Anesthetic propofol overdose causes endothelial cytotoxicity in vitro and endothelial barrier dysfunction in vivo

    International Nuclear Information System (INIS)

    Lin, Ming-Chung; Chen, Chia-Ling; Yang, Tsan-Tzu; Choi, Pui-Ching; Hsing, Chung-Hsi; Lin, Chiou-Feng

    2012-01-01

    An overdose and a prolonged treatment of propofol may cause cellular cytotoxicity in multiple organs and tissues such as brain, heart, kidney, skeletal muscle, and immune cells; however, the underlying mechanism remains undocumented, particularly in vascular endothelial cells. Our previous studies showed that the activation of glycogen synthase kinase (GSK)-3 is pro-apoptotic in phagocytes during overdose of propofol treatment. Regarding the intravascular administration of propofol, we therefore hypothesized that propofol overdose also induces endothelial cytotoxicity via GSK-3. Propofol overdose (100 μg/ml) inhibited growth in human arterial and microvascular endothelial cells. After treatment, most of the endothelial cells experienced caspase-independent necrosis-like cell death. The activation of cathepsin D following lysosomal membrane permeabilization (LMP) determined necrosis-like cell death. Furthermore, propofol overdose also induced caspase-dependent apoptosis, at least in part. Caspase-3 was activated and acted downstream of mitochondrial transmembrane potential (MTP) loss; however, lysosomal cathepsins were not required for endothelial cell apoptosis. Notably, activation of GSK-3 was essential for propofol overdose-induced mitochondrial damage and apoptosis, but not necrosis-like cell death. Intraperitoneal administration of a propofol overdose in BALB/c mice caused an increase in peritoneal vascular permeability. These results demonstrate the cytotoxic effects of propofol overdose, including cathepsin D-regulated necrosis-like cell death and GSK-3-regulated mitochondrial apoptosis, on endothelial cells in vitro and the endothelial barrier dysfunction by propofol in vivo. Highlights: ► Propofol overdose causes apoptosis and necrosis in endothelial cells. ► Propofol overdose triggers lysosomal dysfunction independent of autophagy. ► Glycogen synthase kinase-3 facilitates propofol overdose-induced apoptosis. ► Propofol overdose causes an increase

  10. Anesthetic propofol overdose causes endothelial cytotoxicity in vitro and endothelial barrier dysfunction in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Ming-Chung [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Department of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan, Taiwan (China); Chen, Chia-Ling [Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Yang, Tsan-Tzu; Choi, Pui-Ching [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Hsing, Chung-Hsi [Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan (China); Department of Anesthesiology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Lin, Chiou-Feng, E-mail: cflin@mail.ncku.edu.tw [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China)

    2012-12-01

    An overdose and a prolonged treatment of propofol may cause cellular cytotoxicity in multiple organs and tissues such as brain, heart, kidney, skeletal muscle, and immune cells; however, the underlying mechanism remains undocumented, particularly in vascular endothelial cells. Our previous studies showed that the activation of glycogen synthase kinase (GSK)-3 is pro-apoptotic in phagocytes during overdose of propofol treatment. Regarding the intravascular administration of propofol, we therefore hypothesized that propofol overdose also induces endothelial cytotoxicity via GSK-3. Propofol overdose (100 μg/ml) inhibited growth in human arterial and microvascular endothelial cells. After treatment, most of the endothelial cells experienced caspase-independent necrosis-like cell death. The activation of cathepsin D following lysosomal membrane permeabilization (LMP) determined necrosis-like cell death. Furthermore, propofol overdose also induced caspase-dependent apoptosis, at least in part. Caspase-3 was activated and acted downstream of mitochondrial transmembrane potential (MTP) loss; however, lysosomal cathepsins were not required for endothelial cell apoptosis. Notably, activation of GSK-3 was essential for propofol overdose-induced mitochondrial damage and apoptosis, but not necrosis-like cell death. Intraperitoneal administration of a propofol overdose in BALB/c mice caused an increase in peritoneal vascular permeability. These results demonstrate the cytotoxic effects of propofol overdose, including cathepsin D-regulated necrosis-like cell death and GSK-3-regulated mitochondrial apoptosis, on endothelial cells in vitro and the endothelial barrier dysfunction by propofol in vivo. Highlights: ► Propofol overdose causes apoptosis and necrosis in endothelial cells. ► Propofol overdose triggers lysosomal dysfunction independent of autophagy. ► Glycogen synthase kinase-3 facilitates propofol overdose-induced apoptosis. ► Propofol overdose causes an increase

  11. Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.

    Science.gov (United States)

    Witek, Rafal P; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S; Cheong, Yeiwon; Fearing, Caitlin M; Agboola, Kolade M; Chen, Wei; Diehl, Anna Mae

    2009-01-01

    Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes, and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). MF-HSC and cholangiocytes were exposed to platelet-derived growth factor to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy and immunoblots, and applied to Hh-reporter-containing cells. Microparticles were obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, an Hh signaling inhibitor. Effects on SEC gene expression were evaluated by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Platelet-derived growth factor-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically-active Hh ligands. BDL increased release of Hh-containing exosome-enriched microparticles into plasma and bile. Transmission electron microscopy and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy.

  12. Apoptosis of Endothelial Cells by 13-HPODE Contributes to Impairment of Endothelial Barrier Integrity

    Directory of Open Access Journals (Sweden)

    Valerie E. Ryman

    2016-01-01

    Full Text Available Inflammation is an essential host response during bacterial infections such as bovine mastitis. Endothelial cells are critical for an appropriate inflammatory response and loss of vascular barrier integrity is implicated in the pathogenesis of Streptococcus uberis-induced mastitis. Previous studies suggested that accumulation of linoleic acid (LA oxygenation products derived from 15-lipoxygenase-1 (15-LOX-1 metabolism could regulate vascular functions. The initial LA derivative from the 15-LOX-1 pathway, 13-hydroperoxyoctadecadienoic acid (HPODE, can induce endothelial death, whereas the reduced hydroxyl product, 13-hydroxyoctadecadienoic acid (HODE, is abundantly produced during vascular activation. However, the relative contribution of specific LA-derived metabolites on impairment of mammary endothelial integrity is unknown. Our hypothesis was that S. uberis-induced LA-derived 15-LOX-1 oxygenation products impair mammary endothelial barrier integrity by apoptosis. Exposure of bovine mammary endothelial cells (BMEC to S. uberis did not increase 15-LOX-1 LA metabolism. However, S. uberis challenge of bovine monocytes demonstrated that monocytes may be a significant source of both 13-HPODE and 13-HODE during mastitis. Exposure of BMEC to 13-HPODE, but not 13-HODE, significantly reduced endothelial barrier integrity and increased apoptosis. Changing oxidant status by coexposure to an antioxidant during 13-HPODE treatment prevented adverse effects of 13-HPODE, including amelioration of apoptosis. A better understanding of how the oxidant status of the vascular microenvironment impacts endothelial barrier properties could lead to more efficacious treatments for S. uberis mastitis.

  13. A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

    International Nuclear Information System (INIS)

    Latham, Antony M.; Odell, Adam F.; Mughal, Nadeem A.; Issitt, Theo; Ulyatt, Clare; Walker, John H.; Homer-Vanniasinkam, Shervanthi; Ponnambalam, Sreenivasan

    2012-01-01

    Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: ► Endothelial cells mount a stress response under conditions of low serum. ► Endothelial VEGFR levels are

  14. Increased endothelial cell-leukocyte interaction in murine schistosomiasis: possible priming of endothelial cells by the disease.

    Directory of Open Access Journals (Sweden)

    Suellen D S Oliveira

    Full Text Available BACKGROUND AND AIMS: Schistosomiasis is an intravascular parasitic disease associated with inflammation. Endothelial cells control leukocyte transmigration and vascular permeability being modulated by pro-inflammatory mediators. Recent data have shown that endothelial cells primed in vivo in the course of a disease keep the information in culture. Herein, we evaluated the impact of schistosomiasis on endothelial cell-regulated events in vivo and in vitro. METHODOLOGY AND PRINCIPAL FINDINGS: The experimental groups consisted of Schistosoma mansoni-infected and age-matched control mice. In vivo infection caused a marked influx of leukocytes and an increased protein leakage in the peritoneal cavity, characterizing an inflamed vascular and cellular profile. In vitro leukocyte-mesenteric endothelial cell adhesion was higher in cultured cells from infected mice as compared to controls, either in the basal condition or after treatment with the pro-inflammatory cytokine tumor necrosis factor (TNF. Nitric oxide (NO donation reduced leukocyte adhesion to endothelial cells from control and infected groups; however, in the later group the effect was more pronounced, probably due to a reduced NO production. Inhibition of control endothelial NO synthase (eNOS increased leukocyte adhesion to a level similar to the one observed in the infected group. Besides, the adhesion of control leukocytes to endothelial cells from infected animals is similar to the result of infected animals, confirming that schistosomiasis alters endothelial cells function. Furthermore, NO production as well as the expression of eNOS were reduced in cultured endothelial cells from infected animals. On the other hand, the expression of its repressor protein, namely caveolin-1, was similar in both control and infected groups. CONCLUSION/SIGNIFICANCE: Schistosomiasis increases vascular permeability and endothelial cell-leukocyte interaction in vivo and in vitro. These effects are partially

  15. Propiedades de transporte de una superred de grafeno tipo sinusoidal

    OpenAIRE

    J. A. Briones-Torres; I. Rodríguez-Vargas

    2015-01-01

    En este trabajo usamos el método de la matriz de transferencia para estudiar el tunelamiento de los electrones de Dirac a través de superredes en grafeno. Consideramos una superred con potencial sinusoidal o polaridad invertida, para ello consideramos dos maneras de crearla, una por medio de sustratos mixtos junto con la aplicación de un campo perpendicular sobre el sustrato de Óxido de Silicio (SiO2), la otra por medio de potenciales alternados aplicados perpendicularmente sobre la sábana de...

  16. Sentinel nodes outside lymph node basins in patients with melanoma

    NARCIS (Netherlands)

    Roozendaal, GK; de Vries, JDH; van Poll, D; Jansen, L; Nieweg, OE; Kroon, BBR; Schraffordt Koops, H.

    Background: Lymphoscintigraphy occasionally reveals hot spots outside lymph node basins in patients with melanoma. The aim of this study was to evaluate such abnormally located hot spots. Methods: Sentinel node biopsy was studied prospectively in 379 patients with clinically localized cutaneous

  17. Sinusoidal Order Estimation Using Angles between Subspaces

    Directory of Open Access Journals (Sweden)

    Søren Holdt Jensen

    2009-01-01

    Full Text Available We consider the problem of determining the order of a parametric model from a noisy signal based on the geometry of the space. More specifically, we do this using the nontrivial angles between the candidate signal subspace model and the noise subspace. The proposed principle is closely related to the subspace orthogonality property known from the MUSIC algorithm, and we study its properties and compare it to other related measures. For the problem of estimating the number of complex sinusoids in white noise, a computationally efficient implementation exists, and this problem is therefore considered in detail. In computer simulations, we compare the proposed method to various well-known methods for order estimation. These show that the proposed method outperforms the other previously published subspace methods and that it is more robust to the noise being colored than the previously published methods.

  18. Live and Dead Nodes

    DEFF Research Database (Denmark)

    Jørgensen, Sune Lehman; Jackson, A. D.

    2005-01-01

    In this paper, we explore the consequences of a distinction between `live' and `dead' network nodes; `live' nodes are able to acquire new links whereas `dead' nodes are static. We develop an analytically soluble growing network model incorporating this distinction and show that it can provide...

  19. Defibrotide for the management of sinusoidal obstruction syndrome in patients who undergo haemopoietic stem cell transplantation.

    Science.gov (United States)

    Coutsouvelis, John; Avery, Sharon; Dooley, Michael; Kirkpatrick, Carl; Spencer, Andrew

    2016-11-01

    Sinusoidal obstruction syndrome, previously known as veno-occlusive disease (VOD/SOS), is a complication in patients undergoing haemopoietic stem cell transplantation (HSCT). Severe VOD/SOS, including progression to multi-organ failure, has resulted in a mortality of greater than 80%. Defibrotide's varying pharmacological actions, particularly on endothelial cells, make it is a useful agent to consider for prophylaxis and treatment of VOD/SOS. Barriers to its routine use include the high acquisition cost and the fact that neither the oral or parenteral formulations are licensed products in many countries at this time. This review summarises available literature on the use of defibrotide in the management of VOD/SOS. Publications consist predominantly of single centre cohort studies and case series. Available evidence indicates that defibrotide is effective in the management of VOD/SOS. Using defibrotide prophylaxis should also be considered, especially in the paediatric setting, where there are available results from a large, open label, randomized controlled trial. Patient outcome data from the larger studies and compassionate programs can inform consensus recommendations on dosing regimen and criteria for the treatment of VOD/SOS with defibrotide in the adult population. The reviewed literature indicates an effective and safe dose for treatment is 25mg/kg/day, continued for at least 14days or until complete response is achieved. Further studies are required to determine the optimal dose and duration of treatment in both paediatric patients and adults. Recent recommendations and a phase 3 trial using historical controls indicate that defibrotide should be included as a pharmacotherapy option in protocols guiding management of VOD/SOS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Related Drupal Nodes Block

    NARCIS (Netherlands)

    Van der Vegt, Wim

    2010-01-01

    Related Drupal Nodes Block This module exposes a block that uses Latent Semantic Analysis (Lsa) internally to suggest three nodes that are relevant to the node a user is viewing. This module performs three tasks. 1) It periodically indexes a Drupal site and generates a Lsa Term Document Matrix.

  1. Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation.

    Science.gov (United States)

    Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Kernan, Nancy A; Grupp, Stephan A; Antin, Joseph H; Lehmann, Leslie; Miloslavsky, Maja; Hume, Robin; Hannah, Alison L; Nejadnik, Bijan; Soiffer, Robert J

    2017-07-01

    Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Previously, defibrotide (25 mg/kg/day in 4 divided doses for a recommended ≥21 days) was available through an expanded-access treatment protocol for patients with VOD/SOS. Data from this study were examined post-hoc to determine if the timing of defibrotide initiation post-VOD/SOS diagnosis affected Day +100 survival post-HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis in approximately 30%, and within 7 days in >90%. The relationship between Day +100 survival and treatment initiation before/after specific days post-diagnosis showed superior survival when treatment was initiated closer to VOD/SOS diagnosis with a statistically significant trend over time for better outcomes with earlier treatment initiation (P defibrotide should not be delayed after diagnosis of VOD/SOS. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  2. Iodine-frequency-stabilized laser diode and displacement-measuring interferometer based on sinusoidal phase modulation

    Science.gov (United States)

    Duong, Quang Anh; Vu, Thanh Tung; Higuchi, Masato; Wei, Dong; Aketagawa, Masato

    2018-06-01

    We propose a sinusoidal phase modulation method to achieve both the frequency stabilization of an external-cavity laser diode (ECLD) to an 127I2 saturated absorption transition near 633 nm and displacement measurement using a Mach–Zehnder interferometer. First, the frequency of the ECLD is stabilized to the b 21 hyperfine component of the P(33) 6-3 transition of 127I2 by combining sinusoidal phase modulation by an electro-optic modulator and frequency modulation spectroscopy by chopping the pump beam using an acousto-optic modulator. Even though a small modulation index of m  =  3.768 rad is utilized, a relative frequency stability of 10‑11 order is obtained over a sampling time of 400 s. Secondly, the frequency-stabilized ECLD is applied as a light source to a Mach–Zehnder interferometer. From the two consecutive modulation harmonics (second and third orders) involved in the interferometer signal, the displacement of the moving mirror is determined for four optical path differences (L 0  =  100, 200, 500, and 1000 mm). The measured modulation indexes for the four optical path differences coincide with the designated value (3.768 rad) within 0.5%. Compared with the sinusoidal frequency modulation Michelson interferometer (Vu et al 2016 Meas. Sci. Technol. 27 105201) which was demonstrated by some of the same authors of this paper, the phase modulation Mach–Zhender interferometer could fix the modulation index to a constant value for the four optical path differences. In this report, we discuss the measurement principle, experimental system, and results.

  3. Reduced Ang2 expression in aging endothelial cells

    International Nuclear Information System (INIS)

    Hohensinner, P.J.; Ebenbauer, B.; Kaun, C.; Maurer, G.; Huber, K.; Wojta, J.

    2016-01-01

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of aging before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.

  4. Reduced Ang2 expression in aging endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Hohensinner, P.J., E-mail: philipp.hohensinner@meduniwien.ac.at [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ebenbauer, B. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Kaun, C.; Maurer, G. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Huber, K. [Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); 3rd Medical Department, Wilhelminenhospital, Vienna (Austria); Sigmund Freud University, Medical Faculty, Vienna (Austria); Wojta, J. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Core Facilities, Medical University of Vienna, Vienna (Austria)

    2016-06-03

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of aging before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.

  5. Signaling hierarchy regulating human endothelial cell development.

    Science.gov (United States)

    Kelly, Melissa A; Hirschi, Karen K

    2009-05-01

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. Using human embryonic stem cells as a model system, we were able to reproducibly and robustly generate differentiated endothelial cells via coculture on OP9 marrow stromal cells. We found that, in contrast to studies in the mouse, bFGF and VEGF had no specific effects on the initiation of human vasculogenesis. However, exogenous Ihh promoted endothelial cell differentiation, as evidenced by increased production of cells with cobblestone morphology that coexpress multiple endothelial-specific genes and proteins, form lumens, and exhibit DiI-AcLDL uptake. Inhibition of BMP signaling using Noggin or BMP4, specifically, using neutralizing antibodies suppressed endothelial cell formation; whereas, addition of rhBMP4 to cells treated with the hedgehog inhibitor cyclopamine rescued endothelial cell development. Our studies revealed that Ihh promoted human endothelial cell differentiation from pluripotent hES cells via BMP signaling, providing novel insights applicable to modulating human endothelial cell formation and vascular regeneration for human clinical therapies.

  6. Isolated perifacial lymph node metastasis in oral squamous cell carcinoma with clinically node-negative neck.

    Science.gov (United States)

    Agarwal, Sangeet Kumar; Arora, Sowrabh Kumar; Kumar, Gopal; Sarin, Deepak

    2016-10-01

    The incidence of occult perifacial nodal disease in oral cavity squamous cell carcinoma is not well reported. The purpose of this study was to evaluate the incidence of isolated perifacial lymph node metastasis in patients with oral squamous cell carcinoma with a clinically node-negative neck. The study will shed light on current controversies and will provide valuable clinical and pathological information in the practice of routine comprehensive removal of these lymph node pads in selective neck dissection in the node-negative neck. Prospective analysis. This study was started in August 2011 when intraoperatively we routinely separated the lymph node levels from the main specimen for evaluation of the metastatic rate to different lymph node levels in 231 patients of oral squamous cell cancer with a clinically node-negative neck. The current study demonstrated that 19 (8.22%) out of 231 patients showed ipsilateral isolated perifacial lymph node involvement. The incidence of isolated perifacial nodes did not differ significantly between the oral tongue (7.14%) and buccal mucosa (7.75%). Incidence was statistically significant in cases with lower age group (oral squamous cell carcinoma with a clinically node-negative neck. The incidence of isolated perifacial involvement is high in cases of buccal mucosal and tongue cancers. A meticulous dissection of the perifacial nodes seems prudent when treating the neck in oral cavity squamous cell carcinoma. 4 Laryngoscope, 126:2252-2256, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  7. Evolution of endothelial keratoplasty.

    Science.gov (United States)

    Price, Francis W; Price, Marianne O

    2013-11-01

    Endothelial keratoplasty has evolved into a popular alternative to penetrating keratoplasty (PK) for the treatment of endothelial dysfunction. Although the earliest iterations were challenging and were not widely adopted, the iteration known as Descemet stripping endothelial keratoplasty (DSEK) has gained widespread acceptance. DSEK combines a simplified technique for stripping dysfunctional endothelium from the host cornea and microkeratome dissection of the donor tissue, a step now commonly completed in advance by eye bank technicians. Studies show that a newer endothelial keratoplasty iteration, known as Descemet membrane endothelial keratoplasty (DMEK), provides an even faster and better visual recovery than DSEK does. In addition, DMEK significantly reduces the risk of immunologic graft rejection episodes compared with that in DSEK or in PK. Although the DMEK donor tissue, consisting of the bare endothelium and Descemet membrane without any stroma, is more challenging to prepare and position in the recipient eye, recent improvements in instrumentation and surgical techniques are increasing the ease and the reliability of the procedure. DSEK successfully mitigates 2 of the main liabilities of PK: ocular surface complications and structural problems (including induced astigmatism and perpetually weak wounds), whereas DMEK further mitigates the 2 principal remaining liabilities of PK: immunologic graft reactions and secondary glaucoma from prolonged topical corticosteroid use.

  8. Trifluoperazine: corneal endothelial phototoxicity

    International Nuclear Information System (INIS)

    Hull, D.S.; Csukas, S.; Green, K.

    1983-01-01

    Trifluoperazine is used for the treatment of psychiatric disorders. Perfusion of corneal endothelial cells with trifluoperazine-HC1 concurrent with exposure to long wavelength ultraviolet light resulted in a corneal swelling rate greater than that found in perfused corneas not exposed to ultraviolet light. Exposure of endothelial cells to 25 W incandescent light during perfusion with trifluoperazine-HC1 did not result in a higher corneal swelling rate compared to those perfused in the dark. The increased corneal swelling rate could be produced by pre-exposure of the trifluoperazine-HC1 perfusing solution to ultraviolet light suggesting the production of toxic photoproducts during exposure of trifluoperazine-HC1 to ultraviolet light. Perfusion of corneal endothelial cells with non-ultraviolet illuminated trifluoperazine-HC1 had no effect on endothelial cell membranes or ultrastructure. This is in contrast to cells perfused with trifluoperazine-HC1 that had been exposed to ultraviolet light in which there was an alteration of mitochondria and a loss of cytoplasmic homogeneity. The data imply that the trifluoperazine-HC1 photoproduct had an adverse effect on cellular transport mechanisms. The study also further demonstrates the value of the corneal endothelial cell model for identifying the physiological and anatomical changes occuring in photo-induced toxic reactions. (author)

  9. Lymph Node Yield as a Predictor of Survival in Pathologically Node Negative Oral Cavity Carcinoma.

    Science.gov (United States)

    Lemieux, Aaron; Kedarisetty, Suraj; Raju, Sharat; Orosco, Ryan; Coffey, Charles

    2016-03-01

    Even after a pathologically node-negative (pN0) neck dissection for oral cavity squamous cell carcinoma (SCC), patients may develop regional recurrence. In this study, we (1) hypothesize that an increased number of lymph nodes removed (lymph node yield) in patients with pN0 oral SCC predicts improved survival and (2) explore predictors of survival in these patients using a multivariable model. Case series with chart review. Administrative database analysis. The SEER database was queried for patients diagnosed with all-stage oral cavity SCC between 1988 and 2009 who were determined to be pN0 after elective lymph node dissection. Demographic and treatment variables were extracted. The association of lymph node yield with 5-year all-cause survival was studied with multivariable survival analyses. A total of 4341 patients with pN0 oral SCC were included in this study. The 2 highest lymph node yield quartiles (representing >22 nodes removed) were found to be significant predictors of overall survival (22-35 nodes: hazard ratio [HR] = 0.854, P = .031; 36-98 nodes: HR = 0.827, P = .010). Each additional lymph node removed during neck dissection was associated with increased survival (HR = 0.995, P = .022). These data suggest that patients with oral SCC undergoing elective neck dissection may experience an overall survival benefit associated with greater lymph node yield. Mechanisms behind the demonstrated survival advantage are unknown. Larger nodal dissections may remove a greater burden of microscopic metastatic disease, diminishing the likelihood of recurrence. Lymph node yield may serve as an objective measure of the adequacy of lymphadenectomy. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  10. Prediction of occult lymph node metastasis in squamous cell carcinoma of the oral cavity and the oropharynx using peritumoral Prospero homeobox protein 1 lymphatic nuclear quantification.

    Science.gov (United States)

    Mermod, Maxime; Bongiovanni, Massimo; Petrova, Tatiana V; Dubikovskaya, Elena A; Simon, Christian; Tolstonog, Genrich; Monnier, Yan

    2016-09-01

    The use of lymphatic vessel density as a predictor of occult lymph node metastasis (OLNM) in head and neck squamous cell carcinoma (HNSCC) has never been reported. Staining of the specific lymphatic endothelial cells nuclear marker, PROX1, as an indicator of lymphatic vessel density was determined by counting the number of positive cells in squamous cell carcinomas (SCCs) of the oral cavity and the oropharynx with clinically negative necks. Correlation with histopathological data was established. Peritumoral PROX1 lymphatic nuclear count significantly correlated with the detection of OLNM in multivariate analysis (p oral cavity and the oropharynx allows accurate prediction of occult lymph node metastasis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1407-1415, 2016. © 2016 Wiley Periodicals, Inc.

  11. Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Baffy, Gyorgy

    2018-03-01

    Nonalcoholic fatty liver disease (NAFLD) advanced to cirrhosis is often complicated by clinically significant portal hypertension, which is primarily caused by increased intrahepatic vascular resistance. Liver fibrosis has been identified as a critical determinant of this process. However, there is evidence that portal venous pressure may begin to rise in the earliest stages of NAFLD when fibrosis is far less advanced or absent. The biological and clinical significance of these early changes in sinusoidal homeostasis remains unclear. Experimental and human observations indicate that sinusoidal space restriction due to hepatocellular lipid accumulation and ballooning may impair sinusoidal flow and generate shear stress, increasingly disrupting sinusoidal microcirculation. Sinusoidal endothelial cells, hepatic stellate cells, and Kupffer cells are key partners of hepatocytes affected by NAFLD in promoting endothelial dysfunction through enhanced contractility, capillarization, adhesion and entrapment of blood cells, extracellular matrix deposition, and neovascularization. These biomechanical and rheological changes are aggravated by a dysfunctional gut-liver axis and splanchnic vasoregulation, culminating in fibrosis and clinically significant portal hypertension. We may speculate that increased portal venous pressure is an essential element of the pathogenesis across the entire spectrum of NAFLD. Improved methods of noninvasive portal venous pressure monitoring will hopefully give new insights into the pathobiology of NAFLD and help efforts to identify patients at increased risk for adverse outcomes. In addition, novel drug candidates targeting reversible components of aberrant sinusoidal circulation may prevent progression in NAFLD.

  12. Flow and heat transfer characteristics in a channel having furrowed wall based on sinusoidal wave

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiansheng; Gao, Xiaoming; Li, Weiyi [Tianjin University, Tianjin (Switzerland)

    2015-11-15

    The effect of wall geometry on the flow and heat transfer in a channel with one lower furrowed and an upper flat wall kept at a uniform temperature is investigated by large eddy simulation. Three channels, one with sinusoidal wavy surface having the ratio (amplitude to wavelength) α/λ=0.05 and the other two with furrowed surface derived from the sinusoidal curve, are considered. The numerical results show that the streamwise vortices center is located near the lower wall and vary along the streamwise on various furrow surfaces. The furrow geometry increases the pressure drag and decreases the friction drag of the furrowed surface compared with that of the smooth surface; consequently, the total drag is increased for the augment of pressure drag. As expected, the heat transfer performance has been improved. Finally, a thermal performance factor is defined to evaluate the performance of the furrowed wall.

  13. Obstructive sleep apnoea syndrome, endothelial function and markers of endothelialization. Changes after CPAP.

    Science.gov (United States)

    Muñoz-Hernandez, Rocio; Vallejo-Vaz, Antonio J; Sanchez Armengol, Angeles; Moreno-Luna, Rafael; Caballero-Eraso, Candela; Macher, Hada C; Villar, Jose; Merino, Ana M; Castell, Javier; Capote, Francisco; Stiefel, Pablo

    2015-01-01

    This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy. Observational study, before and after CPAP therapy. We studied 30 patients with apnoea/hypopnoea index (AHI) >15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process. After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, pDNA and MPs significantly decreased (187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p<0.01, and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/μL, p<0.05, respectively) and VEGF levels increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p<0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p<0.005) but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together. CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage.

  14. Radiation Effects on the Cytoskeleton of Endothelial Cells and Endothelial Monolayer Permeability

    International Nuclear Information System (INIS)

    Gabrys, Dorota; Greco, Olga; Patel, Gaurang; Prise, Kevin M.; Tozer, Gillian M.; Kanthou, Chryso

    2007-01-01

    Purpose: To investigate the effects of radiation on the endothelial cytoskeleton and endothelial monolayer permeability and to evaluate associated signaling pathways, which could reveal potential mechanisms of known vascular effects of radiation. Methods and Materials: Cultured endothelial cells were X-ray irradiated, and actin filaments, microtubules, intermediate filaments, and vascular endothelial (VE)-cadherin junctions were examined by immunofluorescence. Permeability was determined by the passage of fluorescent dextran through cell monolayers. Signal transduction pathways were analyzed using RhoA, Rho kinase, and stress-activated protein kinase-p38 (SAPK2/p38) inhibitors by guanosine triphosphate-RhoA activation assay and transfection with RhoAT19N. The levels of junction protein expression and phosphorylation of myosin light chain and SAPK2/p38 were assessed by Western blotting. The radiation effects on cell death were verified by clonogenic assays. Results: Radiation induced rapid and persistent actin stress fiber formation and redistribution of VE-cadherin junctions in microvascular, but not umbilical vein endothelial cells, and microtubules and intermediate filaments remained unaffected. Radiation also caused a rapid and persistent increase in microvascular permeability. RhoA-guanosine triphosphatase and Rho kinase were activated by radiation and caused phosphorylation of downstream myosin light chain and the observed cytoskeletal and permeability changes. SAPK2/p38 was activated by radiation but did not influence either the cytoskeleton or permeability. Conclusion: This study is the first to show rapid activation of the RhoA/Rho kinase by radiation in endothelial cells and has demonstrated a link between this pathway and cytoskeletal remodeling and permeability. The results also suggest that the RhoA pathway might be a useful target for modulating the permeability and other effects of radiation for therapeutic gain

  15. Hepatic sinusoid is not well-stirred: estimation of the degree of axial mixing by analysis of lobular concentration gradients formed during uptake of thyroxine by the perfused rat liver

    International Nuclear Information System (INIS)

    Weisiger, R.A.; Mendel, C.M.; Cavalieri, R.R.

    1986-01-01

    Two general models have been proposed for predicting the effects of metabolism, protein binding, and plasma flow on the removal of drugs by the liver. These models differ in the degree of plasma mixing assumed to exist within each hepatic sinusoid. The venous equilibrium model treats the sinusoid as a single well-stirred compartment, whereas the sinusoidal model effectively breaks up the sinusoid into a large number of sequentially perfused compartments which do not exchange their contents except through plasma flow. As a consequence, the sinusoidal model, but not the venous equilibrium model, predicts that the concentration of highly extracted drugs will decline as the plasma flows through the hepatic lobule. To determine which of these alternative models best describes the hepatic uptake process, we looked for evidence that concentration gradients are formed during the uptake of [ 125 I]thyroxine by the perfused rat liver. Autoradiography of tissue slices after perfusion of the portal vein at physiologic flow rates with protein-free buffer containing [ 125 I]thyroxine demonstrated a rapid exponential fall in grain density with distance from the portal venule, declining by half for each 8% of the mean length of the sinusoid. Reversing the direction of perfusate flow reversed the direction of the autoradiographic gradients, indicating that they primarily reflect differences in the concentration of thyroxine within the hepatic sinusoids rather than differences in the uptake capacity of portal and central hepatocytes. Analysis of the data using models in which each sinusoid was represented by different numbers of sequentially perfused compartments (1-20) indicated that at least eight compartments were necessary to account for the magnitude of the gradients seen

  16. Sentinel node concept in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kiricuta, I.C. [St. Vincenz-Hospital, Limburg (Germany). Inst. for Radiation Oncology

    2000-07-01

    Background/purpose: It seems that there exists a specific lymph node center called sentinel node (SN) which appears to be the primary site of metastases. The sentinel node concept (SNC) is fundamentally based on the orderly progression of tumor cells within the lymphatic system. It is the most important new concept in surgical and radiation oncology. The purpose is to present the biological significance, the diagnostic and clinical basis of the sentinel node concept in breast cancer patients. Material and methods: Lymphoscintigraphy and gamma probe biopsy is necessary to show predictable lymph flow to the regional sentinel node, to multiple sentinel nodes or unpredictable lymph flow to extra-regional sentinel nodes and for performing sentinel node procedure. The standard protocol for the evaluation of the sentinel node metastases consists of extensive histopathological investigation including step Hematoxylin and Eosin (H and E) stained sections and immunohistochemistry. Results: A high rate of success of the identification of the sentinel node for breast cancer was reported. The presence or absence of metastasis in this node is a very accurate predictor of overall nodal status. The temptation to examine the sentinel node with the greatest possible degree of accuracy highlights one of the major problems related to sentinel node biopsy. The success of the sentinel node procedure depends primarily on the adequate functional capacity necessary for sufficient uptake to ensure the accurate identification. In negative sentinel-node patients a complete axillary lymph node dissection is avoidable. In sentinel-node positive patients and clinically negative patients a postoperative radiotherapy would permit an adequate tumor control. The last 2-procedures permit a low morbidity. In the actual TNM classification it was recently introduced a definition of a 'pN0' patient based on sentinel node biopsy. New target volumes are defined for adjuvant radiotherapy or

  17. Sentinel node concept in breast cancer

    International Nuclear Information System (INIS)

    Kiricuta, I.C.

    2000-01-01

    Background/purpose: It seems that there exists a specific lymph node center called sentinel node (SN) which appears to be the primary site of metastases. The sentinel node concept (SNC) is fundamentally based on the orderly progression of tumor cells within the lymphatic system. It is the most important new concept in surgical and radiation oncology. The purpose is to present the biological significance, the diagnostic and clinical basis of the sentinel node concept in breast cancer patients. Material and methods: Lymphoscintigraphy and gamma probe biopsy is necessary to show predictable lymph flow to the regional sentinel node, to multiple sentinel nodes or unpredictable lymph flow to extra-regional sentinel nodes and for performing sentinel node procedure. The standard protocol for the evaluation of the sentinel node metastases consists of extensive histopathological investigation including step Hematoxylin and Eosin (H and E) stained sections and immunohistochemistry. Results: A high rate of success of the identification of the sentinel node for breast cancer was reported. The presence or absence of metastasis in this node is a very accurate predictor of overall nodal status. The temptation to examine the sentinel node with the greatest possible degree of accuracy highlights one of the major problems related to sentinel node biopsy. The success of the sentinel node procedure depends primarily on the adequate functional capacity necessary for sufficient uptake to ensure the accurate identification. In negative sentinel-node patients a complete axillary lymph node dissection is avoidable. In sentinel-node positive patients and clinically negative patients a postoperative radiotherapy would permit an adequate tumor control. The last 2-procedures permit a low morbidity. In the actual TNM classification it was recently introduced a definition of a 'pN0' patient based on sentinel node biopsy. New target volumes are defined for adjuvant radiotherapy or lymphatic basins

  18. СURRENT FILTERING IN A THREE-PHASE THREE-WIRE POWER SYSTEM AT ASYMMETRIC SINUSOIDAL VOLTAGES

    Directory of Open Access Journals (Sweden)

    M. Yu. Artemenko

    2018-04-01

    Full Text Available Purpose. Investigation of the optimal current distribution between source, shunt active filter and reactive compensator of a three-phase three-wire system that provides consumption of a sinusoidal symmetric current under asymmetric source voltages with minimal power losses was provided. Methodology. The tasks were solved by conducting theoretical and experimental studies. The main provisions of the theory of electrical circuits, the apparatus of mathematical analysis, methods for solving linear differential and algebraic equations, elements of matrix and complex calculus and vector algebra are used. During the development, modern methods and software of computer simulation of electrical engineering complexes and dynamic systems were applied: Matlab-Simulink, MATHCAD. Originality. The principle of compensating current distribution between PAF and reactive compensator of a three-phase three-wire power system with asymmetric sinusoidal voltage was proposed at which the input current is equal to the positive-sequence active current and rms value of PAF current is minimal. The feasibility to compensate the inactive sinusoidal Fryze current by reactive elements under arbitrary combination of load and source parameters was proved and expression for direct calculation of the reactive compensator parameters for generation of inactive Fryze current in the source unbalanced mode was obtained. Practical value. The simulative example for transmission line load showed that combined application of PAF and reactive compensator with the specified distribution of compensating currents ensured a reduction of power losses in 3.273 times and rms value of the SAF current is 12.9 % of rms value total compensation current.

  19. Over expression of vascular endothelial growth factor in correlation to Ki-67, grade and stage of breast cancer

    International Nuclear Information System (INIS)

    Al-Harris, Esraah S.; Al-Janabi, Asad A.; Al-Toriahi, Kaswer M.; Yasseen, Akeel A.

    2008-01-01

    Objective was to assess the significance of vascular endothelial growth factor (VEGF) protein over expression in human breast cancer, and its possible correlation with cell proliferation marker (Ki-67), grade and stage of breast cancer. We carried out this study at the Department of Pathology, Kufa University, between November 2006 and September 2007. A retrospective study was employed on paraffin-embedded blocks from 52 female patients with breast cancer. A group of 21 patients with benign breast lesions was included for comparison and 14 cases of normal breast tissue as control group. The investigation designed to employ immunohistochemistry using Avidin-Biotin Complex (ABC) method for detection of both VEGF and Ki-67. A total of 87 samples were included. Vascular endothelial growth factor immunoexpression was considered as positive in 61.5% of malignant and in 19% of benign breast lesions. No over expression sign has been noticed in normal breast tissue (p<0.005). No significant difference in VEGF over expression among different histological types of breast cancer (p<0.05). Vascular endothelial growth factor immunostaining was positively correlated with Ki-67, grade, stage, lymph node metastasis, and recurrence of breast cancer (p<0.05).No such correlation has been seen when the age of the patients has been considered. Vascular endothelial growth factor plays an important role in the pathogenesis of breast cancer evolution and supports the evidence of its role in angiogenesis and cell survival. This study recommended that the blocking of VEGF may be target for blocking angiogenesis and hence improving the efficacy of anti-cancer therapy. (author)

  20. Chemical shift effect predicting lymph node status in rectal cancer using high-resolution MR imaging with node-for-node matched histopathological validation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hongmei; Zhang, Chongda; Ye, Feng; Liu, Yuan; Zhou, Chunwu [Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Diagnostic Radiology, National Cancer Center/Cancer Hospital, ChaoYang District, Beijing (China); Zheng, Zhaoxu [Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Colorectal Oncology, National Cancer Center/Cancer Hospital, ChaoYang District, Beijing (China); Zou, Shuangmei [Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Pathology, National Cancer Center/Cancer Hospital, ChaoYang District, Beijing (China)

    2017-09-15

    To evaluate the value of the chemical shift effect (CSE) as well as other criteria for the prediction of lymph node status. Twenty-nine patients who underwent radical surgery of rectal cancers were studied with pre- and postoperative specimen MRI. Lymph nodes were harvested from transverse whole-mount specimens and compared with in vivo and ex vivo images to obtain a precise slice-for-section match. Preoperative MR characteristics including CSE, as well as other predictors, were evaluated by two readers independently between benign and metastatic nodes. A total of 255 benign and 35 metastatic nodes were obtained; 71.4% and 69.4% of benign nodes were detected with regular CSE for two readers, whereas 80.0% and 74.3% of metastatic nodes with absence of CSE. The CSE rendered areas under the ROC curve (AUC) of 0.879 and 0.845 for predicting nodal status for two readers. The criteria of nodal location, border, signal intensity and minimum distance to the rectal wall were also useful but with AUCs (0.629-0.743) lower than those of CSE. CSE is a reliable predictor for differentiating benign from metastatic nodes. Additional criteria should be taken into account when it is difficult to determine the nodal status by using only a single predictor. (orig.)

  1. Sinusoidal voltage protocols for rapid characterisation of ion channel kinetics.

    Science.gov (United States)

    Beattie, Kylie A; Hill, Adam P; Bardenet, Rémi; Cui, Yi; Vandenberg, Jamie I; Gavaghan, David J; de Boer, Teun P; Mirams, Gary R

    2018-03-24

    Ion current kinetics are commonly represented by current-voltage relationships, time constant-voltage relationships and subsequently mathematical models fitted to these. These experiments take substantial time, which means they are rarely performed in the same cell. Rather than traditional square-wave voltage clamps, we fitted a model to the current evoked by a novel sum-of-sinusoids voltage clamp that was only 8 s long. Short protocols that can be performed multiple times within a single cell will offer many new opportunities to measure how ion current kinetics are affected by changing conditions. The new model predicts the current under traditional square-wave protocols well, with better predictions of underlying currents than literature models. The current under a novel physiologically relevant series of action potential clamps is predicted extremely well. The short sinusoidal protocols allow a model to be fully fitted to individual cells, allowing us to examine cell-cell variability in current kinetics for the first time. Understanding the roles of ion currents is crucial to predict the action of pharmaceuticals and mutations in different scenarios, and thereby to guide clinical interventions in the heart, brain and other electrophysiological systems. Our ability to predict how ion currents contribute to cellular electrophysiology is in turn critically dependent on our characterisation of ion channel kinetics - the voltage-dependent rates of transition between open, closed and inactivated channel states. We present a new method for rapidly exploring and characterising ion channel kinetics, applying it to the hERG potassium channel as an example, with the aim of generating a quantitatively predictive representation of the ion current. We fitted a mathematical model to currents evoked by a novel 8 second sinusoidal voltage clamp in CHO cells overexpressing hERG1a. The model was then used to predict over 5 minutes of recordings in the same cell in response to

  2. Successful treatment of severe sinusoidal obstruction syndrome despite multiple organ failure with defibrotide after allogeneic stem cell transplantation: a case report.

    Science.gov (United States)

    Behre, Gerhard; Theurich, Sebastian; Christopeit, Maximilian; Weber, Thomas

    2009-03-10

    We report a case of sinusoidal obstruction syndrome, a typical and life-threatening complication after allogeneic stem-cell transplantation, successfully treated with defibrotide despite massive multiple organ failure. A 64-year-old Caucasian woman underwent allogeneic peripheral blood stem-cell transplantation from her human leukocyte antigen-identical sister against aggressive lymphoplasmocytoid immunocytoma. Seven days later, the patient developed severe sinusoidal obstruction syndrome according to the modified Seattle criteria. We initiated treatment with defibrotide. Despite early treatment, multiple organ failure with kidney failure requiring dialysis and ventilator-dependent lung failure aggravated the clinical course. Furthermore, central nervous dysfunction occurred as well as transfusion refractory thrombocytopenia. As highlighted in our report, defibrotide is the most promising drug in the treatment of the formerly, almost lethal, severe sinusoidal obstruction syndrome to date. This is demonstrated very clearly in our patient. She improved completely, even after renal, cerebral and respiratory failure.

  3. Postnatal Deletion of Podoplanin in Lymphatic Endothelium Results in Blood Filling of the Lymphatic System and Impairs Dendritic Cell Migration to Lymph Nodes.

    Science.gov (United States)

    Bianchi, Roberta; Russo, Erica; Bachmann, Samia B; Proulx, Steven T; Sesartic, Marko; Smaadahl, Nora; Watson, Steve P; Buckley, Christopher D; Halin, Cornelia; Detmar, Michael

    2017-01-01

    The lymphatic vascular system exerts major physiological functions in the transport of interstitial fluid from peripheral tissues back to the blood circulation and in the trafficking of immune cells to lymph nodes. Previous studies in global constitutive knockout mice for the lymphatic transmembrane molecule podoplanin reported perinatal lethality and a complex phenotype with lung abnormalities, cardiac defects, lymphedema, blood-filled lymphatic vessels, and lack of lymph node organization, reflecting the importance of podoplanin expression not only by the lymphatic endothelium but also by a variety of nonendothelial cell types. Therefore, we aimed to dissect the specific role of podoplanin expressed by adult lymphatic vessels. We generated an inducible, lymphatic-specific podoplanin knockout mouse model (Pdpn ΔLEC ) and induced gene deletion postnatally. Pdpn ΔLEC mice were viable, and their lymphatic vessels appeared morphologically normal with unaltered fluid drainage function. Intriguingly, Pdpn ΔLEC mice had blood-filled lymph nodes and vessels, most frequently in the neck and axillary region, and displayed a blood-filled thoracic duct, suggestive of retrograde filling of blood from the blood circulation into the lymphatic system. Histological and fluorescence-activated cell sorter analyses revealed normal lymph node organization with the presence of erythrocytes within lymph node lymphatic vessels but not surrounding high endothelial venules. Moreover, fluorescein isothiocyanate painting experiments revealed reduced dendritic cell migration to lymph nodes in Pdpn ΔLEC mice. These results reveal an important role of podoplanin expressed by lymphatic vessels in preventing postnatal blood filling of the lymphatic vascular system and in contributing to efficient dendritic cell migration to the lymph nodes. © 2016 American Heart Association, Inc.

  4. Simply Adjustable Sinusoidal Oscillator Based on Negative Three-Port Current Conveyors

    Directory of Open Access Journals (Sweden)

    R. Sotner

    2010-09-01

    Full Text Available The paper deals with sinusoidal oscillator employing two controlled second-generation negative-current conveyors and two capacitors. The proposed oscillator has a simple circuit configuration. Electronic (voltage adjusting of the oscillation frequency and condition of oscillation are possible. The presented circuit is verified in PSpice utilizing macro models of commercially available negative current conveyors. The circuit is also verified by experimental measurements. Important characteristics and drawbacks of the proposed circuit and influences of real active elements in the designed circuit are discussed in detail.

  5. Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma.

    Science.gov (United States)

    Mantel, Hendrik T J; Wiggers, Jim K; Verheij, Joanne; Doff, Jan J; Sieders, Egbert; van Gulik, Thomas M; Gouw, Annette S H; Porte, Robert J

    2015-12-01

    Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The objective of this study was to assess the effect on survival of immunohistochemically detected lymph node micrometastases in patients with node-negative (pN0) hilar cholangiocarcinoma on routine histology. Between 1990 and 2010, a total of 146 patients underwent curative-intent resection of hilar cholangiocarcinoma with regional lymphadenectomy at two university medical centers in the Netherlands. Ninety-one patients (62 %) without lymph node metastases at routine histology were included. Micrometastases were identified by multiple sectioning of all lymph nodes and additional immunostaining with an antibody against cytokeratin 19 (K19). The association with overall survival was assessed in univariable and multivariable analysis. Median follow-up was 48 months. Micrometastases were identified in 16 (5 %) of 324 lymph nodes, corresponding to 11 (12 %) of 91 patients. There were no differences in clinical variables between K19 lymph node-positive and -negative patients. Five-year survival rates in patients with lymph node micrometastases were significantly lower compared to patients without micrometastases (27 vs. 54 %, P = 0.01). Multivariable analysis confirmed micrometastases as an independent prognostic factor for survival (adjusted Hazard ratio 2.4, P = 0.02). Lymph node micrometastases are associated with worse survival after resection of hilar cholangiocarcinoma. Immunohistochemical detection of lymph node micrometastases leads to better staging of patients who were initially diagnosed with node-negative (pN0) hilar cholangiocarcinoma on routine histology.

  6. Obstructive sleep apnoea syndrome, endothelial function and markers of endothelialization. Changes after CPAP.

    Directory of Open Access Journals (Sweden)

    Rocio Muñoz-Hernandez

    Full Text Available This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA syndrome at baseline and after three months with CPAP therapy.Observational study, before and after CPAP therapy.We studied 30 patients with apnoea/hypopnoea index (AHI >15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA and microparticles (MPs were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF was determined as a marker of endothelial restoration process.After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, p< 0.005 cf-DNA and MPs significantly decreased (187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p<0.01, and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/μL, p<0.05, respectively and VEGF levels increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p<0.05. These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p<0.005 but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together.CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage.

  7. Physalis minima Leaves Extract Induces Re-Endothelialization in Deoxycorticosterone Acetate-Salt-Induced Endothelial Dysfunction in Rats

    Directory of Open Access Journals (Sweden)

    Dian Nugrahenny

    2018-02-01

    Full Text Available The administration of deoxy-corticosterone acetate (DOCA-salt can induce oxidative stress leading to decrease the bioavailability of nitric oxide (NO, increase senescence of circulating endothelial progenitor cells (EPCs, thus contributing to endothelial dysfunction. This study was aimed to investigate the effects of Physalis minima L. leaves extract on serum NO levels, circulating EPCs number, and histopathology of tail artery endothelial cells in DOCA-salt-induced endothelial dysfunction in rats. Twenty-five male Wistar rats were randomly divided into five groups: rats without any treatment (normal, rats treated with DOCA (10 mg/kgBW s.c. twice weekly and given 0.9% NaCl to drink ad libitum for 6 weeks, and DOCA-salt-induced rats orally supplemented with P. minima leaves extract at doses of 500, 1500, or 2500 mg/kgBW for 4 weeks. Serum NO levels were measured by colorimetry. The number of circulating EPCs (CD34+/CD133+ cells was determined by flow cytometry. The tail artery sections were histologically processed with hematoxylin-eosin staining. DOCA-salt-induced rats showed significantly (p<0.05 decrease in serum NO levels and circulating EPCs number compared to the normal. There was also more detached tail artery endothelial cells in DOCA-salt-induced rats. P. minima leaves extract at a dose of 500 mg/kgBW significantly (p<0.05 increased serum NO level and circulating EPCs number, and also induced an optimal re-endothelialization in DOCA-salt-induced rats. P. minima leave extract dose-dependently increases NO bioavailability contributing to enhanced EPCs mobilization, thereby promoting re-endothelialization in DOCA-salt-induced endothelial dysfunction in rats.

  8. Deploying Node.js

    CERN Document Server

    Pasquali, Sandro

    2015-01-01

    If you are an intermediate or advanced developer deploying your Node.js applications, then this book is for you. If you have already built a Node application or module and want to take your knowledge to the next level, this book will help you find your way.

  9. Biliary obstruction dissipates bioelectric sinusoidal-canalicular barrier without altering taurocholate uptake

    International Nuclear Information System (INIS)

    Cotting, J.; Zysset, T.; Reichen, J.

    1989-01-01

    To study immediate events during extrahepatic cholestasis, we investigated the effect of short-term biliary obstruction on the bioelectrical sinusoidal-canalicular barrier in the rat using molecular weight-matched uncharged and negatively charged inert solute pairs. The bioelectrical barrier averaged -22 +/- 5 and -18 +/- 4 mV (NS) using the pair carboxy-/methoxyinulin and ferrocyanide/sucrose, respectively. After a 20-min biliary obstruction both decreased by 61 and 11%, respectively, but only the large molecular weight pair (the inulins) returned to base line after release of the obstruction. Inert solute clearances were increased after short biliary obstruction depending on molecular size and negative charge (ferrocyanide greater than sucrose greater than carboxyinulin greater than inulin), suggesting that both permeability and bioelectrical barriers were affected by obstruction. The hepatic extraction in vivo of a passively transported drug not excreted into bile (D-propranolol) was not affected by obstruction, whereas that of an actively transported drug (glycocholate) decreased from 66 +/- 8 to 41 +/- 20% during biliary obstruction (P less than 0.01). Unidirectional transfer of glycocholate was not affected by short-term biliary obstruction in the situ perfused rat liver; however, 2 min after [14C]glycocholate administration, increased return was observed in hepatic venous effluent in obstructed animals. Our findings demonstrate a loss of the bioelectrical barrier immediately after short-term biliary obstruction. Decreased hepatic extraction in the view of unaltered sinusoidal uptake demonstrates regurgitation of bile into blood during short-term biliary obstruction

  10. Sustained apnea induces endothelial activation.

    Science.gov (United States)

    Eichhorn, Lars; Dolscheid-Pommerich, Ramona; Erdfelder, Felix; Ayub, Muhammad Ajmal; Schmitz, Theresa; Werner, Nikos; Jansen, Felix

    2017-09-01

    Apnea diving has gained worldwide popularity, even though the pathophysiological consequences of this challenging sport on the human body are poorly investigated and understood. This study aims to assess the influence of sustained apnea in healthy volunteers on circulating microparticles (MPs) and microRNAs (miRs), which are established biomarkers reflecting vascular function. Short intermittent hypoxia due to voluntary breath-holding affects circulating levels of endothelial cell-derived MPs (EMPs) and endothelial cell-derived miRs. Under dry laboratory conditions, 10 trained apneic divers performed maximal breath-hold. Venous blood samples were taken, once before and at 4 defined points in time after apnea. Samples were analyzed for circulating EMPs and endothelial miRs. Average apnea time was 329 seconds (±103), and SpO 2 at the end of apnea was 79% (±12). Apnea was associated with a time-dependent increase of circulating endothelial cell-derived EMPs and endothelial miRs. Levels of circulating EMPs in the bloodstream reached a peak 4 hours after the apnea period and returned to baseline levels after 24 hours. Circulating miR-126 levels were elevated at all time points after a single voluntary maximal apnea, whereas miR-26 levels were elevated significantly only after 30 minutes and 4 hours. Also miR-21 and miR-92 levels increased, but did not reach the level of significance. Even a single maximal breath-hold induces acute endothelial activation and should be performed with great caution by subjects with preexisting vascular diseases. Voluntary apnea might be used as a model to simulate changes in endothelial function caused by hypoxia in humans. © 2017 Wiley Periodicals, Inc.

  11. Neutrophil-endothelial cell interactions on endothelial monolayers grown on micropore filters.

    Science.gov (United States)

    Taylor, R F; Price, T H; Schwartz, S M; Dale, D C

    1981-01-01

    We have developed a technique for growing endothelial monolayers on micropore filters. These monolayers demonstrate confluence by phase and electron microscopy and provide a functional barrier to passage of radiolabeled albumin. Neutrophils readily penetrate the monolayer in response to chemotaxin, whereas there is little movement in the absence of chemotaxin. This system offers unique advantages over available chemotaxis assays and may have wider applications in the study of endothelial function. Images PMID:7007441

  12. Sentinel node biopsy in penile cancer

    DEFF Research Database (Denmark)

    Jakobsen, J. K.; Krarup, K. P.; Sommer, P.

    2015-01-01

    INTRODUCTION & OBJECTIVES: Nodal involvement is a strong prognosticator in penile cancer and lymph node staging is crucial. Sentinel node biopsy (SNB) has proven a useful staging tool with few complications, but evidence rely mostly on single institution publications with a short follow-up. In th......INTRODUCTION & OBJECTIVES: Nodal involvement is a strong prognosticator in penile cancer and lymph node staging is crucial. Sentinel node biopsy (SNB) has proven a useful staging tool with few complications, but evidence rely mostly on single institution publications with a short follow...... died from complications. CONCLUSIONS: To our knowledge, this is the first complete national study on sentinel node biopsy. Penile cancer sentinel node biopsy with a close follow-up is a reliable lymph node staging and has few complications in a national multicentre setting. Inguinal lymph node...

  13. One-dimensional plasma photonic crystals with sinusoidal densities

    International Nuclear Information System (INIS)

    Qi, L.; Shang, L.; Zhang, S.

    2014-01-01

    Properties of electromagnetic waves with normal and oblique incidence have been studied for one-dimensional plasma layers with sinusoidal densities. Wave transmittance as a function of wave frequency exhibits photonic band gaps characteristic of photonic crystals. For periodic structures, increasing collision frequency is demonstrated to lead to greater absorption, increasing the modulation factor enlarges the gap width, and increasing incidence angle can change the gap locations of the two polarizations. If a defect layer is introduced by inserting a new plasma layer in the center, a defect mode may appear within the gap. Periodic number, collision frequency, and modulation factor can affect magnitude of the defect mode. The incidence angle enables the frequency to be tuned. Defect layer thickness affects both frequency and number of defect modes. These results may provide theoretical guidance in designing tunable narrow-band filters

  14. Successful treatment of severe sinusoidal obstruction syndrome despite multiple organ failure with defibrotide after allogeneic stem cell transplantation: a case report

    Directory of Open Access Journals (Sweden)

    Behre Gerhard

    2009-03-01

    Full Text Available Abstract Introduction We report a case of sinusoidal obstruction syndrome, a typical and life-threatening complication after allogeneic stem-cell transplantation, successfully treated with defibrotide despite massive multiple organ failure. Case presentation A 64-year-old Caucasian woman underwent allogeneic peripheral blood stem-cell transplantation from her human leukocyte antigen-identical sister against aggressive lymphoplasmocytoid immunocytoma. Seven days later, the patient developed severe sinusoidal obstruction syndrome according to the modified Seattle criteria. We initiated treatment with defibrotide. Despite early treatment, multiple organ failure with kidney failure requiring dialysis and ventilator-dependent lung failure aggravated the clinical course. Furthermore, central nervous dysfunction occurred as well as transfusion refractory thrombocytopenia. Conclusion As highlighted in our report, defibrotide is the most promising drug in the treatment of the formerly, almost lethal, severe sinusoidal obstruction syndrome to date. This is demonstrated very clearly in our patient. She improved completely, even after renal, cerebral and respiratory failure.

  15. Scintillations associated with bottomside sinusoidal irregularities in the equatorial F region

    Science.gov (United States)

    Basu, S.; Basu, S.; Valladares, C. E.; Dasgupta, A.; Whitney, H. E.

    1986-01-01

    Multisatellite scintillation observations and spaced receiver drift measurements are presented for a category of equatorial F region plasma irregularities characterized by nearly sinusoidal waveforms in the ion number density. The observations were made at Huancayo, Peru, and the measurements at Ancon, Peru, associated with irregularities observed by the Atmospheric-Explorer-E satellite on a few nights in December 1979. Utilizing ray paths to various geostationary satellites, it was found that the irregularities grow and decay almost simultaneously in long-lived patches extending at least 1000 km in the east-west direction.

  16. Electromagnetic characterization of current transformer with toroidal core under sinusoidal conditions

    Energy Technology Data Exchange (ETDEWEB)

    Koprivica, Branko, E-mail: branko.koprivica@ftn.kg.ac.rs; Milovanovic, Alenka, E-mail: alenka.milovanovic@ftn.kg.ac.rs

    2016-04-01

    The aim of this paper is to present a new procedure for the electromagnetic analysis of a measuring current transformer under sinusoidal conditions in its electrical and magnetic circuit. The influence of the magnetic hysteresis has been taken into account using the measured inverse magnetization curve and phase lag between the time waveforms of the magnetic field and the magnetic induction. Using the proposed analysis, ratio and phase errors of the current transformer have been calculated. The results of the calculation have been compared with experimental results and a good agreement has been found.

  17. Sickle erythrocytes inhibit human endothelial cell DNA synthesis

    International Nuclear Information System (INIS)

    Weinstein, R.; Zhou, M.A.; Bartlett-Pandite, A.; Wenc, K.

    1990-01-01

    Patients with sickle cell anemia experience severe vascular occlusive phenomena including acute pain crisis and cerebral infarction. Obstruction occurs at both the microvascular and the arterial level, and the clinical presentation of vascular events is heterogeneous, suggesting a complex etiology. Interaction between sickle erythrocytes and the endothelium may contribute to vascular occlusion due to alteration of endothelial function. To investigate this hypothesis, human vascular endothelial cells were overlaid with sickle or normal erythrocytes and stimulated to synthesize DNA. The erythrocytes were sedimented onto replicate monolayers by centrifugation for 10 minutes at 17 g to insure contact with the endothelial cells. Incorporation of 3H-thymidine into endothelial cell DNA was markedly inhibited during contact with sickle erythrocytes. This inhibitory effect was enhanced more than twofold when autologous sickle plasma was present during endothelial cell labeling. Normal erythrocytes, with or without autologous plasma, had a modest effect on endothelial cell DNA synthesis. When sickle erythrocytes in autologous sickle plasma were applied to endothelial monolayers for 1 minute, 10 minutes, or 1 hour and then removed, subsequent DNA synthesis by the endothelial cells was inhibited by 30% to 40%. Although adherence of sickle erythrocytes to the endothelial monolayers was observed under these experimental conditions, the effect of sickle erythrocytes on endothelial DNA synthesis occurred in the absence of significant adherence. Hence, human endothelial cell DNA synthesis is partially inhibited by contact with sickle erythrocytes. The inhibitory effect of sickle erythrocytes occurs during a brief (1 minute) contact with the endothelial monolayers, and persists for at least 6 hours of 3H-thymidine labeling

  18. A Longitudinal Comparison of Arm Morbidity in Stage I-II Breast Cancer Patients Treated with Sentinel Lymph Node Biopsy, Sentinel Lymph Node Biopsy Followed by Completion Lymph Node Dissection, or Axillary Lymph Node Dissection

    NARCIS (Netherlands)

    Kootstra, Jan J.; Hoekstra-Weebers, Josette E. H. M.; Rietman, Johan S.; de Vries, Jakob; Baas, Peter C.; Geertzen, Jan H. B.; Hoekstra, Harald J.

    Background. Long-term shoulder and arm function following sentinel lymph node biopsy (SLNB) may surpass that following complete axillary lymph node dissection (CLND) or axillary lymph node dissection (ALND). We objectively examined the morbidity and compared outcomes after SLNB, SLNB + CLND, and

  19. A longitudinal comparison of arm morbidity in stage I-II breast cancer patients treated with sentinel lymph node biopsy, sentinel lymph node biopsy followed by completion lymph node dissection, or axillary lymph node dissection

    NARCIS (Netherlands)

    Kootstra, Jan J.; Hoekstra-Weebers, Josette E.; Rietman, Johan Swanik; de Vries, Jakob; Baas, Peter C.; Geertzen, Jan H.B.; Hoekstra, Harald J.

    2010-01-01

    Background: Long-term shoulder and arm function following sentinel lymph node biopsy (SLNB) may surpass that following complete axillary lymph node dissection (CLND) or axillary lymph node dissection (ALND). We objectively examined the morbidity and compared outcomes after SLNB, SLNB + CLND, and

  20. Endothelial dysfunction in metabolic and vascular disorders.

    Science.gov (United States)

    Polovina, Marija M; Potpara, Tatjana S

    2014-03-01

    Vascular endothelium has important regulatory functions in the cardiovascular system and a pivotal role in the maintenance of vascular health and metabolic homeostasis. It has long been recognized that endothelial dysfunction participates in the pathogenesis of atherosclerosis from early, preclinical lesions to advanced, thrombotic complications. In addition, endothelial dysfunction has been recently implicated in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Considering that states of insulin resistance (eg, metabolic syndrome, impaired fasting glucose, impaired glucose tolerance, and T2DM) represent the most prevalent metabolic disorders and risk factors for atherosclerosis, it is of considerable scientific and clinical interest that both metabolic and vascular disorders have endothelial dysfunction as a common background. Importantly, endothelial dysfunction has been associated with adverse outcomes in patients with established cardiovascular disease, and a growing body of evidence indicates that endothelial dysfunction also imparts adverse prognosis in states of insulin resistance. In this review, we discuss the association of insulin resistance and T2DM with endothelial dysfunction and vascular disease, with a focus on the underlying mechanisms and prognostic implications of the endothelial dysfunction in metabolic and vascular disorders. We also address current therapeutic strategies for the improvement of endothelial dysfunction.

  1. Penile Cancer: Contemporary Lymph Node Management.

    Science.gov (United States)

    O'Brien, Jonathan S; Perera, Marlon; Manning, Todd; Bozin, Mike; Cabarkapa, Sonja; Chen, Emily; Lawrentschuk, Nathan

    2017-06-01

    In penile cancer, the optimal diagnostics and management of metastatic lymph nodes are not clear. Advances in minimally invasive staging, including dynamic sentinel lymph node biopsy, have widened the diagnostic repertoire of the urologist. We aimed to provide an objective update of the recent trends in the management of penile squamous cell carcinoma, and inguinal and pelvic lymph node metastases. We systematically reviewed several medical databases, including the Web of Science® (with MEDLINE®), Embase® and Cochrane databases, according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines. The search terms used were penile cancer, lymph node, sentinel node, minimally invasive, surgery and outcomes, alone and in combination. Articles pertaining to the management of lymph nodes in penile cancer were reviewed, including original research, reviews and clinical guidelines published between 1980 and 2016. Accurate and minimally invasive lymph node staging is of the utmost importance in the surgical management of penile squamous cell carcinoma. In patients with clinically node negative disease, a growing body of evidence supports the use of sentinel lymph node biopsies. Dynamic sentinel lymph node biopsy exposes the patient to minimal risk, and results in superior sensitivity and specificity profiles compared to alternate nodal staging techniques. In the presence of locoregional disease, improvements in inguinal or pelvic lymphadenectomy have reduced morbidity and improved oncologic outcomes. A multimodal approach of chemotherapy and surgery has demonstrated a survival benefit for patients with advanced disease. Recent developments in lymph node management have occurred in penile cancer, such as minimally invasive lymph node diagnosis and intervention strategies. These advances have been met with a degree of controversy in the contemporary literature. Current data suggest that dynamic sentinel lymph node biopsy provides excellent

  2. Targeted endothelial nanomedicine for common acute pathological conditions.

    Science.gov (United States)

    Shuvaev, Vladimir V; Brenner, Jacob S; Muzykantov, Vladimir R

    2015-12-10

    Endothelium, a thin monolayer of specialized cells lining the lumen of blood vessels is the key regulatory interface between blood and tissues. Endothelial abnormalities are implicated in many diseases, including common acute conditions with high morbidity and mortality lacking therapy, in part because drugs and drug carriers have no natural endothelial affinity. Precise endothelial drug delivery may improve management of these conditions. Using ligands of molecules exposed to the bloodstream on the endothelial surface enables design of diverse targeted endothelial nanomedicine agents. Target molecules and binding epitopes must be accessible to drug carriers, carriers must be free of harmful effects, and targeting should provide desirable sub-cellular addressing of the drug cargo. The roster of current candidate target molecules for endothelial nanomedicine includes peptidases and other enzymes, cell adhesion molecules and integrins, localized in different domains of the endothelial plasmalemma and differentially distributed throughout the vasculature. Endowing carriers with an affinity to specific endothelial epitopes enables an unprecedented level of precision of control of drug delivery: binding to selected endothelial cell phenotypes, cellular addressing and duration of therapeutic effects. Features of nanocarrier design such as choice of epitope and ligand control delivery and effect of targeted endothelial nanomedicine agents. Pathological factors modulate endothelial targeting and uptake of nanocarriers. Selection of optimal binding sites and design features of nanocarriers are key controllable factors that can be iteratively engineered based on their performance from in vitro to pre-clinical in vivo experimental models. Targeted endothelial nanomedicine agents provide antioxidant, anti-inflammatory and other therapeutic effects unattainable by non-targeted counterparts in animal models of common acute severe human disease conditions. The results of animal

  3. Voltage-Mode Four-Phase Sinusoidal Generator and Its Useful Extensions

    Directory of Open Access Journals (Sweden)

    Sudhanshu Maheshwari

    2013-01-01

    Full Text Available This paper introduces a new voltage-mode second-order sinusoidal generator circuit with four active elements and six passive elements, including grounded capacitors. The frequency and condition of oscillation can be independently controlled. The effect of active element’s nonidealities and parasitic effects is also studied; the proposed topology is good in absorbing several parasitic elements involved with the active elements. The circuit is advantageous for generating high frequency signals which is demonstrated for 25 MHz outputs. Several circuit extensions are also given which makes the new proposal useful for real circuit adoption. The proposed theory is validated through simulation results.

  4. Identification of a single sinusoidal bile salt uptake system in skate liver

    International Nuclear Information System (INIS)

    Fricker, G.; Hugentobler, G.; Meier, P.J.; Kurz, G.; Boyer, J.L.

    1987-01-01

    To identify the sinusoidal bile acid uptake system(s) of skate liver, photoaffinity labeling and kinetic transport studies were performed in isolated plasma membranes as well as intact hepatocytes. In both preparations photoaffinity labeling with the photolabile bile salt derivative revealed the presence of a predominant bile salt binding polypeptide with an apparent molecular weight of 54,000. The [ 3 H]-labeling of this polypeptide was inhibited by taurocholate and cholate in a concentration-dependent manner and was virtually abolished by 1 mM of the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. Kinetic studies of hepatic uptake with taurocholate, cholate, and the photoreactive bile salt derivative indicated the involvement of a single transport system, and all three substrates mutually competed with the uptake of each other. Finally, irreversible inhibition of the bile salt uptake system of photoaffinity labeling of hepatocytes with high concentrations of photolabile derivative reduced the V max but the K m of taurocholate uptake. These findings strongly indicate that a single polypeptide with an apparent molecular weight of 54,000 is involved in sinusoidal bile salt uptake into skate hepatocytes. These findings contrast with similar studies in rat liver that implicate both a 54,000- and 48,000-K polypeptide in bile salt uptake and are consistent with a single Na + -independent transport mechanism for hepatic bile salt uptake in this primitive vertebrate

  5. Sphingosine 1 Phosphate at the Blood Brain Barrier: Can the Modulation of S1P Receptor 1 Influence the Response of Endothelial Cells and Astrocytes to Inflammatory Stimuli?

    Directory of Open Access Journals (Sweden)

    Simona F Spampinato

    Full Text Available The ability of the Blood Brain Barrier (BBB to maintain proper barrier functions, keeping an optimal environment for central nervous system (CNS activity and regulating leukocytes' access, can be affected in CNS diseases. Endothelial cells and astrocytes are the principal BBB cellular constituents and their interaction is essential to maintain its function. Both endothelial cells and astrocytes express the receptors for the bioactive sphingolipid S1P. Fingolimod, an immune modulatory drug whose structure is similar to S1P, has been approved for treatment in multiple sclerosis (MS: fingolimod reduces the rate of MS relapses by preventing leukocyte egress from the lymph nodes. Here, we examined the ability of S1P and fingolimod to act on the BBB, using an in vitro co-culture model that allowed us to investigate the effects of S1P on endothelial cells, astrocytes, and interactions between the two. Acting selectively on endothelial cells, S1P receptor signaling reduced cell death induced by inflammatory cytokines. When acting on astrocytes, fingolimod treatment induced the release of a factor, granulocyte macrophage colony-stimulating factor (GM-CSF that reduced the effects of cytokines on endothelium. In an in vitro BBB model incorporating shear stress, S1P receptor modulation reduced leukocyte migration across the endothelial barrier, indicating a novel mechanism that might contribute to fingolimod efficacy in MS treatment.

  6. Exercise training improves in vivo endothelial repair capacity of early endothelial progenitor cells in subjects with metabolic syndrome.

    Science.gov (United States)

    Sonnenschein, Kristina; Horváth, Tibor; Mueller, Maja; Markowski, Andrea; Siegmund, Tina; Jacob, Christian; Drexler, Helmut; Landmesser, Ulf

    2011-06-01

    Endothelial dysfunction and injury are considered to contribute considerably to the development and progression of atherosclerosis. It has been suggested that intense exercise training can increase the number and angiogenic properties of early endothelial progenitor cells (EPCs). However, whether exercise training stimulates the capacity of early EPCs to promote repair of endothelial damage and potential underlying mechanisms remain to be determined. The present study was designed to evaluate the effects of moderate exercise training on in vivo endothelial repair capacity of early EPCs, and their nitric oxide and superoxide production as characterized by electron spin resonance spectroscopy analysis in subjects with metabolic syndrome. Twenty-four subjects with metabolic syndrome were randomized to an 8 weeks exercise training or a control group. Superoxide production and nitric oxide (NO) availability of early EPCs were characterized by using electron spin resonance (ESR) spectroscopy analysis. In vivo endothelial repair capacity of EPCs was examined by transplantation into nude mice with defined carotid endothelial injury. Endothelium-dependent, flow-mediated vasodilation was analysed using high-resolution ultrasound. Importantly, exercise training resulted in a substantially improved in vivo endothelial repair capacity of early EPCs (24.0 vs 12.7%; p exercise training, but not in the control group. Moreover, exercise training reduced superoxide production of EPCs, which was not observed in the control group. The present study suggests for the first time that moderate exercise training increases nitric oxide production of early endothelial progenitor cells and reduces their superoxide production. Importantly, this is associated with a marked beneficial effect on the in vivo endothelial repair capacity of early EPCs in subjects with metabolic syndrome.

  7. Status of lymph node staging

    NARCIS (Netherlands)

    Nieweg, O. E.; Estourgie, S. H.; Deurloo, E. E.; Rutgers, E. J. Th; Kroon, B. B. R.

    2002-01-01

    Sentinel node biopsy has the potential to provide more accurate staging information than axillary node dissection. Given the considerable morbidity of axillary node dissection this less invasive approach is attractive. However, there are a number of issues to be resolved before the best technique of

  8. Sentinel lymph node biopsy: clinical relevance

    International Nuclear Information System (INIS)

    Howman-Giles, R.

    2002-01-01

    Sentinel lymph node biopsy (SLNB) has become an important technique in the management of patients with intermediate level melanoma, clinical operable breast cancer and some other cancers. The technique relies on lymphatic mapping to define the lymph drainage from a primary tumour with the premise that the lymph nodes, which directly drain from that area, will reflect the tumour status of the remainder of the node field. Current techniques use lymphoscintigraphy where a radioactive labelled particle and / or blue dye are injected intradermally or intraparenchymally to map the lymph drainage, often in conjunction with a radioactive gamma probe at surgery. In patients with melanoma the SLNB has improved the staging and prognostic information by more accurate determination of whether regional lymph nodes have metastatic spread. This has a major impact on patient management as those patients with negative nodes do not require regional lymph node dissection and have a significantly better prognosis. In our experience of over 3000 patients the combined sentinel node biopsy technique localised accurately 98% of sentinel lymph nodes. Lymphoscintigraphy in patients with melanoma to locate the sentinel lymph nodes involves the intradermal injection of a radiocolloid around the melanoma site or the excision biopsy site. Injections of 5 -10 MBq in 0.05-0.1ml/inj are used and typically 4 injections are usually required. Following tracer injection dynamic imaging is performed to follow the lymphatic collecting vessels until they reach the draining sentinel nodes. An image should be acquired as the vessels reach the node field so that the sentinel nodes directly receiving the channels can be identified and distinguished from any second tier nodes which may sometimes be seen. Delayed scans are performed 2 hours later at which time all regions which can possible drain the primary melanoma site are examined with 5-10 minute static images. The surface location of all sentinel nodes is

  9. The reliability of nonlinear least-squares algorithm for data analysis of neural response activity during sinusoidal rotational stimulation in semicircular canal neurons.

    Science.gov (United States)

    Ren, Pengyu; Li, Bowen; Dong, Shiyao; Chen, Lin; Zhang, Yuelin

    2018-01-01

    Although many mathematical methods were used to analyze the neural activity under sinusoidal stimulation within linear response range in vestibular system, the reliabilities of these methods are still not reported, especially in nonlinear response range. Here we chose nonlinear least-squares algorithm (NLSA) with sinusoidal model to analyze the neural response of semicircular canal neurons (SCNs) during sinusoidal rotational stimulation (SRS) over a nonlinear response range. Our aim was to acquire a reliable mathematical method for data analysis under SRS in vestibular system. Our data indicated that the reliability of this method in an entire SCNs population was quite satisfactory. However, the reliability was strongly negatively depended on the neural discharge regularity. In addition, stimulation parameters were the vital impact factors influencing the reliability. The frequency had a significant negative effect but the amplitude had a conspicuous positive effect on the reliability. Thus, NLSA with sinusoidal model resulted a reliable mathematical tool for data analysis of neural response activity under SRS in vestibular system and more suitable for those under the stimulation with low frequency but high amplitude, suggesting that this method can be used in nonlinear response range. This method broke out of the restriction of neural activity analysis under nonlinear response range and provided a solid foundation for future study in nonlinear response range in vestibular system.

  10. Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification.

    Science.gov (United States)

    Douglas, Gillian; Van Kampen, Erik; Hale, Ashley B; McNeill, Eileen; Patel, Jyoti; Crabtree, Mark J; Ali, Ziad; Hoerr, Robert A; Alp, Nicholas J; Channon, Keith M

    2013-11-01

    Understanding endothelial cell repopulation post-stenting and how this modulates in-stent restenosis is critical to improving arterial healing post-stenting. We used a novel murine stent model to investigate endothelial cell repopulation post-stenting, comparing the response of drug-eluting stents with a primary genetic modification to improve endothelial cell function. Endothelial cell repopulation was assessed en face in stented arteries in ApoE(-/-) mice with endothelial-specific LacZ expression. Stent deployment resulted in near-complete denudation of endothelium, but was followed by endothelial cell repopulation, by cells originating from both bone marrow-derived endothelial progenitor cells and from the adjacent vasculature. Paclitaxel-eluting stents reduced neointima formation (0.423 ± 0.065 vs. 0.240 ± 0.040 mm(2), P = 0.038), but decreased endothelial cell repopulation (238 ± 17 vs. 154 ± 22 nuclei/mm(2), P = 0.018), despite complete strut coverage. To test the effects of selectively improving endothelial cell function, we used transgenic mice with endothelial-specific overexpression of GTP-cyclohydrolase 1 (GCH-Tg) as a model of enhanced endothelial cell function and increased NO production. GCH-Tg ApoE(-/-) mice had less neointima formation compared with ApoE(-/-) littermates (0.52 ± 0.08 vs. 0.26 ± 0.09 mm(2), P = 0.039). In contrast to paclitaxel-eluting stents, reduced neointima formation in GCH-Tg mice was accompanied by increased endothelial cell coverage (156 ± 17 vs. 209 ± 23 nuclei/mm(2), P = 0.043). Drug-eluting stents reduce not only neointima formation but also endothelial cell repopulation, independent of strut coverage. In contrast, selective targeting of endothelial cell function is sufficient to improve endothelial cell repopulation and reduce neointima formation. Targeting endothelial cell function is a rational therapeutic strategy to improve vascular healing and decrease neointima formation after stenting.

  11. Elevated IGFIR expression regulating VEGF and VEGF-C predicts lymph node metastasis in human colorectal cancer

    International Nuclear Information System (INIS)

    Zhang, Chunhui; Hao, Li; Wang, Liang; Xiao, Yichuan; Ge, Hailiang; Zhu, Zhenya; Luo, Yunbao; Zhang, Yi; Zhang, Yanyun

    2010-01-01

    Insulin-like growth factor-I receptor (IGFIR) has been shown to regulate the tumor development. The objective of the current study is to determine the association of IGFIR with lymph node metastasis and to explore the related mechanism in human colorectal cancer in clinic. In a random series of 98 colorectal cancer patients, the expressions of IGFIR, vascular endothelial growth factor (VEGF) and VEGF-C were investigated by immunohistochemistry, and the association of these expressions with lymph node metastasis was statistically analyzed. The expressions of VEGF and VEGF-C in colorectal cancer cells stimulated with IGF-I were also examined by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Higher rates of IGFIR (46%), VEGF (53%), and VEGF-C (46%) expression were found in colorectal cancer tissues than in normal and colorectal adenoma tissues. These expressions were significantly associated with clinicopathologic factors and lymph node status. We also found the concomitant high expressions of IGFIR/VEGF (P < 0.001) and IGFIR/VEGF-C (P = 0.001) had a stronger correlation with lymph node metastasis than did each alone or both low expressions. In addition, IGF-I could effectively induce the VEGF and VEGF-C mRNA expression and protein secretion in colorectal cancer cells expressing IGFIR molecules. Moreover, Patients who had strong staining for IGFIR, VEGF and VEGF-C showed significantly less favorable survival rates compared with patients who had low staining for these molecules (P < 0.001). The survival rates of patients who were both high expression of IGFIR/VEGF and IGFIR/VEGF-C also were significantly lower compared with patients who were negative or one of high expression of these molecules (P < 0.001). Together the findings indicated for the first time that simultaneous examination of the expressions of IGFIR, VEGF and VEGF-C will benefit the diagnosis of lymph node metastasis in order to assay the

  12. Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function.

    Science.gov (United States)

    Rossman, Matthew J; Kaplon, Rachelle E; Hill, Sierra D; McNamara, Molly N; Santos-Parker, Jessica R; Pierce, Gary L; Seals, Douglas R; Donato, Anthony J

    2017-11-01

    Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all P age-related differences were not present (all P > 0.05) in venous ECs from older exercising adults (57 ± 1 yr, n = 13). Furthermore, venous EC protein levels of p53 ( r  = -0.49, P = 0.003), p21 ( r  = -0.38, P = 0.03), and p16 ( r  = -0.58, P = 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both P healthy older sedentary (63 ± 1 yr, n = 18) versus young sedentary (25 ± 1 yr, n = 9) adults; age-related changes in arterial EC p53 and p21 expression were not observed ( P > 0.05) in older habitually exercising adults (59 ± 1 yr, n = 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age. NEW & NOTEWORTHY Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function

  13. New Realizations of Single OTRA-Based Sinusoidal Oscillators

    Directory of Open Access Journals (Sweden)

    Hung-Chun Chien

    2014-01-01

    Full Text Available This study proposes three new sinusoidal oscillators based on an operational transresistance amplifier (OTRA. Each of the proposed oscillator circuits consists of one OTRA combined with a few passive components. The first circuit is an OTRA-based minimum RC oscillator. The second circuit is capable of providing independent control on the condition of oscillation without affecting the oscillation frequency. The third circuit exhibits independent control of oscillation frequency through a capacitor. This study first introduces the OTRA and the related formulations of the proposed oscillator circuits, and then discusses the nonideal effects, sensitivity analyses, and frequency stability of the presented circuits. The proposed oscillators exhibit low sensitivities and good frequency stability. Because the presented circuits feature low impedance output, they can be connected directly to the next stage without cascading additional voltage buffers. HSPICE simulations and experimental results confirm the feasibility of the new oscillator circuits.

  14. COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series)

    Science.gov (United States)

    Polverino, Francesca; Celli, Bartolome R.

    2018-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by chronic expiratory airflow obstruction that is not fully reversible. COPD patients develop varying degrees of emphysema, small and large airway disease, and various co-morbidities. It has not been clear whether these co-morbidities share common underlying pathogenic processes with the pulmonary lesions. Early research into the pathogenesis of COPD focused on the contributions of injury to the extracellular matrix and pulmonary epithelial cells. More recently, cigarette smoke-induced endothelial dysfunction/injury have been linked to the pulmonary lesions in COPD (especially emphysema) and systemic co-morbidities including atherosclerosis, pulmonary hypertension, and chronic renal injury. Herein, we review the evidence linking endothelial injury to COPD, and the pathways underlying endothelial injury and the “vascular COPD phenotype” including: (1) direct toxic effects of cigarette smoke on endothelial cells; (2) generation of auto-antibodies directed against endothelial cells; (3) vascular inflammation; (4) increased oxidative stress levels in vessels inducing increases in lipid peroxidation and increased activation of the receptor for advanced glycation end-products (RAGE); (5) reduced activation of the anti-oxidant pathways in endothelial cells; (6) increased endothelial cell release of mediators with vasoconstrictor, pro-inflammatory, and remodeling activities (endothelin-1) and reduced endothelial cell expression of mediators that promote vasodilation and homeostasis of endothelial cells (nitric oxide synthase and prostacyclin); and (7) increased endoplasmic reticular stress and the unfolded protein response in endothelial cells. We also review the literature on studies of drugs that inhibit RAGE signaling in other diseases (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), or vasodilators developed for idiopathic pulmonary arterial hypertension that have been tested

  15. Aerosol absorption measurement with a sinusoidal phase modulating fiber optic photo thermal interferometer

    Science.gov (United States)

    Li, Shuwang; Shao, Shiyong; Mei, Haiping; Rao, Ruizhong

    2016-10-01

    Aerosol light absorption plays an important role in the earth's atmosphere direct and semi-direct radiate forcing, simultaneously, it also has a huge influence on the visibility impairment and laser engineering application. Although various methods have been developed for measuring aerosol light absorption, huge challenge still remains in precision, accuracy and temporal resolution. The main reason is that, as a part of aerosol light extinction, aerosol light absorption always generates synchronously with aerosol light scattering, and unfortunately aerosol light scattering is much stronger in most cases. Here, a novel photo-thermal interferometry is proposed only for aerosol absorption measurement without disturbance from aerosol scattering. The photo-thermal interferometry consists of a sinusoidal phase-modulating single mode fiber-optic interferometer. The thermal dissipation, caused by aerosol energy from photo-thermal conversion when irritated by pump laser through interferometer, is detected. This approach is completely insensitive to aerosol scattering, and the single mode fiber-optic interferometer is compact, low-cost and insensitive to the polarization shading. The theory of this technique is illustrated, followed by the basic structure of the sinusoidal phase-modulating fiber-optic interferometer and demodulation algorithms. Qualitative and quantitative analysis results show that the new photo-thermal interference is a potential approach for aerosol absorption detection and environmental pollution detection.

  16. The scavenger endothelial cell: a new player in homeostasis and immunity.

    Science.gov (United States)

    Sørensen, Karen Kristine; McCourt, Peter; Berg, Trond; Crossley, Clive; Le Couteur, David; Wake, Kenjiro; Smedsrød, Bård

    2012-12-15

    To maintain homeostasis, the animal body is equipped with a powerful system to remove circulating waste. This review presents evidence that the scavenger endothelial cell (SEC) is responsible for the clearance of blood-borne waste macromolecules in vertebrates. SECs express pattern-recognition endocytosis receptors (mannose and scavenger receptors), and in mammals, the endocytic Fc gamma-receptor IIb2. This cell type has an endocytic machinery capable of super-efficient uptake and degradation of physiological and foreign waste material, including all major classes of biological macromolecules. In terrestrial vertebrates, most SECs line the wall of the liver sinusoid. In phylogenetically older vertebrates, SECs reside instead in heart, kidney, or gills. SECs, thus, by virtue of their efficient nonphagocytic elimination of physiological and microbial substances, play a critical role in the innate immunity of vertebrates. In major invertebrate phyla, including insects, the same function is carried out by nephrocytes. The concept of a dual-cell principle of waste clearance is introduced to emphasize that professional phagocytes (macrophages in vertebrates; hemocytes in invertebrates) eliminate larger particles (>0.5 μm) by phagocytosis, whereas soluble macromolecules and smaller particles are eliminated efficiently and preferentially by clathrin-mediated endocytosis in nonphagocytic SECs in vertebrates or nephrocytes in invertebrates. Including these cells as important players in immunology and physiology provides an additional basis for understanding host defense and tissue homeostasis.

  17. Endogenous Vascular Endothelial Growth Factor-A (VEGF-A) Maintains Endothelial Cell Homeostasis by Regulating VEGF Receptor-2 Transcription*

    Science.gov (United States)

    E, Guangqi; Cao, Ying; Bhattacharya, Santanu; Dutta, Shamit; Wang, Enfeng; Mukhopadhyay, Debabrata

    2012-01-01

    Vascular endothelial growth factor A (VEGF-A) is one of the most important factors controlling angiogenesis. Although the functions of exogenous VEGF-A have been widely studied, the roles of endogenous VEGF-A remain unclear. Here we focused on the mechanistic functions of endogenous VEGF-A in endothelial cells. We found that it is complexed with VEGF receptor 2 (VEGFR-2) and maintains a basal expression level for VEGFR-2 and its downstream signaling activation. Endogenous VEGF-A also controls expression of key endothelial specific genes including VEGFR-2, Tie-2, and vascular endothelial cadherin. Of importance, endogenous VEGF-A differs from exogenous VEGF-A by regulating VEGFR-2 transcription through mediation of FoxC2 binding to the FOX:ETS motif, and the complex formed by endogenous VEGF-A with VEGFR-2 is localized within the EEA1 (early endosome antigen 1) endosomal compartment. Taken together, our results emphasize the importance of endogenous VEGF-A in endothelial cells by regulating key vascular proteins and maintaining the endothelial homeostasis. PMID:22167188

  18. Generation of hyperchaos from the Chen-Lee system via sinusoidal perturbation

    International Nuclear Information System (INIS)

    Tam, L.M.; Chen, J.H.; Chen, H.K.; Wai Meng Si Tou

    2008-01-01

    A system with more than one positive Lyapunov exponent can be classified as a hyperchaotic system. In this study, a sinusoidal perturbation was designed for generating hyperchaos from the Chen-Lee chaotic system. The hyperchaos was identified by the existence of two positive Lyapunov exponents and bifurcation diagrams. The system is hyperchaotic in several different regions of the parameters c, ε, and ω. It was found that this method not only can enhance or suppress chaotic behavior, but also induces chaos in non-chaotic parameter ranges. In addition, two interesting dynamical behaviors, Hopf bifurcation and intermittency, were also found in this study

  19. Generation of hyperchaos from the Chen-Lee system via sinusoidal perturbation

    Energy Technology Data Exchange (ETDEWEB)

    Tam, L.M. [Department of Electromechanical Engineering, Faculty of Science and Technology, University of Macau, Av. Padre Thomas Pereira S.J., Taipa, Macau (China)], E-mail: fstlmt@umac.mo; Chen, J.H. [Department of Mechanical Engineering, Chung Hua University, Hsinchu, Taiwan (China); Chen, H.K. [Department of Mechanical Engineering, Hsiuping Institute of Technology, Taichung, Taiwan (China); Wai Meng Si Tou [Department of Electromechanical Engineering, Faculty of Science and Technology, University of Macau, Av. Padre Thomas Pereira S.J., Taipa, Macau (China)

    2008-11-15

    A system with more than one positive Lyapunov exponent can be classified as a hyperchaotic system. In this study, a sinusoidal perturbation was designed for generating hyperchaos from the Chen-Lee chaotic system. The hyperchaos was identified by the existence of two positive Lyapunov exponents and bifurcation diagrams. The system is hyperchaotic in several different regions of the parameters c, {epsilon}, and {omega}. It was found that this method not only can enhance or suppress chaotic behavior, but also induces chaos in non-chaotic parameter ranges. In addition, two interesting dynamical behaviors, Hopf bifurcation and intermittency, were also found in this study.

  20. Current and Voltage Mode Multiphase Sinusoidal Oscillators Using CBTAs

    Directory of Open Access Journals (Sweden)

    M. Sagbas

    2013-04-01

    Full Text Available Current-mode (CM and voltage-mode (VM multiphase sinusoidal oscillator (MSO structures using current backward transconductance amplifier (CBTA are proposed. The proposed oscillators can generate n current or voltage signals (n being even or odd equally spaced in phase. n+1 CBTAs, n grounded capacitors and a grounded resistor are used for nth-state oscillator. The oscillation frequency can be independently controlled through transconductance (gm of the CBTAs which are adjustable via their bias currents. The effects caused by the non-ideality of the CBTA on the oscillation frequency and condition have been analyzed. The performance of the proposed circuits is demonstrated on third-stage and fifth-stage MSOs by using PSPICE simulations based on the 0.25 µm TSMC level-7 CMOS technology parameters.

  1. Circulating endothelial cells as marker of endothelial damage in male hypogonadism.

    Science.gov (United States)

    Milardi, Domenico; Grande, Giuseppe; Giampietro, Antonella; Vendittelli, Francesca; Palumbo, Sara; Tartaglione, Linda; Marana, Riccardo; Pontecorvi, Alfredo; de Marinis, Laura; Zuppi, Cecilia; Capoluongo, Ettore

    2012-01-01

    Testosterone deficiency has become a frequently diagnosed condition in today's society affected by epidemic obesity, and is associated with cardiovascular risk. Recent studies have established the importance of altered vascular endothelium function in cardiovascular disease. The damage to the endothelium might also cause endothelial cell detachment, resulting in increased numbers of circulating endothelial cells (CEC) within the bloodstream. To evaluate whether hypogonadism could modify CEC count in peripheral bloodstream, we investigated peripheral blood CEC count using the CellSearch System, a semiautomatic method to accurately and reliably enumerate CECs, which are sorted based on a CD146(+), CD105(+), DAPI(+), CD45(-) phenotype, in a population of 20 patients with hypogonadism. The control group comprised 10 age- and sex-matched healthy participants. CEC count per milliliter was significantly increased in patients with hypogonadism vs the control group. In the group with hypogonadism, an inverse exponential correlation was present between testosterone levels and CEC count per milliliter. A direct linear correlation was present between waist circumference and CECs and between body mass index and CECs. The regression analysis showed that testosterone was the significant independent determinant of CECs. Our results underline that male hypogonadism is associated with endothelial dysfunction. The correlation between CEC and waist circumference underlines that visceral obesity may be synergically implicated in this regulation. Future studies are required to unveil the mechanisms involved in the pathogenesis of testosterone-induced endothelial disfunction, which may provide novel therapeutic targets to be incorporated in the management of hypogonadism.

  2. Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema

    Science.gov (United States)

    Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham

    2017-01-01

    Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826

  3. Activation of Endothelial Nitric Oxide (eNOS Occurs through Different Membrane Domains in Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Jason Tran

    Full Text Available Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC with cholesterol and the oxysterol 7-ketocholesterol (7KC. Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1 colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells.

  4. Sentinel lymph node biopsy in node-negative squamous cell carcinoma of the oral cavity and oropharynx.

    LENUS (Irish Health Repository)

    Burns, P

    2012-02-01

    OBJECTIVES: Considerable controversy exists regarding the merits of elective neck dissection in patients with early stage oral cavity and oropharyngeal squamous cell carcinoma. It is highly desirable to have a method of identifying those patients who would benefit from further treatment of the neck when they are clinically node-negative. The purpose of the present study was to examine the use of sentinel lymph node biopsy in identifying occult neck disease in a cohort of patients with node-negative oral cavity and oropharyngeal squamous cell carcinoma. DESIGN: We evaluated a total of 13 patients with oral cavity and oropharyngeal cancer who were clinically and radiologically node-negative. RESULTS: A sentinel lymph node was found in all 13 patients, revealing metastatic disease in five patients, four of whom had one or more positive sentinel lymph nodes. There was one false negative result, in which the sentinel lymph node was negative for tumour whereas histological examination of the neck dissection specimen showed occult disease. CONCLUSION: In view of these findings, we would recommend the use of sentinel lymph node biopsy in cases of oral cavity and oropharyngeal squamous cell carcinoma, in order to aid the differentiation of those patients whose necks are harbouring occult disease and who require further treatment.

  5. Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma

    NARCIS (Netherlands)

    Mantel, Hendrik T. J.; Wiggers, Jim K.; Verheij, Joanne; Doff, Jan J.; Sieders, Egbert; van Gulik, Thomas M.; Gouw, Annette S. H.; Porte, Robert J.

    2015-01-01

    Background. Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The

  6. Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma

    NARCIS (Netherlands)

    Mantel, Hendrik T. J.; Wiggers, Jim K.; Verheij, Joanne; Doff, Jan J.; Sieders, Egbert; van Gulik, Thomas M.; Gouw, Annette S. H.; Porte, Robert J.

    2015-01-01

    Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The objective of

  7. Testnodes: a Lightweight node-testing infrastructure

    International Nuclear Information System (INIS)

    Fay, R; Bland, J

    2014-01-01

    A key aspect of ensuring optimum cluster reliability and productivity lies in keeping worker nodes in a healthy state. Testnodes is a lightweight node testing solution developed at Liverpool. While Nagios has been used locally for general monitoring of hosts and services, Testnodes is optimised to answer one question: is there any reason this node should not be accepting jobs? This tight focus enables Testnodes to inspect nodes frequently with minimal impact and provide a comprehensive and easily extended check with each inspection. On the server side, Testnodes, implemented in python, interoperates with the Torque batch server to control the nodes production status. Testnodes remotely and in parallel executes client-side test scripts and processes the return codes and output, adjusting the node's online/offline status accordingly to preserve the integrity of the overall batch system. Testnodes reports via log, email and Nagios, allowing a quick overview of node status to be reviewed and specific node issues to be identified and resolved quickly. This presentation will cover testnodes design and implementation, together with the results of its use in production at Liverpool, and future development plans.

  8. CT perfusion study of neck lymph nodes

    International Nuclear Information System (INIS)

    Zhong Jin; Liu Jun; Hua Rui; Qiao Hui; Gong Yi

    2011-01-01

    Objective: To study the CT perfusion features of various lymph nodes in the neck. Methods: Dynamic perfusion CT scanning was performed in 83 neck lymph nodes proved by pathology, including tuberculosis lymph nodes, lymphoma and metastatic lymph nodes. The shapes, blood flow modes, and perfusion parameters of these lymph nodes were compared among 3 groups. Statistical analysis of L/T and CT perfusion parameters was performed by one-way ANOVA and LSD test. Results: The values of MTT of tuberculosis lymph nodes, lymphoma and metastatic lymph nodes were (28.13±5.08), (31.08±5.82), and (11.24±5.31) s, respectively. The MTT of metastatic lymph nodes was statistically lower than that of tuberculosis lymph nodes and lymphoma (P -1 · 100 g -1 , respectively. The values of BV were (24.68±2.84), (25.30±3.16), and (25.15± 8.81) ml·100 g -1 respectively. The values of TTP were (40.90±8.85), (40.67±6.45), and (40.98±6.62) s, respectively. There were no significant differences in L/T, BF, BV and TTP among tuberculosis lymph nodes, lymphoma and metastatic lymph nodes (P>0.05). Conclusion: CT perfusion, especially combination functional imaging with perfusion images may be helpful in judging the nature of neck lymph nodes. (authors)

  9. Sinusoidal excitation on the Chua's circuit simulation of limit cycles and chaos

    DEFF Research Database (Denmark)

    Lindberg, Erik

    1994-01-01

    of charging”, and stable limit cycle behaviour based on the balance between the energy lost in the regions with mainly positive losses and the energy gained in the regions with mainly negative losses. Convergence problems observed in connection with simulation of the ideal piecewise-linear model are solved......Experiments with modelling and simulation of sinusoidal excitation on Chua's circuit are presented. It is demonstrated that the behaviour of the circuit is based on the interaction of two different kinds of energy balance: chaotic behaviour based on a balance between two unstable “states...

  10. Descemet Stripping Automated Endothelial Keratoplasty for Endothelial Dysfunction in Xeroderma Pigmentosum: A Clinicopathological Correlation and Review of Literature.

    Science.gov (United States)

    Vira, Divya; Fernandes, Merle; Mittal, Ruchi

    2016-07-01

    Xeroderma pigmentosum (XP) mainly affects the ocular surface; however, endothelial damage may also occur. We would like to report changes in the endothelial-Descemet layer and review the literature on similar findings in patients with XP, including the role of Descemet stripping automated endothelial keratoplasty (DSAEK) in the management of a 21-year-old man who presented with nonresolving corneal edema in the right eye after excision biopsy for conjunctival intraepithelial neoplasia. His best-corrected visual acuity (BCVA) was 20/200 in the right eye and 20/20 in the left eye. On general examination, there was patchy hyperpigmentation of the exposed areas of skin suggestive of XP. On examination of the right eye, there was stromal edema involving the exposed half of cornea. The left eye appeared normal. Pachymetry readings were 860 and 600 μm in the right and left eye, respectively. Descemet stripping automated endothelial keratoplasty was performed for endothelial dysfunction and the stripped endothelium, and Descemet membrane (DM) was sent for histopathologic evaluation. Postoperatively, the donor lenticule was well apposed and the overlying stromal edema resolved. The patient achieved a BCVA of 20/30 in the right eye without progression of corneal scarring at 1-year follow-up. In the meanwhile, however, the left eye developed corneal edema. Histopathology revealed gross attenuation of endothelial cells with uniform thickness of the DM. Corneal endothelial dysfunction in XP is amenable to treatment with DSAEK.

  11. The electronic states calculated using the sinusoidal potential for Cd1-xZnxS quantum dot superlattices

    International Nuclear Information System (INIS)

    Sakly, A.; Safta, N.; Mejri, H.; Lamine, A. Ben

    2011-01-01

    Research highlights: → This paper is dedicated to structures based on Cd 1-x Zn x S. - Abstract: The present work reports on a theoretical investigation of superlattices based on Cd 1-x Zn x S quantum dots embedded in an insulating material. The system to model is assumed to be a series of flattened cylindrical quantum dots with a finite barrier at the boundary and is studied using a sinusoidal potential. The electronic states of both Γ 1 - (ground) and Γ 2 - (first excited) minibands have been computed as a function of inter-quantum dot separation and Zn composition. An analysis of the results shows that the widths of Γ 1 - and Γ 2 - minibands decrease as the superlattice period and Zn content increase separately. Moreover, the sinusoidal shape of the confining potential accounts for the coupling between quantum dots quantitatively less than the Kronig-Penney potential model.

  12. Strategies to reverse endothelial progenitor cell dysfunction in diabetes.

    Science.gov (United States)

    Petrelli, Alessandra; Di Fenza, Raffaele; Carvello, Michele; Gatti, Francesca; Secchi, Antonio; Fiorina, Paolo

    2012-01-01

    Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial), their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs). Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

  13. Strategies to Reverse Endothelial Progenitor Cell Dysfunction in Diabetes

    Directory of Open Access Journals (Sweden)

    Alessandra Petrelli

    2012-01-01

    Full Text Available Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial, their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs. Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

  14. Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells

    Science.gov (United States)

    Butler, Jason M.; Nolan, Daniel J.; L.Vertes, Eva; Varnum-Finney, Barbara; Kobayashi, Hideki; Hooper, Andrea T.; Seandel, Marco; Shido, Koji; White, Ian A.; Kobayashi, Mariko; Witte, Larry; May, Chad; Shawber, Carrie; Kimura, Yuki; Kitajewski, Jan; Rosenwaks, Zev; Bernstein, Irwin D.; Rafii, Shahin

    2010-01-01

    Bone marrow endothelial cells (ECs) are essential for reconstitution of hematopoiesis, but their role in self-renewal of long term-hematopoietic stem cells (LT-HSCs) is unknown. We have developed angiogenic models to demonstrate that EC-derived angiocrine growth factors support in vitro self-renewal and in vivo repopulation of authentic LT-HSCs. In serum/cytokine-free co-cultures, ECs through direct cellular contact, stimulated incremental expansion of repopulating CD34−Flt3−cKit+Lineage−Sca1+ LT-HSCs, which retained their self-renewal ability, as determined by single cell and serial transplantation assays. Angiocrine expression of Notch-ligands by ECs promoted proliferation and prevented exhaustion of LT-HSCs derived from wild-type, but not Notch1/Notch2 deficient mice. In transgenic notch-reporter (TNR.Gfp) mice, regenerating TNR.Gfp+ LT-HSCs were detected in cellular contact with sinusoidal ECs and interfering with angiocrine, but not perfusion function, of SECs impaired repopulation of TNR.Gfp+ LT-HSCs. ECs establish an instructive vascular niche for clinical scale expansion of LT-HSCs and a cellular platform to identify stem cell-active trophogens. PMID:20207228

  15. Arachidonic acid metabolites in normal and autoimmune mice do not influence lymphocyte-high endothelial venule interactions.

    Science.gov (United States)

    Manolios, N; Bakiera, B; Geczy, C L; Schrieber, L

    1991-02-01

    In peripheral lymphoid organs the number of lymphocytes and the proportion of functional lymphocyte subsets are regulated by multiple factors including the control of lymphocyte migration by selective lymphocyte-high endothelial venule (HEV) interactions. In this study, prostaglandin E2 (PGE2) levels from normal and autoimmune mouse lymph node cells were measured. The contribution of eicosanoids to lymphocyte-HEV interactions in normal (CBA/T6) and autoimmune (MRL/n) mice was examined. There was no association between PGE2 production in normal or autoimmune mice and the age of onset of disease activity in the latter strains. Arachidonic acid metabolites, in particular PGE2 and leukotriene B4 (LTB4), did not have any effects on lymphocyte-HEV binding. Likewise, lymphocytes treated in vivo and/or in vitro with arachidonic acid metabolite inhibitors (acetyl salicylic acid, indomethacin, BW755C) did not alter lymphocyte-HEV binding interactions in both normal and autoimmune mice. No clinical significance could be attributed to lymph node PGE2 production and the age of onset of autoimmune disease. In summary, these findings cast doubt on the role of arachidonic acid metabolites in lymphocyte-HEV binding interactions.

  16. The Malnutrition-Related Increase in Early Visceralization of Leishmania donovani Is Associated with a Reduced Number of Lymph Node Phagocytes and Altered Conduit System Flow

    Science.gov (United States)

    Ibrahim, Marwa K.; Barnes, Jeffrey L.; Anstead, Gregory M.; Jimenez, Fabio; Travi, Bruno L.; Peniche, Alex G.; Osorio, E. Yaneth; Ahuja, Seema S.; Melby, Peter C.

    2013-01-01

    In a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4–5-fold increase in early visceralization of L. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (pmalnutrition-related parasite dissemination we analyzed the cellularity, architecture, and function of the skin-draining lymph node. There was no difference in the localization of multiple cell populations in the lymph node of polynutrient deficient (PND) mice, but there was reduced cellularity with fewer CD11c+dendritic cells (DCs), fibroblastic reticular cells (FRCs), MOMA-2+ macrophages, and CD169+ subcapsular sinus macrophage (p<0.05 for all) compared to the well-nourished (WN) mice. The parasites were equally co-localized with DCs associated with the lymph node conduit network in the WN and PND mice, and were found in the high endothelial venule into which the conduits drain. When a fluorescent low molecular weight (10 kD) dextran was delivered in the skin, there was greater efflux of the marker from the lymph node conduit system to the spleens of PND mice (p<0.04), indicating that flow through the conduit system was altered. There was no evidence of disruption of the conduit or subcapsular sinus architecture, indicating that the movement of parasites into the subcortical conduit region was due to an active process and not from passive movement through a leaking barrier. These results indicate that the impaired capacity of the lymph node to act as a barrier to dissemination of L. donovani infection is associated with a reduced number of lymph node phagocytes, which most likely leads to reduced capture of parasites as they transit through the sinuses and conduit system. PMID:23967356

  17. Reduced Ang2 expression in aging endothelial cells.

    Science.gov (United States)

    Hohensinner, P J; Ebenbauer, B; Kaun, C; Maurer, G; Huber, K; Wojta, J

    2016-06-03

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Subcarinal lymph node in upper lobe non-small cell lung cancer patients: is selective lymph node dissection valid?

    Science.gov (United States)

    Aokage, Keiju; Yoshida, Junji; Ishii, Genichiro; Hishida, Tomoyuki; Nishimura, Mitsuyo; Nagai, Kanji

    2010-11-01

    Little is known about selective lymph node dissection in non-small cell lung cancer (NSCLC) patients. We sought to gain insight into subcarinal node involvement for its frequency and impact on outcome to evaluate whether it is valid to omit subcarinal lymph node dissection in upper lobe NSCLC patients. We reviewed node metastases distribution according to node region, tumor location, and histology among 1099 patients with upper lobe NSCLC. We paid special attention to subcarinal metastases patients without superior mediastinal node metastases, because their pathological stages would have been underdiagnosed if subcarinal node dissection had been omitted. We also assessed the outcome and the pattern of failure among subcarinal metastases patients. To identify subcarinal node involvement predictors, we analyzed 7 clinical factors. Subcarinal node metastases were found in 20 patients and were least frequent among squamous cell carcinoma patients (0.5%). Two of them were free from superior mediastinal metastases but died of the disease at 1 month and due to an unknown cause at 18 months, respectively. Seventeen of the 20 patients developed multi-site recurrence within 37 months. The 5-year survival rate of the 20 patients with subcarinal metastases was 9.0%, which was significantly lower than 32.0% of patients with only superior mediastinal metastases. Clinical diagnosis of node metastases was significantly predictive of subcarinal metastases. Subcarinal node metastases from upper lobe NSCLC were rare and predicted an extremely poor outcome. It appears valid to omit subcarinal node dissection in upper lobe NSCLC patients, especially in clinical N0 squamous cell carcinoma patients. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  19. Dai-kenchu-to attenuates rat sinusoidal obstruction syndrome by inhibiting the accumulation of neutrophils in the liver.

    Science.gov (United States)

    Narita, Masato; Hatano, Etsuro; Tamaki, Nobuyuki; Yamanaka, Kenya; Yanagida, Atsuko; Nagata, Hiromitsu; Asechi, Hiroyuki; Takada, Yasutsugu; Ikai, Iwao; Uemoto, Shinji

    2009-06-01

    Sinusoidal obstruction syndrome (SOS) is drug-induced liver injury that occurs in patients who receive hematopoietic cell transplantation and oxaliplatin-contained chemotherapy. The aim of study was to investigate the pharmacological treatment of SOS using a traditional Japanese medicine, Dai-kenchu-to (DKT). Male Sprague-Dawley rats were treated with monocrotaline (MCT) to induce SOS. The rats were divided into three groups: control, MCT and MCT+DKT groups. In the MCT+DKT group, DKT was gavaged at 12 h after MCT treatment and given every 12 h until the end of the protocol. The rats of MCT group were treated with water instead of DKT. At 48 h after MCT treatment, blood and liver samples were collected. In the MCT+DKT group, the macroscopic and histological findings revealed liver congestion, sinusoidal alteration and the destruction of sinusoidal lining, which were comparable with those of the MCT group. However, the area of hepatic necrosis and serum AST levels significantly decreased in the MCT+DKT group compared with those of the MCT group. Treatment with DKT resulted in the reduction of neutrophil accumulation, myeloperoxidase activity and the expression of cytokine-induced neutrophil chemoattractant (CINC) and intracellular adhesion molecule-1 (ICAM-1) mRNA in the liver compared with those of the MCT group. Treatment with processed ginger, one of the ingredients in DKT, resulted in similar effects to those shown by DKT. Dai-kenchu-to attenuates MCT-induced liver injury by preventing neutrophil-induced liver injury through blockage of upregulation of CINC and ICAM-1 mRNA level.

  20. Endothelial Protein C–Targeting Liposomes Show Enhanced Uptake and Improved Therapeutic Efficacy in Human Retinal Endothelial Cells

    DEFF Research Database (Denmark)

    Arta, Anthoula; Eriksen, Anne Z.; Melander, Fredrik

    2018-01-01

    PURPOSE. To determine whether human retinal endothelial cells (HRECs) express the endothelial cell protein C receptor (EPCR) and to realize its potential as a targeting moiety by developing novel single and dual corticosteroid–loaded functionalized liposomes that exhibit both enhanced uptake by H...... of cell tube formations in contrast to nontargeting liposomes. CONCLUSIONS. We show that HRECs express EPCR and this receptor could be a promising nanomedicine target in ocular diseases where the endothelial barrier of the retina is compromised....

  1. Oxidative stress induced pulmonary endothelial cell proliferation is ...

    African Journals Online (AJOL)

    Cellular hyper-proliferation, endothelial dysfunction and oxidative stress are hallmarks of the pathobiology of pulmonary hypertension. Indeed, pulmonary endothelial cells proliferation is susceptible to redox state modulation. Some studies suggest that superoxide stimulates endothelial cell proliferation while others have ...

  2. Endothelial glycocalyx on brain endothelial cells is lost in experimental cerebral malaria

    DEFF Research Database (Denmark)

    Hempel, Casper; Hyttel, Poul; Kurtzhals, Jørgen Al

    2014-01-01

    We hypothesized that the glycocalyx, which is important for endothelial integrity, is lost in severe malaria. C57BL/6 mice were infected with Plasmodium berghei ANKA, resulting in cerebral malaria, or P. chabaudi AS, resulting in uncomplicated malaria. We visualized the glycocalyx with transmission...... electron microscopy and measured circulating glycosaminoglycans by dot blot and ELISA. The glycocalyx was degraded in brain vasculature in cerebral and to a lesser degree uncomplicated malaria. It was affected on both intact and apoptotic endothelial cells. Circulating glycosaminoglycan levels suggested...

  3. The endothelial border to health

    DEFF Research Database (Denmark)

    Hansen, Nina Wærling; Hansen, Anker Jon; Sams, Anette

    2017-01-01

    player for maintenance of health and for development of a number of diseases. Endothelial dysfunction is known to be an important component of type 2 diabetes, but is also assumed to be involved in many other diseases, for example, rheumatoid arthritis, inflammatory bowel disease, asthma...... extracellular proteins form epitopes for potential specific antibody formation upon interactions with reducing sugars. This paper reviews the endothelial metabolism, biology, inflammatory processes, physical barrier functions, and summarizes evidence that although stochastic in nature, endothelial responses...... to hyperglycemia are major contributors to disease pathophysiology. We present molecular and mechanistic evidence that both biological and physical barriers, protein function, specific immunity, and inflammatory processes are compromised by hyperglycemic events and thus, hyperglycemic events alone should...

  4. Radioprotection of mouse CNS endothelial cells in vivo

    International Nuclear Information System (INIS)

    Lyubimova, N.; Coultas, P.; Martin, R.

    1996-01-01

    Full text: Radioprotection using the minor groove binding DNA ligand Hoechst 33342 has been demonstrated in vitro, and more recently in vivo, in mouse lung. Intravenous administration was used for the lung studies, and both endothelial and alveolar epithelial cells-showed good up-take. Radiation damage to the endothelial cell population has also been postulated as important in late developing radionecrosis of spinal cord and brain. Endothelial cell density in brain can be readily determined by a fluorescent-histochemical technique. Treatment with a monoamine oxidase inhibitor and subsequent injection with L-DOPA results in an accumulation of dopamine (DA) in CNS endothelial cells. DA is converted to a fluorophore by exposure to paraformaldehyde, and cell numbers assayed by fluorescence microscopy. Earlier studies used this technique to monitor post-irradiation changes in endothelial cell density in rodent brain and showed the loss, within 24 hours, of a sensitive subpopulation comprising about 15% of the endothelial cells. Ten minutes after intravenous injection of Hoechst 33342 (80mg/kg) the ligand is confined by its limited penetration to the endothelial cells in mouse brain. When we irradiated at this time, there was protection against early endothelial cell loss. Ablation of the sensitive subpopulation in unprotected mice takes place over a dose range of 1 to 3 Gy γ-rays, but doses between 12 to 20 Gy are required in the presence of ligand. This protection equates to a very high dose modification factor of about 7 and possibly reflects a suppression of apoptosis in the sensitive endothelial subpopulation. The extent to which there is enhanced survival in the endothelial population as a whole and how the observed protection affects late CNS necrosis development has yet to be determined. However present results clearly show potential for the use of DNA-binding radioprotectors with limited penetration for investigations into the relative significance of

  5. Endothelial remodelling and intracellular calcium machinery.

    Science.gov (United States)

    Moccia, F; Tanzi, F; Munaron, L

    2014-05-01

    Rather being an inert barrier between vessel lumen and surrounding tissues, vascular endothelium plays a key role in the maintenance of cardiovascular homeostasis. The de-endothelialization of blood vessels is regarded as the early event that results in the onset of severe vascular disorders, including atherosclerosis, acute myocardial infarction, brain stroke, and aortic aneurysm. Restoration of the endothelial lining may be accomplished by the activation of neighbouring endothelial cells (ECs) freed by contact inhibition and by circulating endothelial progenitor cells (EPCs). Intracellular Ca(2+) signalling is essential to promote wound healing: however, the molecular underpinnings of the Ca(2+) response to injury are yet to be fully elucidated. Similarly, the components of the Ca(2+) toolkit that drive EPC incorporation into denuded vessels are far from being fully elucidated. The present review will survey the current knowledge on the role of Ca(2+) signalling in endothelial repair and in EPC activation. We propose that endothelial regeneration might be boosted by intraluminal release of specific Ca(2+) channel agonists or by gene transfer strategies aiming to enhance the expression of the most suitable Ca(2+) channels at the wound site. In this view, connexin (Cx) channels/hemichannels and store-operated Ca(2+) entry (SOCE) stand amid the most proper routes to therapeutically induce the regrowth of denuded vessels. Cx stimulation might trigger the proliferative and migratory behaviour of ECs facing the lesion site, whereas activation of SOCE is likely to favour EPC homing to the wounded vessel.

  6. Dietary phosphorus acutely impairs endothelial function.

    Science.gov (United States)

    Shuto, Emi; Taketani, Yutaka; Tanaka, Rieko; Harada, Nagakatsu; Isshiki, Masashi; Sato, Minako; Nashiki, Kunitaka; Amo, Kikuko; Yamamoto, Hironori; Higashi, Yukihito; Nakaya, Yutaka; Takeda, Eiji

    2009-07-01

    Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

  7. Endothelial network formed with human dermal microvascular endothelial cells in autologous multicellular skin substitutes.

    Science.gov (United States)

    Ponec, Maria; El Ghalbzouri, Abdoelwaheb; Dijkman, Remco; Kempenaar, Johanna; van der Pluijm, Gabri; Koolwijk, Pieter

    2004-01-01

    A human skin equivalent from a single skin biopsy harboring keratinocytes and melanocytes in the epidermal compartment, and fibroblasts and microvascular dermal endothelial cells in the dermal compartment was developed. The results of the study revealed that the nature of the extracellular matrix of the dermal compartments plays an important role in establishment of endothelial network in vitro. With rat-tail type I collagen matrices only lateral but not vertical expansion of endothelial networks was observed. In contrast, the presence of extracellular matrix of entirely human origin facilitated proper spatial organization of the endothelial network. Namely, when human dermal fibroblasts and microvascular endothelial cells were seeded on the bottom of an inert filter and subsequently epidermal cells were seeded on top of it, fibroblasts produced extracellular matrix throughout which numerous branched tubes were spreading three-dimensionally. Fibroblasts also facilitated the formation of basement membrane at the epidermal/matrix interface. Under all culture conditions, fully differentiated epidermis was formed with numerous melanocytes present in the basal epidermal cell layer. The results of the competitive RT-PCR revealed that both keratinocytes and fibroblasts expressed VEGF-A, -B, -C, aFGF and bFGF mRNA, whereas fibroblasts also expressed VEGF-D mRNA. At protein level, keratinocytes produced 10 times higher amounts of VEGF-A than fibroblasts did. The generation of multicellular skin equivalent from a single human skin biopsy will stimulate further developments for its application in the treatment of full-thickness skin defects. The potential development of biodegradable, biocompatible material suitable for these purposes is a great challenge for future research.

  8. Verocytotoxin-induced apoptosis of human microvascular endothelial cells.

    Science.gov (United States)

    Pijpers, A H; van Setten, P A; van den Heuvel, L P; Assmann, K J; Dijkman, H B; Pennings, A H; Monnens, L A; van Hinsbergh, V W

    2001-04-01

    The pathogenesis of the epidemic form of hemolytic uremic syndrome is characterized by endothelial cell damage. In this study, the role of apoptosis in verocytotoxin (VT)-mediated endothelial cell death in human glomerular microvascular endothelial cells (GMVEC), human umbilical vein endothelial cells, and foreskin microvascular endothelial cells (FMVEC) was investigated. VT induced apoptosis in GMVEC and human umbilical vein endothelial cells when the cells were prestimulated with the inflammatory mediator tumor necrosis factor-alpha (TNF-alpha). FMVEC displayed strong binding of VT and high susceptibility to VT under basal conditions, which made them suitable for the study of VT-induced apoptosis without TNF-alpha interference. On the basis of functional (flow cytometry and immunofluorescence microscopy using FITC-conjugated annexin V and propidium iodide), morphologic (transmission electron microscopy), and molecular (agarose gel electrophoresis of cellular DNA fragments) criteria, it was documented that VT induced programmed cell death in microvascular endothelial cells in a dose- and time-dependent manner. Furthermore, whereas partial inhibition of protein synthesis by VT was associated with a considerable number of apoptotic cells, comparable inhibition of protein synthesis by cycloheximide was not. This suggests that additional pathways, independent of protein synthesis inhibition, may be involved in VT-mediated apoptosis in microvascular endothelial cells. Specific inhibition of caspases by Ac-Asp-Glu-Val-Asp-CHO, but not by Ac-Tyr-Val-Ala-Asp-CHO, was accompanied by inhibition of VT-induced apoptosis in FMVEC and TNF-alpha-treated GMVEC. These data indicate that VT can induce apoptosis in human microvascular endothelial cells.

  9. Resveratrol: A Multifunctional Compound Improving Endothelial Function

    OpenAIRE

    Li, Huige; F?rstermann, Ulrich

    2009-01-01

    The red wine polyphenol resveratrol boosts endothelium-dependent and -independent vasorelaxations. The improvement of endothelial function by resveratrol is largely attributable to nitric oxide (NO) derived from endothelial NO synthase (eNOS). By stimulating eNOS expression, eNOS phosphorylation and eNOS deacetylation, resveratrol enhances endothelial NO production. By upregulating antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and suppressing the expression a...

  10. Lectin I of Ulex europaeus as a marker for a subset of histiocytic tumours of the lymph node.

    Science.gov (United States)

    Ruco, L P; Pescarmona, E; Pezzella, F; Uccini, S; Testi, A M; Cartoni, C; Baroni, C D

    1985-01-01

    We describe four lymph node based tumours in which numerous neoplastic cells and some mitotic figures were characterized by staining affinity for Lectin I of Ulex europaeus (UEA-I). The patients had no vascular or epithelial tumours and presented symptoms suggestive of a systemic lymphoproliferative disease. Histologically, the tumours were composed of large, cohesive, cells which were mainly located in the paracortex. UEA-I reactivity was more evident in the Golgi area and was present in large mononucleated cells often arranged to delimit vascular-like spaces. The neoplastic cells were weakly muramidase-positive in one case, and were ANAE+/AP+ in two other cases. Large dots of UEA-I reactivity were detected in S-100+/muramidase-negative Langerhans-like cells present in one case of Letterer-Siwe disease. UEA-I staining was consistently negative in 20 cases of B cell- or T cell lymphoma and in 9 other cases of histiocytic lymphoma. It is suggested that UEA-I+ tumours of the lymph nodes are part of a distinct subset of histiocytic malignancies whose neoplastic cells present some morphological and phenotypic properties normally associated with endothelial cells.

  11. Beginning Amazon Web Services with Node.js

    CERN Document Server

    Shackelford, Adam

    2015-01-01

    Beginning Amazon Web Services with Node.js teaches any novice Node.js developer to configure, deploy, and maintain scalable small to large scale Node.js applications in Amazon Web Services. Hosting a Node.js application in a production environment usually means turning to PaaS hosting, but this approach brings problems. Deploying Node.js directly to AWS solves the problems you encounter in these situations, enabling you to cut out the middle man. You will begin with a basic RESTful web service in Node.js, using the popular Express.js framework, pre-built and ready to run in your local env

  12. Endothelial dysfunction – A predictor of atherosclerosis | Chhabra ...

    African Journals Online (AJOL)

    Endothelial dysfunction is a systemic disorder and a critical element in the pathogenesis of atherosclerotic diseases and its complications. Growing evidences suggest that the individual burden of currently known cardiovascular risk factors is not the only determinant of endothelial function; rather endothelial integrity ...

  13. Secure message authentication system for node to node network

    Science.gov (United States)

    Sindhu, R.; Vanitha, M. M.; Norman, J.

    2017-10-01

    The Message verification remains some of the best actual methods for prevent the illegal and dis honored communication after presence progressed to WSNs (Wireless Sensor Networks). Intend for this purpose, several message verification systems must stand established, created on both symmetric key cryptography otherwise public key cryptosystems. Best of them will have some limits for great computational then statement above in count of deficiency of climb ability then flexibility in node settlement occurrence. In a polynomial based system was newly presented for these problems. Though, this system then situations delay will must the dimness of integral limitation firm in the point of polynomial: once the amount of message transferred remains the greater than the limitation then the opponent will completely improve the polynomial approaches. This paper suggests using ECC (Elliptic Curve Cryptography). Though using the node verification the technique in this paper permits some nodes to transfer a limitless amount of messages lacking misery in the limit problem. This system will have the message cause secrecy. Equally theoretic study then model effects show our planned system will be effective than the polynomial based method in positions of calculation then statement above in privacy points though message basis privacy.

  14. An all digital phase locked loop for synchronization of a sinusoidal signal embedded in white Gaussian noise

    Science.gov (United States)

    Reddy, C. P.; Gupta, S. C.

    1973-01-01

    An all digital phase locked loop which tracks the phase of the incoming sinusoidal signal once per carrier cycle is proposed. The different elements and their functions and the phase lock operation are explained in detail. The nonlinear difference equations which govern the operation of the digital loop when the incoming signal is embedded in white Gaussian noise are derived, and a suitable model is specified. The performance of the digital loop is considered for the synchronization of a sinusoidal signal. For this, the noise term is suitably modelled which allows specification of the output probabilities for the two level quantizer in the loop at any given phase error. The loop filter considered increases the probability of proper phase correction. The phase error states in modulo two-pi forms a finite state Markov chain which enables the calculation of steady state probabilities, RMS phase error, transient response and mean time for cycle skipping.

  15. Responses of Medullary Lateral Line Units of the Goldfish, Carassius auratus, to Amplitude-Modulated Sinusoidal Wave Stimuli

    Directory of Open Access Journals (Sweden)

    Ramadan Ali

    2010-01-01

    Full Text Available This paper describes the responses of brainstem lateral line units in goldfish, Carassius auratus, to constant-amplitude and to amplitude-modulated sinusoidal water motions. If stimulated with constant-amplitude sinusoidal water motions, units responded with phasic (50% or with sustained (50% increases in dicharge rate. Based on isodisplacement curves, units preferred low (33 Hz, 12.5%, mid (50 Hz, 10% and 100 Hz, 30% or high (200 Hz, 47.5% frequencies. In most units, responses were weakly phase locked to the carrier frequency. However, at a carrier frequency of 50 Hz or 100 Hz, a substantial proportion of the units exhibited strong phase locking. If stimulated with amplitude-modulated water motions, units responded with a burst of discharge to each modulation cycle, that is, units phase locked to the amplitude modulation frequency. Response properties of brainstem units were in many respects comparable to those of midbrain units, suggesting that they emerge first in the lateral line brainstem.

  16. Offloading of a Wireless Node Authentication with Core Network

    DEFF Research Database (Denmark)

    2017-01-01

    An example technique may include controlling receiving, by a second node from a first node in a wireless network, a request to offload authentication of the first node with the core network to the second node, controlling receiving, by the second node from the first node, data to be forwarded...... to the core network, performing, by the second node based on the request, an authentication with the core network on behalf of the first node while the first node is not connected with the second node, and controlling forwarding the received data from the second node to the core network while the first node...

  17. Node Immunization with Time-Sensitive Restrictions

    Directory of Open Access Journals (Sweden)

    Wen Cui

    2016-12-01

    Full Text Available When we encounter a malicious rumor or an infectious disease outbreak, immunizing k nodes of the relevant network with limited resources is always treated as an extremely effective method. The key challenge is how we can insulate limited nodes to minimize the propagation of those contagious things. In previous works, the best k immunised nodes are selected by learning the initial status of nodes and their strategies even if there is no feedback in the propagation process, which eventually leads to ineffective performance of their solutions. In this paper, we design a novel vaccines placement strategy for protecting much more healthy nodes from being infected by infectious nodes. The main idea of our solution is that we are not only utilizing the status of changing nodes as auxiliary knowledge to adjust our scheme, but also comparing the performance of vaccines in various transmission slots. Thus, our solution has a better chance to get more benefit from these limited vaccines. Extensive experiments have been conducted on several real-world data sets and the results have shown that our algorithm has a better performance than previous works.

  18. Cilostazol activates function of bone marrow-derived endothelial progenitor cell for re-endothelialization in a carotid balloon injury model.

    Directory of Open Access Journals (Sweden)

    Rie Kawabe-Yako

    Full Text Available BACKGROUND: Cilostazol(CLZ has been used as a vasodilating anti-platelet drug clinically and demonstrated to inhibit proliferation of smooth muscle cells and effect on endothelial cells. However, the effect of CLZ on re-endothelialization including bone marrow (BM-derived endothelial progenitor cell (EPC contribution is unclear. We have investigated the hypothesis that CLZ might accelerate re-endothelialization with EPCs. METHODOLOGY/PRINCIPAL FINDINGS: Balloon carotid denudation was performed in male Sprague-Dawley rats. CLZ group was given CLZ mixed feed from 2 weeks before carotid injury. Control group was fed normal diet. CLZ accelerated re-endothelialization at 2 weeks after surgery and resulted in a significant reduction of neointima formation 4 weeks after surgery compared with that in control group. CLZ also increased the number of circulating EPCs throughout the time course. We examined the contribution of BM-derived EPCs to re-endothelialization by BM transplantation from Tie2/lacZ mice to nude rats. The number of Tie2-regulated X-gal positive cells on injured arterial luminal surface was increased at 2 weeks after surgery in CLZ group compared with that in control group. In vitro, CLZ enhanced proliferation, adhesion and migration activity, and differentiation with mRNA upregulation of adhesion molecule integrin αvβ3, chemokine receptor CXCR4 and growth factor VEGF assessed by real-time RT-PCR in rat BM-derived cultured EPCs. In addition, CLZ markedly increased the expression of SDF-1α that is a ligand of CXCR4 receptor in EPCs, in the media following vascular injury. CONCLUSIONS/SIGNIFICANCE: CLZ promotes EPC mobilization from BM and EPC recruitment to sites of arterial injury, and thereby inhibited neointima formation with acceleration of re-endothelialization with EPCs as well as pre-existing endothelial cells in a rat carotid balloon injury model. CLZ could be not only an anti-platelet agent but also a promising tool for

  19. A Comparison Study of Sinusoidal PWM and Space Vector PWM Techniques for Voltage Source Inverter

    Directory of Open Access Journals (Sweden)

    Ömer Türksoy

    2017-06-01

    Full Text Available In this paper, the methods used to control voltage source inverters which have been intensively investigated in recent years are compared. Although the most efficient result is obtained with the least number of switching elements in the inverter topologies, the method used in the switching is at least as effective as the topology. Besides, the selected switching method to control the inverter will play an effective role in suppressing harmonic components while producing the ideal output voltage. There are many derivatives of pulse width modulation techniques that are commonly used to control voltage source inverters. Some of widespread methods are sinusoidal pulse width modulation and space vector pulse width modulation techniques. These modulation techniques used for generating variable frequency and amplitude output voltage in voltage source inverters, have been simulated by using MATLAB/SIMULINK. And, the total harmonic distortions of the output voltages are compared. As a result of simulation studies, sinusoidal pulse width modulation has been found to have more total harmonic distortion in output voltages of voltage source inverters in the simulation. Space vector pulse width modulation has been shown to produce a more efficient output voltage with less total harmonic distortion.

  20. Realisation and advanced engineering of true optical rugate filters based on nanoporous anodic alumina by sinusoidal pulse anodisation

    Science.gov (United States)

    Santos, Abel; Yoo, Jeong Ha; Rohatgi, Charu Vashisth; Kumeria, Tushar; Wang, Ye; Losic, Dusan

    2016-01-01

    This study is the first realisation of true optical rugate filters (RFs) based on nanoporous anodic alumina (NAA) by sinusoidal waves. An innovative and rationally designed sinusoidal pulse anodisation (SPA) approach in galvanostatic mode is used with the aim of engineering the effective medium of NAA in a sinusoidal fashion. A precise control over the different anodisation parameters (i.e. anodisation period, anodisation amplitude, anodisation offset, number of pulses, anodisation temperature and pore widening time) makes it possible to engineer the characteristic reflection peaks and interferometric colours of NAA-RFs, which can be finely tuned across the UV-visible-NIR spectrum. The effect of the aforementioned anodisation parameters on the photonic properties of NAA-RFs (i.e. characteristic reflection peaks and interferometric colours) is systematically assessed in order to establish for the first time a comprehensive rationale towards NAA-RFs with fully controllable photonic properties. The experimental results are correlated with a theoretical model (Looyenga-Landau-Lifshitz - LLL), demonstrating that the effective medium of these photonic nanostructures can be precisely described by the effective medium approximation. NAA-RFs are also demonstrated as chemically selective photonic platforms combined with reflectometric interference spectroscopy (RIfS). The resulting optical sensing system is used to assess the reversible binding affinity between a model drug (i.e. indomethacin) and human serum albumin (HSA) in real-time. Our results demonstrate that this system can be used to determine the overall pharmacokinetic profile of drugs, which is a critical aspect to be considered for the implementation of efficient medical therapies.This study is the first realisation of true optical rugate filters (RFs) based on nanoporous anodic alumina (NAA) by sinusoidal waves. An innovative and rationally designed sinusoidal pulse anodisation (SPA) approach in galvanostatic

  1. A two-level voltage source inverter with differentially sinusoidal pulse width modulation used in the interconnection system of a wind turbine generator

    Directory of Open Access Journals (Sweden)

    Alexandros C. Charalampidis

    2014-10-01

    Full Text Available This study analyses an interconnection system based on differentially sinusoidal pulse width modulation, used for the interconnection to the grid of a variable speed wind turbine. The modulation technique used provides specific advantages in comparison with the commonly used sinusoidal pulse width modulation (SPWM technique, such as lower DC bus voltage requirements, smaller switching losses for the same switching frequency as well as less higher harmonic content in the voltage waveforms produced. The respective control system is also described in detail. Thus this study provides a guide enabling the design of any interconnection system based on this modulation technique.

  2. Magnetizable stent-grafts enable endothelial cell capture

    Energy Technology Data Exchange (ETDEWEB)

    Tefft, Brandon J. [Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (United States); Uthamaraj, Susheil [Division of Engineering, Mayo Clinic, Rochester, MN (United States); Harburn, J. Jonathan [School of Medicine, Pharmacy and Health, Durham University, Stockton-on-Tees (United Kingdom); Hlinomaz, Ota [Department of Cardioangiology, St. Anne' s University Hospital, Brno (Czech Republic); Lerman, Amir [Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (United States); Dragomir-Daescu, Dan [Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN (United States); Sandhu, Gurpreet S., E-mail: sandhu.gurpreet@mayo.edu [Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (United States)

    2017-04-01

    Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance. - Highlights: • Magnetic stent-grafts were made from 2205 steel stents and polyurethane nanofibers. • Stent-grafts remained patent and formed a thin and uniform neointima when implanted. • Stent-grafts captured endothelial cells labeled with magnetic nanoparticles.

  3. Human Brain Microvascular Endothelial Cells and Umbilical Vein Endothelial Cells Differentially Facilitate Leukocyte Recruitment and Utilize Chemokines for T Cell Migration

    Directory of Open Access Journals (Sweden)

    Shumei Man

    2008-01-01

    Full Text Available Endothelial cells that functionally express blood brain barrier (BBB properties are useful surrogates for studying leukocyte-endothelial cell interactions at the BBB. In this study, we compared two different endothelial cellular models: transfected human brain microvascular endothelial cells (THBMECs and human umbilical vein endothelial cells (HUVECs. With each grow under optimal conditions, confluent THBMEC cultures showed continuous occludin and ZO-1 immunoreactivity, while HUVEC cultures exhibited punctate ZO-1 expression at sites of cell-cell contact only. Confluent THBMEC cultures on 24-well collagen-coated transwell inserts had significantly higher transendothelial electrical resistance (TEER and lower solute permeability than HUVECs. Confluent THBMECs were more restrictive for mononuclear cell migration than HUVECs. Only THBMECs utilized abluminal CCL5 to facilitate T-lymphocyte migration in vitro although both THBMECs and HUVECs employed CCL3 to facilitate T cell migration. These data establish baseline conditions for using THBMECs to develop in vitro BBB models for studying leukocyte-endothelial interactions during neuroinflammation.

  4. Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells.

    Science.gov (United States)

    Mendoza, Alejandra; Fang, Victoria; Chen, Cynthia; Serasinghe, Madhavika; Verma, Akanksha; Muller, James; Chaluvadi, V Sai; Dustin, Michael L; Hla, Timothy; Elemento, Olivier; Chipuk, Jerry E; Schwab, Susan R

    2017-06-01

    Effective adaptive immune responses require a large repertoire of naive T cells that migrate throughout the body, rapidly identifying almost any foreign peptide. Because the production of T cells declines with age, naive T cells must be long-lived. However, it remains unclear how naive T cells survive for years while constantly travelling. The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid organs, including spleen, lymph nodes and Peyer's patches, where T cells search for antigens. The concentration of S1P is higher in circulatory fluids than in lymphoid organs, and the S1P 1 receptor (S1P 1 R) directs the exit of T cells from the spleen into blood, and from lymph nodes and Peyer's patches into lymph. Here we show that S1P is essential not only for the circulation of naive T cells, but also for their survival. Using transgenic mouse models, we demonstrate that lymphatic endothelial cells support the survival of T cells by secreting S1P via the transporter SPNS2, that this S1P signals through S1P 1 R on T cells, and that the requirement for S1P 1 R is independent of the established role of the receptor in guiding exit from lymph nodes. S1P signalling maintains the mitochondrial content of naive T cells, providing cells with the energy to continue their constant migration. The S1P signalling pathway is being targeted therapeutically to inhibit autoreactive T cell trafficking, and these findings suggest that it may be possible simultaneously to target autoreactive or malignant cell survival.

  5. Endothelial cells in the eyes of an immunologist.

    Science.gov (United States)

    Young, M Rita

    2012-10-01

    Endothelial cell activation in the process of tumor angiogenesis and in various aspects of vascular biology has been extensively studied. However, endothelial cells also function in other capacities, including in immune regulation. Compared to the more traditional immune regulatory populations (Th1, Th2, Treg, etc.), endothelial cells have received far less credit as being immune regulators. Their regulatory capacity is multifaceted. They are critical in both limiting and facilitating the trafficking of various immune cell populations, including T cells and dendritic cells, out of the vasculature and into tissue. They also can be induced to stimulate immune reactivity or to be immune inhibitory. In each of these parameters (trafficking, immune stimulation and immune inhibition), their role can be physiological, whereby they have an active role in maintaining health. Alternatively, their role can be pathological, whereby they contribute to disease. In theory, endothelial cells are in an ideal location to recruit cells that can mediate immune reactivity to tumor tissue. Furthermore, they can activate the immune cells as they transmigrate across the endothelium into the tumor. However, what is seen is the absence of these protective effects of endothelial cells and, instead, the endothelial cells succumb to the defense mechanisms of the tumor, resulting in their acquisition of a tumor-protective role. To understand the immune regulatory potential of endothelial cells in protecting the host versus the tumor, it is useful to better understand the other circumstances in which endothelial cells modulate immune reactivities. Which of the multitude of immune regulatory roles that endothelial cells can take on seems to rely on the type of stimulus that they are encountering. It also depends on the extent to which they can be manipulated by potential dangers to succumb and contribute toward attack on the host. This review will explore the physiological and pathological roles

  6. Phonological awareness and sinusoidal amplitude modulation in phonological dislexia.

    Science.gov (United States)

    Peñaloza-López, Yolanda; Herrera-Rangel, Aline; Pérez-Ruiz, Santiago J; Poblano, Adrián

    2016-04-01

    Dyslexia is the difficulty of children in learning to read and write as results of neurological deficiencies. The objective was to test the Phonological awareness (PA) and Sinusoidal amplitude modulation (SAM) threshold in children with Phonological dyslexia (PD). We performed a case-control, analytic, cross sectional study. We studied 14 children with PD and 14 control children from 7 to 11 years of age, by means of PA measurement and by SAM test. The mean age of dyslexic children was 8.39 years and in the control group was 8.15. Children with PD exhibited inadequate skills in PA, and SAM. We found significant correlations between PA and SAM at 4 Hertz frequency, and calculated regression equations that predicts between one-fourth and one-third of variance of measurements. Alterations in PA and SAM found can help to explain basis of deficient language processing exhibited by children with PD.

  7. T.Node, industrial version of supernode

    Science.gov (United States)

    Flieller, Sylvain

    1989-12-01

    The Esprit I P1085 "SuperNode" project developed a modular reconfigurable archtecture, based on transputers. This highly parallel machine is now marketed by Telmat Informatique under the name T.Node. This paper presents the P1085 project, the architecture of SuperNode, its industrial implementation and its software enviroment.

  8. The hidden sentinel node in breast cancer

    International Nuclear Information System (INIS)

    Tanis, P.J.; Sandick, J.W. van; Nieweg, O.E.; Rutgers, E.J.T.; Kroon, B.B.R.; Valdes Olmos, R.A.; Hoefnagel, C.A.

    2002-01-01

    The purpose of this study was to analyse the occurrence of non-visualisation during preoperative lymphoscintigraphy for sentinel node identification in breast cancer. Preoperative lymphoscintigraphy was performed in 495 clinically node-negative breast cancer patients (501 sentinel node procedures) after injection of technetium-99m nanocolloid. Anterior and prone lateral (hanging breast) planar images were obtained a few minutes and 4 h after injection. The sentinel node was intraoperatively identified with the aid of patent blue dye and a gamma-ray detection probe. A sentinel node was visualised on the 4-h images in 449 of 501 procedures (90%). This visualisation rate improved from 76% to 94% during the study period. Delayed imaging (5-23 h) in 19 patients whose sentinel nodes failed to show, resulted in visualisation in four of them. A repeat injection of radiocolloid in 11 patients revealed a sentinel node in six. In the end, the visualisation rate was 92%. The sentinel node was surgically retrieved in 24 of the remaining 42 patients with non-visualisation (57%). Sentinel nodes that were visualised were tumour-positive in 38% and non-visualised sentinel nodes were involved in 50% (χ 2 , P=0.17). In a multivariate regression analysis, scintigraphic non-visualisation was independently associated with increased patient age (P<0.001), decreased tracer dose (P<0.001) and increased number of tumour-positive lymph nodes (P=0.013). The use of a sufficient amount of radioactivity (at least 100 MBq) is recommended for lymphatic mapping in breast cancer, especially in elderly women. Delayed imaging and re-injection of the radioactive tracer increase the visualisation rate. The non-visualised sentinel node can be identified intraoperatively in more than half of the patients. (orig.)

  9. The hidden sentinel node in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tanis, P.J.; Sandick, J.W. van; Nieweg, O.E.; Rutgers, E.J.T.; Kroon, B.B.R. [Department of Surgery, Netherlands Cancer Institute, Amsterdam (Netherlands); Valdes Olmos, R.A.; Hoefnagel, C.A. [Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam (Netherlands)

    2002-03-01

    The purpose of this study was to analyse the occurrence of non-visualisation during preoperative lymphoscintigraphy for sentinel node identification in breast cancer. Preoperative lymphoscintigraphy was performed in 495 clinically node-negative breast cancer patients (501 sentinel node procedures) after injection of technetium-99m nanocolloid. Anterior and prone lateral (hanging breast) planar images were obtained a few minutes and 4 h after injection. The sentinel node was intraoperatively identified with the aid of patent blue dye and a gamma-ray detection probe. A sentinel node was visualised on the 4-h images in 449 of 501 procedures (90%). This visualisation rate improved from 76% to 94% during the study period. Delayed imaging (5-23 h) in 19 patients whose sentinel nodes failed to show, resulted in visualisation in four of them. A repeat injection of radiocolloid in 11 patients revealed a sentinel node in six. In the end, the visualisation rate was 92%. The sentinel node was surgically retrieved in 24 of the remaining 42 patients with non-visualisation (57%). Sentinel nodes that were visualised were tumour-positive in 38% and non-visualised sentinel nodes were involved in 50% ({chi}{sup 2}, P=0.17). In a multivariate regression analysis, scintigraphic non-visualisation was independently associated with increased patient age (P<0.001), decreased tracer dose (P<0.001) and increased number of tumour-positive lymph nodes (P=0.013). The use of a sufficient amount of radioactivity (at least 100 MBq) is recommended for lymphatic mapping in breast cancer, especially in elderly women. Delayed imaging and re-injection of the radioactive tracer increase the visualisation rate. The non-visualised sentinel node can be identified intraoperatively in more than half of the patients. (orig.)

  10. Sentinel lymph node biopsy in oral cancer

    DEFF Research Database (Denmark)

    Thomsen, Jørn Bo; Sørensen, Jens Ahm; Grupe, Peter

    2005-01-01

    PURPOSE: To validate lymphatic mapping combined with sentinel lymph node biopsy as a staging procedure, and to evaluate the possible clinical implications of added oblique lymphoscintigraphy and/or tomography and test the intra- and interobserver reproducibility of lymphoscintigraphy. MATERIAL......: Eleven (28%) patients were upstaged. The sentinel lymph node identification rate was 97.5%. Sentinel lymph node biopsy significantly differentiated between patients with or without lymph node metastasis (P = 0.001). Lymphatic mapping revealed 124 hotspots and 144 hot lymph nodes were removed by sentinel...

  11. Wine and endothelial function.

    Science.gov (United States)

    Caimi, G; Carollo, C; Lo Presti, R

    2003-01-01

    In recent years many studies have focused on the well-known relationship between wine consumption and cardiovascular risk. Wine exerts its protective effects through various changes in lipoprotein profile, coagulation and fibrinolytic cascades, platelet aggregation, oxidative mechanisms and endothelial function. The last has earned more attention for its implications in atherogenesis. Endothelium regulates vascular tone by a delicate balancing among vasorelaxing (nitric oxide [NO]) and vasoconstrincting (endothelins) factors produced by endothelium in response to various stimuli. In rat models, wine and other grape derivatives exerted an endothelium-dependent vasorelaxing capacity especially associated with the NO-stimulating activity of their polyphenol components. In experimental conditions, reservatrol (a stilbene polyphenol) protected hearts and kidneys from ischemia-reperfusion injury through antioxidant activity and upregulation of NO production. Wine polyphenols are also able to induce the expression of genes involved in the NO pathway within the arterial wall. The effects of wine on endothelial function in humans are not yet clearly understood. A favorable action of red wine or dealcoholized wine extract or purple grape juice on endothelial function has been observed by several authors, but discrimination between ethanol and polyphenol effects is controversial. It is, however likely that regular and prolonged moderate wine drinking positively affects endothelial function. The beneficial effects of wine on cardiovascular health are greater if wine is associated with a healthy diet. The most recent nutritional and epidemiologic studies show that the ideal diet closely resembles the Mediterranean diet.

  12. Selective sentinel lymph node biopsy in papillary thyroid carcinoma in patients with no preoperative evidence of lymph node metastasis.

    Science.gov (United States)

    González, Óscar; Zafon, Carles; Caubet, Enric; García-Burillo, Amparo; Serres, Xavier; Fort, José Manuel; Mesa, Jordi; Castell, Joan; Roca, Isabel; Ramón Y Cajal, Santiago; Iglesias, Carmela

    2017-10-01

    Lymphadenectomy is recommended during surgery for papillary thyroid carcinoma when there is evidence of cervical lymph node metastasis (therapeutic) or in high-risk patients (prophylactic) such as those with T3 and T4 tumors of the TNM classification. Selective sentinel lymph node biopsy may improve preoperative diagnosis of nodal metastases. To analyze the results of selective sentinel lymph node biopsy in a group of patients with papillary thyroid carcinoma and no evidence of nodal involvement before surgery. A retrospective, single-center study in patients with papillary thyroid carcinoma and no clinical evidence of lymph node involvement who underwent surgery between 2011 and 2013. The sentinel node was identified by scintigraphy. When the sentinel node was positive, the affected compartment was removed, and when sentinel node was negative, central lymph node dissection was performed. Forty-three patients, 34 females, with a mean age of 52.3 (±17) years, were enrolled. Forty-six (27%) of the 170 SNs resected from 24 (55.8%) patients were positive for metastasis. In addition, 94 (15.6%) out of the 612 lymph nodes removed in the lymphadenectomies were positive for metastases. Twelve of the 30 (40%) low risk patients (cT1N0 and cT2N0) changed their stage to pN1, whereas 12 of 13 (92%) high risk patients (cT3N0 and cT4N0) changed to pN1 stage. Selective sentinel lymph node biopsy changes the stage of more than 50% of patients from cN0 to pN1. This confirms the need for lymph node resection in T3 and T4 tumors, but reveals the presence of lymph node metastases in 40% of T1-T2 tumors. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. [Effect of 50 Hz 1.8 mT sinusoidal electromagnetic fields on bone mineral density in growing rats].

    Science.gov (United States)

    Gao, Yu-Hai; Zhou, Yan-Feng; Li, Shao-Feng; Li, Wen-Yuan; Xi, Hui-Rong; Yang, Fang-Fang; Chen, Ke-Ming

    2017-12-25

    To study effects of 50 Hz 1.8 mT sinusoidal electromagnetic fields (SEMFs) on bone mineral density (BMD) in SD rats. Thirty SD rats weighted(110±10) and aged 1 month were randomly divided into control group and electromagnetic field group, 15 in each group. Normal control group of 50 Hz 0 mT density and sinusoidal electromagnetic field group of 50 Hz 1.8 mT were performed respectively with 1.5 h/d and weighted weight once a week, and observed food-intake. Rats were anesthesia by intraperitoneal injection and dual energy X-ray absorptiometry were used to detect bone density of whole body, and detected bone density of femur and vertebral body. Osteocalcin and tartrate-resistant acid phosphatase 5b were detected by ELSA; weighted liver, kidney and uterus to calculate purtenance index, then detected pathologic results by HE. Compared with control group, there was no significant change in weight every week, food-intake every day; no obvious change of bone density of whole body at 2 and 4 weeks, however bone density of whole body, bone density of excised femur and vertebra were increased at 6 weeks. Expression of OC was increased, and TRACP 5b expression was decreased. No change of HE has been observed in liver, kidney and uterus and organic index. 50 Hz 1.8 mT sinusoidal electromagnetic fields could improve bone formation to decrease relevant factors of bone absorbs, to improve peak bone density of young rats, in further provide a basis for clinical research electromagnetic fields preventing osteoporosis foundation.

  14. Mining Important Nodes in Directed Weighted Complex Networks

    Directory of Open Access Journals (Sweden)

    Yunyun Yang

    2017-01-01

    Full Text Available In complex networks, mining important nodes has been a matter of concern by scholars. In recent years, scholars have focused on mining important nodes in undirected unweighted complex networks. But most of the methods are not applicable to directed weighted complex networks. Therefore, this paper proposes a Two-Way-PageRank method based on PageRank for further discussion of mining important nodes in directed weighted complex networks. We have mainly considered the frequency of contact between nodes and the length of time of contact between nodes. We have considered the source of the nodes (in-degree and the whereabouts of the nodes (out-degree simultaneously. We have given node important performance indicators. Through numerical examples, we analyze the impact of variation of some parameters on node important performance indicators. Finally, the paper has verified the accuracy and validity of the method through empirical network data.

  15. Ionizing radiation activates vascular endothelial growth factor-A transcription in human umbilical vein endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyounji; Kim, Kwang Seok; Jeong, Jae Hoon; Lim, Young Bin [Radiation Cancer Biology Team, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2016-12-15

    Vascular endothelial growth factor (VEGF) is an essential paracrine factor for developmental and pathological angiogenesis. VEGF also exerts its effects in an autocrine manner in VEGF-producing cells. For instance, autocrine VEGF signaling occurs in tumor cells and contributes to key aspects of tumorigenesis, such as in the function of cancer stem cells and tumor initiation, which are independent of angiogenesis. In addition to tumors cells, non-transformed cells also express VEGF. For example, a VEGF dependent intracellular autocrine mechanism is crucial for the survival of hematopoietic stem cells and hematopoiesis. Stereotactic body radiation therapy (SBRT) is a novel treatment modality for early primary cancer and oligometastatic disease. SBRT delivers high-dose hypofractionated radiation, such as 20-60 Gy, to tumors in a single fraction or 2-5 fractions. As VEGF is a critical regulator of functional integrity and viability of vascular endothelial cells, we examined whether high-dose irradiation alters VEGF signaling by measuring the expression levels of VEGFA transcript. It is generally believed that endothelial cells do not produce VEGF in response to radiation. In present study, however, we provide the first demonstration of transcriptional regulation of VEGFA in human vascular endothelial cells by IR treatment. Irradiation with doses higher than 10 Gy in a single exposure triggers up-regulation of VEGFA transcription within 2 hours in HUVECs, whereas irradiation with 10 Gy does not alter VEGFA levels. Our data have shown that high-dose irradiation triggers immediate transactivation of VEGFA in human vascular endothelial cells.

  16. Factors associated with involvement of four or more axillary nodes for sentinel lymph node-positive patients

    International Nuclear Information System (INIS)

    Katz, Angela; Niemierko, Andrzej; Gage, Irene; Evans, Sheila; Shaffer, Margaret; Smith, Frederick P.; Taghian, Alphonse; Magnant, Colette

    2006-01-01

    Purpose: Sentinel lymph node-positive (SLN+) patients who are unlikely to have 4 or more involved axillary nodes might be treated with less extensive regional nodal radiation. The purpose of this study was to define possible predictors of having 4 or more involved axillary nodes. Methods and Materials: The records of 224 patients with breast cancer and 1 to 3 involved SLNs, who underwent completion axillary dissection without neoadjuvant chemotherapy or hormonal therapy were reviewed. Factors associated with the presence of 4 or more involved axillary nodes (SLNs plus non-SLNs) were evaluated by Pearson chi-square test of association and by simple and multiple logistic-regression analysis. Results: Of 224 patients, 42 had involvement of 4 or more axillary nodes. On univariate analysis, the presence of 4 or more involved axillary nodes was positively associated with increased tumor size, lobular histology, lymphovascular space invasion (LVSI), increased number of involved SLNs, decreased number of uninvolved SLNs, and increased size of SLN metastasis. On multivariate analysis, the presence of 4 or more involved axillary nodes was associated with LVSI, increased number of involved SLNs, increased size of SLN metastasis, and lobular histology. Conclusions: Patients with 1 or more involved SLN, LVSI, or SLN macrometastasis should be treated to the supraclavicular fossa/axillary apex if they do not undergo completion axillary dissection. Other SLN+ patients might be adequately treated with less extensive radiation fields

  17. Identifying Vulnerable Nodes of Complex Networks in Cascading Failures Induced by Node-Based Attacks

    Directory of Open Access Journals (Sweden)

    Shudong Li

    2013-01-01

    Full Text Available In the research on network security, distinguishing the vulnerable components of networks is very important for protecting infrastructures systems. Here, we probe how to identify the vulnerable nodes of complex networks in cascading failures, which was ignored before. Concerned with random attack (RA and highest load attack (HL on nodes, we model cascading dynamics of complex networks. Then, we introduce four kinds of weighting methods to characterize the nodes of networks including Barabási-Albert scale-free networks (SF, Watts-Strogatz small-world networks (WS, Erdos-Renyi random networks (ER, and two real-world networks. The simulations show that, for SF networks under HL attack, the nodes with small value of the fourth kind of weight are the most vulnerable and the ones with small value of the third weight are also vulnerable. Also, the real-world autonomous system with power-law distribution verifies these findings. Moreover, for WS and ER networks under both RA and HL attack, when the nodes have low tolerant ability, the ones with small value of the fourth kind of weight are more vulnerable and also the ones with high degree are easier to break down. The results give us important theoretical basis for digging the potential safety loophole and making protection strategy.

  18. cGMP and nitric oxide modulate thrombin-induced endothelial permeability : Regulation via different pathways in human aortic and umbilical vein endothelial cells

    NARCIS (Netherlands)

    Draijer, R.; Atsma, D.E.; Laarse, A. van der; Hinsbergh, V.W.M. van

    1995-01-01

    Previous studies have demonstrated that cGMP and cAMP reduce the endothelial permeability for fluids and macromolecules when the endothelial permeability is increased by thrombin. In this study, we have investigated the mechanism by which cGMP improves the endothelial barrier function and examined

  19. Glyoxalase I reduces glycative and oxidative stress and prevents age-related endothelial dysfunction through modulation of endothelial nitric oxide synthase phosphorylation.

    Science.gov (United States)

    Jo-Watanabe, Airi; Ohse, Takamoto; Nishimatsu, Hiroaki; Takahashi, Masao; Ikeda, Yoichiro; Wada, Takehiko; Shirakawa, Jun-ichi; Nagai, Ryoji; Miyata, Toshio; Nagano, Tetsuo; Hirata, Yasunobu; Inagi, Reiko; Nangaku, Masaomi

    2014-06-01

    Endothelial dysfunction is a major contributor to cardiovascular disease (CVD), particularly in elderly people. Studies have demonstrated the role of glycation in endothelial dysfunction in nonphysiological models, but the physiological role of glycation in age-related endothelial dysfunction has been poorly addressed. Here, to investigate how vascular glycation affects age-related endothelial function, we employed rats systemically overexpressing glyoxalase I (GLO1), which detoxifies methylglyoxal (MG), a representative precursor of glycation. Four groups of rats were examined, namely young (13 weeks old), mid-age (53 weeks old) wild-type, and GLO1 transgenic (WT/GLO1 Tg) rats. Age-related acceleration in glycation was attenuated in GLO1 Tg rats, together with lower aortic carboxymethyllysine (CML) and urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Age-related impairment of endothelium-dependent vasorelaxation was attenuated in GLO1 Tg rats, whereas endothelium-independent vasorelaxation was not different between WT and GLO1 Tg rats. Nitric oxide (NO) production was decreased in mid-age WT rats, but not in mid-age GLO1 Tg rats. Age-related inactivation of endothelial NO synthase (eNOS) due to phosphorylation of eNOS on Thr495 and dephosphorylation on Ser1177 was ameliorated in GLO1 Tg rats. In vitro, MG increased phosphorylation of eNOS (Thr495) in primary human aortic endothelial cells (HAECs), and overexpression of GLO1 decreased glycative stress and phosphorylation of eNOS (Thr495). Together, GLO1 reduced age-related endothelial glycative and oxidative stress, altered phohphorylation of eNOS, and attenuated endothelial dysfunction. As a molecular mechanism, GLO1 lessened inhibitory phosphorylation of eNOS (Thr495) by reducing glycative stress. Our study demonstrates that blunting glycative stress prevents the long-term impact of endothelial dysfunction on vascular aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons

  20. Tumor and Endothelial Cell Hybrids Participate in Glioblastoma Vasculature

    Directory of Open Access Journals (Sweden)

    Soufiane El Hallani

    2014-01-01

    Full Text Available Background. Recently antiangiogenic therapy with bevacizumab has shown a high but transient efficacy in glioblastoma (GBM. Indeed, GBM is one of the most angiogenic human tumors and endothelial proliferation is a hallmark of the disease. We therefore hypothesized that tumor cells may participate in endothelial proliferation of GBM. Materials and Methods. We used EGFR FISH Probe to detect EGFR amplification and anti-CD31, CD105, VE-cadherin, and vWF to identify endothelial cells. Endothelial and GBM cells were grown separately, labeled with GFP and DsRed lentiviruses, and then cocultured with or without contact. Results. In a subset of GBM tissues, we found that several tumor endothelial cells carry EGFR amplification, characteristic of GBM tumor cells. This observation was reproduced in vitro: when tumor stem cells derived from GBM were grown in the presence of human endothelial cells, a fraction of them acquired endothelial markers (CD31, CD105, VE-cadherin, and vWF. By transduction with GFP and DsRed expressing lentiviral vectors, we demonstrate that this phenomenon is due to cell fusion and not transdifferentiation. Conclusion. A fraction of GBM stem cells thus has the capacity to fuse with endothelial cells and the resulting hybrids may participate in tumor microvascular proliferation and in treatment resistance.

  1. Resveratrol induces mitochondrial biogenesis in endothelial cells.

    Science.gov (United States)

    Csiszar, Anna; Labinskyy, Nazar; Pinto, John T; Ballabh, Praveen; Zhang, Hanrui; Losonczy, Gyorgy; Pearson, Kevin; de Cabo, Rafael; Pacher, Pal; Zhang, Cuihua; Ungvari, Zoltan

    2009-07-01

    Pathways that regulate mitochondrial biogenesis are potential therapeutic targets for the amelioration of endothelial dysfunction and vascular disease. Resveratrol was shown to impact mitochondrial function in skeletal muscle and the liver, but its role in mitochondrial biogenesis in endothelial cells remains poorly defined. The present study determined whether resveratrol induces mitochondrial biogenesis in cultured human coronary arterial endothelial cells (CAECs). In CAECs resveratrol increased mitochondrial mass and mitochondrial DNA content, upregulated protein expression of electron transport chain constituents, and induced mitochondrial biogenesis factors (proliferator-activated receptor-coactivator-1alpha, nuclear respiratory factor-1, mitochondrial transcription factor A). Sirtuin 1 (SIRT1) was induced, and endothelial nitric oxide (NO) synthase (eNOS) was upregulated in a SIRT1-dependent manner. Knockdown of SIRT1 (small interfering RNA) or inhibition of NO synthesis prevented resveratrol-induced mitochondrial biogenesis. In aortas of type 2 diabetic (db/db) mice impaired mitochondrial biogenesis was normalized by chronic resveratrol treatment, showing the in vivo relevance of our findings. Resveratrol increases mitochondrial content in endothelial cells via activating SIRT1. We propose that SIRT1, via a pathway that involves the upregulation of eNOS, induces mitochondrial biogenesis. Resveratrol induced mitochondrial biogenesis in the aortas of type 2 diabetic mice, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases.

  2. Papillary endothelial hyperplasia in angiokeratoma.

    Science.gov (United States)

    Mehta, Anurag; Sayal, Satish Kumar; Raman, Deep Kumar; Sood, Aradhana

    2003-01-01

    Papillary endothelial hyperplasia (Masson's tumour) is a reactive proliferation of endothelium producing papillary structures with fibrovascular cores. Dilatation, stasis and accompanying inflammation have been incriminated as the inciting events, evident by the presence of this lesion in haemorrhoids, urethral caruncles and laryngeal polyps. We present here a case of papillary endothelial hyperplasia in angiokeratoma hitherto undescribed despite sharing common etiopathogenetic features of dilatation and stasis with other aforementioned lesions.

  3. Endothelial juxtaposition of distinct adult stem cells activates angiogenesis signaling molecules in endothelial cells.

    Science.gov (United States)

    Mohammadi, Elham; Nassiri, Seyed Mahdi; Rahbarghazi, Reza; Siavashi, Vahid; Araghi, Atefeh

    2015-12-01

    Efficacy of therapeutic angiogenesis needs a comprehensive understanding of endothelial cell (EC) function and biological factors and cells that interplay with ECs. Stem cells are considered the key components of pro- and anti-angiogenic milieu in a wide variety of physiopathological states, and interactions of EC-stem cells have been the subject of controversy in recent years. In this study, the potential effects of three tissue-specific adult stem cells, namely rat marrow-derived mesenchymal stem cells (rBMSCs), rat adipose-derived stem cells (rADSCs) and rat muscle-derived satellite cells (rSCs), on the endothelial activation of key angiogenic signaling molecules, including VEGF, Ang-2, VEGFR-2, Tie-2, and Tie2-pho, were investigated. Human umbilical vein endothelial cells (HUVECs) and rat lung microvascular endothelial cells (RLMECs) were cocultured with the stem cells or incubated with the stem cell-derived conditioned media on Matrigel. Following HUVEC-stem cell coculture, CD31-positive ECs were flow sorted and subjected to western blotting to analyze potential changes in the expression of the pro-angiogenic signaling molecules. Elongation and co-alignment of the stem cells were seen along the EC tubes in the EC-stem cell cocultures on Matrigel, with cell-to-cell dye communication in the EC-rBMSC cocultures. Moreover, rBMSCs and rADSCs significantly improved endothelial tubulogenesis in both juxtacrine and paracrine manners. These two latter stem cells dynamically up-regulated VEGF, Ang-2, VREGR-2, and Tie-2 but down-regulated Tie2-pho and the Tie2-pho/Tie-2 ratio in HUVECs. Induction of pro-angiogenic signaling in ECs by marrow- and adipose-derived MSCs further indicates the significance of stem cell milieu in angiogenesis dynamics.

  4. Lymphoscintigraphic Identification of Sentinel Nodes in Malignant Melanoma

    International Nuclear Information System (INIS)

    Andries, G.; Dindelegan, G.; Ciule, Larisa; Cosgarea, Rodica; Cobzac, Gh.

    2006-01-01

    Full text: The most important prognostic factor in malignant melanoma is the presence or absence of metastasis in lymph nodes. It has been demonstrated the orderly progression of different types of tumours. Sentinel lymph node identification is done lymphoscintigraphically, followed by surgical excision and morpho pathological exam. Material and methods: We studied 33 patients with malignant melanoma (age 26-84 years) divided in 2 subgroups: group A without gamma probe (18 patients) and group B with gamma probe (15 patients). The lymphoscintigraphy (LS) was performed with a totally dose of 20-30 MBq of 99mTc-nanocoloid (Amersham) injected peritumoral or pericicatriceal in 4-6 points in volume of 0,1-0,2 ml per point. Acquisition was performed dynamic for 10-15 min and static at 30-60 min p.i. on perpendicular projections. Patent blue dye was injected prior surgery. In group A has performed sentinel node excision (13 patients) or ELND (4), one patient has died before surgery. In group B sentinel nodes were surgically excised with gamma probe and ELND was performed in patients with positive lymph nodes. Histopathologically, sentinel nodes were stained with HE and in 6 cases with HMB45. Results: In group A we identified the sentinel nodes scintigraphically in all patients (median 1,83±-1,50 nodes, range 1-7). Surgically with PBD were identified 1,69±1,18 sentinel nodes, in 2 patients the SN lymphadenectomy was negative. All nodes excised were histopathologically negative, but in 4 patients loco-regional recurrence or distant metastasis developed. In group B we identified scintigraphically 33 SNs (median 2,20±1,37 nodes, range 1-5) and 4 in transit nodes in 14 patients, 24 of them being blue dye positive (80%), in 1 patient LS was negative. With gamma probe surgeon excised 39 radioactive nodes and 1 SN blue dye positive only, 10 of them being histopathologically positive (25% node metastasis). No metastasis were identified after ELND in patients with positive SNs

  5. Adhesion and endothelialization of endothelial cells on the surface of endovascular stents by the novel rotational culture of cells

    International Nuclear Information System (INIS)

    Tang Chaojun; Wang Guixue; Cao Yi; Wu Xue; Xie Xiang; Xiao Li

    2008-01-01

    Recent researches indicate that the initial event in the implantation of endovascular stents involves mechanical injury to the vessel wall. Confluent endothelialization of vascular grafts in vitro before implantation has been suggested as a way to reduce injury of the blood vessel. The purpose of this study is to establish a useful way to improve the adhesion of endothelial cells and accelerate endothelialization on the surface of endovascular stents by a novel rotational culture device. Numerical simulation was used to predict the shear stress on the surface of stents. The number of cellular adhesion was calculated by cell counting, the cell growth was observed by scanning electron microscope and fluorescence microscope. Numerical simulation results showed that the stents was exposed to shear stress of 2.66 x 10 -3 to 8.88 x 10 -2 Pa. Rotational culture of human umbilical vein endothelial cells could enhance the adhesion of cells and accelerate endothelialization on the surface of stents when the culture conditions for EC adhesion were intermediate rotation speed, higher dynamic incubation times, lower cell densities

  6. High risk of non-sentinel node metastases in a group of breast cancer patients with micrometastases in the sentinel node

    DEFF Research Database (Denmark)

    Tvedskov, Tove Filtenborg; Jensen, Maj-Britt; Lisse, Ida Marie

    2012-01-01

    Axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel nodes is under debate. We aimed to establish two models to predict non-sentinel node (NSN) metastases in patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes, to guide the decision for ...

  7. Low-Intensity Pulsed Ultrasound Prevents the Oxidative Stress Induced Endothelial-Mesenchymal Transition in Human Aortic Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Jiamin Li

    2018-02-01

    Full Text Available Background/Aims: Endothelial-mesenchymal transition (EndMT has been shown to take part in the generation and progression of diverse diseases, involving a series of changes leading to a loss of their endothelial characteristics and an acquirement of properties typical of mesenchymal cells. Low-intensity pulsed ultrasound (LIPUS is a new therapeutic option that has been successfully used in fracture healing. However, whether LIPUS can inhibit oxidative stress-induced endothelial cell damages through inhibiting EndMT remained unknown. This study aimed to investigate the protective effects of LIPUS against oxidative stress-induced endothelial cell damages and the underlying mechanisms. Methods: EndMT was induced by H2O2 (100 µm for seven days. Human aortic endothelial cells (HAECs were exposed to H2O2 with or without LIPUS treatment for seven days. The expression of EndMT markers (CD31, VE-cadherin, FSP1 and α-SMA were analyzed. The levels of total and phosphorylated PI3K and AKT proteins were detected by Western Blot analysis. Cell chemotaxis was determined by wound healing and transwell assay. Results: LIPUS relieved EndMT by decreasing ROS accumulation and increasing activation of the PI3K signaling cascade. LIPUS alleviated the migration of EndMT-derived mesenchymal-like cells through reducing extracellular matrix (ECM deposition that is associated with matrix metallopeptidase (MMP proteolytic activity and collagen production. Conclusion: LIPUS produces cytoprotective effects against oxidative injuries to endothelial cells through suppressing the oxidative stress-induced EndMT, activating the PI3K/AKT pathway under oxidative stress, and limiting cell migration and excessive ECM deposition.

  8. Neuropilin-2 expression in breast cancer: correlation with lymph node metastasis, poor prognosis, and regulation of CXCR4 expression

    International Nuclear Information System (INIS)

    Yasuoka, Hironao; Kodama, Rieko; Tsujimoto, Masahiko; Yoshidome, Katsuhide; Akamatsu, Hiroki; Nakahara, Masaaki; Inagaki, Michiya; Sanke, Tokio; Nakamura, Yasushi

    2009-01-01

    Neuropilin-2 (Nrp2) is a receptor for vascular endothelial growth factor-C (VEGF-C), which is a well-known lymphangiogenic factor and plays an important role in lymph node metastasis of various human cancers, including breast cancer. Recently, Nrp2 was shown to play a role in cancer by promoting tumor cell metastasis. CXC chemokine receptor 4 (CXCR4) also promotes tumor metastasis. In the previous studies, we demonstrated that VEGF-C and cytoplasmic CXCR4 expressions were correlated with poorer patient prognosis (BMC Cancer 2008,8:340; Breast Cancer Res Treat 2005, 91:125–132). The relationship between Nrp2 expression and lymph node metastasis, VEGF-C expression, CXCR4 expression, and other established clinicopathological variables (these data were cited in our previous papers), including prognosis, was analyzed in human breast cancer. Effects of neutralizing anti-Nrp2 antibody on CXCR4 expression and chemotaxis were assessed in MDA-MB-231 breast cancer cells. Nrp2 expression was observed in 53.1% (60 of 113) of the invasive breast carcinomas. Nrp2 expression was significantly correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Survival curves determined by the Kaplan-Meier method showed that Nrp2 expression was associated with reduced overall survival. In multivariate analysis, Nrp2 expression emerged as a significant independent predictor for overall survival. Neutralizing anti-Nrp2 antibody blocks cytoplasmic CXCR4 expression and CXCR4-induced migration in MDA-MB-231 cells. Nrp2 expression was correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Nrp2 expression may serve as a significant prognostic factor for long-term survival in breast cancer. Our data also showed a role for Nrp2 in regulating cytoplasmic CXCR4 expression in vitro

  9. On the Fully-Developed Heat Transfer Enhancing Flow Field in Sinusoidally, Spirally Corrugated Tubes Using Computational Fluid Dynamics

    DEFF Research Database (Denmark)

    Hærvig, Jakob; Sørensen, Kim; Condra, Thomas Joseph

    2017-01-01

    A numerical study has been carried out to investigate heat transfer enhancing flow field in 28 geometrically different sinusoidally, spirally corrugated tubes. To vary the corrugation, the height of corrugation e/D and the length between two successive corrugated sections p/D are varied in the ra...

  10. Nipah virus infection and glycoprotein targeting in endothelial cells

    Directory of Open Access Journals (Sweden)

    Maisner Andrea

    2010-11-01

    Full Text Available Abstract Background The highly pathogenic Nipah virus (NiV causes fatal respiratory and brain infections in animals and humans. The major hallmark of the infection is a systemic endothelial infection, predominantly in the CNS. Infection of brain endothelial cells allows the virus to overcome the blood-brain-barrier (BBB and to subsequently infect the brain parenchyma. However, the mechanisms of NiV replication in endothelial cells are poorly elucidated. We have shown recently that the bipolar or basolateral expression of the NiV surface glycoproteins F and G in polarized epithelial cell layers is involved in lateral virus spread via cell-to-cell fusion and that correct sorting depends on tyrosine-dependent targeting signals in the cytoplasmic tails of the glycoproteins. Since endothelial cells share many characteristics with epithelial cells in terms of polarization and protein sorting, we wanted to elucidate the role of the NiV glycoprotein targeting signals in endothelial cells. Results As observed in vivo, NiV infection of endothelial cells induced syncytia formation. The further finding that infection increased the transendothelial permeability supports the idea of spread of infection via cell-to-cell fusion and endothelial cell damage as a mechanism to overcome the BBB. We then revealed that both glycoproteins are expressed at lateral cell junctions (bipolar, not only in NiV-infected primary endothelial cells but also upon stable expression in immortalized endothelial cells. Interestingly, mutation of tyrosines 525 and 542/543 in the cytoplasmic tail of the F protein led to an apical redistribution of the protein in endothelial cells whereas tyrosine mutations in the G protein had no effect at all. This fully contrasts the previous results in epithelial cells where tyrosine 525 in the F, and tyrosines 28/29 in the G protein were required for correct targeting. Conclusion We conclude that the NiV glycoprotein distribution is responsible for

  11. Endothelial actions of atrial and B-type natriuretic peptides.

    Science.gov (United States)

    Kuhn, Michaela

    2012-05-01

    The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the

  12. Qidantongmai Protects Endothelial Cells Against Hypoxia-Induced ...

    African Journals Online (AJOL)

    induced damage. The ability of QDTM to modulate the serum VEGF-A level may play an important role in its effects on endothelial cells. Key words: Traditional Chinese Medicine, human umbilical vein endothelial cells, hypoxia, VEGF ...

  13. Infection of endothelial cells by common human viruses.

    Science.gov (United States)

    Friedman, H M

    1989-01-01

    Common human viruses were evaluated for their ability to replicate in the endothelial cells of human umbilical vein and bovine thoracic aorta in vitro. Infection occurred with most viruses. The susceptibilities of endothelial cells derived from bovine aorta, pulmonary artery, and vena cava were compared. Among the viruses studied, no differences were noted in the ability to grow in endothelial cells from these three large vessels. One virus, herpes simplex virus type 1, was evaluated for its ability to produce persistent infection of endothelial cells. Infection developed and persisted for up to 3 months. After the first week, productive infection was found in less than 1% of cells. Nevertheless, the infection markedly affected the growth and morphology of the endothelial monolayer. Infection with any of several different viruses was noted to alter endothelial cell functions, including adherence of granulocytes, production of colony-stimulating factor, and synthesis of matrix protein. In addition, herpes simplex virus type 1 induced receptors for the Fc portion of IgG and for complement component C3b. These findings indicate that common human viruses can profoundly affect the biology of the endothelium.

  14. Temporal-varying failures of nodes in networks

    Science.gov (United States)

    Knight, Georgie; Cristadoro, Giampaolo; Altmann, Eduardo G.

    2015-08-01

    We consider networks in which random walkers are removed because of the failure of specific nodes. We interpret the rate of loss as a measure of the importance of nodes, a notion we denote as failure centrality. We show that the degree of the node is not sufficient to determine this measure and that, in a first approximation, the shortest loops through the node have to be taken into account. We propose approximations of the failure centrality which are valid for temporal-varying failures, and we dwell on the possibility of externally changing the relative importance of nodes in a given network by exploiting the interference between the loops of a node and the cycles of the temporal pattern of failures. In the limit of long failure cycles we show analytically that the escape in a node is larger than the one estimated from a stochastic failure with the same failure probability. We test our general formalism in two real-world networks (air-transportation and e-mail users) and show how communities lead to deviations from predictions for failures in hubs.

  15. The sentinel node concept in breast cancer: A commentary

    International Nuclear Information System (INIS)

    Canizales, A.L. . E-mail A.L.Canizales@qmul.ac.uk; Al-Yasi, A.; Gambhir, S.; Morris, G.; Granowska, M.; Britton, K.E.

    2004-01-01

    As there are multiple lymphatic pathways from the breast to the axilla with multiple possible choices for a cancer cell or a colloid, it appears intuitively unusual that one node is preferentially 'chosen'. The intuitive response would be that there is an equal chance for a breast cancer cell to travel by any lymphatic pathway to any axillary node at level 1. If this were true, then after a colloid injection into the peritumoural lymphatics or the periareolar lymphatic plexus, such a colloid has a similar chance to travel to any level 1 axillary node, be it an involved node or an uninvolved node. We have tried to resolve this conflict between intuition and practice. It was tested by identifying and measuring the activity of the radiolabelled colloid in the nodes removed in an axillary clearance and in the sentinel node or nodes after applying a sentinel node technique similar to that of Veronesi et al. The histology of all the nodes that were counted was analysed so that the colloid activity in each node was able to be correlated with its histology, whether it was involved with cancer or not involved. Measurements were obtained in those patients, in whom there were both involved and uninvolved nodes in the axillae. The colloid counts in cpm/g of each node were compared with the related sentinel node findings either involved with cancer or not involved. These were calculated either as the involved to uninvolved that is a 'positive' to 'negative' ratio. The results were that the activity ratio of all involved axillary nodes to uninvolved axillary nodes was about 4:1. The involved Sentinel nodes had on average over 25 times the uptake of the uninvolved Sentinel nodes. P value was <0.009 for a significant difference between colloid uptake in sentinel nodes with positive histology and those with negative histology. It is a new observation that involved axillary nodes show greater uptake of the colloid than uninvolved nodes in all patients where there are both involved

  16. Vascular endothelial growth factor A-stimulated signaling from endosomes in primary endothelial cells.

    Science.gov (United States)

    Fearnley, Gareth W; Smith, Gina A; Odell, Adam F; Latham, Antony M; Wheatcroft, Stephen B; Harrison, Michael A; Tomlinson, Darren C; Ponnambalam, Sreenivasan

    2014-01-01

    The vascular endothelial growth factor A (VEGF-A) is a multifunctional cytokine that stimulates blood vessel sprouting, vascular repair, and regeneration. VEGF-A binds to VEGF receptor tyrosine kinases (VEGFRs) and stimulates intracellular signaling leading to changes in vascular physiology. An important aspect of this phenomenon is the spatiotemporal coordination of VEGFR trafficking and intracellular signaling to ensure that VEGFR residence in different organelles is linked to downstream cellular outputs. Here, we describe a series of assays to evaluate the effects of VEGF-A-stimulated intracellular signaling from intracellular compartments such as the endosome-lysosome system. These assays include the initial isolation and characterization of primary human endothelial cells, performing reverse genetics for analyzing protein function; methods used to study receptor trafficking, signaling, and proteolysis; and assays used to measure changes in cell migration, proliferation, and tubulogenesis. Each of these assays has been exemplified with studies performed in our laboratories. In conclusion, we describe necessary techniques for studying the role of VEGF-A in endothelial cell function. © 2014 Elsevier Inc. All rights reserved.

  17. Triazole RGD antagonist reverts TGFβ1-induced endothelial-to-mesenchymal transition in endothelial precursor cells.

    Science.gov (United States)

    Bianchini, Francesca; Peppicelli, Silvia; Fabbrizzi, Pierangelo; Biagioni, Alessio; Mazzanti, Benedetta; Menchi, Gloria; Calorini, Lido; Pupi, Alberto; Trabocchi, Andrea

    2017-01-01

    Fibrosis is the dramatic consequence of a dysregulated reparative process in which activated fibroblasts (myofibroblasts) and Transforming Growth Factor β1 (TGFβ1) play a central role. When exposed to TGFβ1, fibroblast and epithelial cells differentiate in myofibroblasts; in addition, endothelial cells may undergo endothelial-to-mesenchymal transition (EndoMT) and actively participate to the progression of fibrosis. Recently, the role of αv integrins, which recognize the Arg-Gly-Asp (RGD) tripeptide, in the release and signal transduction activation of TGFβ1 became evident. In this study, we present a class of triazole-derived RGD antagonists that interact with αvβ3 integrin. Above different compounds, the RGD-2 specifically interferes with integrin-dependent TGFβ1 EndoMT in Endothelial Colony-Forming Cells (ECPCs) derived from circulating Endothelial Precursor Cells (ECPCs). The RGD-2 decreases the amount of membrane-associated TGFβ1, and reduces both ALK5/TGFβ1 type I receptor expression and Smad2 phosphorylation in ECPCs. We found that RGD-2 antagonist reverts EndoMT, reducing α-smooth muscle actin (α-SMA) and vimentin expression in differentiated ECPCs. Our results outline the critical role of integrin in fibrosis progression and account for the opportunity of using integrins as target for anti-fibrotic therapeutic treatment.

  18. The hidden sentinel node in breast cancer

    NARCIS (Netherlands)

    Tanis, P. J.; van Sandick, J. W.; Nieweg, O. E.; Valdés Olmos, R. A.; Rutgers, E. J. T.; Hoefnagel, C. A.; Kroon, B. B. R.

    2002-01-01

    The purpose of this study was to analyse the occurrence of non-visualisation during preoperative lymphoscintigraphy for sentinel node identification in breast cancer. Preoperative lymphoscintigraphy was performed in 495 clinically node-negative breast cancer patients (501 sentinel node procedures)

  19. Increased Expression of Cytotoxic T-Lymphocyte-Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure

    DEFF Research Database (Denmark)

    Khamri, Wafa; Abeles, Robin D; Hou, Tie Zheng

    2017-01-01

    , hepatic sinusoidal endothelial cells, and biliary epithelial cells from healthy or diseased liver tissues. We also measured levels of soluble B7 serum samples from patients and controls, and mice with acetaminophen-induced liver injury using enzyme-linked immunosorbent assays. RESULTS: Peripheral blood...... were found to have increased concentrations of soluble B7 compared to sera from controls. Necrotic human primary hepatocytes exposed to acetaminophen, but not hepatic sinusoidal endothelial cells and biliary epithelial cells from patients with ALF, secreted high levels of soluble B7. Sera from mice...... with acetaminophen-induced liver injury contained high levels of soluble B7 compared to sera from mice without liver injury. Plasma exchange reduced circulating levels of soluble B7 in patients with ALF and expression of CTLA4 on T cells. CONCLUSIONS: Peripheral CD4+T cells from patients with ALF have increased...

  20. Defining nodes in complex brain networks

    Directory of Open Access Journals (Sweden)

    Matthew Lawrence Stanley

    2013-11-01

    Full Text Available Network science holds great promise for expanding our understanding of the human brain in health, disease, development, and aging. Network analyses are quickly becoming the method of choice for analyzing functional MRI data. However, many technical issues have yet to be confronted in order to optimize results. One particular issue that remains controversial in functional brain network analyses is the definition of a network node. In functional brain networks a node represents some predefined collection of brain tissue, and an edge measures the functional connectivity between pairs of nodes. The characteristics of a node, chosen by the researcher, vary considerably in the literature. This manuscript reviews the current state of the art based on published manuscripts and highlights the strengths and weaknesses of three main methods for defining nodes. Voxel-wise networks are constructed by assigning a node to each, equally sized brain area (voxel. The fMRI time-series recorded from each voxel is then used to create the functional network. Anatomical methods utilize atlases to define the nodes based on brain structure. The fMRI time-series from all voxels within the anatomical area are averaged and subsequently used to generate the network. Functional activation methods rely on data from traditional fMRI activation studies, often from databases, to identify network nodes. Such methods identify the peaks or centers of mass from activation maps to determine the location of the nodes. Small (~10-20 millimeter diameter spheres located at the coordinates of the activation foci are then applied to the data being used in the network analysis. The fMRI time-series from all voxels in the sphere are then averaged, and the resultant time series is used to generate the network. We attempt to clarify the discussion and move the study of complex brain networks forward. While the correct method to be used remains an open, possibly unsolvable question that

  1. Lymphoscintigraphic diagnosis of the lymph node metastasis of esophageal cancer

    International Nuclear Information System (INIS)

    Terui, Shoji; Kawai, Hideo; Hirashima, Toshio; Yamaguchi, Hajime; Kato, Hoichi; Iizuka, Norifumi

    1985-01-01

    Lymphoscintigraphy with 99m Tc-labeled rhenium sulfur colloid was performed preoperatively in 30 patients with esopohageal cancer. It showed hot nodes in a total of 267 lymph nodes, 176 mediastinal nodes and 91 celiac artery nodes. Of these 267 nodes, 47 (18 %) were found to have metastasis, including 34 (19 %) mediastinal nodes and 13 (14 %) celiac artery nodes. On the other hand, the number of non-visualized lymph nodes (cold nodes) was 542. Of them, 78 (14 %) had metastasis; 46 (15 %) were mediastinal nodes and 32 (14 %) were celiac artery nodes. (Namekawa, K.)

  2. Telmisartan activates endothelial nitric oxide synthase via Ser1177 phosphorylation in vascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Masahiro Myojo

    Full Text Available Because endothelial nitric oxide synthase (eNOS has anti-inflammatory and anti-arteriosclerotic functions, it has been recognized as one of the key molecules essential for the homeostatic control of blood vessels other than relaxation of vascular tone. Here, we examined whether telmisartan modulates eNOS function through its pleiotropic effect. Administration of telmisartan to mice significantly increased the phosphorylation level of eNOS (Ser1177 in the aortic endothelium, but administration of valsartan had no effect. Similarly, telmisartan treatment of human umbilical vein endothelial cells significantly increased the phosphorylation levels of AMP-activated protein kinase (Thr172 and eNOS and the concentration of intracellular guanosine 3',5'-cyclic monophosphate (cGMP. Furthermore, pretreatment with a p38 mitogen-activated protein kinase (p38 MAPK inhibitor suppressed the increased phosphorylation level of eNOS and intracellular cGMP concentration. These data show that telmisartan increases eNOS activity through Ser1177 phosphorylation in vascular endothelial cells mainly via p38 MAPK signaling.

  3. Magnetizable stent-grafts enable endothelial cell capture

    Science.gov (United States)

    Tefft, Brandon J.; Uthamaraj, Susheil; Harburn, J. Jonathan; Hlinomaz, Ota; Lerman, Amir; Dragomir-Daescu, Dan; Sandhu, Gurpreet S.

    2017-04-01

    Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.

  4. Diagnosis of sinusoidal obstruction syndrome by positron emission tomography/computed tomography: report of two cases treated by defibrotide.

    Science.gov (United States)

    Gauthé, Mathieu; Bozec, Laurence; Bedossa, Pierre

    2014-11-01

    Sinusoidal obstruction syndrome (SOS) is a potentially fatal liver injury that mainly occurs after myeloablative chemotherapy. We report two cases of SOS investigated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and treated with defibrotide. © 2014 by the American Association for the Study of Liver Diseases.

  5. Lymphatic drainage and sentinel node location in breast cancer

    International Nuclear Information System (INIS)

    Uren, R.F.; Howman-Giles, R.B.; Roberts, J.; Renwick, S.; Gillett, D.; Neische, F.; Ramsay-Stewart, G.

    1999-01-01

    Full text: Mammary lymphoscintigraphy using small volume (0.1-0.2 ml) peritumoral injections of 99 Tc m -antimony sulphide colloid provided a map of the lymph drainage of a breast cancer to its draining sentinel lymph nodes in 92 of 102 patients (over 90%). Non-migration of tracer is reduced by post-injection massage for 5 min but may occur especially if the lymphatics are blocked by metastases. Drainage included the axilla in 92%, internal mammary nodes in 43%, supraclavicular nodes in 12% and intramammary interval nodes in 10% of patients. One patient drained to an interpectoral node. Drainage across the centre-line of the breast occurred in 46% of patients but direct drainage to the contralateral side of the patient was not seen. Lymphatic drainage occurred to 1 node field in 52 patients, 2 node fields in 34 patients and 3 node fields in 6 patients, so that 43% of patients had multiple draining node fields. Drainage to non-axillary sites occurred in 51% of patients. In conclusion, mammary lymphoscintigraphy accurately maps sentinel node location in breast cancer. Approximately half of the patients will have sentinel nodes outside the axilla. To achieve complete lymph node staging in patients with breast cancer, it is logical to biopsy these non-axillary sentinel nodes as well as the sentinel nodes in the axilla. Failure to do so will potentially understage the node status in 50% of patients

  6. Nomogram for prediction of level 2 axillary lymph node metastasis in proven level 1 node-positive breast cancer patients.

    Science.gov (United States)

    Jiang, Yanlin; Xu, Hong; Zhang, Hao; Ou, Xunyan; Xu, Zhen; Ai, Liping; Sun, Lisha; Liu, Caigang

    2017-09-22

    The current management of the axilla in level 1 node-positive breast cancer patients is axillary lymph node dissection regardless of the status of the level 2 axillary lymph nodes. The goal of this study was to develop a nomogram predicting the probability of level 2 axillary lymph node metastasis (L-2-ALNM) in patients with level 1 axillary node-positive breast cancer. We reviewed the records of 974 patients with pathology-confirmed level 1 node-positive breast cancer between 2010 and 2014 at the Liaoning Cancer Hospital and Institute. The patients were randomized 1:1 and divided into a modeling group and a validation group. Clinical and pathological features of the patients were assessed with uni- and multivariate logistic regression. A nomogram based on independent predictors for the L-2-ALNM identified by multivariate logistic regression was constructed. Independent predictors of L-2-ALNM by the multivariate logistic regression analysis included tumor size, Ki-67 status, histological grade, and number of positive level 1 axillary lymph nodes. The areas under the receiver operating characteristic curve of the modeling set and the validation set were 0.828 and 0.816, respectively. The false-negative rates of the L-2-ALNM nomogram were 1.82% and 7.41% for the predicted probability cut-off points of level 1 axillary lymph node metastasis. Patients with a low probability of L-2-ALNM could be spared level 2 axillary lymph node dissection, thereby reducing postoperative morbidity.

  7. Endothelial function and dysfunction: clinical significance and assessment

    Directory of Open Access Journals (Sweden)

    Shaghayegh Haghjooyejavanmard

    2008-08-01

    Full Text Available

    • Over the past two decades, investigators have increasingly recognized the importance of the endothelium as a centralregulator of vascular and body homeostasis. The endothelial lining represents an organ of 1.5 kg in an adult, which is distributed throughout the body. The endothelium is versatile and multifunctional. In addition to its role as a selective permeability barrier, it has many synthetic and metabolic properties, including modulation of vascular tone and blood flow, regulation of immune and inflammatory responses, and regulation of coagulation, fibrinolysis and thrombosis. Endothelial dysfunction (ED is a frequently used term, which can be referred to abnormalities in various physiological functions of the endothelium, and it is known as a key variable in the pathogenesis of several diseases and their complications. Finding suitable markers for endothelial damage or ED is certainly of interest. Established and emerging techniques to detect ED are divided into three large families of functional, cellular, and biochemical markers. Instead of performing single assessments, it may be much more valuable to determine various biological aspects of endothelium. It seems that there is likely a spectrum between normality, endothelial activation (by inflammatory cytokines, endothelial dysfunction (e.g., impairment of nitric oxide, resulting in loss of regulation of vascular tone and endothelial damage (e.g., atherosclerosis. In this review we review the importance of endothelium and its activation, biomarkers and dysfunction.
    •  KEYWORDS: Endothelial function, endothelium, Disease.

  8. In smokers, Sonic hedgehog modulates pulmonary endothelial function through vascular endothelial growth factor.

    Science.gov (United States)

    Henno, Priscilla; Grassin-Delyle, Stanislas; Belle, Emeline; Brollo, Marion; Naline, Emmanuel; Sage, Edouard; Devillier, Philippe; Israël-Biet, Dominique

    2017-05-23

    Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The Sonic hedgehog (SHH) pathway is involved in vascular physiology. We sought to establish whether the SHH pathway has a role in pulmonary endothelial dysfunction in smokers. The ex vivo endothelium-dependent relaxation of pulmonary artery rings in response to acetylcholine (Ach) was compared in 34 current or ex-smokers and 8 never-smokers. The results were expressed as a percentage of the contraction with phenylephrine. We tested the effects of SHH inhibitors (GANT61 and cyclopamine), an SHH activator (SAG) and recombinant VEGF on the Ach-induced relaxation. The level of VEGF protein in the pulmonary artery ring was measured in an ELISA. SHH pathway gene expression was quantified in reverse transcriptase-quantitative polymerase chain reactions. Ach-induced relaxation was much less intense in smokers than in never-smokers (respectively 24 ± 6% and 50 ± 7% with 10 -4 M Ach; p = 0.028). All SHH pathway genes were expressed in pulmonary artery rings from smokers. SHH inhibition by GANT61 reduced Ach-induced relaxation and VEGF gene expression in the pulmonary artery ring. Recombinant VEGF restored the ring's endothelial function. VEGF gene and protein expression levels in the pulmonary artery rings were positively correlated with the degree of Ach-induced relaxation and negatively correlated with the number of pack-years. SHH pathway genes and proteins are expressed in pulmonary artery rings from smokers, where they modulate endothelial function through VEGF.

  9. Enhancement characteristics of retroperitoneal lymphomatous lymph nodes

    International Nuclear Information System (INIS)

    Hagtvedt, Trond; Smith, Hans-Joergen; Kolbenstvedt, Alf; Aaloekken, Trond Mogens; Graff, Bjoern Anton; Holte, Harald

    2013-01-01

    Background: Previous studies of CT enhancement of lymphomatous lymph nodes (LLN) of the neck and the mediastinum showed that the LLN had lower enhancement values than normal lymph nodes. Purpose: To elucidate the contrast medium enhancement curves of LLN in the retroperitoneum by comparing the curves of LLN with those of normal lymph nodes, to test whether differences between these curves could be of diagnostic value, and to compare the present enhancement curves of LLN of the retroperitoneum with the curves of LLN of the neck and the mediastinum from previous similar investigations. Material and Methods: Twenty-eight consecutive patients with LLN of the retroperitoneum (three with Hodgkin's lymphoma [HL]) and 21 control patients with sarcomas and thus presumably normal retroperitoneal nodes underwent dynamic CT examinations. The previous, similar investigation of lymph nodes of the neck comprised 28 patients with LLN and the investigation of mediastinal lymph nodes comprised 24 patients with LLN. Results: The enhancement curves of the retroperitoneal LLN had significantly lower attenuation than those of the retroperitoneal control nodes. A combination of peak contrast value and time to peak adjusted to total body weight yielded a diagnostic accuracy which at the best showed a sensitivity of 90.5% with a specificity of 82.6%. The LLN of the retroperitoneum had higher attenuation values than corresponding nodes of the mediastinum but no significant difference was found between LLN of the retroperitoneum and LLN of the neck in previous similar investigations. Conclusion: The comparison of enhancement curves of retroperitoneal LLN with retroperitoneal control nodes showed a marked similarity with and substantiates our previous findings in lymph nodes of the neck and of the mediastinum. The best diagnostic accuracy was achieved by combining the parameters peak contrast value and time to peak and adjusting these values to the body weight. Peak enhancement of the

  10. Contrast enhanced ultrasound of sentinel lymph nodes

    Directory of Open Access Journals (Sweden)

    XinWu Cui

    2013-03-01

    Full Text Available Sentinel lymph nodes are the first lymph nodes in the region that receive lymphatic drainage from a primary tumor. The detection or exclusion of sentinel lymph node micrometastases is critical in the staging of cancer, especially breast cancer and melanoma because it directly affects patient’s prognosis and surgical management. Currently, intraoperative sentinel lymph node biopsies using blue dye and radioisotopes are the method of choice for the detection of sentinel lymph node with high identification rate. In contrast, conventional ultrasound is not capable of detecting sentinel lymph nodes in most cases. Contrast enhanced ultrasound with contrast specific imaging modes has been used for the evaluation and diagnostic work-up of peripherally located suspected lymphadenopathy. The method allows for real-time analysis of all vascular phases and the visualization of intranodal focal “avascular” areas that represent necrosis or deposits of neoplastic cells. In recent years, a number of animal and human studies showed that contrast enhanced ultrasound can be also used for the detection of sentinel lymph node, and may become a potential application in clinical routine. Several contrast agents have been used in those studies, including albumin solution, hydroxyethylated starch, SonoVue®, Sonazoid® and Definity®. This review summarizes the current knowledge about the use of ultrasound techniques in detection and evaluation of sentinel lymph node.

  11. Variations in DNA synthesis and mitotic indices in hepatocytes and sinusoid litoral cells of adult intact male mouse along a circadian time span.

    Science.gov (United States)

    Surur, J M; Moreno, F R; Badrán, A F; Llanos, J M

    1985-01-01

    Variations of DNA synthesis (DNAS) and mitotic indices along a circadian time span are described in the hepatocyte and sinusoid litoral cell populations of adult intact male mouse liver. Standardized (light from 0600 to 1800) mice were killed in groups of six to nine animals, every 2-4 hr along a circadian time span. Hepatocytes show significant peaks in the synthesis of DNA and the mitotic activity at 0200 and 1400, respectively. These results correspond to those previously described by us in young immature liver, regenerating liver and hepatomas. The phase differences between these peaks and the differences between their absolute values are discussed. Also considered are the practical consequences of our findings for experimental design. The curve of DNA synthesis of sinusoid litoral cells show a peak at 0200. The mitotic index show a bimodal waveform with peaks at 0800 and 2000. The existence of four different cell populations composing the so called sinusoid litoral cells and also the migration into and out of the liver of some macrophages considered as litoral (Kupffer) cells in our counts, makes interpretation of the curves somewhat complicated and deserves further analysis.

  12. Successful transplantation of in vitro expanded human corneal endothelial precursors to corneal endothelial surface using a nanocomposite sheet

    Directory of Open Access Journals (Sweden)

    Parikumar P

    2011-01-01

    Full Text Available Background: Though the transplantation of in vitro expanded human corneal endothelial precursors in animal models of endothelial damage by injecting into the anterior chamber has been reported, the practical difficulties of accomplishing such procedure in human patients have been a hurdle to clinical translation. Here we report the successful transplantation of in vitro expanded human corneal precursor cells to an animal eye using a transparent Nano-composite sheet and their engraftment.Materials and Methods: Human Corneal endothelial cells (HCEC were isolated from human cadaver eyes with informed consent and expanded in the lab using a sphere forming assay in a novel Thermoreversible Gelation Polymer (TGP for 26 days. HCEC obtained by sphere forming assay were seeded in a novel Nano-composite sheet, which was made of PNIPA-NC gels by in-situ, free-radical polymerization of NIPA monomer in the presence of exfoliated clay (synthetic hectorite “Laponite XLG” uniformly dispersed in aqueous media. After a further seven days in vitro culture of HCEC in the Nano-composite sheet, cells were harvested and transplanted on cadaver-bovine eyes (n=3. The cells were injected between the corneal endothelial layer and the Nano-composite sheet that had been placed prior to the injection in close proximity to the endothelial layer. After three hours, the transplanted Nano-composite sheets were removed from the bovine eyes and subjected to microscopic examination. The corneas were subjected to Histo-pathological studies along with controls. Results: HCEC formed sphere like colonies in TGP which expressed relevant markers as confirmed by RT-PCR. Microscopic studies of the Nanosheets and histopathological studies of the cornea of the Bull’s eye revealed that the HCEC got engrafted to the corneal endothelial layer of the bovine eyes with no remnant cells in the Nanosheet. Conclusion: Transplantation of in vitro expanded donor human corneal endothelial cells

  13. Initial afferent lymphatic vessels controlling outbound leukocyte traffic from skin to lymph nodes.

    Directory of Open Access Journals (Sweden)

    Ignacio eMelero

    2013-12-01

    Full Text Available Tissue drains fluid and macromolecules through lymphatic vessels, which are lined by a specialized endothelium that expresses peculiar differentiation proteins, not found in blood vessels (i.e: LYVE-1, Podoplanin, PROX-1 and VEGFR-3. Lymphatic capillaries are characteristically devoid of a continuous basal membrane and are anchored to the ECM by elastic fibers that act as pulling ropes which open the vessel to avoid oedema if tissue volume increases, as it occurs upon inflammation. Lymphatic vessels are also crucial for the transit of T lymphocytes and antigen presenting cells from tissue to draining lymph nodes. Importantly, cell traffic control across lymphatic endothelium is differently regulated under resting and inflammatory conditions. Under steady-state non-inflammatory conditions, leukocytes enter into the lymphatic capillaries through basal membrane gaps (portals. This entrance is integrin-independent and seems to be mainly guided by CCL21 chemokine gradients acting on leukocytes expressing CCR7. In contrast, inflammatory processes in lymphatic capillaries involve a plethora of cytokines, chemokines, leukocyte integrins and other adhesion molecules. Importantly, under inflammation a role for integrins and their ligands becomes apparent and, as a consequence, the number of leukocytes entering the lymphatic capillaries multiplies several-fold. Enhancing transmigration of dendritic cells en route to lymph nodes is conceivably useful for vaccination and cancer immunotherapy, whereas interference with such key mechanisms may ameliorate autoimmunity or excessive inflammation. Recent findings illustrate how, transient cell-to-cell interactions between lymphatic endothelial cells and leukocytes contribute to shape the subsequent behaviour of leukocytes and condition the lymphatic vessel for subsequent trans-migratory events.

  14. Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

    Directory of Open Access Journals (Sweden)

    Jaroslaw Suchanski

    Full Text Available In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first

  15. Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

    Science.gov (United States)

    Suchanski, Jaroslaw; Tejchman, Anna; Zacharski, Maciej; Piotrowska, Aleksandra; Grzegrzolka, Jedrzej; Chodaczek, Grzegorz; Nowinska, Katarzyna; Rys, Janusz; Dziegiel, Piotr; Kieda, Claudine; Ugorski, Maciej

    2017-01-01

    In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first time, that such

  16. Ratios of involved nodes in early breast cancer

    International Nuclear Information System (INIS)

    Vinh-Hung, Vincent; Royce, Melanie; Verschraegen, Claire; Promish, Donald I; Cserni, Gábor; Van de Steene, Jan; Tai, Patricia; Vlastos, Georges; Voordeckers, Mia; Storme, Guy

    2004-01-01

    The number of lymph nodes found to be involved in an axillary dissection is among the most powerful prognostic factors in breast cancer, but it is confounded by the number of lymph nodes that have been examined. We investigate an idea that has surfaced recently in the literature (since 1999), namely that the proportion of node-positive lymph nodes (or a function thereof) is a much better predictor of survival than the number of excised and node-positive lymph nodes, alone or together. The data were abstracted from 83,686 cases registered in the Surveillance, Epidemiology, and End Results (SEER) program of women diagnosed with nonmetastatic T1–T2 primary breast carcinoma between 1988 and 1997, in whom axillary node dissection was performed. The end-point was death from breast cancer. Cox models based on different expressions of nodal involvement were compared using the Nagelkerke R 2 index (R 2 N ). Ratios were modeled as percentage and as log odds of involved nodes. Log odds were estimated in a way that avoids singularities (zero values) by using the empirical logistic transform. In node-negative cases both the number of nodes excised and the log odds were significant, with hazard ratios of 0.991 (95% confidence interval 0.986–0.997) and 1.150 (1.058–1.249), respectively, but without improving R 2 N . In node-positive cases the hazard ratios were 1.003–1.088 for the number of involved nodes, 0.966–1.005 for the number of excised nodes, 1.015–1.017 for the percentage, and 1.344–1.381 for the log odds. R 2 N improved from 0.067 (no nodal covariate) to 0.102 (models based on counts only) and to 0.108 (models based on ratios). Ratios are simple optimal predictors, in that they provide at least the same prognostic value as the more traditional staging based on counting of involved nodes, without replacing them with a needlessly complicated alternative. They can be viewed as a per patient standardization in which the number of involved nodes is standardized

  17. Aging-associated oxidized albumin promotes cellular senescence and endothelial damage

    Directory of Open Access Journals (Sweden)

    Luna C

    2016-02-01

    Full Text Available Carlos Luna,1,* Matilde Alique,2,* Estefanía Navalmoral,2 Maria-Victoria Noci,3 Lourdes Bohorquez-Magro,2 Julia Carracedo,1 Rafael Ramírez2 1Nephrology Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC, Reina Sofía University Hospital, Córdoba, Spain; 2Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Madrid, Spain; 3Anesthesia Unit, Reina sofía University Hospital, Córdoba, Spain*These authors contributed equally to this work Abstract: Increased levels of oxidized proteins with aging have been considered a cardiovascular risk factor. However, it is unclear whether oxidized albumin, which is the most abundant serum protein, induces endothelial damage. The results of this study indicated that with aging processes, the levels of oxidized proteins as well as endothelial microparticles release increased, a novel marker of endothelial damage. Among these, oxidized albumin seems to play a principal role. Through in vitro studies, endothelial cells cultured with oxidized albumin exhibited an increment of endothelial damage markers such as adhesion molecules and apoptosis levels. In addition, albumin oxidation increased the amount of endothelial microparticles that were released. Moreover, endothelial cells with increased oxidative stress undergo senescence. In addition, endothelial cells cultured with oxidized albumin shown a reduction in endothelial cell migration measured by wound healing. As a result, we provide the first evidence that oxidized albumin induces endothelial injury which then contributes to the increase of cardiovascular disease in the elderly subjects.Keywords: elderly, oxidative stress, microparticles, vascular damage

  18. Node-node correlations and transport properties in scale-free networks

    Science.gov (United States)

    Obregon, Bibiana; Guzman, Lev

    2011-03-01

    We study some transport properties of complex networks. We focus our attention on transport properties of scale-free and small-world networks and compare two types of transport: Electric and max-flow cases. In particular, we construct scale-free networks, with a given degree sequence, to estimate the distribution of conductances for different values of assortative/dissortative mixing. For the electric case we find that the distributions of conductances are affect ed by the assortative mixing of the network whereas for the max-flow case, the distributions almost do not show changes when node-node correlations are altered. Finally, we compare local and global transport in terms of the average conductance for the small-world (Watts-Strogatz) model

  19. Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability.

    Science.gov (United States)

    Salmon, Andrew H J; Satchell, Simon C

    2012-03-01

    Appreciation of the glomerular microcirculation as a specialized microcirculatory bed, rather than as an entirely separate entity, affords important insights into both glomerular and systemic microvascular pathophysiology. In this review we compare regulation of permeability in systemic and glomerular microcirculations, focusing particularly on the role of the endothelial glycocalyx, and consider the implications for disease processes. The luminal surface of vascular endothelium throughout the body is covered with endothelial glycocalyx, comprising surface-anchored proteoglycans, supplemented with adsorbed soluble proteoglycans, glycosaminoglycans and plasma constituents. In both continuous and fenestrated microvessels, this endothelial glycocalyx provides resistance to the transcapillary escape of water and macromolecules, acting as an integral component of the multilayered barrier provided by the walls of these microvessels (ie acting in concert with clefts or fenestrae across endothelial cell layers, basement membranes and pericytes). Dysfunction of any of these capillary wall components, including the endothelial glycocalyx, can disrupt normal microvascular permeability. Because of its ubiquitous nature, damage to the endothelial glycocalyx alters the permeability of multiple capillary beds: in the glomerulus this is clinically apparent as albuminuria. Generalized damage to the endothelial glycocalyx can therefore manifest as both albuminuria and increased systemic microvascular permeability. This triad of altered endothelial glycocalyx, albuminuria and increased systemic microvascular permeability occurs in a number of important diseases, such as diabetes, with accumulating evidence for a similar phenomenon in ischaemia-reperfusion injury and infectious disease. The detection of albuminuria therefore has implications for the function of the microcirculation as a whole. The importance of the endothelial glycocalyx for other aspects of vascular function

  20. Signaling hierarchy regulating human endothelial cell development

    Science.gov (United States)

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these stud...

  1. Arm morbidity following sentinel lymph node biopsy or axillary lymph node dissection: a study from the Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Husted, Madsen A.; Haugaard, K.; Soerensen, J.

    2008-01-01

    BACKGROUND: Sentinel lymph node biopsy was implemented in the treatment of early breast cancer with the aim of reducing shoulder and arm morbidity. Relatively few prospective studies have been published where the morbidity was assessed by clinical examination. Very few studies have examined...... lymph node biopsy with node negative patients having a lymph node dissection of levels I and II of the axilla, we found significant increase in arm volume among the patients who had an axillary dissection. Only minor, but significant, differences in shoulder mobility were observed comparing the two...... groups of node negative patients. Highly significant difference was found comparing sensibility. Comparing the morbidity in node positive patients who had a one-step axillary dissection with patients having a two-step procedure (sentinel lymph node biopsy followed by delayed axillary dissection) revealed...

  2. Error Control in Distributed Node Self-Localization

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    2008-03-01

    Full Text Available Location information of nodes in an ad hoc sensor network is essential to many tasks such as routing, cooperative sensing, and service delivery. Distributed node self-localization is lightweight and requires little communication overhead, but often suffers from the adverse effects of error propagation. Unlike other localization papers which focus on designing elaborate localization algorithms, this paper takes a different perspective, focusing on the error propagation problem, addressing questions such as where localization error comes from and how it propagates from node to node. To prevent error from propagating and accumulating, we develop an error-control mechanism based on characterization of node uncertainties and discrimination between neighboring nodes. The error-control mechanism uses only local knowledge and is fully decentralized. Simulation results have shown that the active selection strategy significantly mitigates the effect of error propagation for both range and directional sensors. It greatly improves localization accuracy and robustness.

  3. Endothelial adhesion molecules and leukocyte integrins in preeclamptic patients.

    Science.gov (United States)

    Haller, H; Ziegler, E M; Homuth, V; Drab, M; Eichhorn, J; Nagy, Z; Busjahn, A; Vetter, K; Luft, F C

    1997-01-01

    Endothelial cell activation is important in the pathogenesis of preeclampsia; however, the nature of the activation is unknown. We investigated 22 patients with preeclampsia. 29 normotensive pregnancies, and 18 nonpregnant women to test the hypothesis that serum from preeclamptic patients induces expression of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) and stimulates intracellular free calcium concentrations [Ca2+]i in cultured endothelial cells. We then asked whether the corresponding integrin adhesive counter receptors lymphocyte function-associated antigen-1 (CD11a/CD18), macrophage-1 antigen (CD11b/CD18), p150,95 (CD11c/CD18), and very late activation antigen-4 (CD49/CD29) are increased in patients with preeclampsia. In the pregnant women, the measurements were conducted both before and after delivery. Integrin expression was measured by fluorescent antibody cell sorting analysis using monoclonal antibodies. ICAM-1 and VCAM-1 were analyzed on endothelial cells by enzyme-linked immunosorbent assay. [Ca2+]i was measured with fura 2. Serum from preeclamptic patients increased endothelial cell ICAM-1 expression but not VCAM-1 expression. Preeclamptic patients' serum also increased [Ca2+]i in endothelial cells compared with serum from normal nonpregnant or normal pregnant women. Endothelial cell [Ca2+]i concentrations were correlated with the ICAM-1 expression in preeclamptic patients (r = .80, P preclampsia and normal pregnancy compared with the nonpregnant state. The expression decreased significantly after delivery in both groups. Our results demonstrate that serum from preeclamptic women induces increased ICAM-1 surface expression on endothelial cells, while the expression of the integrin counterreceptors was not different. The effect on endothelial cells may be related to an increase in [Ca2+]i. The effect on cultured endothelial cells and the rapid decrease after delivery suggests the presence of a circulating serum

  4. An ?All-laser? Endothelial Transplant

    OpenAIRE

    Rossi, Francesca; Canovetti, Annalisa; Malandrini, Alex; Lenzetti, Ivo; Pini, Roberto; Menabuoni, Luca

    2015-01-01

    The ?all laser? assisted endothelial keratoplasty is a procedure that is performed with a femtosecond laser used to cut the donor tissue at an intended depth, and a near infrared diode laser to weld the corneal tissue. The proposed technique enables to reach the three main goals in endothelial keratoplasty: a precise control in the thickness of the donor tissue; its easy insertion in the recipient bed and a reduced risk of donor lenticule dislocation. The donor cornea thickness is measured in...

  5. Erasure code-based low storage blockchain node

    OpenAIRE

    Perard, Doriane; Lacan, Jérôme; Bachy, Yann; Detchart, Jonathan

    2018-01-01

    The concept of a decentralized ledger usually implies that each node of a blockchain network stores the entire blockchain. However, in the case of popular blockchains, which each weigh several hundreds of GB, the large amount of data to be stored can incite new or low-capacity nodes to run lightweight clients. Such nodes do not participate to the global storage effort and can result in a centralization of the blockchain by very few nodes, which is contrary to the basic concepts of a blockchai...

  6. Syncytin is involved in breast cancer-endothelial cell fusions

    DEFF Research Database (Denmark)

    Bjerregaard, Bolette; Holck, S.; Christensen, I.J.

    2006-01-01

    Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer...... specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to express ASCT-2, a receptor for syncytin. Syncytin antisense treatment decreases syncytin expression...... and inhibits fusions between breast cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial cell fusions....

  7. Localization of integrin alpha(v)beta3 and vascular endothelial growth factor receptor-2 (KDR/Flk-1) in cutaneous and oral melanomas of dog.

    Science.gov (United States)

    Rawlings, N G; Simko, E; Bebchuk, T; Caldwell, S J; Singh, B

    2003-07-01

    Melanomas are common neoplasms of dogs and arise from pigment-producing cells called melanocytes or melanoblasts. Melanomas of skin are often easily cured by surgical excision, but those of oral mucosa are aggressive, metastasize to the regional lymph nodes and lungs, and respond poorly to conventional therapy. Tumor growth is sustained by proliferation of microvessels via a process called angiogenesis. Integrin alpha(v)beta3 is expressed in proliferating but not in quiescent microvessels suggesting a role in angiogenesis. Vascular endothelial growth factor (VEGF) manifests its mitogenic and angiogenic effects mainly via VEGF receptor-2 (VEGFR-2/Flk-1). We conducted this immunocytochemical study to investigate the expression of integrin alpha(v)beta3 and VEGFR-2 in archival and fresh samples from cases of canine melanomas. Results show that integrin alpha(v)beta3 was expressed in 72% and 88% of cutaneous and oral melanomas, respectively, and the expression was restricted to and immediately around the melanocytes and endothelial cells. VEGFR-2 staining of selected cases of melanoma revealed that its expression overlapped with the alpha(v)beta3 integrin. Dual immuno-gold electron microscopy confirmed co-localization of integrin alpha(v)beta3 and VEGFR-2 in melanocytes and endothelial cells. These data demonstrate expression and co-localization of integrin alpha(v)beta3 and VEGFR-2 in cutaneous and oral melanomas of dogs.

  8. Suppressing epidemics on networks by exploiting observer nodes.

    Science.gov (United States)

    Takaguchi, Taro; Hasegawa, Takehisa; Yoshida, Yuichi

    2014-07-01

    To control infection spreading on networks, we investigate the effect of observer nodes that recognize infection in a neighboring node and make the rest of the neighbor nodes immune. We numerically show that random placement of observer nodes works better on networks with clustering than on locally treelike networks, implying that our model is promising for realistic social networks. The efficiency of several heuristic schemes for observer placement is also examined for synthetic and empirical networks. In parallel with numerical simulations of epidemic dynamics, we also show that the effect of observer placement can be assessed by the size of the largest connected component of networks remaining after removing observer nodes and links between their neighboring nodes.

  9. Suppressing epidemics on networks by exploiting observer nodes

    Science.gov (United States)

    Takaguchi, Taro; Hasegawa, Takehisa; Yoshida, Yuichi

    2014-07-01

    To control infection spreading on networks, we investigate the effect of observer nodes that recognize infection in a neighboring node and make the rest of the neighbor nodes immune. We numerically show that random placement of observer nodes works better on networks with clustering than on locally treelike networks, implying that our model is promising for realistic social networks. The efficiency of several heuristic schemes for observer placement is also examined for synthetic and empirical networks. In parallel with numerical simulations of epidemic dynamics, we also show that the effect of observer placement can be assessed by the size of the largest connected component of networks remaining after removing observer nodes and links between their neighboring nodes.

  10. Predictive Factors for Nonsentinel Lymph Node Metastasis in Patients With Positive Sentinel Lymph Nodes After Neoadjuvant Chemotherapy: Nomogram for Predicting Nonsentinel Lymph Node Metastasis.

    Science.gov (United States)

    Ryu, Jai Min; Lee, Se Kyung; Kim, Ji Young; Yu, Jonghan; Kim, Seok Won; Lee, Jeong Eon; Han, Se Hwan; Jung, Yong Sik; Nam, Seok Jin

    2017-11-01

    Axillary lymph node (ALN) status is an important prognostic factor for breast cancer patients. With increasing numbers of patients undergoing neoadjuvant chemotherapy (NAC), issues concerning sentinel lymph node biopsy (SLNB) after NAC have emerged. We analyzed the clinicopathologic features and developed a nomogram to predict the possibility of nonsentinel lymph node (NSLN) metastases in patients with positive SLNs after NAC. A retrospective medical record review was performed of 140 patients who had had clinically positive ALNs at presentation, had a positive SLN after NAC on subsequent SLNB, and undergone axillary lymph node dissection (ALND) from 2008 to 2014. On multivariate stepwise logistic regression analysis, pathologic T stage, lymphovascular invasion, SLN metastasis size, and number of positive SLN metastases were independent predictors for NSLN metastases (P Samsung Medical Center NAC nomogram was developed to predict the likelihood of additional positive NSLNs. The Samsung Medical Center NAC nomogram could provide information to surgeons regarding whether to perform additional ALND when the permanent biopsy revealed positive findings, although the intraoperative SLNB findings were negative. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Differentiation state determines neural effects on microvascular endothelial cells

    International Nuclear Information System (INIS)

    Muffley, Lara A.; Pan, Shin-Chen; Smith, Andria N.; Ga, Maricar; Hocking, Anne M.; Gibran, Nicole S.

    2012-01-01

    Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. ► Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. ► Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell production of nitric oxide. ► Neural progenitor cells and dorsal root

  12. Perception of the dynamic visual vertical during sinusoidal linear motion.

    Science.gov (United States)

    Pomante, A; Selen, L P J; Medendorp, W P

    2017-10-01

    The vestibular system provides information for spatial orientation. However, this information is ambiguous: because the otoliths sense the gravitoinertial force, they cannot distinguish gravitational and inertial components. As a consequence, prolonged linear acceleration of the head can be interpreted as tilt, referred to as the somatogravic effect. Previous modeling work suggests that the brain disambiguates the otolith signal according to the rules of Bayesian inference, combining noisy canal cues with the a priori assumption that prolonged linear accelerations are unlikely. Within this modeling framework the noise of the vestibular signals affects the dynamic characteristics of the tilt percept during linear whole-body motion. To test this prediction, we devised a novel paradigm to psychometrically characterize the dynamic visual vertical-as a proxy for the tilt percept-during passive sinusoidal linear motion along the interaural axis (0.33 Hz motion frequency, 1.75 m/s 2 peak acceleration, 80 cm displacement). While subjects ( n =10) kept fixation on a central body-fixed light, a line was briefly flashed (5 ms) at different phases of the motion, the orientation of which had to be judged relative to gravity. Consistent with the model's prediction, subjects showed a phase-dependent modulation of the dynamic visual vertical, with a subject-specific phase shift with respect to the imposed acceleration signal. The magnitude of this modulation was smaller than predicted, suggesting a contribution of nonvestibular signals to the dynamic visual vertical. Despite their dampening effect, our findings may point to a link between the noise components in the vestibular system and the characteristics of dynamic visual vertical. NEW & NOTEWORTHY A fundamental question in neuroscience is how the brain processes vestibular signals to infer the orientation of the body and objects in space. We show that, under sinusoidal linear motion, systematic error patterns appear in the

  13. Lymph node metastasis of carcinomas of transverse colon including flexures. Consideration of the extramesocolic lymph node stations.

    Science.gov (United States)

    Perrakis, Aristotelis; Weber, Klaus; Merkel, Susanne; Matzel, Klaus; Agaimy, Abbas; Gebbert, Carol; Hohenberger, Werner

    2014-10-01

    Complete mesocolic excision (CME) is nowadays state of the art in the treatment of colon cancer. In cases of carcinoma of transverse colon and of both flexures an extramesocolic lymph node metastasis can be found in the infrapancreatic lymph node region (ILR) and across the gastroepiploic arcade (GLR). These direct metastatic routes were not previously systematically considered. In order to validate our hypothesis of these direct metastatic pathways and to obtain evidence of our approach of including dissection of these areas as part of CME, we initiated a prospective study evaluating these lymph node regions during surgery. Forty-five consecutive patients with primary tumour manifestation in transverse colon and both flexures between May 2010 and January 2013 were prospectively analyzed. Patients were followed up for at least 6 months. Mode of surgery, histopathology, morbidity and mortality were evaluated. Twenty-six patients had a carcinoma of transverse colon, 16 patients one of hepatic flexure and four patients one of splenic flexure. The median lymph node yield was 40. Occurrence of lymph node metastasis in ILR was registered in five patients and in GLR in four patients. The mean lymph node ratio was 0.085. Postoperative complications occurred in nine patients, and postoperative mortality was 2 %. We were able to demonstrate this novel metastatic route of carcinomas of the transverse colon and of both flexures in ILR and GLR. These could be considered as regional lymph node regions and have to be included into surgery for cancer of the transverse colon including both flexures.

  14. The role of corneal endothelial morphology in graft assessment and prediction of endothelial cell loss during organ culture of human donor corneas.

    Science.gov (United States)

    Hermel, Martin; Salla, Sabine; Fuest, Matthias; Walter, Peter

    2017-03-01

    Endothelial assessment is crucial in the release of corneas for grafting. We retrospectively analysed the role of endothelial morphology parameters in predicting endothelial cell loss during organ culture. Human donor corneas were cultured in minimal essential medium with 2% fetal calf serum and antibiotics. Initial endothelial morphology was assessed microscopically using score parameters polymegethism (POL), pleomorphism (PLE), granulation (GRA), vacuolization (VAC), segmentation of cell membranes (SEG), Descemet's folds (DF), trypan blue-positive cells (TBPC) and endothelial cell-free areas (ECFA). Some corneas were primarily rejected based on endothelial assessment. Endothelial cell density (ECD) was assessed at the beginning (I-ECD) and end of culture. Corneas were then placed in dehydration medium (as above + 5% dextran 500). In a subgroup, ECD was reassessed after dehydration. Endothelial cell loss during culture (ECL@Culture) and culture+dehydration (ECL-Culture&Dehydration) were calculated. Data were given as mean ± SD and analysed using multiple linear and logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. I-ECD was 2812 ± 360/mm 2 (n = 2356). The decision to reject a cornea due to endothelial assessment was associated negatively with I-ECD (OR = 0.77/100 cells, CI 0.7-0.82) and positively with ECFA (OR = 2.7, CI 1.69-4.35), SEG (OR =1.3, CI 1.01-1.68) and donor age (OR = 1.26/decade, CI 1.33-1.41). ECL@Culture was 153 ± 201/mm 2 (n = 1277), ECL@Culture&Dehydration was 169 ± 183/mm 2 (n = 918). ECL@Culture was associated positively with donor age, I-ECD, GRA and TBPC, and negatively with PLE, and DF. ECL@Culture&Dehydration was associated positively with age, sex, initial ECD, POL, PLE, VAC and TBPC. Morphological parameters displayed associations with the exclusion of corneas from culture and with endothelial cell loss. Appropriate parameter selection for screening purposes may help improve

  15. The Deletion of Endothelial Sodium Channel α (αENaC Impairs Endothelium-Dependent Vasodilation and Endothelial Barrier Integrity in Endotoxemia in Vivo

    Directory of Open Access Journals (Sweden)

    Magdalena Sternak

    2018-04-01

    Full Text Available The role of epithelial sodium channel (ENaC activity in the regulation of endothelial function is not clear. Here, we analyze the role of ENaC in the regulation of endothelium-dependent vasodilation and endothelial permeability in vivo in mice with conditional αENaC subunit gene inactivation in the endothelium (endo-αENaCKO mice using unique MRI-based analysis of acetylcholine-, flow-mediated dilation and vascular permeability. Mice were challenged or not with lipopolysaccharide (LPS, from Salmonella typhosa, 10 mg/kg, i.p.. In addition, changes in vascular permeability in ex vivo organs were analyzed by Evans Blue assay, while changes in vascular permeability in perfused mesenteric artery were determined by a FITC-dextran-based assay. In basal conditions, Ach-induced response was completely lost, flow-induced vasodilation was inhibited approximately by half but endothelial permeability was not changed in endo-αENaCKO vs. control mice. In LPS-treated mice, both Ach- and flow-induced vasodilation was more severely impaired in endo-αENaCKO vs. control mice. There was also a dramatic increase in permeability in lungs, brain and isolated vessels as evidenced by in vivo and ex vivo analysis in endotoxemic endo-αENaCKO vs. control mice. The impaired endothelial function in endotoxemia in endo-αENaCKO was associated with a decrease of lectin and CD31 endothelial staining in the lung as compared with control mice. In conclusion, the activity of endothelial ENaC in vivo contributes to endothelial-dependent vasodilation in the physiological conditions and the preservation of endothelial barrier integrity in endotoxemia.

  16. Sentinel lymph node detection in canine oncological patients

    International Nuclear Information System (INIS)

    Balogh, L.; Andocs, G.; Mathe, D.

    2002-01-01

    Sentinel lymph node detection was investigated in dogs with spontaneously occurring tumours. In this pilot study, 24 client-owned spontaneously tumorous dogs presented for sentinel lymph node detection. A multiple method was used with a nuclear medicine technique (injection of 99mT c human serum albumin colloid) with scintigraphy and intraoperative guidance, and blue dye injection. Of the 35 lymph nodes histologically demonstrated to contain metastases, 34 (97%) were found by radioguided surgery, which means that one would have been missed in the intraoperative localisation process; 31 nodes (89%) were clearly visualised in the gamma camera images; only 27 (77%) were blue-stained by vital dye; a mere 8 lymph nodes (23%) were enlarged and therefore easily detectable by palpation. Data obtained from the harmless application of the sentinel node concept are useful for the radiopharmaceutist. The sentinel lymph node concept is well applicable in the veterinary clinic. (author)

  17. 5-Hydroxytryptamine 4 Receptor in the Endothelial Cells

    DEFF Research Database (Denmark)

    Profirovic, Jasmina; Vardya, Irina; Voyno-Yasenetskaya, Tatyana

    2006-01-01

    39 5-HYDROXYTRYPTAMINE 4 RECEPTOR IN THE ENDOTHELIAL CELLS. J. Profirovic, I. Vardya, T. Voyno-Yasenetskaya, Department of Pharmacology, University of Illinois at Chicago, Chicago, IL. Serotonin (5-hydroxytryptamine [5-HT]) is an important neurotransmitter that regulates multiple events in the ce......39 5-HYDROXYTRYPTAMINE 4 RECEPTOR IN THE ENDOTHELIAL CELLS. J. Profirovic, I. Vardya, T. Voyno-Yasenetskaya, Department of Pharmacology, University of Illinois at Chicago, Chicago, IL. Serotonin (5-hydroxytryptamine [5-HT]) is an important neurotransmitter that regulates multiple events...... gap formation in HUVECs. We are currently investigating the mechanism underlying 5-HT4 receptor-induced actin cytoskeleton changes in the endothelial cells. These data suggest that by activating 5-HT4 receptor, serotonin could be involved in regulation of actin cytoskeleton dynamics in the endothelial...

  18. Endothelial Function in Migraine With Aura – A Systematic Review

    DEFF Research Database (Denmark)

    Butt, Jawad H; Franzmann, Ulriche; Kruuse, Christina

    2015-01-01

    in migraineurs, and several studies on endothelial markers in the areas of inflammation, oxidative stress, and coagulation found increased endothelial activation in migraineurs, particularly in MA. One study, assessing cerebral endothelial function using transcranial Doppler sonography, reported lower...

  19. The complex network reliability and influential nodes

    Science.gov (United States)

    Li, Kai; He, Yongfeng

    2017-08-01

    In order to study the complex network node important degree and reliability, considering semi-local centrality, betweenness centrality and PageRank algorithm, through the simulation method to gradually remove nodes and recalculate the importance in the random network, small world network and scale-free network. Study the relationship between the largest connected component and node removed proportion, the research results show that betweenness centrality and PageRank algorithm based on the global information network are more effective for evaluating the importance of nodes, and the reliability of the network is related to the network topology.

  20. [The sequential use of local vacuum magnetotherapy and papaverine electrophoresis with sinusoidal modulated currents in impotence].

    Science.gov (United States)

    Karpukhin, I V; Bogomol'nyĭ, V A

    1997-01-01

    105 patients with chronic nonspecific prostatitis were examined and treated with papaverin electrophoresis using sinusoidal modulated currents (SMC) and local vacuum magnetotherapy (LVMT). Papaverin SMC electrophoresis and LVMT stimulated cavernous circulation. The highest stimulation was achieved at successive use of LVMT and the electrophoresis. LVMT followed by the electrophoresis maintained good cavernous circulation for 5-6 hours after the procedure in the course of which several spontaneous erections were observed.

  1. Sinusoidal oscillators with lower gain requirements at higher frequencies based on an explicit tanh(x) nonlinearity

    KAUST Repository

    Elwakil, Ahmed S.

    2009-04-28

    Two novel sinusoidal oscillator structures with an explicit tanh(x) nonlinearity are proposed. The oscillators have the attractive feature: the higher the operating frequency, the lower the necessary gain required to start oscillations. A nonlinear model for the two oscillators is derived and verified numerically. Spice simulations using AMS BiCMOS 0.35 μ model parameters and experimental results are shown. Copyright © 2009 John Wiley & Sons, Ltd.

  2. Response of resonant gravitational wave detectors to damped sinusoid signals

    International Nuclear Information System (INIS)

    Pai, A; Celsi, C; Pallottino, G V; D'Antonio, S; Astone, P

    2007-01-01

    Till date, the search for burst signals with resonant gravitational wave (GW) detectors has been done using the δ-function approximation for the signal, which was reasonable due to the very small bandwidth of these detectors. However, now with increased bandwidth (of the order of 10 or more Hz) and with the possibility of comparing results with interferometric GW detectors (broad-band), it is very important to exploit the resonant detectors' capability to detect also signals with specific wave shapes. As a first step, we present a study of the response of resonant GW detectors to damped sinusoids with given frequency and decay time and report on the development of a filter matched to these signals. This study is a preliminary step towards the comprehension of the detector response and of the filtering for signals such as the excitation of stellar quasi-normal modes

  3. Real-time detection of musical onsets with linear prediction and sinusoidal modeling

    Science.gov (United States)

    Glover, John; Lazzarini, Victor; Timoney, Joseph

    2011-12-01

    Real-time musical note onset detection plays a vital role in many audio analysis processes, such as score following, beat detection and various sound synthesis by analysis methods. This article provides a review of some of the most commonly used techniques for real-time onset detection. We suggest ways to improve these techniques by incorporating linear prediction as well as presenting a novel algorithm for real-time onset detection using sinusoidal modelling. We provide comprehensive results for both the detection accuracy and the computational performance of all of the described techniques, evaluated using Modal, our new open source library for musical onset detection, which comes with a free database of samples with hand-labelled note onsets.

  4. Sensitivity of echo enabled harmonic generation to sinusoidal electron beam energy structure

    Directory of Open Access Journals (Sweden)

    E. Hemsing

    2017-06-01

    Full Text Available We analytically examine the bunching factor spectrum of a relativistic electron beam with sinusoidal energy structure that then undergoes an echo-enabled harmonic generation (EEHG transformation to produce high harmonics. The performance is found to be described primarily by a simple scaling parameter. The dependence of the bunching amplitude on fluctuations of critical parameters is derived analytically, and compared with simulations. Where applicable, EEHG is also compared with high gain harmonic generation (HGHG and we find that EEHG is generally less sensitive to several types of energy structure. In the presence of intermediate frequency modulations like those produced by the microbunching instability, EEHG has a substantially narrower intrinsic bunching pedestal.

  5. Broadband Control of Topological Nodes in Electromagnetic Fields

    Science.gov (United States)

    Song, Alex Y.; Catrysse, Peter B.; Fan, Shanhui

    2018-05-01

    We study topological nodes (phase singularities) in electromagnetic wave interactions with structures. We show that, when the nodes exist, it is possible to bind certain nodes to a specific plane in the structure by a combination of mirror and time-reversal symmetry. Such binding does not rely on any resonances in the structure. As a result, the nodes persist on the plane over a wide wavelength range. As an implication of such broadband binding, we demonstrate that the topological nodes can be used for hiding of metallic objects over a broad wavelength range.

  6. The Influence of Total Nodes Examined, Number of Positive Nodes, and Lymph Node Ratio on Survival After Surgical Resection and Adjuvant Chemoradiation for Pancreatic Cancer: A Secondary Analysis of RTOG 9704

    Energy Technology Data Exchange (ETDEWEB)

    Showalter, Timothy N. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Winter, Kathryn A. [Radiation Therapy Oncology Group, RTOG Statistical Center, Philadelphia, PA (United States); Berger, Adam C., E-mail: adam.berger@jefferson.edu [Department of Surgery, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Safran, Howard [Department of Medicine, Miriam Hospital, Brown University Oncology Group, Providence, RI (United States); Hoffman, John P. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA (United States); Benson, Al B. [Division of Hematology-Oncology, Northwestern University, Chicago, IL (United States); MacDonald, John S. [St. Vincent' s Cancer Care Center, New York, NY (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

    2011-12-01

    Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors-number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)-on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluate associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.

  7. Exact solution of unsteady flow generated by sinusoidal pressure gradient in a capillary tube

    Directory of Open Access Journals (Sweden)

    M. Abdulhameed

    2015-12-01

    Full Text Available In this paper, the mathematical modeling of unsteady second grade fluid in a capillary tube with sinusoidal pressure gradient is developed with non-homogenous boundary conditions. Exact analytical solutions for the velocity profiles have been obtained in explicit forms. These solutions are written as the sum of the steady and transient solutions for small and large times. For growing times, the starting solution reduces to the well-known periodic solution that coincides with the corresponding solution of a Newtonian fluid. Graphs representing the solutions are discussed.

  8. The influence of biomaterials on endothelial cell thrombogenicity

    Science.gov (United States)

    McGuigan, Alison P.; Sefton, Michael V.

    2007-01-01

    Driven by tissue engineering and regenerative medicine, endothelial cells are being used in combination with biomaterials in a number of applications for the purpose of improving blood compatibility and host integration. Endothelialized vascular grafts are beginning to be used clinically with some success in some centers, while endothelial seeding is being explored as a means of creating a vasculature within engineered tissues. The underlying assumption of this strategy is that when cultured on artificial biomaterials, a confluent layer of endothelial cells maintain their non-thrombogenic phenotype. In this review the existing knowledge base of endothelial cell thrombogenicity cultured on a number of different biomaterials is summarized. The importance of selecting appropriate endpoint measures that are most reflective of overall surface thrombogenicity is the focus of this review. Endothelial cells inhibit thrombosis through three interconnected regulatory systems (1) the coagulation cascade (2) the cellular components of the blood such as leukocytes and platelets and (3) the complement cascade, and also through effects on fibrinolysis and vascular tone, the latter which influences blood flow. Thus, in order to demonstrate the thromobgenic benefit of seeding a biomaterial with EC, the conditions under which EC surfaces are more likely to exhibit lower thrombogenicity than unseeded biomaterial surfaces need to be consistent with the experimental context. The endpoints selected should be appropriate for the dominant thrombotic process that occurs under the given experimental conditions. PMID:17316788

  9. Role of glutathione biosynthesis in endothelial dysfunction and fibrosis

    Directory of Open Access Journals (Sweden)

    Cristina Espinosa-Díez

    2018-04-01

    Full Text Available Glutathione (GSH biosynthesis is essential for cellular redox homeostasis and antioxidant defense. The rate-limiting step requires glutamate-cysteine ligase (GCL, which is composed of the catalytic (GCLc and the modulatory (GCLm subunits. To evaluate the contribution of GCLc to endothelial function we generated an endothelial-specific Gclc haplo-insufficient mouse model (Gclc e/+ mice. In murine lung endothelial cells (MLEC derived from these mice we observed a 50% reduction in GCLc levels compared to lung fibroblasts from the same mice. MLEC obtained from haplo-insufficient mice showed significant reduction in GSH levels as well as increased basal and stimulated ROS levels, reduced phosphorylation of eNOS (Ser 1177 and increased eNOS S-glutathionylation, compared to MLEC from wild type (WT mice. Studies in mesenteric arteries demonstrated impaired endothelium-dependent vasodilation in Gclc(e/+ male mice, which was corrected by pre-incubation with GSH-ethyl-ester and BH4. To study the contribution of endothelial GSH synthesis to renal fibrosis we employed the unilateral ureteral obstruction model in WT and Gclc(e/+ mice. We observed that obstructed kidneys from Gclc(e/+ mice exhibited increased deposition of fibrotic markers and reduced Nrf2 levels. We conclude that the preservation of endothelial GSH biosynthesis is not only critical for endothelial function but also in anti-fibrotic responses. Keywords: Glutamate-cysteine ligase, ROS, Glutathione, Endothelial dysfunction, Kidney Fibrosis

  10. Insomnia and endothelial function - the HUNT 3 fitness study.

    Directory of Open Access Journals (Sweden)

    Linn B Strand

    Full Text Available BACKGROUND: Insomnia is associated with increased risk of coronary heart disease (CHD, but the underlying mechanisms are not understood. To our knowledge, no previous studies have examined insomnia in relation to endothelial function, an indicator of preclinical atherosclerosis. Our aim was to assess the association of insomnia with endothelial function in a large population based study of healthy individuals. METHODS: A total of 4 739 participants free from known cardiovascular or pulmonary diseases, cancer, and sarcoidosis, and who were not using antihypertensive medication were included in the study. They reported how often they had experienced difficulties falling asleep at night, repeated awakenings during the night, early awakenings without being able to go back to sleep, and daytime sleepiness. Endothelial function was measured by flow mediated dilation (FMD derived from the brachial artery. RESULTS: We found no consistent association between the insomnia symptoms and endothelial function in multiadjusted models, but individual insomnia symptoms may be related to endothelial function. Among women who reported early awakenings, endothelial function may be lower than in women without this symptom (p = 0.03. CONCLUSIONS: This study provided no evidence that endothelial function, an early indicator of atherosclerosis, is an important linking factor between insomnia and CHD. Further studies are needed to explore the complex interrelation between sleep and cardiovascular pathology.

  11. Exact asymptotic expansion for the resistance between the center node and a node on the cobweb network boundary

    Directory of Open Access Journals (Sweden)

    R. Kenna

    2014-09-01

    Full Text Available We analyze the resistance between two nodes in a cobweb network of resistors. Based on an exact expression, we derive the asymptotic expansions for the resistance between the center node and a node on the boundary of the M x N cobweb network with resistors r and s in the two spatial directions. All coefficients in this expansion are expressed through analytical functions.

  12. Perfluorooctane sulfonate (PFOS) induces reactive oxygen species (ROS) production in human microvascular endothelial cells: role in endothelial permeability.

    Science.gov (United States)

    Qian, Yong; Ducatman, Alan; Ward, Rebecca; Leonard, Steve; Bukowski, Valerie; Lan Guo, Nancy; Shi, Xianglin; Vallyathan, Val; Castranova, Vincent

    2010-01-01

    Perfluorooctane sulfonate (PFOS) is a member of the perfluoroalkyl acids (PFAA) containing an eight-carbon backbone. PFOS is a man-made chemical with carbon-fluorine bonds that are among the strongest in organic chemistry, and PFOS is widely used in industry. Human occupational and environmental exposure to PFOS occurs globally. PFOS is non-biodegradable and is persistent in the human body and environment. In this study, data demonstrated that exposure of human microvascular endothelial cells (HMVEC) to PFOS induced the production of reactive oxygen species (ROS) at both high and low concentrations. Morphologically, it was found that exposure to PFOS induced actin filament remodeling and endothelial permeability changes in HMVEC. Furthermore, data demonstrated that the production of ROS plays a regulatory role in PFOS-induced actin filament remodeling and the increase in endothelial permeability. Our results indicate that the generation of ROS may play a role in PFOS-induced aberrations of the endothelial permeability barrier. The results generated from this study may provide a new insight into the potential adverse effects of PFOS exposure on humans at the cellular level.

  13. On node replication attack in wireless sensor networks

    International Nuclear Information System (INIS)

    Qabulio, M.; Malkani, Y.A.

    2015-01-01

    WSNs (Wireless Sensor Networks) comprise a large number of small, inexpensive, low power and memory constrained sensing devices (called sensor nodes) that are densely deployed to measure a given physical phenomenon. Since WSNs are commonly deployed in a hostile and unattended environment, it is easy for an adversary to physically capture one or more legitimate sensor nodes, re-program and redeploy them in the network. As a result, the adversary becomes able to deploy several identical copies of physically captured nodes in the network in order to perform illegitimate activities. This type of attack is referred to as Node Replication Attack or Clone Node Attack. By launching node replication attack, an adversary can easily get control on the network which consequently is the biggest threat to confidentiality, integrity and availability of data and services. Thus, detection and prevention of node replication attack in WSNs has become an active area of research and to date more than two dozen schemes have been proposed, which address this issue. In this paper, we present a comprehensive review, classification and comparative analysis of twenty five of these schemes which help to detect and/or prevent node replication attack in WSNs. (author)

  14. On Node Replication Attack in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Mumtaz Qabulio

    2016-04-01

    Full Text Available WSNs (Wireless Sensor Networks comprise a large number of small, inexpensive, low power and memory constrained sensing devices (called sensor nodes that are densely deployed to measure a given physical phenomenon. Since WSNs are commonly deployed in a hostile and unattended environment, it is easy for an adversary to physically capture one or more legitimate sensor nodes, re-program and redeploy them in the network. As a result, the adversary becomes able to deploy several identical copies of physically captured nodes in the network in order to perform illegitimate activities. This type of attack is referred to as Node Replication Attack or Clone Node Attack. By launching node replication attack, an adversary can easily get control on the network which consequently is the biggest threat to confidentiality, integrity and availability of data and services. Thus, detection and prevention of node replication attack in WSNs has become an active area of research and to date more than two dozen schemes have been proposed, which address this issue. In this paper, we present a comprehensive review, classification and comparative analysis of twenty five of these schemes which help to detect and/or prevent node replication attack in WSNs

  15. Hydrogen sulfide metabolism regulates endothelial solute barrier function

    Directory of Open Access Journals (Sweden)

    Shuai Yuan

    2016-10-01

    Full Text Available Hydrogen sulfide (H2S is an important gaseous signaling molecule in the cardiovascular system. In addition to free H2S, H2S can be oxidized to polysulfide which can be biologically active. Since the impact of H2S on endothelial solute barrier function is not known, we sought to determine whether H2S and its various metabolites affect endothelial permeability. In vitro permeability was evaluated using albumin flux and transendothelial electrical resistance. Different H2S donors were used to examine the effects of exogenous H2S. To evaluate the role of endogenous H2S, mouse aortic endothelial cells (MAECs were isolated from wild type mice and mice lacking cystathionine γ-lyase (CSE, a predominant source of H2S in endothelial cells. In vivo permeability was evaluated using the Miles assay. We observed that polysulfide donors induced rapid albumin flux across endothelium. Comparatively, free sulfide donors increased permeability only with higher concentrations and at later time points. Increased solute permeability was associated with disruption of endothelial junction proteins claudin 5 and VE-cadherin, along with enhanced actin stress fiber formation. Importantly, sulfide donors that increase permeability elicited a preferential increase in polysulfide levels within endothelium. Similarly, CSE deficient MAECs showed enhanced solute barrier function along with reduced endogenous bound sulfane sulfur. CSE siRNA knockdown also enhanced endothelial junction structures with increased claudin 5 protein expression. In vivo, CSE genetic deficiency significantly blunted VEGF induced hyperpermeability revealing an important role of the enzyme for barrier function. In summary, endothelial solute permeability is critically regulated via exogenous and endogenous sulfide bioavailability with a prominent role of polysulfides.

  16. Ultrasound differentiation of benign and malignant cervical lymph nodes

    Directory of Open Access Journals (Sweden)

    Md. Mizanur Rahman

    2009-01-01

    Full Text Available This study was conducted to see whether the size (measured by maximal short axis diameter, shape (expressed in terms of ratio dividing long axis diameter of the node by short axis diameter or L/S ratio, marginal clarity (regular or irregular margin, internal echo-pattern (homogeneous hypoechoic or heterogeneous and hilar echogenicity (presence or absence of echo-genicity in hilum are good criteria for differentiating benign from malignant cervical lymph nodes using high frequency (high resolution ultrasound probe. The study was carried out from January 1998 to December 1998, among patients with enlarged cervical lymph nodes who were scanned with a high frequency (5.0 MHz curvilinear probe. Chi-Square test was done to see the statistical correlation between two groups of nodes. A p value of <0.05 was taken as significant. Out of 65 nodes studied, 26 (100% enlarged cervical nodes with short axis diameter more than 1 cm were all malignant. In contrast 31 (79.5% of 39 enlarged nodes with short axis diameter less than 1cm were benign and rest were malignant (p<0.001. Of 34 enlarged nodes with L/S ratio <2, 30 (88.2% nodes were found malignant and 4 (11.8% were benign. Among the rest 31 enlarged nodes, 27 (87.1% with L/S ratio  2 were benign while 4 (12.9% were malignant (p <0.001. Among the 39 nodes with regular margin 28 (71.8% were found benign, where as among 26 nodes with irregular margin 23 (88.5% were malignant (p <0.001. When the internal echopattern was taken in account, 32 nodes had homogeneous hypoechoic echo of which 28 (87.5% were benign and among 33 nodes with heterogeneous echopattern 30 (90.9% were malignant (p <0.001. Among the 43 enlarged nodes with presence of hilar echogenicity 31(72.1% were found benign and 22 (100% nodes with no hilar echogenicity were all malignant (p <0.001. Such findings suggest that real time high resolution ultrasound might assist in differentiation of benign and malignant enlarged cervical lymph nodes

  17. Number of evaluated lymph nodes and positive lymph nodes, lymph node ratio, and log odds evaluation in early-stage pancreatic ductal adenocarcinoma: numerology or valid indicators of patient outcome?

    Science.gov (United States)

    Lahat, G; Lubezky, N; Gerstenhaber, F; Nizri, E; Gysi, M; Rozenek, M; Goichman, Y; Nachmany, I; Nakache, R; Wolf, I; Klausner, J M

    2016-09-29

    We evaluated the prognostic significance and universal validity of the total number of evaluated lymph nodes (ELN), number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in a relatively large and homogenous cohort of surgically treated pancreatic ductal adenocarcinoma (PDAC) patients. Prospectively accrued data were retrospectively analyzed for 282 PDAC patients who had pancreaticoduodenectomy (PD) at our institution. Long-term survival was analyzed according to the ELN, PLN, LNR, and LODDS. Of these patients, 168 patients (59.5 %) had LN metastasis (N1). Mean ELN and PLN were 13.5 and 1.6, respectively. LN positivity correlated with a greater number of evaluated lymph nodes; positive lymph nodes were identified in 61.4 % of the patients with ELN ≥ 13 compared with 44.9 % of the patients with ELN < 13 (p = 0.014). Median overall survival (OS) and 5-year OS rate were higher in N0 than in N1 patients, 22.4 vs. 18.7 months and 35 vs. 11 %, respectively (p = 0.008). Mean LNR was 0.12; 91 patients (54.1 %) had LNR < 0.3. Among the N1 patients, median OS was comparable in those with LNR ≥ 0.3 vs. LNR < 0.3 (16.7 vs. 14.1 months, p = 0.950). Neither LODDS nor various ELN and PLN cutoff values provided more discriminative information within the group of N1 patients. Our data confirms that lymph node positivity strongly reflects PDAC biology and thus patient outcome. While a higher number of evaluated lymph nodes may provide a more accurate nodal staging, it does not have any prognostic value among N1 patients. Similarly, PLN, LNR, and LODDS had limited prognostic relevance.

  18. Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals.

    Science.gov (United States)

    Choi, Eun-Yong; Lee, Hansongyi; Woo, Jong Shin; Jang, Hyun Hee; Hwang, Seung Joon; Kim, Hyun Soo; Kim, Woo-Sik; Kim, Young-Seol; Choue, Ryowon; Cha, Yong-Jun; Yim, Jung-Eun; Kim, Weon

    2015-09-01

    Acute or chronic intake of polyphenol-rich foods has been reported to improve endothelial function. Quercetin, found abundantly in onion, is a potent antioxidant flavonoid. The aim of this study was to investigate whether consumption of onion peel extract (OPE) improves endothelial function in healthy overweight and obese individuals. This was a randomized double-blind, placebo-controlled study. Seventy-two healthy overweight and obese participants were randomly assigned to receive a red, soft capsule of OPE (100 mg quercetin/d, 50 mg quercetin twice daily; n = 36 participants) or an identical placebo capsule (n = 36) for 12 wk. Endothelial function, defined by flow-mediated dilation (FMD), circulating endothelial progenitor cells (EPCs) by flow cytometry, and laboratory test were determined at baseline and after treatment. Baseline characteristics and laboratory findings did not significantly differ between the two groups. Compared with baseline values, the OPE group showed significantly improved FMD at 12 wk (from 12.5 ± 5.2 to 15.2 ± 6.1; P = 0.002), whereas the placebo group showed no difference. Nitroglycerin-mediated dilation did not change in either group. EPC counts (44.2 ± 25.6 versus 52.3 ± 18.6; P = 0.005) and the percentage of EPCs were significantly increased in the OPE group. When FMD was divided into quartiles, rate of patients with endothelial dysfunction defined as lowest quartile (cutoff value, 8.6%) of FMD improved from 26% to 9% by OPE. Medium-term administration of OPE an improvement in FMD and circulating EPCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Isothermal sinusoidal analysis of balanced compound Vuilleumier heat pumps

    International Nuclear Information System (INIS)

    Finkelstein, T.

    1992-01-01

    This paper reports on Vuilleumier heat pumps with balanced compounding which have been under investigation for about fifteen years but have not yet reached the stage of commercial utilization. Previously published analytical treatment based upon isothermal treatment of the variable-volume spaces resulted in closed form solution of considerable complexity of the coupled differential equations but applied only to free piston machines. In contrast, the procedure presented here is based on previously demonstrated sinusoidal excursions of the reciprocators. It is of the same order of accuracy, but much more simple and usable. It was found that there is only negligible difference between the results of the present and the previous approach. Additionally, the treatment presented here is applicable to kinematic machines, as well as to free piston machines. For the latter design, an equation for the natural frequency is also derived. Ideal proportions and practical expressions for the energy streams are derived. Gas forces are plotted versus displacement and it is shown that they are equivalent to a linear spring, which is of importance for the concept of a free-piston design

  20. The 3-D alignment of objects in dynamic PET scans using filtered sinusoidal trajectories of sinogram

    International Nuclear Information System (INIS)

    Kostopoulos, Aristotelis E.; Happonen, Antti P.; Ruotsalainen, Ulla

    2006-01-01

    In this study, our goal is to employ a novel 3-D alignment method for dynamic positron emission tomography (PET) scans. Because the acquired data (i.e. sinograms) often contain noise considerably, filtering of the data prior to the alignment presumably improves the final results. In this study, we utilized a novel 3-D stackgram domain approach. In the stackgram domain, the signals along the sinusoidal trajectory signals of the sinogram can be processed separately. In this work, we performed angular stackgram domain filtering by employing well known 1-D filters: the Gaussian low-pass filter and the median filter. In addition, we employed two wavelet de-noising techniques. After filtering we performed alignment of objects in the stackgram domain. The local alignment technique we used is based on similarity comparisons between locus vectors (i.e. the signals along the sinusoidal trajectories of the sinogram) in a 3-D neighborhood of sequences of the stackgrams. Aligned stackgrams can be transformed back to sinograms (Method 1), or alternatively directly to filtered back-projected images (Method 2). In order to evaluate the alignment process, simulated data with different kinds of additive noises were used. The results indicated that the filtering prior to the alignment can be important concerning the accuracy

  1. Sentinel lymph node biopsy is indicated for patients with thick clinically lymph node-negative melanoma.

    Science.gov (United States)

    Yamamoto, Maki; Fisher, Kate J; Wong, Joyce Y; Koscso, Jonathan M; Konstantinovic, Monique A; Govsyeyev, Nicholas; Messina, Jane L; Sarnaik, Amod A; Cruse, C Wayne; Gonzalez, Ricardo J; Sondak, Vernon K; Zager, Jonathan S

    2015-05-15

    Sentinel lymph node biopsy (SLNB) is indicated for the staging of clinically lymph node-negative melanoma of intermediate thickness, but its use is controversial in patients with thick melanoma. From 2002 to 2012, patients with melanoma measuring ≥4 mm in thickness were evaluated at a single institution. Associations between survival and clinicopathologic characteristics were explored. Of 571 patients with melanomas measuring ≥4 mm in thickness and no distant metastases, the median age was 66 years and 401 patients (70.2%) were male. The median Breslow thickness was 6.2 mm; the predominant subtype was nodular (45.4%). SLNB was performed in 412 patients (72%) whereas 46 patients (8.1%) presented with clinically lymph node-positive disease and 113 patients (20%) did not undergo SLNB. A positive SLN was found in 161 of 412 patients (39.1%). For SLNB performed at the study institution, 14 patients with a negative SLNB developed disease recurrence in the mapped lymph node basin (false-negative rate, 12.3%). The median disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) for the entire cohort were 62.1 months, 42.5 months, and 21.2 months, respectively. The DSS and OS for patients with a negative SLNB were 82.4 months and 53.4 months, respectively; 41.2 months and 34.7 months, respectively, for patients with positive SLNB; and 26.8 months and 22 months, respectively, for patients with clinically lymph node-positive disease (Pthick melanoma and a negative SLNB appear to have significantly prolonged RFS, DSS, and OS compared with those with a positive SLNB. Therefore, SLNB should be considered as indicated for patients with thick, clinically lymph node-negative melanoma. © 2015 American Cancer Society.

  2. Axillary Lymph Nodes and Breast Cancer

    Science.gov (United States)

    ... white blood cells that help fight illness. If breast cancer spreads, the lymph nodes in the underarm (called ... if they contain cancer cells. This helps determine breast cancer stage and guide treatment. Sentinel node biopsy and ...

  3. The generation of random directed networks with prescribed 1-node and 2-node degree correlations

    International Nuclear Information System (INIS)

    Zamora-Lopez, Gorka; Kurths, Juergen; Zhou Changsong; Zlatic, Vinko

    2008-01-01

    The generation of random networks is a very common problem in complex network research. In this paper, we have studied the correlation nature of several real networks and found that, typically, a large number of links are deterministic, i.e. they cannot be randomized. This finding permits fast generation of ensembles of maximally random networks with prescribed 1-node and 2-node degree correlations. When the introduction of self-loops or multiple-links are not desired, random network generation methods typically reach blocked states. Here, a mechanism is proposed, the 'force-and-drop' method, to overcome such states. Our algorithm can be easily simplified for undirected graphs and reduced to account for any subclass of 2-node degree correlations

  4. Differential Effects of Leptin and Adiponectin in Endothelial Angiogenesis

    Directory of Open Access Journals (Sweden)

    Raghu Adya

    2015-01-01

    Full Text Available Obesity is a major health burden with an increased risk of cardiovascular morbidity and mortality. Endothelial dysfunction is pivotal to the development of cardiovascular disease (CVD. In relation to this, adipose tissue secreted factors termed “adipokines” have been reported to modulate endothelial dysfunction. In this review, we focus on two of the most abundant circulating adipokines, that is, leptin and adiponectin, in the development of endothelial dysfunction. Leptin has been documented to influence a multitude of organ systems, that is, central nervous system (appetite regulation, satiety factor and cardiovascular system (endothelial dysfunction leading to atherosclerosis. Adiponectin, circulating at a much higher concentration, exists in different molecular weight forms, essentially made up of the collagenous fraction and a globular domain, the latter being investigated minimally for its involvement in proinflammatory processes including activation of NF-κβ and endothelial adhesion molecules. The opposing actions of the two forms of adiponectin in endothelial cells have been recently demonstrated. Additionally, a local and systemic change to multimeric forms of adiponectin has gained importance. Thus detailed investigations on the potential interplay between these adipokines would likely result in better understanding of the missing links connecting CVD, adipokines, and obesity.

  5. Osteoblastic and Vascular Endothelial Niches, Their Control on Normal Hematopoietic Stem Cells, and Their Consequences on the Development of Leukemia

    Directory of Open Access Journals (Sweden)

    Bella S. Guerrouahen

    2011-01-01

    Full Text Available Stem cell self-renewal is regulated by intrinsic mechanisms and extrinsic signals mediated via specialized microenvironments called “niches.” The best-characterized stem cell is the hematopoietic stem cell (HSC. Self-renewal and differentiation ability of HSC are regulated by two major elements: endosteal and vascular regulatory elements. The osteoblastic niche localized at the inner surface of the bone cavity might serve as a reservoir for long-term HSC storage in a quiescent state. Whereas the vascular niche, which consists of sinusoidal endothelial cell lining blood vessel, provides an environment for short-term HSC proliferation and differentiation. Both niches act together to maintain hematopoietic homeostasis. In this paper, we provide some principles applying to the hematopoietic niches, which will be useful in the study and understanding of other stem cell niches. We will discuss altered microenvironment signaling leading to myeloid lineage disease. And finally, we will review some data on the development of acute myeloid leukemia from a subpopulation called leukemia-initiating cells (LIC, and we will discuss on the emerging evidences supporting the influence of the microenvironment on chemotherapy resistance.

  6. Detection of sentinel nodes with radiopharmaceuticals

    International Nuclear Information System (INIS)

    Yokoyama, Kunihiko; Michigishi, Takatoshi; Kinuya, Seigo; Konishi, Shota; Nakajima, Kenichi; Tonami, Norihisa

    2000-01-01

    Sentinel lymph nodes have been found to be an indicator of lymph node metastasis in breast cancer. In Japan, the theory and concept of sentinel lymph nodes in breast cancer have begun to be applied to carcinomas of the digestive system. Based on clinical experience in the detection of sentinel lymph nodes with radiopharmaceuticals, differences and similarities between the radiopharmaceuticals, methods, and techniques used to detect sentinel lymph nodes have been assessed in relation to breast cancer and carcinomas of the digestive system (including carcinomas of the esophagus and large intestine). The greatest difference between the methods used for breast and digestive cancers is the site of administration of the radiopharmaceutical. In breast cancer, the radiopharmaceutical is administered into a superficial organ (i.e., the mammary gland), whereas in carcinomas of the digestive system, it is administered into a deep organ (i.e., digestive tract). Another obvious difference is in lymph flow, i.e., the flow of the mammary glands is subcutaneous whereas lymph flow in the digestive tract is submucosal. Two radionuclide diagnostic methods are available to detect sentinel lymph nodes: sentinel lymphoscintigraphy with a gamma camera and a method that involves the use of a gamma probe intraoperatively. Radiopharmaceuticals used to detect sentinel lymph nodes must be smoothly transferred from the site of administration into the lymph, and uptake by the sentinel lymph node must continue for a long time without excessive flowing to lower reaches. The optimal particle size remains a matter of controversy, and no radiopharmaceuticals appropriate for lymphoscintigraphy have ever been approved in Japan. The authors compared the pharmacokinetics of three different radiopharmaceuticals used for sentinel lymphoscintigraphy in breast cancer ( 99m Tc-labeled albumin, 99m Tc-labeled tin colloid, and 99m Tc-labeled phytic acid) and founded that the detection rate was lowest with

  7. Localizing and placement of network node functions in a network

    NARCIS (Netherlands)

    Strijkers, R.J.; Meulenhoff, P.J.

    2014-01-01

    The invention enables placement and use of a network node function in a second network node instead of using the network node function in a first network node. The network node function is e.g. a server function or a router function. The second network node is typically located in or close to the

  8. [Radiotherapy in node-positive prostate cancer].

    Science.gov (United States)

    Bottke, D; Bartkowiak, D; Bolenz, C; Wiegel, T

    2016-03-01

    There are numerous randomized trials to guide the management of patients with localized (and metastatic) prostate cancer, but only a few (mostly retrospective) studies have specifically addressed node-positive patients. Therefore, there is uncertainty regarding optimal treatment in this situation. Current guidelines recommend long-term androgen deprivation therapy (ADT) alone or radiotherapy plus long-term ADT as treatment options. This overview summarizes the existing literature on the use of radiotherapy for node-positive prostate cancer as definitive treatment and as adjuvant or salvage therapy after radical prostatectomy. In this context, we also discuss several PET tracers in the imaging evaluation of patients with biochemical recurrence of prostate cancer after radical prostatectomy. As for definitive treatment, retrospective studies suggest that ADT plus radiotherapy improves overall survival compared with ADT alone. These studies also consistently demonstrated that many patients with node-positive prostate cancer can achieve long-term survival - and are likely curable - with aggressive therapy. The beneficial impact of adjuvant radiotherapy on survival in patients with pN1 prostate cancer seems to be highly influenced by tumor characteristics. Men with ≤ 2 positive lymph nodes in the presence of intermediate- to high-grade disease, or positive margins, and those with 3 or 4 positive lymph nodes are the ideal candidates for adjuvant radiotherapy (plus long-term ADT) after surgery. There is a need for randomized trials to further examine the potential role of radiotherapy as either definitive or adjuvant treatment, for patients with node-positive prostate cancer.

  9. Alcoholic liver injury: defenestration in noncirrhotic livers--a scanning electron microscopic study

    DEFF Research Database (Denmark)

    Horn, T; Christoffersen, P; Henriksen, Jens Henrik Sahl

    1987-01-01

    The fenestration of hepatic sinusoidal endothelial cells in 15 needle biopsies obtained from chronic alcoholics without cirrhosis was studied by scanning electron microscopy. As compared to nonalcoholics, a significant reduction in the number of fenestrae and porosity of the sinusoidal lining wall...... (fractional area of fenestrae) was observed in acinar Zone 3, both in biopsies with and without Zone 3 fibrosis as judged by light microscopy. A significant reduction of porosity as shown in this study may influence the blood hepatocytic exchange and contribute to the alcohol-induced liver injury....

  10. Topographic characteristics after Descemet's membrane endothelial keratoplasty and Descemet's stripping automated endothelial keratoplasty.

    Directory of Open Access Journals (Sweden)

    Takahiko Hayashi

    Full Text Available To investigate the topographic characteristics of the posterior corneal surface after Descemet's endothelial membrane keratoplasty (DMEK and Descemet's stripping automated endothelial keratoplasty (DSAEK and their effects on postoperative visual acuity.Nineteen eyes of 19 patients after DMEK, 23 eyes of 23 patients after DSAEK, and 18 eyes of 18 control subjects were retrospectively analyzed. Best spectacle-corrected visual acuity (BSCVA, aberration factors (higher-order aberrations [HOAs], spherical aberrations [SAs], and coma aberrations [Comas] at 6.0 mm were evaluated preoperatively and at 1, 3, and 6 months postoperatively. The posterior refractive pattern of the topography map was classified into 5 grades (0-5 (posterior color grade using anterior segment optical coherence tomography. Correlations between BSCVA and some factors (abbreviation factors, posterior color grade were analyzed.BSCVA was significantly better after DMEK than after DSAEK (P < 0.001. Posterior HOAs, SAs, and Comas after each type of endothelial keratoplasty were significantly greater compared to control (P < 0.01. Posterior HOAs, total/anterior/posterior SAs, and posterior color grade were significantly lower in the DMEK group than in the DSAEK group at 3 months (P < 0.024 [posterior HOAs], P = 0.047 [total SA], P < 0.001 [anterior SAs], P = 0.021 [posterior SAs], and P < 0.001 [posterior color grade] and 6 months postoperatively (P = 0.034 [posterior HOAs], P < 0.001 [total SAs], P < 0.001 [anterior SAs], P = 0.013 [posterior SAs], and P = 0.004 [posterior color grade]. BSCVA was significantly correlated with HOAs, SAs, and posterior color grade (P < 0.001 for all except anterior HOAs [P = 0.004].High posterior color grades were associated with larger aberration factors and had a negative effect on visual function after endothelial keratoplasty. Rapid improvement of visual function after DMEK may be attributed to less change at the posterior surface.

  11. Instant node package module

    CERN Document Server

    Ali, Juzer

    2013-01-01

    Get to grips with a new technology, understand what it is and what it can do for you, and then get to work with the most important features and tasks. A practical exploration of the lifecycle of creating node modules as well as learning all of the top features that npm has to offer.Intended for readers who want to create their first node.js modules. The programming paradigm of JavaScript is not covered so a foundation in these concepts would be beneficial.

  12. VE-Cadherin-Mediated Epigenetic Regulation of Endothelial Gene Expression.

    Science.gov (United States)

    Morini, Marco F; Giampietro, Costanza; Corada, Monica; Pisati, Federica; Lavarone, Elisa; Cunha, Sara I; Conze, Lei L; O'Reilly, Nicola; Joshi, Dhira; Kjaer, Svend; George, Roger; Nye, Emma; Ma, Anqi; Jin, Jian; Mitter, Richard; Lupia, Michela; Cavallaro, Ugo; Pasini, Diego; Calado, Dinis P; Dejana, Elisabetta; Taddei, Andrea

    2018-01-19

    The mechanistic foundation of vascular maturation is still largely unknown. Several human pathologies are characterized by deregulated angiogenesis and unstable blood vessels. Solid tumors, for instance, get their nourishment from newly formed structurally abnormal vessels which present wide and irregular interendothelial junctions. Expression and clustering of the main endothelial-specific adherens junction protein, VEC (vascular endothelial cadherin), upregulate genes with key roles in endothelial differentiation and stability. We aim at understanding the molecular mechanisms through which VEC triggers the expression of a set of genes involved in endothelial differentiation and vascular stabilization. We compared a VEC-null cell line with the same line reconstituted with VEC wild-type cDNA. VEC expression and clustering upregulated endothelial-specific genes with key roles in vascular stabilization including claudin-5 , vascular endothelial-protein tyrosine phosphatase ( VE-PTP ), and von Willebrand factor ( vWf ). Mechanistically, VEC exerts this effect by inhibiting polycomb protein activity on the specific gene promoters. This is achieved by preventing nuclear translocation of FoxO1 (Forkhead box protein O1) and β-catenin, which contribute to PRC2 (polycomb repressive complex-2) binding to promoter regions of claudin-5 , VE-PTP , and vWf . VEC/β-catenin complex also sequesters a core subunit of PRC2 (Ezh2 [enhancer of zeste homolog 2]) at the cell membrane, preventing its nuclear translocation. Inhibition of Ezh2/VEC association increases Ezh2 recruitment to claudin-5 , VE-PTP , and vWf promoters, causing gene downregulation. RNA sequencing comparison of VEC-null and VEC-positive cells suggested a more general role of VEC in activating endothelial genes and triggering a vascular stability-related gene expression program. In pathological angiogenesis of human ovarian carcinomas, reduced VEC expression paralleled decreased levels of claudin-5 and VE-PTP. These

  13. Node-Dependence-Based Dynamic Incentive Algorithm in Opportunistic Networks

    Directory of Open Access Journals (Sweden)

    Ruiyun Yu

    2014-01-01

    Full Text Available Opportunistic networks lack end-to-end paths between source nodes and destination nodes, so the communications are mainly carried out by the “store-carry-forward” strategy. Selfish behaviors of rejecting packet relay requests will severely worsen the network performance. Incentive is an efficient way to reduce selfish behaviors and hence improves the reliability and robustness of the networks. In this paper, we propose the node-dependence-based dynamic gaming incentive (NDI algorithm, which exploits the dynamic repeated gaming to motivate nodes relaying packets for other nodes. The NDI algorithm presents a mechanism of tolerating selfish behaviors of nodes. Reward and punishment methods are also designed based on the node dependence degree. Simulation results show that the NDI algorithm is effective in increasing the delivery ratio and decreasing average latency when there are a lot of selfish nodes in the opportunistic networks.

  14. A Statistical and Spectral Model for Representing Noisy Sounds with Short-Time Sinusoids

    Directory of Open Access Journals (Sweden)

    Myriam Desainte-Catherine

    2005-07-01

    Full Text Available We propose an original model for noise analysis, transformation, and synthesis: the CNSS model. Noisy sounds are represented with short-time sinusoids whose frequencies and phases are random variables. This spectral and statistical model represents information about the spectral density of frequencies. This perceptually relevant property is modeled by three mathematical parameters that define the distribution of the frequencies. This model also represents the spectral envelope. The mathematical parameters are defined and the analysis algorithms to extract these parameters from sounds are introduced. Then algorithms for generating sounds from the parameters of the model are presented. Applications of this model include tools for composers, psychoacoustic experiments, and pedagogy.

  15. Sentinel node detection in pre-operative axillary staging.

    Science.gov (United States)

    Trifirò, Giuseppe; Viale, Giuseppe; Gentilini, Oreste; Travaini, Laura Lavinia; Paganelli, Giovanni

    2004-06-01

    The concept of sentinel lymph node biopsy in breast cancer surgery is based on the fact that the tumour drains in a logical way via the lymphatic system, from the first to upper levels. Since axillary node dissection does not improve the prognosis of patients with breast cancer, sentinel lymph node biopsy might replace complete axillary dissection for staging of the axilla in clinically N0 patients. Sentinel lymph node biopsy would represent a significant advantage as a minimally invasive procedure, considering that about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Subdermal or peritumoural injection of small aliquots (and very low activity) of radiotracer is preferred to intratumoural administration, and (99m)Tc-labelled colloids with most of the particles in the 100-200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. The success rate of radioguidance in localising the sentinel lymph node in breast cancer surgery is about 97% in institutions where a high number of procedures are performed, and the success rate of lymphoscintigraphy in sentinel node detection is about 100%. The sentinel lymph node should be processed for intraoperative frozen section examination in its entirety, based on conventional histopathology and, when necessary, immune staining with anti-cytokeratin antibody. Nowadays, lymphoscintigraphy is a useful procedure in patients with different clinical evidence of breast cancer.

  16. Research on centrality of urban transport network nodes

    Science.gov (United States)

    Wang, Kui; Fu, Xiufen

    2017-05-01

    Based on the actual data of urban transport in Guangzhou, 19,150 bus stations in Guangzhou (as of 2014) are selected as nodes. Based on the theory of complex network, the network model of Guangzhou urban transport is constructed. By analyzing the degree centrality index, betweenness centrality index and closeness centrality index of nodes in the network, the level of centrality of each node in the network is studied. From a different point of view to determine the hub node of Guangzhou urban transport network, corresponding to the city's key sites and major transfer sites. The reliability of the network is determined by the stability of some key nodes (transport hub station). The research of network node centralization can provide a theoretical basis for the rational allocation of urban transport network sites and public transport system planning.

  17. Tumor endothelial markers define novel subsets of cancer-specific circulating endothelial cells associated with antitumor efficacy

    Science.gov (United States)

    Mehran, Reza; Nilsson, Monique; Khajavi, Mehrdad; Du, Zhiqiang; Cascone, Tina; Wu, Hua Kang; Cortes, Andrea; Xu, Li; Zurita, Amado; Schier, Robert; Riedel, Bernhard; El-Zein, Randa; Heymach, John V.

    2014-01-01

    Circulating endothelial cells (CEC) are derived from multiple sources including bone marrow (circulating endothelial progenitors [CEP]) and established vasculature (mature CEC). Although CEC have shown promise as a biomarker for cancer patients, their utility has been limited in part by the lack of specificity for tumor vasculature and the different non-malignant causes that can impact CEC. Tumor endothelial markers (TEM) are antigens enriched in tumor vs non-malignant endothelia. We hypothesized that TEMs may be detectable on CEC and that these circulating TEM+ endothelial cells (CTEC) may be a more specific marker for cancer and tumor response than standard CEC. We found that tumor-bearing mice had a relative increase in numbers of circulating CTEC, specifically with increased levels of TEM7 and TEM8 expression. Following treatment with various vascular targeting agents, we observed a decrease in CTEC that correlated with the reductions in tumor growth. We extended these findings to human clinical samples and observed that CTEC were present in esophageal cancer and non-small cell lung cancer (NSCLC) patients (N=40) and their levels decreased after surgical resection. These results demonstrate that CTEC are detectable in preclinical cancer models and cancer patients. Further, they suggest that CTEC offer a novel cancer-associated marker that may be useful as a blood-based surrogate for assessing the presence of tumor vasculature and antiangiogenic drug activity. PMID:24626092

  18. MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction

    Directory of Open Access Journals (Sweden)

    Maskomani Silambarasan

    2016-04-01

    Full Text Available Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. Under hyperglycemic conditions, the endothelial cells become dysfunctional. In this study, we investigated the miRNA expression changes in human umbilical vein endothelial cells exposed to different glucose concentrations (5, 10, 25 and 40 mM glucose and at various time intervals (6, 12, 24 and 48 h. miRNA microarray analyses showed that there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico pathways analyses on the altered miRNA expression showed that the majority of the affected biological pathways appeared to be associated to endothelial cell dysfunction and apoptosis. We found the expression of ten miRNAs (miR-26a-5p, -26b-5p, 29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -140-5p, -192-5p, -221-3p and -320a to increase gradually with increasing concentration of glucose. These miRNAs were also found to be involved in endothelial dysfunction. At least seven of them, miR-29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -221-3p, -320a and -192-5p, can be correlated to endothelial cell apoptosis.

  19. Mesenchymal Stem/Multipotent Stromal Cells from Human Decidua Basalis Reduce Endothelial Cell Activation.

    Science.gov (United States)

    Alshabibi, Manal A; Al Huqail, Al Joharah; Khatlani, Tanvir; Abomaray, Fawaz M; Alaskar, Ahmed S; Alawad, Abdullah O; Kalionis, Bill; Abumaree, Mohamed Hassan

    2017-09-15

    Recently, we reported the isolation and characterization of mesenchymal stem cells from the decidua basalis of human placenta (DBMSCs). These cells express a unique combination of molecules involved in many important cellular functions, which make them good candidates for cell-based therapies. The endothelium is a highly specialized, metabolically active interface between blood and the underlying tissues. Inflammatory factors stimulate the endothelium to undergo a change to a proinflammatory and procoagulant state (ie, endothelial cell activation). An initial response to endothelial cell activation is monocyte adhesion. Activation typically involves increased proliferation and enhanced expression of adhesion and inflammatory markers by endothelial cells. Sustained endothelial cell activation leads to a type of damage to the body associated with inflammatory diseases, such as atherosclerosis. In this study, we examined the ability of DBMSCs to protect endothelial cells from activation through monocyte adhesion, by modulating endothelial proliferation, migration, adhesion, and inflammatory marker expression. Endothelial cells were cocultured with DBMSCs, monocytes, monocyte-pretreated with DBMSCs and DBMSC-pretreated with monocytes were also evaluated. Monocyte adhesion to endothelial cells was examined following treatment with DBMSCs. Expression of endothelial cell adhesion and inflammatory markers was also analyzed. The interaction between DBMSCs and monocytes reduced endothelial cell proliferation and monocyte adhesion to endothelial cells. In contrast, endothelial cell migration increased in response to DBMSCs and monocytes. Endothelial cell expression of adhesion and inflammatory molecules was reduced by DBMSCs and DBMSC-pretreated with monocytes. The mechanism of reduced endothelial proliferation involved enhanced phosphorylation of the tumor suppressor protein p53. Our study shows for the first time that DBMSCs protect endothelial cells from activation by

  20. Data driven CAN node reliability assessment for manufacturing system

    Science.gov (United States)

    Zhang, Leiming; Yuan, Yong; Lei, Yong

    2017-01-01

    The reliability of the Controller Area Network(CAN) is critical to the performance and safety of the system. However, direct bus-off time assessment tools are lacking in practice due to inaccessibility of the node information and the complexity of the node interactions upon errors. In order to measure the mean time to bus-off(MTTB) of all the nodes, a novel data driven node bus-off time assessment method for CAN network is proposed by directly using network error information. First, the corresponding network error event sequence for each node is constructed using multiple-layer network error information. Then, the generalized zero inflated Poisson process(GZIP) model is established for each node based on the error event sequence. Finally, the stochastic model is constructed to predict the MTTB of the node. The accelerated case studies with different error injection rates are conducted on a laboratory network to demonstrate the proposed method, where the network errors are generated by a computer controlled error injection system. Experiment results show that the MTTB of nodes predicted by the proposed method agree well with observations in the case studies. The proposed data driven node time to bus-off assessment method for CAN networks can successfully predict the MTTB of nodes by directly using network error event data.

  1. Insulin resistance in vascular endothelial cells promotes intestinal tumour formation

    DEFF Research Database (Denmark)

    Wang, X; Häring, M-F; Rathjen, Thomas

    2017-01-01

    in vascular endothelial cells. Strikingly, these mice had 42% more intestinal tumours than controls, no change in tumour angiogenesis, but increased expression of vascular cell adhesion molecule-1 (VCAM-1) in primary culture of tumour endothelial cells. Insulin decreased VCAM-1 expression and leukocyte...... adhesion in quiescent tumour endothelial cells with intact insulin receptors and partly prevented increases in VCAM-1 and leukocyte adhesion after treatment with tumour necrosis factor-α. Knockout of insulin receptors in endothelial cells also increased leukocyte adhesion in mesenteric venules...

  2. Importance of Metastatic Lymph Node Ratio in Non-Metastatic, Lymph Node-Invaded Colon Cancer: A Clinical Trial

    Science.gov (United States)

    Isik, Arda; Peker, Kemal; Firat, Deniz; Yilmaz, Bahri; Sayar, Ilyas; Idiz, Oguz; Cakir, Coskun; Demiryilmaz, Ismail; Yilmaz, Ismayil

    2014-01-01

    Background The aim of this study was to evaluate the prognostic importance of the metastatic lymph node ratio for stage III colon cancer patients and to find a cut-off value at which the overall survival and disease-free survival change. Material/Methods Patients with pathological stage III colon cancer were retrospectively evaluated for: age; preoperative values of Crp, Cea, Ca 19-9, and Afp; pathologic situation of vascular, perineural, lymphatic, and serosal involvement; and metastatic lymph node ratio values were calculated. Results The study included 58 stage III colon cancer patients: 20 (34.5%) females and 38 (65.5%) males were involved in the study. Multivariate analysis was applied to the following variables to evaluate significance for overall survival and disease-free survival: age, Crp, Cea, perineural invasion, and metastatic lymph node ratio. The metastatic lymph node ratio (<0.25 or ≥0.25) is the only independent variable significant for overall and disease-free survival. Conclusions Metastatic lymph node ratio is an ideal prognostic marker for stage III colon cancer patients, and 0.25 is the cut-off value for prognosis. PMID:25087904

  3. Functional and gene expression analysis of hTERT overexpressed endothelial cells

    Directory of Open Access Journals (Sweden)

    Haruna Takano

    2008-09-01

    Full Text Available Haruna Takano1, Satoshi Murasawa1,2, Takayuki Asahara1,2,31Institute of Biomedical Research and Innovation, Kobe, Japan; 2RIKEN Center for Developmental Biology, Kobe 650-0047, Japan; 3Tokai University of School of Medicine, Tokai, JapanAbstract: Telomerase dysfunction contributes to cellular senescence. Recent advances indicate the importance of senescence in maintaining vascular cell function in vitro. Human telomerase reverse transcriptase (hTERT overexpression is thought to lead to resistance to apoptosis and oxidative stress. However, the mechanism in endothelial lineage cells is unclear. We tried to generate an immortal endothelial cell line from human umbilical vein endothelial cells using a no-virus system and examine the functional mechanisms of hTERT overexpressed endothelial cell senescence in vitro. High levels of hTERT genes and endothelial cell-specific markers were expressed during long-term culture. Also, angiogenic responses were observed in hTERT overexpressed endothelial cell. These cells showed a delay in senescence and appeared more resistant to stressed conditions. PI3K/Akt-related gene levels were enhanced in hTERT overexpressed endothelial cells. An up-regulated PI3K/Akt pathway caused by hTERT overexpression might contribute to anti-apoptosis and survival effects in endothelial lineage cells.Keywords: endothelial, telomerase, senescence, oxidative stress, anti-apoptosis, PI3K/Akt pathway

  4. Dynamical Systems Approach to Endothelial Heterogeneity

    Science.gov (United States)

    Regan, Erzsébet Ravasz; Aird, William C.

    2012-01-01

    Rationale Objective Here we reexamine our current understanding of the molecular basis of endothelial heterogeneity. We introduce multistability as a new explanatory framework in vascular biology. Methods We draw on the field of non-linear dynamics to propose a dynamical systems framework for modeling multistability and its derivative properties, including robustness, memory, and plasticity. Conclusions Our perspective allows for both a conceptual and quantitative description of system-level features of endothelial regulation. PMID:22723222

  5. Experimental studies of metastases of esophageal carcinoma to lymph nodes

    International Nuclear Information System (INIS)

    Inoue, Kazumasa

    1977-01-01

    Marked progress has been made in surgery for esophageal carcinoma, however, when compared to results of surgery for other carcinomas of the digestive tract, much research remains to be done. The author transplanted VX2 carcinoma, a transplantable tumor of the rabbit, to the esophagus in attempt to determine the mode of metastases of esophageal carcinoma to lymph nodes and also to observe the effect of chemotherapy (Bleomycin) and radiotherapy (Betatron). Carcinoma of the cervical esophagus metastasized to the cervical lymph nodes and then to the paratracheal lymph nodes. Carcinoma of the upper thoracic esophagus metastasized to the paratracheal lymph nodes and then to the cervical lymph nodes. Carcinoma of the mid-thoracic esophagus metastasized to the intrathoracic lymph nodes and then to the intraperitoneal lymph nodes. Carcinoma of the abdominal esophagus metastasized to the intraperitoneal lymph nodes and then to the intrathoracic lymph nodes. Skipping metastasis was rarely observed. Carcinoma of the thoracic esophagus with metastases of lymph nodes in the cervical or abdominal portion was considerably advanced, therefore it is considered that cleaning of the intrathoracic lymph nodes and simultaneous chemotherapy are required when such cases are encountered clinically. Irradiation resulted in regression in the size of the tumor and metastases to lymph nodes and there was a decrease in metastases to the distant lymph nodes. Effects of irradiation were similar on tumors and lymph nodes with positive metastases located within the field of irradiation. Bleomycin medication resulted in regression in the size of tumor and metastases to lymph nodes. Effects of Bleomycin medication were similar on tumors and lymph nodes with positive metastases. (auth.)

  6. A random network based, node attraction facilitated network evolution method

    Directory of Open Access Journals (Sweden)

    WenJun Zhang

    2016-03-01

    Full Text Available In present study, I present a method of network evolution that based on random network, and facilitated by node attraction. In this method, I assume that the initial network is a random network, or a given initial network. When a node is ready to connect, it tends to link to the node already owning the most connections, which coincides with the general rule (Barabasi and Albert, 1999 of node connecting. In addition, a node may randomly disconnect a connection i.e., the addition of connections in the network is accompanied by the pruning of some connections. The dynamics of network evolution is determined of the attraction factor Lamda of nodes, the probability of node connection, the probability of node disconnection, and the expected initial connectance. The attraction factor of nodes, the probability of node connection, and the probability of node disconnection are time and node varying. Various dynamics can be achieved by adjusting these parameters. Effects of simplified parameters on network evolution are analyzed. The changes of attraction factor Lamda can reflect various effects of the node degree on connection mechanism. Even the changes of Lamda only will generate various networks from the random to the complex. Therefore, the present algorithm can be treated as a general model for network evolution. Modeling results show that to generate a power-law type of network, the likelihood of a node attracting connections is dependent upon the power function of the node's degree with a higher-order power. Matlab codes for simplified version of the method are provided.

  7. The generation of random directed networks with prescribed 1-node and 2-node degree correlations

    Energy Technology Data Exchange (ETDEWEB)

    Zamora-Lopez, Gorka; Kurths, Juergen [Institute of Physics, University of Potsdam, PO Box 601553, 14415 Potsdam (Germany); Zhou Changsong [Department of Physics, Hong Kong Baptist University, Kowloon Tong, Hong Kong (China); Zlatic, Vinko [Rudjer Boskovic Institute, PO Box 180, HR-10002 Zagreb (Croatia)

    2008-06-06

    The generation of random networks is a very common problem in complex network research. In this paper, we have studied the correlation nature of several real networks and found that, typically, a large number of links are deterministic, i.e. they cannot be randomized. This finding permits fast generation of ensembles of maximally random networks with prescribed 1-node and 2-node degree correlations. When the introduction of self-loops or multiple-links are not desired, random network generation methods typically reach blocked states. Here, a mechanism is proposed, the 'force-and-drop' method, to overcome such states. Our algorithm can be easily simplified for undirected graphs and reduced to account for any subclass of 2-node degree correlations.

  8. High risk of non-sentinel node metastases in a group of breast cancer patients with micrometastases in the sentinel node.

    Science.gov (United States)

    Tvedskov, Tove Filtenborg; Jensen, Maj-Britt; Lisse, Ida Marie; Ejlertsen, Bent; Balslev, Eva; Kroman, Niels

    2012-11-15

    Axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel nodes is under debate. We aimed to establish two models to predict non-sentinel node (NSN) metastases in patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes, to guide the decision for ALND. A total of 1,577 breast cancer patients with micrometastases and 304 with ITC in sentinel nodes, treated by sentinel lymph node dissection and ALND in 2002-2008 were identified in the Danish Breast Cancer Cooperative Group database. Risk of NSN metastases was calculated according to clinicopathological variables in a logistic regression analysis. We identified tumor size, proportion of positive sentinel nodes, lymphovascular invasion, hormone receptor status and location of tumor in upper lateral quadrant of the breast as risk factors for NSN metastases in patients with micrometastases. A model based on these risk factors identified 5% of patients with a risk of NSN metastases on nearly 40%. The model was however unable to identify a subgroup of patients with a very low risk of NSN metastases. Among patients with ITC, we identified tumor size, age and proportion of positive sentinel nodes as risk factors. A model based on these risk factors identified 32% of patients with risk of NSN metastases on only 2%. Omission of ALND would be acceptable in this group of patients. In contrast, ALND may still be beneficial in the subgroup of patients with micrometastases and a high risk of NSN metastases. Copyright © 2012 UICC.

  9. Weight loss improves biomarkers endothelial function and systemic ...

    African Journals Online (AJOL)

    Background: Although postmenopausal associated disorders are important public health problems worldwide, to date limited studies evaluated the endothelial function and systemic inflammation response to weight loss in obese postmenopausal women. Objective: This study was done to evaluate the endothelial function ...

  10. Node-based measures of connectivity in genetic networks.

    Science.gov (United States)

    Koen, Erin L; Bowman, Jeff; Wilson, Paul J

    2016-01-01

    At-site environmental conditions can have strong influences on genetic connectivity, and in particular on the immigration and settlement phases of dispersal. However, at-site processes are rarely explored in landscape genetic analyses. Networks can facilitate the study of at-site processes, where network nodes are used to model site-level effects. We used simulated genetic networks to compare and contrast the performance of 7 node-based (as opposed to edge-based) genetic connectivity metrics. We simulated increasing node connectivity by varying migration in two ways: we increased the number of migrants moving between a focal node and a set number of recipient nodes, and we increased the number of recipient nodes receiving a set number of migrants. We found that two metrics in particular, the average edge weight and the average inverse edge weight, varied linearly with simulated connectivity. Conversely, node degree was not a good measure of connectivity. We demonstrated the use of average inverse edge weight to describe the influence of at-site habitat characteristics on genetic connectivity of 653 American martens (Martes americana) in Ontario, Canada. We found that highly connected nodes had high habitat quality for marten (deep snow and high proportions of coniferous and mature forest) and were farther from the range edge. We recommend the use of node-based genetic connectivity metrics, in particular, average edge weight or average inverse edge weight, to model the influences of at-site habitat conditions on the immigration and settlement phases of dispersal. © 2015 John Wiley & Sons Ltd.

  11. Edge- and Node-Disjoint Paths in P Systems

    Directory of Open Access Journals (Sweden)

    Michael J. Dinneen

    2010-10-01

    Full Text Available In this paper, we continue our development of algorithms used for topological network discovery. We present native P system versions of two fundamental problems in graph theory: finding the maximum number of edge- and node-disjoint paths between a source node and target node. We start from the standard depth-first-search maximum flow algorithms, but our approach is totally distributed, when initially no structural information is available and each P system cell has to even learn its immediate neighbors. For the node-disjoint version, our P system rules are designed to enforce node weight capacities (of one, in addition to edge capacities (of one, which are not readily available in the standard network flow algorithms.

  12. Sentinel lymph node imaging in breast cancer

    International Nuclear Information System (INIS)

    Kim, Byung Tae

    1999-01-01

    Currently, dissection of the axillary or regional lymph nodes is considered the standard staging procedure in breast cancer. However, accumulating evidence is becoming available that the sentinel node concept may provide the same or even better staging information. In the case of melanoma, it is proven that the histological characteristics of the sentinel node reflect the histological characteristics of the distal part of the lymphatic basin. Morbidity can be reduced significantly by the use of sentinel node dissection as several authors have reported successful introduction of this technique into clinical practice. But in breast cancer patients, there are significant differences in practice relating to the technology, such as radiopharmaceuticals, injection sites, volume of injectate, combination with vital blue dye, preoperative lymphoscintigraphy, etc. Valuable reports on these topics appeared in recent journals. This review is a summary of those reports for nuclear physicians interested in sentinel node detection by lymphoscintigraphy in breast cancer patients

  13. Bottomside sinusoidal irregularities in the equatorial F region. II - Cross-correlation and spectral analysis

    Science.gov (United States)

    Cragin, B. L.; Hanson, W. B.; Mcclure, J. P.; Valladares, C. E.

    1985-01-01

    Equatorial bottomside sinusoidal (BSS) irregularities have been studied by applying techniques of cross-correlation and spectral analysis to the Atmosphere Explorer data set. The phase of the cross-correlations of the plasma number density is discussed and the two drift velocity components observed using the retarding potential analyzer and ion drift meter on the satellite are discussed. Morphology is addressed, presenting the geographical distributions of the occurrence of BSS events for the equinoxes and solstices. Physical processes including the ion Larmor flux, interhemispheric plasma flows, and variations in the lower F region Pedersen conductivity are invoked to explain the findings.

  14. Sinusoidal Obstruction Syndrome During Chemotherapy of Pediatric Cancers and its Successful Management With Defibrotide.

    Science.gov (United States)

    Kizilocak, Hande; Dikme, Gürcan; Özdemir, Nihal; Kuruğoğlu, Sebuh; Adaletli, İbrahim; Erkan, Tülay; Celkan, Tiraje

    2017-10-01

    Sinusoidal obstruction syndrome (SOS) is a life-threatening complication generally occurring after hematopoietic stem cell transplantation. SOS after standard dose chemotherapy in malignancies is rare. Between the year 1995 and 2016, 414 patients were diagnosed with acute lymphoblastic leukemia and 113 patients were diagnosed with Wilms tumor in our institution. Among these patients, 4 patients with acute lymphoblastic leukemia (0.96%) and 2 patients with Wilms tumor (1.7%) developed SOS during treatment. SOS behaves like a local disseminated intravascular coagulation. Defibrotide has proved to be effective in SOS. In this article, we report our experience with defibrotide in SOS.

  15. Checkpointing for a hybrid computing node

    Science.gov (United States)

    Cher, Chen-Yong

    2016-03-08

    According to an aspect, a method for checkpointing in a hybrid computing node includes executing a task in a processing accelerator of the hybrid computing node. A checkpoint is created in a local memory of the processing accelerator. The checkpoint includes state data to restart execution of the task in the processing accelerator upon a restart operation. Execution of the task is resumed in the processing accelerator after creating the checkpoint. The state data of the checkpoint are transferred from the processing accelerator to a main processor of the hybrid computing node while the processing accelerator is executing the task.

  16. Endothelial dysfunction: a comprehensive appraisal

    Directory of Open Access Journals (Sweden)

    Vilariño Jorge O

    2006-02-01

    Full Text Available Abstract The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the

  17. Additional Energy Losses from Asymmetric and Non-Sinusoidal Current in an Electrical Facility and Methods of their Reduction

    Directory of Open Access Journals (Sweden)

    Tarasov Evgeniy V.

    2015-01-01

    Full Text Available Influence of the asymmetry and higher harmonics of current on the operation of an electrical facility is analyzed. The level of additional losses from the asymmetric and non-sinusoidal currents is evaluated for a 110 kV electrical network in the Siberian Region of the Russian Federation. Methods for reducing the additional energy losses in the electrical facility are suggested.

  18. Additional Energy Losses from Asymmetric and Non-Sinusoidal Current in an Electrical Facility and Methods of their Reduction

    OpenAIRE

    Tarasov, Evgeny Vladimirovich; Bulyga, Leonid Leonidovich; Ushakov, Vasily Yakovlevich; Kharlov, Nikolay Nikolaevich

    2015-01-01

    Influence of the asymmetry and higher harmonics of current on the operation of an electrical facility is analyzed. The level of additional losses from the asymmetric and non-sinusoidal currents is evaluated for a 110 kV electrical network in the Siberian Region of the Russian Federation. Methods for reducing the additional energy losses in the electrical facility are suggested.

  19. Lymph Node Metastases and Prognosis in Left Upper Division Non-Small Cell Lung Cancers: The Impact of Interlobar Lymph Node Metastasis.

    Directory of Open Access Journals (Sweden)

    Hiroaki Kuroda

    Full Text Available Left upper division segmentectomy is one of the major pulmonary procedures; however, it is sometimes difficult to completely dissect interlobar lymph nodes. We attempted to clarify the prognostic importance of hilar and mediastinal nodes, especially of interlobar lymph nodes, in patients with primary non-small cell lung cancer (NSCLC located in the left upper division.We retrospectively studied patients with primary left upper lobe NSCLC undergoing surgical pulmonary resection (at least lobectomy with radical lymphadenectomy. The representative evaluation of therapeutic value from the lymph node dissection was determined using Sasako's method. This analysis was calculated by multiplying the frequency of metastasis to the station and the 5-year survival rate of the patients with metastasis to the station.We enrolled 417 patients (237 men, 180 women. Tumors were located in the lingular lobe and at the upper division of left upper lobe in 69 and 348 patients, respectively. The pathological nodal statuses were pN0 in 263 patients, pN1 in 70 patients, and pN2 in 84 patients. Lymph nodes #11 and #7 were significantly correlated with differences in node involvement in patients with left upper lobe NSCLC. Among those with left upper division NSCLC, the 5-year overall survival in pN1 was 31.5% for #10, 39.3% for #11, and 50.4% for #12U. The involvement of node #11 was 1.89-fold higher in the anterior segment than that in the apicoposterior segment. The therapeutic index of estimated benefit from lymph node dissection for #11 was 3.38, #4L was 1.93, and the aortopulmonary window was 4.86 in primary left upper division NSCLC.Interlobar node involvement is not rare in left upper division NSCLC, occurring in >20% cases. Furthermore, dissection of interlobar nodes was found to be beneficial in patients with left upper division NSCLC.

  20. The targeting expression of the vascular endothelial growth factor gene in endothelial cells regulated by HRE.ppET-1.

    Science.gov (United States)

    Zheng, Xiangrong; Zhang, Shangshang; Yang, Yujia; Wang, Xia; Zhong, Le; Yu, Xiaohe

    2008-11-01

    The success of gene therapy depends largely on the efficacy of gene delivery vector systems that can deliver genes to target organs or cells selectively and efficiently with minimal toxicity. Here, we show that by using the HRE.ppET-1 regulatory element, we were able to restrict expression of the transgene of vascular endothelial growth factor (VEGF) to endothelial cells exclusively in hypoxic conditions. Eukaryotic expression vectors such as pEGFP-HRE.ppET-1, pcDNA3.1-VEGF+Pa, pcDNA3.1-ppET-1+ EGF+Pa, and pcDNA3.1-HRE.ppET-1+VEGF+Pa were constructed by using a series of nuclear molecule handling methods like PCR, enzyme digestion. The recombinant vectors were transfected into HUVEC cells and HL7702 cells by the lipofectin method. GFP expression was observed with a fluorescence microscope to validate the specificity of expression in endothelial cells under the regulation of HRE.ppET-1 element. Cobalt chloride (final concentration 100 mumol/L) was added to the medium to mimic hypoxia in vitro. After transfection of vectors, the expression of VEGF mRNA was detected by RT-PCR, and the expression of VEGF was detected by Western blotting and ELISA methods under normoxia and hypoxia, respectively. The cell proliferation rate was detected by the MTT test. The expression of GFP revealed that the exterior gene was transcripted effectively in endothelial cells regulated by the HRE.ppET-1 element, while the expression of GFP was very weak in nonendothelial cells. The results of RT-PCR, Western blotting and ELISA showed that VEGF gene expression in the pcDNA3.1-HRE.ppET-1+VEGF+Pa group and in the pcDNA3.1-ppET-1+VEGF+Pa group was higher in hypoxia than it was in normoxia (PHRE.ppET-1 element was expressed specifically in endothelial cells, and can increase the expression of VEGF in hypoxia and stimulate proliferation of endothelial cells. Taking advantage of these facts could greatly improve the efficiency of gene therapy. The vector would be valuable for various gene transfer

  1. Evaluation of Sentinel Node Biopsy in Locally Advanced Breast Cancer Patients Who Become Clinically Node-Negative after Neoadjuvant Chemotherapy: A Preliminary Study

    International Nuclear Information System (INIS)

    Thomas, Sh.; Prakash, A.; Goyal, V.; Agarwal, Sh.; Choudhury, M.; Popli, M.B.

    2011-01-01

    Introduction. Controversy continues over the appropriate timing of sentinel lymph node (SLN) biopsy in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy. We evaluated the feasibility and accuracy of SLN biopsy in LABC patients with cytology-proven axillary nodal metastasis who become clinically node-negative after neoadjuvant chemotherapy. Materials. 30 consecutive patients with LABC, who had become clinically node-negative after 3 cycles of neoadjuvant chemotherapy, were included in the study. They were then subjected to SLN biopsy, axillary lymph node dissection, and breast surgery. Results. Sentinel nodes were successfully identified in 26 of the 30 patients, resulting in an identification rate of 86.67%, sensitivity of 83.33%, false negative rate of 20%, negative predictive value of 72.73%, and an overall accuracy of 88.46%. No complications were observed as a result of dye injection. Conclusions. SLN biopsy is feasible and safe in LABC patients with cytology-positive nodes who become clinically node-negative after neoadjuvant chemotherapy. Our accuracy rate, identification rate, and false negative rate are comparable to those in node-negative LABC patients. SLN biopsy as a therapeutic option in LABC after neoadjuvant chemotherapy is a promising option which should be further investigated

  2. Tumor endothelial marker 5 expression in endothelial cells during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Vallon, Mario, E-mail: m.vallon@arcor.de [Nuklearmedizinische Klinik und Poliklinik, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich (Germany); Rohde, Franziska; Janssen, Klaus-Peter [Chirurgische Klinik und Poliklinik, Technische Universitaet Muenchen, Munich (Germany); Essler, Markus [Nuklearmedizinische Klinik und Poliklinik, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich (Germany)

    2010-02-01

    Tumor endothelial marker (TEM) 5 is an adhesion G-protein-coupled receptor upregulated in endothelial cells during tumor and physiologic angiogenesis. So far, the mechanisms leading to upregulation of TEM5 and its function during angiogenesis have not been identified. Here, we report that TEM5 expression in endothelial cells is induced during capillary-like network formation on Matrigel, during capillary morphogenesis in a three-dimensional collagen I matrix, and upon confluence on a two-dimensional matrix. TEM5 expression was not induced by a variety of soluble angiogenic factors, including VEGF and bFGF, in subconfluent endothelial cells. TEM5 upregulation was blocked by toxin B from Clostridium difficile, an inhibitor of the small GTPases Rho, Rac, and Cdc42. The Rho inhibitor C3 transferase from Clostridium botulinum did not affect TEM5 expression, whereas the Rac inhibitor NSC23766 suppressed TEM5 upregulation. An excess of the soluble TEM5 extracellular domain or an inhibitory monoclonal TEM5 antibody blocked contact inhibition of endothelial cell proliferation resulting in multilayered islands within the endothelial monolayer and increased vessel density during capillary formation. Based on our results we conclude that TEM5 expression during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of proliferation in endothelial cells.

  3. Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

    Science.gov (United States)

    Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

    2016-08-19

    Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

  4. The Expression Profiles of Lysophospholipid Receptors (LPLRs in Different Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Yu-Wei Lee

    2006-03-01

    Full Text Available Sphingosine-1-phosphate (S1P and lysophosphatidic acid (LPA are two bioactive lysophospholipids (LPLs, stored primarily in platelets and released during platelet activation. Both LPLs are capable of regulating endothelial cell functions. The physiological functions of S1P and LPA are mediated by interacting with eight different G-protein coupled receptors: S1P1 through 5 and LPA1 through 3, which activate three different heterotrimeric GTP proteins-including Gi、Gq and G(12/13. The expression of LPL receptors in endothelial cells would affect the responses of S1P and LPA to these cells. There is no previous report discussing the expression profiles of LPL receptors in different endothelial cells from various species. In this study, we aim to investigate the expression profiles of S1P and LPA receptors in different endothelial cells isolated from human, rat, mouse and bovine origin. We used RT-PCR to determine LPLs receptors expression profiles in different endothelial cells. Our results indicated that endothelial cells from various species express different LPL receptors. Endothelial cells isolated from the same source of different species also had different LPLs receptors expression profiles. Therefore, different endothelial cells should respond to LPLs in different manners.

  5. The sentinel lymph node spread determines quantitatively melanoma seeding to non-sentinel lymph nodes and survival.

    Science.gov (United States)

    Ulmer, Anja; Dietz, Klaus; Werner-Klein, Melanie; Häfner, Hans-Martin; Schulz, Claudia; Renner, Philipp; Weber, Florian; Breuninger, Helmut; Röcken, Martin; Garbe, Claus; Fierlbeck, Gerhard; Klein, Christoph A

    2018-03-01

    Complete lymph node dissection (CLND) after a positive sentinel node (SN) biopsy provides important prognostic information in melanoma patients but has been questioned for therapeutic use recently. We explored whether quantification of the tumour spread to SNs may replace histopathology of non-sentinel nodes (NSNs) for staging purposes. We quantified melanoma spread in SNs and NSNs in 128 patients undergoing CLND for a positive SN. In addition to routine histopathology, one-half of each of all 1496 SNs and NSNs was disaggregated into a single cell suspension and stained immunocytochemically to determine the number of melanoma cells per 10 6 lymph node cells, i.e. the disseminated cancer cell density (DCCD). We uncovered melanoma spread to NSNs in the majority of patients; however, the tumour load and the proportion of positive nodes were significantly lower in NSNs than in SNs. The relation between SN and NSN spread could be described by a mathematical function with DCCD NSN  = DCCD SN c /10 1 - c (c = 0.69; 95% confidence interval [CI]: 0.62-0.76). At a median follow-up of 67 months, multivariable Cox regression analyses revealed that DCCD SN (p = 0.02; HR 1.34, 95% CI: 1.05-1.71) and the total number of pathologically positive nodes (p = 0.02; HR 1.53, 95% CI: 1.07-2.22) were significant risk factors after controlling for age, gender, thickness of melanoma and ulceration status. A prognostic model based on DCCD SN and melanoma thickness predicted outcome as accurately as a model including pathological information of both SNs and NSNs. The assessment of DCCD SN renders CLND for staging purposes unnecessary. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Endothelial cell chimerism associated with graft rejection after human lung transplantation.

    OpenAIRE

    Ratajczak , Philippe; Murata , Hideyuki; Meignin , Véronique; Groussard , Odile; Fournier , Michel; Socié , Gérard; Mal , Hervé; Janin , Anne

    2008-01-01

    International audience; Endotheliitis is a major sign of graft rejection. Recipient-derived endothelial cells found in two series of liver and kidney transplants were related to graft rejection. Here, we assessed the presence and the number of chimeric endothelial cells in lung transplants, and their relation with graft rejection. In six males grafted with female lungs out of 193 lung transplantations, endothelial chimerism was studied by combined XY-fluorescent in situ hybridization with CD3...

  7. Injuries to the vascular endothelium: vascular wall and endothelial dysfunction.

    Science.gov (United States)

    Fisher, Mark

    2008-01-01

    Vascular endothelial injury has multiple elements, and this article focuses on ischemia-related processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte-endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation.

  8. Intraoperative examination of sentinel lymph nodes using scrape ...

    African Journals Online (AJOL)

    Background. In breast cancer, sentinel lymph node biopsy (SLNB) is widely used to assess the axilla when the nodes appear normal on palpation and ultrasonography. When the sentinel lymph nodes (SLNs) are negative, no further dissection is required. Surgical dissection or radiotherapy of the axilla is indicated for ...

  9. Role of axillary lymph node ultra-sound and large core biopsy in the preoperative assessment of patients selected for sentinel node biopsy

    International Nuclear Information System (INIS)

    Nori, Jacopo; Boeri, Cecilia; Vanzi, Ermanno; Nori Bufalini, Filippo; Masi, Andrea; Bazzocchi, Massimo; Londero, Viviana; Mangialavori, Giuseppe; Distante, Vito; Simoncini, Roberta

    2005-01-01

    Purpose: To aim of this study was to evaluate the diagnostic accuracy of axillary lymph node sonography, if necessary in collaboration with US-guided large core biopsy, in the preoperative evaluation of breast cancer patients scheduled for quadrantectomy and sentinel lymph node excision. Materials and methods: From July 2001 to December 2002, we evaluated 117 breast cancer patients with ultrasound and, where indicated, FNAB. Breast lesions has diameters between 4 and 26 mm (mean diameter 11 mm). Fifteen (13%) of the 117 patients were excluded from the series as they did not found fulfil the criteria for preliminary sonography of the axilla: in 9 patients fewer than 4 nodes were detected and in 6 patients the breast lesions were intraoperatively found to be benign. Eleven patients (10.7%) with sonographically suspicious axillary nodes were sampled by US-guided core biopsy using a 14 or 16 Gauge Tru-Cut needle. Results: The ultrasound study aims to evaluate the dimensions and morphology of the breast lesion as well as detect and assess at least 4 axillary nodes. These were evaluated for hilar and cortical thickening and radio between the sinus diameter and the total longitudinal diameter. Lymph nodes with hilar diameters equal to or greater than 50% of the longitudinal diameter were considered normal. Of the 102 patients evaluated, 77 (75.7%) had normal axillary nodes according to the US criteria adopted. Negativity was confirmed by histology in 56 cases (72.7%, true negative); 21 (27.3%, false negative) were found to be positive, in contrast with the sonographic appearance. The false negative cases were due to lymph node micrometastasis which probably did not cause morphologic alterations perceptible at ultrasound. The remaining 25 patients (24.5%) had axillary lymph nodes classified as suspicious. In 13 cases of (52%, true positive) there was agreement with histology, whereas in 12 cases (48%, false positive) the US suspicion was not confirmed at surgery. The most

  10. Implementing asyncronous collective operations in a multi-node processing system

    Science.gov (United States)

    Chen, Dong; Eisley, Noel A.; Heidelberger, Philip; Kumar, Sameer; Salapura, Valentina; Steinmacher-Burow, Burkhard

    2014-07-08

    A method, system, and computer program product are disclosed for implementing an asynchronous collective operation in a multi-node data processing system. In one embodiment, the method comprises sending data to a plurality of nodes in the data processing system, broadcasting a remote get to the plurality of nodes, and using this remote get to implement asynchronous collective operations on the data by the plurality of nodes. In one embodiment, each of the nodes performs only one task in the asynchronous operations, and each nodes sets up a base address table with an entry for a base address of a memory buffer associated with said each node. In another embodiment, each of the nodes performs a plurality of tasks in said collective operations, and each task of each node sets up a base address table with an entry for a base address of a memory buffer associated with the task.

  11. VE-Cadherin–Mediated Epigenetic Regulation of Endothelial Gene Expression

    Science.gov (United States)

    Morini, Marco F.; Giampietro, Costanza; Corada, Monica; Pisati, Federica; Lavarone, Elisa; Cunha, Sara I.; Conze, Lei L.; O’Reilly, Nicola; Joshi, Dhira; Kjaer, Svend; George, Roger; Nye, Emma; Ma, Anqi; Jin, Jian; Mitter, Richard; Lupia, Michela; Cavallaro, Ugo; Pasini, Diego; Calado, Dinis P.

    2018-01-01

    Rationale: The mechanistic foundation of vascular maturation is still largely unknown. Several human pathologies are characterized by deregulated angiogenesis and unstable blood vessels. Solid tumors, for instance, get their nourishment from newly formed structurally abnormal vessels which present wide and irregular interendothelial junctions. Expression and clustering of the main endothelial-specific adherens junction protein, VEC (vascular endothelial cadherin), upregulate genes with key roles in endothelial differentiation and stability. Objective: We aim at understanding the molecular mechanisms through which VEC triggers the expression of a set of genes involved in endothelial differentiation and vascular stabilization. Methods and Results: We compared a VEC-null cell line with the same line reconstituted with VEC wild-type cDNA. VEC expression and clustering upregulated endothelial-specific genes with key roles in vascular stabilization including claudin-5, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and von Willebrand factor (vWf). Mechanistically, VEC exerts this effect by inhibiting polycomb protein activity on the specific gene promoters. This is achieved by preventing nuclear translocation of FoxO1 (Forkhead box protein O1) and β-catenin, which contribute to PRC2 (polycomb repressive complex-2) binding to promoter regions of claudin-5, VE-PTP, and vWf. VEC/β-catenin complex also sequesters a core subunit of PRC2 (Ezh2 [enhancer of zeste homolog 2]) at the cell membrane, preventing its nuclear translocation. Inhibition of Ezh2/VEC association increases Ezh2 recruitment to claudin-5, VE-PTP, and vWf promoters, causing gene downregulation. RNA sequencing comparison of VEC-null and VEC-positive cells suggested a more general role of VEC in activating endothelial genes and triggering a vascular stability-related gene expression program. In pathological angiogenesis of human ovarian carcinomas, reduced VEC expression paralleled decreased

  12. Lymph node culture

    Science.gov (United States)

    Culture - lymph node ... or viruses grow. This process is called a culture. Sometimes, special stains are also used to identify specific cells or microorganisms before culture results are available. If needle aspiration does not ...

  13. Intraoperative examination of sentinel lymph nodes using scrape ...

    African Journals Online (AJOL)

    2014-08-03

    Aug 3, 2014 ... Background. In breast cancer, sentinel lymph node biopsy (SLNB) is widely used to assess the axilla when the nodes appear normal on palpation and ultrasonography. When the sentinel lymph nodes (SLNs) are negative, no further dissection is required. Surgical dissection or radiotherapy of the axilla is ...

  14. Effects of node buffer and capacity on network traffic

    International Nuclear Information System (INIS)

    Ling Xiang; Ding Jian-Xun; Hu Mao-Bin

    2012-01-01

    In this paper, we study the optimization of network traffic by considering the effects of node buffer ability and capacity. Two node buffer settings are considered. The node capacity is considered to be proportional to its buffer ability. The node effects on network traffic systems are studied with the shortest path protocol and an extension of the optimal routing [Phys. Rev. E 74 046106 (2006)]. In the diagrams of flux—density relationships, it is shown that a nodes buffer ability and capacity have profound effects on the network traffic

  15. SpicyNodes Radial Map Engine

    Science.gov (United States)

    Douma, M.; Ligierko, G.; Angelov, I.

    2008-10-01

    The need for information has increased exponentially over the past decades. The current systems for constructing, exploring, classifying, organizing, and searching information face the growing challenge of enabling their users to operate efficiently and intuitively in knowledge-heavy environments. This paper presents SpicyNodes, an advanced user interface for difficult interaction contexts. It is based on an underlying structure known as a radial map, which allows users to manipulate and interact in a natural manner with entities called nodes. This technology overcomes certain limitations of existing solutions and solves the problem of browsing complex sets of linked information. SpicyNodes is also an organic system that projects users into a living space, stimulating exploratory behavior and fostering creative thought. Our interactive radial layout is used for educational purposes and has the potential for numerous other applications.

  16. Methodology of sentinel node detection

    International Nuclear Information System (INIS)

    Maublant, J.

    2000-01-01

    The isotopic localisation of the sentinel node, i.e., the first functional lymph node in a tumor basin, is probably the fastest growing field ever experienced in nuclear medicine. Although based on the simple concept of the lymphatic migration of Tc-labeled colloids, the choice of the optimal technique remains controversial. We review and discuss the role of the colloids, of the site of injection, of the injected volume, of early imaging and of the colorimetric approach. Initially applied to melanoma and breast cancer, the sentinel node detection is now tested in other types of cancer such as lung, colon and prostate. It could become one of the leading tools in minimally invasive surgical oncology. The nuclear medicine physician has to remain aware of the rapid evolutions in this field in order to be able to answer to a rapidly growing demand. (author)

  17. Secondhand smoke exposure and endothelial stress in children and adolescents.

    Science.gov (United States)

    Groner, Judith A; Huang, Hong; Nagaraja, Haikady; Kuck, Jennifer; Bauer, John Anthony

    2015-01-01

    Links between secondhand smoke exposure and cardiovascular disease in adults are well established. Little is known about the impact of this exposure on cardiovascular status during childhood. The purpose of this study was to investigate relationships between secondhand smoke exposure in children and adolescents and cardiovascular disease risk--systemic inflammation, endothelial stress, and endothelial repair. A total of 145 subjects, aged 9 to 18 years, were studied. Tobacco smoke exposure was determined by hair nicotine level. Cardiovascular risk was assessed by markers of systemic inflammation (C-reactive protein [CRP] and adiponectin); by soluble intercellular adhesion molecule 1 (s-ICAM1), which measures endothelial activation after surface vascular injury; and by endothelial repair. This was measured by prevalence of endothelial progenitor cells (EPCs), which are bone marrow-derived cells that home preferentially to sites of vascular damage. Hair nicotine was directly correlated with s-ICAM1 (r = 0.4090, P Secondhand smoke exposure during childhood and adolescence is detrimental to vascular health because s-ICAM1 is a marker for endothelial activation and stress after vascular surface injury, and EPCs contribute to vascular repair. The fact that body mass index is also a factor in the model predicting s-ICAM1 is concerning, in that 2 risk factors may both contribute to endothelial stress. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  18. Contrast-enhanced ultrasonography of hepatocellular carcinoma: Correlation between quantitative parameters and arteries in neoangiogenesis or sinusoidal capillarization

    International Nuclear Information System (INIS)

    Pei Xiaoqing; Liu Longzhong; Zheng Wei; Cai Muyan; Han Feng; He Jiehua; Li Anhua; Chen Minshan

    2012-01-01

    Objective: The quantitative parameters in contrast-enhanced ultrasonography-time–intensity curve of hepatocellular carcinoma (HCC) were studied to explore their potential importance in monitoring the effects of anti-angiogenic therapy for HCC. Methods: 115 HCC patients were studied with contrast-enhanced ultrasonography-time–intensity curve (CEUS-TIC) and with immunohistochemical analysis of tissue sections. The CEUS images were analyzed off-line to obtained quantitative parameters including maximum of intensity (IMAX), rise time (RT), time to peak (TTP), mean transit time (mTT), rise slope (RS), and washout time (WT). Monoclonal antibodies specific for smooth muscle actin and anti-CD34 were used to observe unpaired arteries (UAs) and microvessel area (MVA) of sinusoidal capillarization, respectively. The UAs and MVA of 82 HCC cases were successfully stained. Results: The number of UAs had moderate correlation with RT (r = −0.446), TTP (r = −0.432), and RS (r = 0.431) (P < 0.05), and it had mild correlation with IMAX (r = 0.303) and WT (r = 0.285) (P < 0.05). MVA of sinusoidal capillarization had no correlation with perfusion parameters. Conclusion: Quantitative CEUS-TIC parameters reflecting hemodynamics of tumors are correlated with UAs, but not with MVA, and they might be used to monitor the effects of anti-angiogenic therapy on HCC.

  19. Sentinel Node Biopsy in Melanoma: A Short Update

    Science.gov (United States)

    Ferrara, Gerardo; Partenzi, Antonietta; Filosa, Alessandra

    2018-01-01

    Several controversies are still ongoing about sentinel node biopsy in melanoma. It is basically a staging procedure for melanoma > 0.75 mm in thickness or for thinner melanoma in the presence of ulceration, high mitotic rate, and/or lymphovascular invasion. Complete lymph node dissection after a positive sentinel node can also allow a better locoregional disease control but seems not to prevent the development of distant metastases. The use of sentinel node biopsy in atypical Spitz tumors should be discouraged because of their peculiar biological properties. PMID:29719827

  20. Sentinel Lymph Node Biopsy in Breast Cancer: Predictors of Axillary and Non-Sentinel Lymph Node Involvement

    Directory of Open Access Journals (Sweden)

    Hakan Postacı

    2013-12-01

    Full Text Available Background: Sentinel lymph node biopsy is a standard method for the evaluation of axillary status in patients with T1-2N0M0 breast cancers. Aims: To determine the prognostic significance of primary tumour-related clinico-histopathological factors on axillary and non-sentinel lymph node involvement of patients who underwent sentinel lymph node biopsy. Study design: Retrospective clinical study. Methods: In the present study, 157 sentinel lymph node biopsies were performed in 151 consecutive patients with early stage breast cancer between June 2008 and December 2011. Results: Successful lymphatic mapping was obtained in 157 of 158 procedures (99.4%. The incidence of larger tumour size (2.543±1.21 vs. 1.974±1.04, lymphatic vessel invasion (70.6% vs. 29.4%, blood vessel invasion (84.2% vs. 15.8%, and invasive lobular carcinoma subtype (72.7% vs. 27.3% were statistically significantly higher in patients with positive SLNs. Logistic stepwise regression analysis disclosed tumour size (odds ratio: 1.51, p=0.0021 and lymphatic vessel invasion (odds ratio: 4.68, p=0.001 as significant primary tumour-related prognostic determinants of SLN metastasis. Conclusion: A close relationship was identified between tumour size and lymphatic vessel invasion of the primary tumour and axillary lymph node involvement. However, the positive predictive value of these two independent variables is low and there is no compelling evidence to recommend their use in routine clinical practice.

  1. Tumor-derived circulating endothelial cell clusters in colorectal cancer.

    KAUST Repository

    Cima, Igor; Kong, Say Li; Sengupta, Debarka; Tan, Iain B; Phyo, Wai Min; Lee, Daniel; Hu, Min; Iliescu, Ciprian; Alexander, Irina; Goh, Wei Lin; Rahmani, Mehran; Suhaimi, Nur-Afidah Mohamed; Vo, Jess H; Tai, Joyce A; Tan, Joanna H; Chua, Clarinda; Ten, Rachel; Lim, Wan Jun; Chew, Min Hoe; Hauser, Charlotte; van Dam, Rob M; Lim, Wei-Yen; Prabhakar, Shyam; Lim, Bing; Koh, Poh Koon; Robson, Paul; Ying, Jackie Y; Hillmer, Axel M; Tan, Min-Han

    2016-01-01

    Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be u