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Sample records for 2-hour urokinase regime

  1. Efficacy and safety of 2-hour urokinase regime in acute pulmonary embolism: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Huang Kewu

    2009-12-01

    Full Text Available Abstract Backgrounds Urokinase (UK 2 200 U/kg·h for 12 hours infusion(UK-12 his an ACCP recommended regimen in treating acute pulmonary embolism (PE. It is unclear whether this dose and time can be reduced further. We compared the efficacy and safety of 20, 000 U/kg for 2 hours (UK-2 h with the UK-12 h regime in selected PE patients. Methods A randomized trial involving 129 patients was conducted. Patients with acute PE were randomly assigned to receive either UK-12 h (n = 70, or UK-2 h (n = 59. The efficacy was determined by the improvement of right heart dysfunction and perfusion defect at 24 h and 14 d post UK treatment. The bleeding incidence, death rate and PE recurrence were also evaluated. Results Similarly significant improvements in right heart dysfunction and lung perfusion defects were observed in both groups. Overall bleeding incidents were low in both groups. Major bleeding directly associated with UK infusion occurred in one patient in the UK-2 h group and one in the UK-12 h group. Mortality rates were low, with one reported fatal recurrent in the UK-12 h group and none in the UK-2 h group. When the rate of bleeding, death and PE recurrence were compared separately in the hemodynamic instability and the massive anatomic obstruction subgroups, no significant difference was found. Conclusions The UK-2 h regimen exhibits similar efficacy and safety as the UK-12 h regimen for acute PE. Trial Registration Clinical trial registered with http://clinicaltrials.gov/ct2/show/NCT00799968 (Identifier: NCT 00799968

  2. 7 positions in 2 hours

    Directory of Open Access Journals (Sweden)

    Jessica Ackerman

    2013-07-01

    Full Text Available 7 positions in 2 hours (2013 is a drawing that documents the process of making the short film Role Reversal Rehearsal. It became quickly apparent that the process of making the work was more dynamic and interesting than the finished piece itself. Relationships between the childcare arrangements of the participants and the collective working process brought about the necessity of collaboration for parent artists. Each participant gave their time, energy and creative insight towards filming a series of birthing positions with roles reversed. The male performer became the central figure in an attempt to prompt empathy, humour, and to embody the importance of the male role in childbirth. There were two hours to choreograph, rehearse, and film the sequence. The drawing by Ackerman encapsulates the 'rhizomatic' approach to producing creative work under the constraints of parenthood. The 'arborescent' structure of hierarchy encouraged in industrial filmmaking is subsumed in favour of a horizontal structure. This new structure allows for the creative input, and flow of collaboration between all people involved - including the 3 and 5 year olds, who contributed ideas for camera and soundtrack in situ.

  3. Transferring PSM craft skills in a 2 hour session

    NARCIS (Netherlands)

    Zijderveld, E.J.A. van; Morill, N.; Shaw, D.; Belton, V.; Harvey, P.; Rouwette, E.

    2007-01-01

    Many of those involved in the Problem Structuring Methods (PSM) community have commented on the struggle that novices face in building the craft skills associated with conducting a PSM intervention. As part of this year's Operational Research Society Conference, we have three 2-hour practical

  4. Quantitative method of measuring cancer cell urokinase and metastatic potential

    Science.gov (United States)

    Morrison, Dennis R. (Inventor)

    1993-01-01

    The metastatic potential of tumors can be evaluated by the quantitative detection of urokinase and DNA. The cell sample selected for examination is analyzed for the presence of high levels of urokinase and abnormal DNA using analytical flow cytometry and digital image analysis. Other factors such as membrane associated urokinase, increased DNA synthesis rates and certain receptors can be used in the method for detection of potentially invasive tumors.

  5. Inflight Exercise Regimen for the 2-Hour Prebreathe Protocol

    Science.gov (United States)

    Foster, Philip P.; Gernhardt, Michael L.; Woodruff, Kristin K.; Schneider, Susan M.; Homick, Jerry L. (Technical Monitor)

    2000-01-01

    A 10 min aerobic prebreathe exercise up to 75% V-O2(sub max) on a dual-cycle ergometer, included in the 2-hour prebreathe protocol, has been shown to dramatically reduce the incidence of decompression sickness (DCS) at altitude. In-flight only leg ergometry will be available. A balanced exercise was developed using surgical tubing with the ergometer on-orbit. We hypothesize that a 75% V02max workload, individually prescribed, would be achieved using a target heart rate to regulate the intensity of the arm exercise. VO2, heart rate (HR) / ECG, V-CO2 /V-O2, V(sub E), and V(sub T), and rate of perceived exertion (Borg scale) were measured in eleven healthy subjects who passed a US Air Force Class III Physical examination. A V-O2 peak test was performed to assess the sub-maximal exercise prescription. Two series of sub-maximal tests were performed: (1) leg ergometer/hand ergometer and (2) leg ergometer/surgical tubes. We found no significant differences (P > 0.05) in comparing the means for V-O2 and HR between the predicted and measured values during the final 4 minute-stage at "75% V-O2 workload" or between the two types of sub-maximal tests. The prescribed prebreathe sub-maximal exercise performed with flight certified surgical tubes was achieved using the target HR.

  6. Urokinase-catalysed cleavage of the urokinase receptor requires an intact glycolipid anchor

    DEFF Research Database (Denmark)

    Høyer-Hansen, G; Pessara, U; Holm, A;

    2001-01-01

    Urokinase (uPA) has the striking ability to cleave its receptor, uPAR, thereby inactivating the binding potential of this molecule. Here we demonstrate that the glycosylphosphatidylinositol (GPI) anchor of uPAR, which is attached to the third domain, is an important determinant in governing this ...

  7. The receptor for urokinase-type plasminogen activator and urokinase is translocated from two distinct intracellular compartments to the plasma membrane on stimulation of human neutrophils

    DEFF Research Database (Denmark)

    Plesner, T; Ploug, M; Ellis, V

    1994-01-01

    The cellular receptor for urokinase-type plasminogen activator (uPAR) binds pro-urokinase (pro-uPA) and facilitates its conversion to enzymatically active urokinase (uPA). uPA in turn activates surface-bound plasminogen to plasmin, a process of presumed importance for a number of biologic process...

  8. The intact urokinase receptor is required for efficient vitronectin binding

    DEFF Research Database (Denmark)

    Høyer-Hansen, G; Behrendt, N; Ploug, M;

    1997-01-01

    The urokinase receptor (uPAR) is a receptor for both urokinase plasminogen activator (uPA) and the adhesion protein vitronectin. There are two forms of cell surface-bound uPAR; intact uPAR and a cleaved form, uPAR(2+3), which is formed by uPA-catalyzed cleavage of uPAR. In ligand-blotting experim...

  9. Urokinase, urokinase receptor, and plasminogen activator inhibitor-1 expression on podocytes in immunoglobulin A glomerulonephritis

    OpenAIRE

    Lee, Ji-Hye; Oh, Mee-Hye; Park, Jae-seok; Na, Gyoung-Jae; Gil, Hye-Wook; Yang, Jong-Oh; Lee, Eun-Young; Hong, Sae-Yong

    2014-01-01

    Background/Aims The purpose of this study was to investigate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 on podocytes in immunoglobulin A (IgA) glomerulonephritis (GN). Methods Renal biopsy specimens from 52 IgA GN patients were deparaffinized and subjected to immunohistochemical staining for uPA, PAI-1, and uPAR. The biopsies were classified into three groups according to the expression of uPA and uPAR on podo...

  10. The urokinase receptor associated protein (uPARAP/endo180)

    DEFF Research Database (Denmark)

    Engelholm, L H; Nielsen, B S; Danø, K

    2001-01-01

    The urokinase-mediated plasminogen activation system plays a central role in the extracellular proteolytic degradation reactions in cancer invasion. In this review article we discuss a number of recent findings identifying a new cellular receptor protein, uPARAP, that interacts with components...

  11. [The fibrinolytic treatment with urokinase of acute arterial thrombosis].

    Science.gov (United States)

    Ballester, A; Donato di Paola, M; Saccà, A; Cappello, I; D'Addato, M

    1993-01-01

    We present our experiences on 86 patients with acute arterial thrombosis of the legs, undergoing a fibrinolytic treatment with urokinase. Results from the treatment are analyzed according to: the administration way (systemic, locoregional, intrathrombotic), the level of thrombosis (upper or lower legs), the associated morbidity and mortality.

  12. Acceleration of the thrombin inactivation of single chain urokinase-type plasminogen activator (pro-urokinase) by thrombomodulin

    NARCIS (Netherlands)

    Munk, G.A.W. de; Groeneveld, E.; Rijken, D.C.

    1991-01-01

    The in vitro effects of thrombomodulin on the inactivation of single chain urokinase-type plasminogen activator (scu-PA) by thrombin were investigated by incubating scu-PA with varying concentrations of human thrombin, in both the absence and presence of soluble rabbit thrombomodulin. 50%

  13. The pro-urokinase plasminogen-activation system in the presence of serpin-type inhibitors and the urokinase receptor

    DEFF Research Database (Denmark)

    Behrendt, Niels; List, Karin; Andreasen, Peter A;

    2003-01-01

    The reciprocal pro-enzyme activation system of plasmin, urokinase-type plasminogen activator (uPA) and their respective zymogens is a potent mechanism in the generation of extracellular proteolytic activity. Plasminogen activator inhibitor type 1 (PAI-1) acts as a negative regulator. This system ...

  14. The urokinase plasminogen activator receptor-associated protein/endo180 is coexpressed with its interaction partners urokinase plasminogen activator receptor and matrix metalloprotease-13 during osteogenesis

    DEFF Research Database (Denmark)

    Engelholm, L H; Nielsen, B S; Netzel-Arnett, S

    2001-01-01

    The urokinase plasminogen activator receptor-associated protein/Endo180 (uPARAP/Endo180) is a newly discovered member of the macrophage mannose receptor family that was reported to interact with ligand-bound urokinase plasminogen activator receptor (uPAR), matrix metalloprotease-13 (MMP-13), and ...

  15. Cell-surface acceleration of urokinase-catalyzed receptor cleavage

    DEFF Research Database (Denmark)

    Høyer-Hansen, G; Ploug, M; Behrendt, N

    1997-01-01

    The urokinase-type plasminogen activator (uPA) binds to a specific cell-surface receptor, uPAR. On several cell types uPAR is present both in the full-length form and a cleaved form, uPAR(2+3), which is devoid of binding activity. The formation of uPAR(2+3) on cultured U937 cells is either direct...

  16. A composite role of vitronectin and urokinase in the modulation of cell morphology upon expression of the urokinase receptor

    DEFF Research Database (Denmark)

    Hillig, Thore; Engelholm, Lars H; Ingvarsen, Signe

    2008-01-01

    The urokinase receptor, urokinase receptor (uPAR), is a glycosylphosphatidylinositol-anchored membrane protein engaged in pericellular proteolysis and cellular adhesion, migration, and modulation of cell morphology. A direct matrix adhesion is mediated through the binding of uPAR to vitronectin......, and this event is followed by downstream effects including changes in the cytoskeletal organization. However, it remains unclear whether the adhesion through uPAR-vitronectin is the only event capable of initiating these morphological rearrangements or whether lateral interactions between uPAR and integrins can...... a different single-site mutant, uPAR(Y57A), in the presence of a synthetic uPAR-binding peptide, as well as with wild-type uPAR, which underwent cytoskeletal rearrangements even when cultivated in uPA-deficient serum. Blocking of integrins with an Arg-Gly-Asp-containing peptide counteracted the matrix...

  17. Method and tool for prognosticating HIV infection in a subject by measuring soluble urokinase plasminogen activator receptor, degradation products thereof, and urokinase plasminogen activator receptor

    DEFF Research Database (Denmark)

    2000-01-01

    Method of diagnosing and/or prognosticating HIV infection in a subject comprising the steps of: (a) performing in vitro a measurement of the level of a marker in the form of (i) urokinase plasminogen activator receptor (uPAR), (ii) soluble urokinase plasminogen activator receptor (suPAR), (iii......) urokinase-type plasminogen activator (uPA), (iv) one or more degradation products of (i), (ii), or (iii), and/or (v) an mRNA for (i), (ii) or (iii), in a biological fluid sample from a subject, and (b) using the measurement value obtained to evaluate the state of the subject....

  18. Dissecting the Urokinase Activation Pathway Using Urokinase-Activated Anthrax Toxin

    Science.gov (United States)

    Liu, Shihui; Bugge, Thomas H.; Frankel, Arthur E.; Leppla, Stephen H.

    2012-01-01

    Anthrax toxin is a three-part toxin secreted by Bacillus anthracis, consisting of protective antigen (PrAg), edema factor (EF), and lethal factor (LF). To intoxicate host mammalian cells, PrAg, the cell-binding moiety of the toxin, binds to cells and is then proteolytically activated by furin on the cell surface, resulting in the active heptameric form of PrAg. This heptamer serves as a protein-conducting channel that translocates EF and LF, the two enzymatic moieties of the toxin, into the cytosol of the cells where they exert cytotoxic effects. The anthrax toxin delivery system has been well characterized. The amino-terminal PrAg-binding domain of LF (residues 1–254, LFn) is sufficient to allow translocation of fused “passenger” polypeptides, such as the ADP-ribosylation domain of Pseudomonas exotoxin A, to the cytosol of the cells in a PrAg-dependent process. The protease specificity of the anthrax toxin delivery system can also be reengineered by replacing the furin cleavage target sequence of PrAg with other protease substrate sequences. PrAg-U2 is such a PrAg variant, one that is selectively activated by urokinase plasminogen activator (uPA). The uPA-dependent proteolytic activation of PrAg-U2 on the cell surface is readily detected by Western blotting analysis of cell lysates in vitro, or cell or animal death in vivo. Here we describe the use of PrAg-U2 as a molecular reporter tool to test the controversial question of what components are required for uPAR-mediated cell surface pro-uPA activation. The results demonstrate that both uPAR and plasminogen play critical roles in pro-uPA activation both in vitro and in vivo. PMID:19377974

  19. Plasma soluble urokinase plasminogen activator receptor in children with urinary tract infection

    DEFF Research Database (Denmark)

    Wittenhagen, Per; Andersen, Jesper Brandt; Hansen, Anita

    2011-01-01

    In this prospective study we investigated the role of plasma levels of soluble urokinase plasminogen activator receptor (suPAR) in children with urinary tract infection.......In this prospective study we investigated the role of plasma levels of soluble urokinase plasminogen activator receptor (suPAR) in children with urinary tract infection....

  20. Urokinase receptor forms in serum from non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Almasi, Charlotte Elberling; Christensen, Ib Jarle; Høyer-Hansen, Gunilla;

    2011-01-01

    To study the prognostic impact of the different forms of the receptor for urokinase plasminogen activator (uPAR) in serum from 171 non-small cell lung cancer (NSCLC) patients.......To study the prognostic impact of the different forms of the receptor for urokinase plasminogen activator (uPAR) in serum from 171 non-small cell lung cancer (NSCLC) patients....

  1. A urokinase receptor-associated protein with specific collagen binding properties

    DEFF Research Database (Denmark)

    Behrendt, N; Jensen, Ole Nørregaard; Engelholm, L H

    2000-01-01

    membrane-bound lectin with hitherto unknown function. The human cDNA was cloned and sequenced. The protein, designated uPARAP, is a member of the macrophage mannose receptor protein family and contains a putative collagen-binding (fibronectin type II) domain in addition to 8 C-type carbohydrate recognition......The plasminogen activation cascade system, directed by urokinase and the urokinase receptor, plays a key role in extracellular proteolysis during tissue remodeling. To identify molecular interaction partners of these trigger proteins on the cell, we combined covalent protein cross-linking with mass...... spectrometry based methods for peptide mapping and primary structure analysis of electrophoretically isolated protein conjugates. A specific tri-molecular complex was observed upon addition of pro-urokinase to human U937 cells. This complex included the urokinase receptor, pro-urokinase, and an unknown, high...

  2. Vectors and methods for recombinant production of uPA-binding fragments of the human urokinase-type plasminogen receptor (uPAR)

    DEFF Research Database (Denmark)

    1999-01-01

    Activation of plasminogen to plasma is inhibited by preventing the binding of a receptor binding form of urokinase-type plasminogen activator to a urokinase-type plasminogen activator receptor in a mammal, thereby preventing the urokinase-type plasminogen activator from converting plasminogen int...... into plasmin. DNA fragments which encode for soluble, active fragments of the urokinase-type plasminogen activator are provided....

  3. Urokinase treatment for arteriovenous fistulae declotting in dialyzed patients.

    Science.gov (United States)

    Mangiarotti, G; Canavese, C; Thea, A; Segoloni, G P; Stratta, P; Salomone, M; Vercellone, A

    1984-01-01

    Urokinase treatment, previously employed with success in the declotting of deep venous thrombosis and arteriovenous shunts in patients undergoing regular dialytic treatment (RDT), was used in 23 cases of arteriovenous fistula thrombotic occlusion in 18 RDT patients. The treatment was successful in 65.2% of the cases without any negative side effects, except 1 case which may have developed a pulmonary embolism. Patients with severe hypofibrinolysis may need larger doses or may have a recurrence of the thrombotic episode. All therapeutic failures correlated with the presence of fibrosis or sclerosis.

  4. Reduced pulmonary blood flow in regions of injury 2 hours after acid aspiration in rats.

    Science.gov (United States)

    Richter, Torsten; Bergmann, Ralf; Musch, Guido; Pietzsch, Jens; Koch, Thea

    2015-01-01

    Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following acid aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after acid aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after acid instillation by measuring the concentration of [(68)Ga]-radiolabeled microspheres using positron emission tomography. CT scans revealed increased lung density in areas of acid aspiration. Lung injury was accompanied by impaired gas exchange. Acid aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes (P < 0.001). The PBF ratio of the middle region of the injured versus uninjured lungs of the aspiration group (0.86 [0.7;0.9], median [25%;75%]) was significantly lower than the PBF ratio in the left versus right lung of the control group (1.02 [1.0;1.05]; P = 0.016). The PBF pattern 2 hours after aspiration-induced lung injury showed a redistribution of PBF away from injured regions that was likely responsible for the partial recovery from hypoxemia over time. Treatments given intravenously 2 hours after acid-induced lung injury may not preferentially reach the injured lung regions, contrary to what occurs during the first hour of inflammation. Please see related article: http://dx.doi.org/10.1186/s12871-015-0014-z.

  5. Macroeconomic regimes

    NARCIS (Netherlands)

    Baele, L.T.M.; Bekaert, G.R.J.; Cho, S.; Inghelbrecht, K.; Moreno, A.

    2015-01-01

    A New-Keynesian macro-model is estimated accommodating regime-switching behavior in monetary policy and macro-shocks. A key to our estimation strategy is the use of survey-based expectations for inflation and output. Output and inflation shocks shift to the low volatility regime around 1985 and 1990

  6. Transgenic chickens expressing human urokinase-type plasminogen activator.

    Science.gov (United States)

    Lee, Sung Ho; Gupta, Mukesh Kumar; Ho, Young Tae; Kim, Teoan; Lee, Hoon Taek

    2013-09-01

    Urokinase-type plasminogen activator is a serine protease that is clinically used in humans for the treatment of thrombolytic disorders and vascular diseases such as acute ischemic stroke and acute peripheral arterial occlusion. This study explored the feasibility of using chickens as a bioreactor for producing human urokinase-type plasminogen activator (huPA). Recombinant huPA gene, under the control of a ubiquitous Rous sarcoma virus promoter, was injected into the subgerminal cavity of freshly laid chicken eggs at stage X using the replication-defective Moloney murine leukemia virus (MoMLV)-based retrovirus vectors encapsidated with VSV-G (vesicular stomatitis virus G) glycoprotein. A total of 38 chicks, out of 573 virus-injected eggs, hatched and contained the huPA gene in their various body parts. The mRNA transcript of the huPA gene was present in various organs, including blood and egg, and was germ-line transmitted to the next generation. The level of active huPA protein was 16-fold higher in the blood of the transgenic chicken than in the nontransgenic chicken (P pharming of the huPA drug but also be useful for studying huPA-induced bleeding and other disorders.

  7. A Novel Gene Delivery System Targeting Urokinase Receptor

    Institute of Scientific and Technical Information of China (English)

    Xing-Hui SUN; Li TAN; Chun-Yang LI; Chang TONG; Jin FAN; Ping LI; Yun-Song ZHU

    2004-01-01

    Recombinant proteins that combine different functions required for cell targeting and intracellular delivery of DNA present an attractive approach for the development of nonviral gene delivery vectors. Here, we described a novel protein termed ATF-lys10 which facilitated cell-specific gene transfer via receptor-mediated endocytosis. ATF-lys 10 was composed of the amino-terminal fragment of urokinase and ten lysines at the carboxyl terminus. Bacterially expressed ATF-lys 10 protein existed in soluble form, and had antigenicity of human urokinase. Purified ATF-lys 10 specifically bound to uPAR-expressing cells and formed protein-DNA complexes with plasmid pGL3-control. After neutralization of excess negative charge with poly-L-lysine, these complexes served as a specific gene delivery vector for uPAR-expressing cells. Lysosomotropic compounds, such as chloroquine, drastically increased the ATF-lysl0 mediated gene delivery efficiency. Our results suggest that the recombinant protein ATF-lys 10 with the properties of DNA binding and tumor cell targeting represents a promising method for gene transfer and expression in tumor cells.

  8. Ionospheric effects during first 2 hours after the Chelyabinsk meteorite impact

    CERN Document Server

    Berngardt, O I; Zherebtsov, G A; Kusonski, O A; Grigorieva, S A

    2013-01-01

    This paper presents the analysis of ionospheric effects in the region close to the Chelyabinsk meteorite explosion at 03:20UT 2013 February 15 from the Institute of Solar-Terrestrial Physics of Siberian Branch of Russian Academy of Sciences (ISTP SB RAS) EKB radar data, and from the Institute of Geophysics of Ural Branch of Russian Academy of Sciences (IG UB RAS) PARUS ionosonde data. Both instruments are located within the IG UB RAS Arti Observatory approximately 200 km northward from the estimated explosion site. According to the data obtained, the ionospheric disturbance caused by the meteorite flyby, explosion, and impact had high dynamics and amplitude. However, it obviously did not lead to a variation in the ionosphere mean parameters in the region above the disturbance center during the first 2 hours. Essential effects, however, were observed at more than 100-200 km from the explosion site and farther up to 1500 km.

  9. Expression of urokinase receptors by human trophoblast. A histochemical and ultrastructural analysis

    DEFF Research Database (Denmark)

    Multhaupt, H A; Mazar, A; Cines, D B

    1994-01-01

    BACKGROUND: Through their ability to invade endometrium, remodel the uterine spiral arteries, and sustain placental blood fluidity, trophoblast cells play a central role in establishing and maintaining the integrity of the uteroplacental vasculature. The expression of urokinase receptors by troph...

  10. Activation of human pro-urokinase by unrelated proteases secreted by Pseudomonas aeruginosa.

    NARCIS (Netherlands)

    Beaufort, N.; Seweryn, P.; Bentzmann, S. de; Tang, A.; Kellermann, J.; Grebenchtchikov, N.J.; Schmitt, M.; Sommerhoff, C.P.; Pidard, D.; Magdolen, V.

    2010-01-01

    Pathogenic bacteria, including Pseudomonas aeruginosa, interact with and engage the host plasminogen (Plg) activation system, which encompasses the urokinase (uPA)-type Plg activator, and is involved in extracellular proteolysis, including matrilysis and fibrinolysis. We hypothesized that secreted b

  11. Enhanced levels of urokinase plasminogen activator and its soluble receptor in common variable immunodeficiency

    DEFF Research Database (Denmark)

    Fevang, Børre; Eugen-Olsen, Jesper; Yndestad, Arne;

    2009-01-01

    Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by defective immunoglobulin production and high frequency of bacterial infections, autoimmunity and manifestations of chronic inflammation. The urokinase plasminogen activator (uPA), its cell bound and soluble recep...

  12. Bicyclic Peptide Inhibitor of Urokinase-Type Plasminogen Activator

    DEFF Research Database (Denmark)

    Roodbeen, Renée; Paaske, Berit; Jiang, Longguang;

    2013-01-01

    The development of protease inhibitors for pharmacological intervention has taken a new turn with the use of peptidebased inhibitors. Here, we report the rational design of bicyclic peptide inhibitors of the serine protease urokinase-type plasminogen activator (uPA), based on the established...... monocyclic peptide, upain-2. It was successfully converted to a bicyclic peptide, without loss of inhibitory properties. The aim was to produce a peptide cyclised by an amide bond with an additional stabilising across-the-ring covalent bond. We expected this bicyclic peptide to exhibit a lower entropic...... burden upon binding. Two bicyclic peptides were synthesised with affinities similar to that of upain-2, and their binding energetics were evaluated by isothermal titration calorimetry. Indeed, compared to upain-2, the bicyclic peptides showed reduced loss of entropy upon binding to uPA. We also...

  13. Prolonged radiation damage in rat colon and urokinase expression in epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Hayashida, Masayuki; Minami, Kazunori; Okimoto, Tomoaki [Nagasaki Univ. (Japan). School of Medicine; Shichijo, Kazuko; Matsuu, Mutsumi; Nakayama, Toshiyuki; Sekine, Ichiro

    2001-12-01

    Although radiation therapy plays important role in the treatment of gynecological tumors, it may cause radiation injury as a late effect. Several recent reports show that urokinase such as urokinase type plasminogen activator (uPA) contributes to the repair of ulcerative lesions of the colon epithelium. We studied radiation induced enterocolitis using rat animal models. Seventy-two female Wistar rats were irradiated by a single fraction dose of 36 Gy at laparotomy. Histological changes and activity of urokinase system were investigated after irradiation. Ulcers were observed in irradiated field in 12 of 19 animals (63%) even at 60th week after irradiation. Urokinase expressions were observed in the margins of active ulcer. Urokinase was thought to play important role in exacerbation of ulcer formation. Expression of uPA was also observed in submucosal glands. Ischaemic changes were not observed in irradiated colon despite sclerosing vasculitis. It is suggested that uPA played reciprocal roles in radiation induced enterocolitis: healing and aggravation of ulcer. (author)

  14. Usefulness of intracavitary urokinase injection under sonographic guidance in treatment for periappendiceal abscess

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Jong Soo; Cha, Sang Hoon; Kim, Beak Hyun; Jung, Hwan Hoon; Kim, Taik Kun [Ansan Hospital, Korea University School of Medicine, Ansan (Korea, Republic of); Seo, Bo Kyoung; Chung, Kyoo Byung [Anam Hospital, Korea University School of Medicine, Seoul (Korea, Republic of); Park, Cheol Min [Guro Hospital, Korea University School of Medicine, Seoul (Korea, Republic of)

    2002-12-15

    To evaluate usefulness of intracavitary urokinase injection for the treatment of small sized periappendiceal abscess which was not unsuitable for percutaneous catheter drainage. From December 1997 to December 1999, we performed intracavitary injection of urokinase as a treatment of periappendiceal abscess in six patients. Initially, aspiration of the abscess was done using a 18 G needle under sonographic guidance. We measured the maximal length of residual abscess and injected 5000 IU of urokinase per centimeter of the diameter of the residual abscess. 24 hours after the injection of urokinase, repeated aspiration of the residual abscess was done, and follow-up sonographic examination was performed. The size of initial abscesses in each patients was ranged from 1.6 X 1.2 to 5.8 X 3.4 cm (mean=3.9 X 2.4 cm), and initial volume of aspirated pus was ranged from 3 to 31 cc (mean=11.8 cc).24 hour after the injection, the volume of respirated pus was ranged from 4 to 13.5 cc (mean=10.4 cc). Follow-up sonography performed 3 to 10 days later revealed no residual abscess. The mean duration of hospitalization was 5.5 days. Intracavitary urokinase injection under the sonographic guidance can be a useful method for the treatment of small sized periappendiceal abscess which is not suitable for percutaneous catheter drainage.

  15. Application of Molecular Modeling to Urokinase Inhibitors Development

    Directory of Open Access Journals (Sweden)

    V. B. Sulimov

    2014-01-01

    Full Text Available Urokinase-type plasminogen activator (uPA plays an important role in the regulation of diverse physiologic and pathologic processes. Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, and shortened survival in patients, whereas suppression of proteolytic activity of uPA leads to evident decrease of metastasis. Therefore, uPA has been considered as a promising molecular target for development of anticancer drugs. The present study sets out to develop the new selective uPA inhibitors using computer-aided structural based drug design methods. Investigation involves the following stages: computer modeling of the protein active site, development and validation of computer molecular modeling methods: docking (SOL program, postprocessing (DISCORE program, direct generalized docking (FLM program, and the application of the quantum chemical calculations (MOPAC package, search of uPA inhibitors among molecules from databases of ready-made compounds to find new uPA inhibitors, and design of new chemical structures and their optimization and experimental examination. On the basis of known uPA inhibitors and modeling results, 18 new compounds have been designed, calculated using programs mentioned above, synthesized, and tested in vitro. Eight of them display inhibitory activity and two of them display activity about 10 μM.

  16. Regimes internacionais

    OpenAIRE

    Meireles, André Bezerra

    2004-01-01

    Dissertação (mestraddo) - Universidade Federal de Santa Catarina, Centro de Ciências Jurídicas. Programa de Pós-Graduação em Direito. Qual o papel dos regimes internacionais com relação ao comportamento dos agentes das relações internacionais contemporâneas, em especial, o Estado? Dentro das negociações de uma esfera internacional caracterizada por uma forte interdependência econômica, verificada a existência de múltiplos canais de conexões entre as sociedades, e uma tendência contínua p...

  17. Intracavitary urokinase in the treatment of multiloculated liver abscess : a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Min; Lee, Mi Suk; Lee, Jin Hee; Ym, Seong Hee [Namwon Medical Center, Namwon (Korea, Republic of); Kim, Chong Soo; Han, Young Min; Choi, Ki Chul [Chonbuk National Univ. College of Medicine, Chonju (Korea, Republic of)

    1997-08-01

    Radiologically-guided percutaneous abscess drainage has been preferred as a therapeutic modality for hepatic abscesses, though where these have been septated or multilocular, its success rate has often been low. The results of several clinical and in vitro studies have recently suggested that in difficult cases, where abscesses occur in the peritoneal cavity and retroperitoneum, or multiloculated empyema of the thorax, urokinase may be useful. To our knowledge, however, there has been only one report of a case of liver abscess in which intracavitary urokinase was administered. The authors therefore report a case of multiseptated hepatic abscess occuring in a 53-year-man. Conventional percutaneous tube drainage failed, but the use of transcatheter intracavitary urokinase was successful. Diagnosis and continuing assessment involved a combination of ultrasound and CT scanning.

  18. Adsorption and Step Elution of Urokinase Using, Affinity Chromatography -Comparison of Data with Rate Model Simulation

    Institute of Scientific and Technical Information of China (English)

    MohammadRezaAboudzadehRovais; JiawenZhu; BinWu

    2004-01-01

    A non-equilibrium chromatographic rate model was employed to simulate the affinity chromatography of urokinase. The chromatography process was developed to a yield of high purity product of urokinase from crude materials. The affinity gel used in the process was prepared by an epichlorohydrin-activation method using epichlorohydrin activated Sepharose 4B as a matrix and p-aminobenzamidine as a ligand. The chromatographic process were numerically simulated and analyzed with the aid of VERSE-LC computer simulator. Considering the basic principles, rate model with the back mixing in column inlet was utilized in simulating and studying the effect of the column inlet pattern on other parameters. Comparison of the simulation results with the experimental data showed that the rate model can be used to describe the affinity chromatography of urokinase in a fixed bed column with satisfactory accuracy.

  19. Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases

    DEFF Research Database (Denmark)

    Illemann, Martin; Bird, Nigel; Majeed, Ali;

    2009-01-01

    Metastatic growth and invasion by colon cancer cells in the liver requires the ability of the cancer cells to interact with the new tissue environment. Plasmin(ogen) is activated on cell surfaces by urokinase-type PA (uPA), and is regulated by uPAR and plasminogen activator inhibitor-1 (PAI-1......). To compare the expression patterns of uPA, uPAR and PAI-1 in colon cancer with that in their liver metastases, we analysed matched samples from 14 patients. In all 14 primary colon cancers, we found upregulation of uPAR, uPA mRNA and PAI-1 in primarily stromal cells at the invasive front. In 5 of the 14......, whereas 8 of the remaining 9 showed direct contact between the cancer cells and the liver parenchyma. We conclude that there are 2 distinct patterns of expression of uPAR, uPA and PAI-1 in colon cancer liver metastases and that these correlate closely with 2 morphological growth patterns. These findings...

  20. Efficacy of 2-hour post glucose insulin levels in predicting insulin resistance in polycystic ovarian syndrome with infertility

    Directory of Open Access Journals (Sweden)

    Pikee Saxena

    2011-01-01

    Full Text Available Background : Insulin resistance (IR is central to the pathogenesis of polycystic ovarian syndrome (PCOS, but tests for determining IR are elaborate, tedious and expensive. Aims : To evaluate if "2-hour post-glucose insulin level" is an effective indicator of IR and can aid in diagnosing IR in infertile PCOS women. Settings and Design : Observational study at infertility clinic of a tertiary care center. Materials and Methods : 50 infertile women with PCOS and 20 females with tubal/male factor infertility were evaluated for the presence of IR, as defined by the fasting/2-hour post-glucose insulin levels cutoffs of >25/>41 μU/mL, respectively. The clinical, metabolic and endocrinologic profile was determined in both the groups. Statistical Analysis : Statistical analysis was performed using SPSS (Chicago, IL, USA. Results : Body mass index, post load glucose, insulin, glucose/insulin ratio, area under curve (AUC of glucose and insulin and insulinogenic index were significantly lower in the controls as compared to the PCOS group. "2-hour post-glucose insulin levels" were elevated in 88% of PCOS individuals but were normal in all females not suffering from PCOS. These levels significantly correlated with AUC of glucose and insulin, and insulinogenic index and inversely correlated with 2-hour glucose to insulin ratio (r=0.827, 0.749 and −0.732, respectively. Conclusions : "2-hour post-glucose insulin levels" appears to be a good indicator of IR. It can be a useful tool, especially in low resource setting where a single sample can confirm the diagnosis, thus reducing cost and repeat visits.

  1. Neuroprotection by urokinase plasminogen activator in the hippocampus.

    Science.gov (United States)

    Cho, Eunsil; Lee, Kyung Jin; Seo, Jung-Woo; Byun, Catherine Jeonghae; Chung, Sun-Ju; Suh, Dae Chul; Carmeliet, Peter; Koh, Jae-Young; Kim, Jong S; Lee, Joo-Yong

    2012-04-01

    Tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), which are both used for thrombolytic treatment of acute ischemic stroke, are serine proteases that convert plasminogen to active plasmin. Although recent experimental evidences have raised controversy about the neurotoxic versus neuroprotective roles of tPA in acute brain injury, uPA remains unexplored in this context. In this study, we evaluated the effect of uPA on neuronal death in the hippocampus of mice after kainate-induced seizures. In the normal brain, uPA was localized to both nuclei and cytosol of neurons. Following severe kainate-induced seizures, uPA completely disappeared in degenerating neurons, whereas uPA-expressing astrocytes substantially increased, suggesting reactive astrogliosis. uPA-knockout mice were more vulnerable to kainate-induced neuronal death than wild-type mice. Consistent with this, inhibition of uPA by intracerebral injection of the uPA inhibitor UK122 increased the level of neuronal death. In contrast, prior administration of recombinant uPA significantly attenuated neuronal death. Collectively, these results indicate that uPA renders neurons resistant to kainate-induced excitotoxicity. Moreover, recombinant uPA suppressed cell death in primary cultures of hippocampal neurons exposed to H2O2, zinc, or various excitotoxins, suggesting that uPA protects against neuronal injuries mediated by the glutamate receptor, or by oxidation- or zinc-induced death signaling pathways. Considering that tPA may facilitate neurodegeneration in acute brain injury, we suggest that uPA, as a neuroprotectant, might be beneficial for the treatment of acute brain injuries such as ischemic stroke.

  2. Comparative Evaluation of 2-Hour Rapid Diagnostic Algorithms for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin T.

    Science.gov (United States)

    McRae, Andrew D; Innes, Grant; Graham, Michelle; Lang, Eddy; Andruchow, James E; Yang, Hong; Ji, Yunqi; Vatanpour, Shabnam; Southern, Danielle A; Wang, Dongmei; Seiden-Long, Isolde; DeKoning, Lawrence; Kavsak, Peter

    2017-08-01

    Symptoms of acute coronary syndrome account for a large proportion of emergency department (ED) visits and hospitalizations. High-sensitivity troponin can rapidly rule out or rule in acute myocardial infarction (AMI) within a short time of ED arrival. We sought to validate test characteristics and classification performance of 2-hour high-sensitivity troponin T (hsTnT) algorithms for the rapid diagnosis of AMI. We included consecutive patients from 4 academic EDs with suspected cardiac chest pain who had hsTnT assays performed 2 hours apart (± 30 minutes) as part of routine care. The primary outcome was AMI at 7 days. Secondary outcomes included major adverse cardiac events (mortality, AMI, and revascularization). Test characteristics and classification performance for multiple 2-hour algorithms were quantified. Seven hundred twenty-two patients met inclusion criteria. Seven-day AMI incidence was 10.9% and major adverse cardiac event incidence was 13.7%. A 2-hour rule-out algorithm proposed by Reichlin and colleagues ruled out AMI in 59.4% of patients with 98.7% sensitivity and 99.8% negative predictive value (NPV). The 2-hour rule-out algorithm proposed by the United Kingdom National Institute for Health and Care Excellence ruled out AMI in 50.3% of patients with similar sensitivity and NPV. Other exploratory algorithms had similar sensitivity but marginally better classification performance. According to Reichlin et al., the 2-hour rule-in algorithm ruled in AMI in 16.5% of patients with 92.4% specificity and 58.5% positive predictive value. Two-hour hsTnT algorithms can rule out AMI with very high sensitivity and NPV. The algorithm developed by Reichlin et al. had superior classification performance. Reichlin and colleagues' 2-hour rule-in algorithm had poor positive predictive value and might not be suitable for early rule-in decision-making. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Randomized clinical trial between hourly titrated and 2 hourly static oral misoprostol solution for induction of labor.

    Science.gov (United States)

    Rouzi, Abdulrahim A; Alsahly, Nora; Alamoudi, Rana; Almansouri, Nisma; Alsinani, Nawal; Alkafy, Souzan; Rozzah, Rayyan; Abduljabbar, Hassan

    2017-04-01

    Misoprostol is an effective agent for the induction of labor. Existing guidelines recommend oral misoprostol solution 25 μg every 2 hours. However, more research is required to optimize the use of oral misoprostol solution for the induction of labor. The purpose of this study was to compare efficacy and safety of hourly titrated-dose oral misoprostol solution with static-dose oral misoprostol solution every 2 hours for labor induction. In this randomized controlled study, oral misoprostol solution was administered as (1) 20 μg hourly (≤4 doses) that was increased in the absence of regular uterine contractions to 40 μg hourly (≤4 doses) and then to 60 μg hourly (≤16 doses) or (2) 25 μg every 2 hours until active labor began (≤12 doses). A sample size of 146 women was planned with the use of a projected 95% rate for the primary endpoint (vaginal delivery within 24 hours) for hourly titrated-dose misoprostol and 80% rate for static-dose misoprostol every 2 hours. Safety outcomes included maternal morbidity and adverse neonatal outcomes. From December 2013 to July 2015, 146 women were assigned randomly to treatment. Demographic and clinical factors were similar between groups, except for age. Vaginal delivery was achieved within 24 hours in 47 women (64.4%) who received hourly titrated-doses of misoprostol solution and 48 women (65.8%) who received 2-hourly static-dose misoprostol solution (P=1.00). Rates of vaginal delivery within 24 hours did not differ significantly between treatment groups for women who were nulliparous (P=1.00) or who had postterm pregnancies (P=.66), a Bishop score of ≤3 (P=.84), or oxytocin augmentation (P=.83). Cesarean deliveries were performed within 24 hours in 9 women who received hourly titrated-dose misoprostol solution and 2 women who received 2-hourly static-dose misoprostol solution (P=.056). Pyrexia and meconium-stained liquor occurred more frequently with the hourly titrated-dose regimen. The static-dose oral

  4. Effects of acute and 2-hour postphysical activity on the estimation of body fat made by the bod pod.

    Science.gov (United States)

    Harrop, Bradley J; Woodruff, Sarah J

    2015-06-01

    The Bod Pod has been found to be reliable/valid against several criterion methods, including hydrostatic weighing and dual-energy x-ray absorptiometry, and under different conditions, such as clothing, dehydrated states, and body temperature changes. However, questions remain regarding the effects of an acute bout of exercise. Therefore, the purpose was to determine the effects of an acute bout of exercise on the estimations made by the Bod Pod. Participants (15 men and 22 women) were of age 18-27 years and were currently exercising. Baseline Bod Pod measures were completed followed by a 30-minute cycling trial at 75% of maximum heart rate. Bod Pod measures were taken immediately after exercise and 2 hours after exercise. Differences between men and women were found at baseline between height (p Bod Pod testing seems to alter the estimate of %BF, and continues to affect the prediction 2 hours after exercise in women.

  5. The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi

    NARCIS (Netherlands)

    Hovius, J.W.R.; Bijlsma, M.F.; van der Windt, G.J.W.; Wiersinga, W.J.; Boukens, B.J.D.; Coumou, J.; Oei, A.; de Beer, R.; de Vos, A.F.; van 't Veer, C.; van Dam, A.P.; Wang, P.; Fikrig, E.; Levi, M.M.; Roelofs, J.J.T.H.; van der Poll, T.

    2009-01-01

    The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR); however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also

  6. Jet and ultrasonic nebulization of single chain urokinase plasminogen activator (scu-PA)

    DEFF Research Database (Denmark)

    Münster, Anna-Marie; Bendstrup, E; Jensen, J.I.

    2000-01-01

    Recent studies have indicated that the deposition of intra-alveolar fibrin may play a central role in the pathogenesis of acute respiratory distress syndrome (ARDS). Our aim was to study whether the indigenous fibrinolytic agent (urokinase) normally present in the alveoli can be administered...

  7. Regulation of urokinase receptors in monocytelike U937 cells by phorbol ester phorbol myristate acetate

    DEFF Research Database (Denmark)

    Picone, R; Kajtaniak, E L; Nielsen, L S

    1989-01-01

    A specific surface receptor for urokinase plasminogen activator (uPA) recognizes the amino-terminal growth factor-like sequence of uPA, a region independent from and not required for the catalytic activity of this enzyme. The properties of the uPA receptor (uPAR) and the localization and distribu...

  8. Urokinase mediates endothelial cell survival via induction of the X-linked inhibitor of apoptosis protein

    DEFF Research Database (Denmark)

    Prager, Gerald W; Mihaly, Judit; Brunner, Patrick M;

    2008-01-01

    Urokinase-type plasminogen activator (uPA) additionally elicits a whole array of pro-angiogenic responses, such as differentiation, proliferation, and migration. In this study, we demonstrate that in endothelial cells uPA also protects against apoptosis by transcriptional up-regulation and partia...

  9. Dynamics of urokinase receptor interaction with Peptide antagonists studied by amide hydrogen exchange and mass spectrometry

    DEFF Research Database (Denmark)

    Jørgensen, Thomas J D; Gårdsvoll, Henrik; Danø, Keld

    2004-01-01

    Using amide hydrogen exchange combined with electrospray ionization mass spectrometry, we have in this study determined the number of amide hydrogens on several peptides that become solvent-inaccessible as a result of their high-affinity interaction with the urokinase-type plasminogen activator r...

  10. A sensitive bioimmunoassay for thrombin-cleaved two-chain urokinase-type plasminogen activator (abstract)

    NARCIS (Netherlands)

    Braat, E.A.M.; Nauland, U.; Dooijewaard, G.; Rijken, P.C.

    1996-01-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T). Little is known about the physiological importance of tcu-PA/T. To examine the occurrence of tcu-PA/T in vivo, we developed a sensitive and specific bioimmunoassay (BIA) f

  11. Circulating intact and cleaved forms of the urokinase-type plasminogen activator receptor

    DEFF Research Database (Denmark)

    Sørensen, Tine Thurison; Christensen, Ib J; Lund, Ida K;

    2015-01-01

    BACKGROUND: High levels of circulating forms of the urokinase-type plasminogen activator receptor (uPAR) are significantly associated to poor prognosis in cancer patients. Our aim was to determine biological variations and reference intervals of the uPAR forms in blood, and in addition, to test t...

  12. Characterization of human endothelial cell urokinase-type plasminogen activator receptor protein and messenger RNA

    DEFF Research Database (Denmark)

    Barnathan, E S; Kuo, A; Karikó, K

    1990-01-01

    Human umbilical vein endothelial cells in culture (HUVEC) express receptors for urokinase-type plasminogen activators (u-PA). The immunochemical nature of this receptor and its relationship to u-PA receptors expressed by other cell types is unknown. Cross-linking active site-blocked u-PA to HUVEC...

  13. Therapeutic effectiveness of intracavitary urokinase in the management of stage II empyema patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyu Sik; Jeong, Tae Gon; Lee, Dong Won; Lee, Jeong Min; Han, Young Min; Kim, Chong Soo; Chung, Gyung Ho; Lee, Sang Yong; Sohn, Myung Hee; Choi, Ki Chul [Chonbuk National Univ. Medical School, Chonju (Korea, Republic of)

    1997-06-01

    To compare the therapeutic effectiveness of urokinase instillation via PCD catheter with other conventional therapeutic modalities, namely thoracentesis, closed thoracostomy and peroutaneous catheter drainage, in the management of patients with early and late stage II empyema Twenty seven early and 19 late stage II empyema patients were reviewed. We compared the results of treatment including average length of hospitalization, success rate, and the interval between first procedure and 75% improvement as seen on simple chest film. The average length of hospitalization and average improvement interval of stage II empyema patients treated with urokinase instillation via PCD catheter, were shortest of all : 11.8 and 8.5 days in early stage II patients, and 16.7 and 9.4 days in late stage II. For other modalities, the corresponding figures were as follows: 17.2 and 11.5, and 24.3 and 16.2 days; closed thoracostomy: 48.0 and 32.3, and 37.7 and 24.0 days; percutaneous catheter drainage: 35.2 and 17.2, and 34.8, and 20.0 days. All patients treated with intracavitary urokinase showed complete drainage of empyema. Intracavitary urokinase facilitates percutaneous catheter drainage of empyema, with a resultant reduction of hospitalization days. This method also has a high success rate.

  14. Reduction of mouse atherosclerosis by urokinase inhibition or with a limited-spectrum matrix metalloproteinase inhibitor

    DEFF Research Database (Denmark)

    Hu, Jie Hong; Touch, Phanith; Zhang, Jingwan

    2015-01-01

    AIMS: Elevated activity of urokinase plasminogen activator (uPA) and MMPs in human arteries is associated with accelerated atherosclerosis, aneurysms, and plaque rupture. We used Apoe-null mice with macrophage-specific uPA overexpression (SR-uPA mice; a well-characterized model of protease-accele...

  15. Structure and ligand interactions of the urokinase receptor (uPAR)

    DEFF Research Database (Denmark)

    Kjaergaard, Magnus; Hansen, Line V.; Jacobsen, Benedikte

    2008-01-01

    The urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycolipid-anchored membrane glycoprotein, which is responsible for focalizing plasminogen activation to the cell surface through its high-affinity binding to the serine protease uPA. This tight interaction (KD less than 1 nM) ...

  16. Elevated plasma urokinase receptor predicts low birth weight in maternal malaria

    DEFF Research Database (Denmark)

    Ostrowski, S R; Shulman, C E; Peshu, N

    2007-01-01

    The blood level of soluble urokinase receptor (suPAR) is increased and associated with a poor clinical or fatal outcome in children with acute malaria. This study hypothesized that the suPAR level would be associated with foetal outcome in maternal malaria. suPAR was measured by ELISA in maternal...

  17. Soluble Urokinase Plasminogen Activator Receptor for Risk Prediction in Patients Admitted with Acute Chest Pain

    DEFF Research Database (Denmark)

    Lyngbæk, Stig; Andersson, Charlotte; Marott, Jacob L

    2013-01-01

    Plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict mortality in several clinical settings, but the long-term prognostic importance of suPAR in chest pain patients admitted on suspicion of non-ST-segment elevation acute coronary syndrome (NSTEACS) is uncertain....

  18. A sensitive bioimmunoassay for thrombin-cleaved two-chain urokinase-type plasminogen activator (abstract)

    NARCIS (Netherlands)

    Braat, E.A.M.; Nauland, U.; Dooijewaard, G.; Rijken, P.C.

    1996-01-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T). Little is known about the physiological importance of tcu-PA/T. To examine the occurrence of tcu-PA/T in vivo, we developed a sensitive and specific bioimmunoassay (BIA)

  19. Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide

    DEFF Research Database (Denmark)

    Llinas, Paola; Le Du, Marie Hélène; Gårdsvoll, Henrik

    2005-01-01

    We report the crystal structure of a soluble form of human urokinase-type plasminogen activator receptor (uPAR/CD87), which is expressed at the invasive areas of the tumor-stromal microenvironment in many human cancers. The structure was solved at 2.7 A in association with a competitive peptide...... inhibitor of the urokinase-type plasminogen activator (uPA)-uPAR interaction. uPAR is composed of three consecutive three-finger domains organized in an almost circular manner, which generates both a deep internal cavity where the peptide binds in a helical conformation, and a large external surface...... accessible for other protein interactions (vitronectin and integrins). By this unique structural assembly, uPAR can orchestrate the fine interplay with the partners that are required to guide uPA-focalized proteolysis on the cell surface and control cell adhesion and migration....

  20. Regulation of urokinase receptors in monocytelike U937 cells by phorbol ester phorbol myristate acetate

    DEFF Research Database (Denmark)

    Picone, R; Kajtaniak, E L; Nielsen, L S

    1989-01-01

    A specific surface receptor for urokinase plasminogen activator (uPA) recognizes the amino-terminal growth factor-like sequence of uPA, a region independent from and not required for the catalytic activity of this enzyme. The properties of the uPA receptor (uPAR) and the localization and distribu......A specific surface receptor for urokinase plasminogen activator (uPA) recognizes the amino-terminal growth factor-like sequence of uPA, a region independent from and not required for the catalytic activity of this enzyme. The properties of the uPA receptor (uPAR) and the localization...... and distribution of uPA in tumor cells and tissues suggest that the uPA/uPAR interaction may be important in regulating extracellular proteolysis-dependent processes (e.g., invasion, tissue destruction). Phorbol myristate acetate (PMA), an inducer of U937 cell differentiation to macrophage-like cells, elicits...

  1. Proteolytic modulation of thrombopoietin activity: comparison of thrombin, plasmin, and urokinase.

    Science.gov (United States)

    Reiner, A P; Aramaki, K M

    2000-06-01

    Several observations suggest that limited proteolysis of full-length 70 kD human thrombopoietin (Tpo) may be important for Tpo biology. Recently, it was reported that thrombin cleaves full-length recombinant human Tpo (rhTpo) sequentially at two sites, Arg(195) within the glycan domain followed by Arg(117) within the cytokine domain, and that these cleavages modulate Tpo activity in vitro. We demonstrate that urokinase and plasmin also cleave rhTpo in a time-dependent manner. Urokinase cleavage is confined to the glycan domain, and generates a 35 kD N-terminal fragment that contains the intact cytokine domain, and is associated with increased Tpo activity. In contrast, plasmin cleaves Tpo sequentially at two specific sites (Arg(205) within the glycan domain followed by Lys(52) within the cytokine domain), and is associated with a marked decrease in Tpo activity. These proteolytic events have potential implications for regulation of Tpo activity in vivo.

  2. Urokinase receptor (uPAR) ligand based recombinant toxins for human cancer therapy.

    Science.gov (United States)

    de Virgilio, Maddalena; Silvestris, Franco

    2011-01-01

    The urokinase receptor (uPAR) exerts essential functions in the pathophysiology of cancers and therefore constitutes an important drug target. In order to generate efficient drugs against uPAR, a new approach includes chimeric proteins associating one molecular address to specifically target uPAR and one bacterial or plant toxin that will eventually kill the tumoural cell. Using this frame, several recombinant toxins have been designed namely DTAT, DTAT13, EGFATFKDEL 7 mut, and ATF-SAP. As molecular address, all of these fusion proteins use the amino-terminal fragment of urokinase that binds with high affinity to uPAR through its growth factor domain (GFD). The various toxin moieties were derived from either diphtheria toxin, Pseudomonas exotoxin A (PE38), or saporin. In this review, we describe the rational, design, production and therapeutic anti-cancer potential of these chimeric toxins.

  3. Urokinase Separation from Cell Culture Broth of a Human Kidney Cell Line

    Directory of Open Access Journals (Sweden)

    Vibha Bansal, Pradip K. Roychoudhury, Ashok Kumar

    2007-01-01

    Full Text Available A single step ion-exchange chromatography on a sulfo-propyl (SP- Sepharose column was performed to separate both the high molecular weight (HMW- and low molecular weight (LMW- forms of enzymatically active urokinase type plasminogen activator from human kidney (HT1080 cell culture media. The level of urokinase secreted by the cell line reached to about 145 Plough units/ml culture broth within 48 h of cultivation. The conditioned cell culture media was applied directly to the column without any prior concentration steps. Polyacrylamide gel electrophoresis of the column eluates in the presence of sodium dodecyl sulphate showed that the cell line secretes three forms of two-chain high molecular weight (HMW urokinase of molecular weights (Mr 64,000, 60,900 and 55,000. In addition, two low molecular weight (LMW forms of Mr 22,000 and 20,000; proteolytic cleavage products of HMW, were also found. The HMW and LMW forms had intrinsic plasminogen dependent proteolytic activity as judged by zymographic analysis. The specific activity of the pooled peak fractions increased (approximately 93-fold to values as high as 1481 Plough units/ mg protein. Both HMW as well as LMW forms were obtained in significantly high yields.

  4. Anterograde Intra-Arterial Urokinase Injection for Salvaging Fibular Free Flap

    Directory of Open Access Journals (Sweden)

    Dae-Sung Lee

    2013-05-01

    Full Text Available We present a case of a 57-year-old male patient who presented with squamous cell carcinoma on his mouth floor with cervical and mandibular metastases. Wide glossectomy with intergonial mandibular ostectomy, and sequential reconstruction using fibular osteomyocutaneous free flap were planned. When the anastomosis between the peroneal artery of the fibular free flap and the right lingual artery was performed, no venous flow was observed at the vena comitans. Then re-anastomosis followed by topical application of papaverine and lidocaine was attempted. However, the blood supply was not recovered. Warm saline irrigation over 30 minutes was also useless. Microvascular thromboses of donor vessels were clinically suspected, so a solution of 100,000 units of urokinase was infused once through a 26-gauge angiocatheter inserted into the recipient artery just at the arterial anastomotic site, until the solution gushed out through the flap vena comitans. Immediately after the application of urokinase, arterial flow and venous return were restored. There were no complications during the follow-up period of 11 months. We believe that vibrating injuries from the reciprocating saw during osteotomies and flap insetting might be the cause of microvascular thromboses. The use of urokinase may provide a viable option for the treatment of suspicious intraoperative arterial thrombosis.

  5. Anterograde intra-arterial urokinase injection for salvaging fibular free flap.

    Science.gov (United States)

    Lee, Dae-Sung; Jung, Sun-Il; Kim, Deok-Woo; Dhong, Eun-Sang

    2013-05-01

    We present a case of a 57-year-old male patient who presented with squamous cell carcinoma on his mouth floor with cervical and mandibular metastases. Wide glossectomy with intergonial mandibular ostectomy, and sequential reconstruction using fibular osteomyocutaneous free flap were planned. When the anastomosis between the peroneal artery of the fibular free flap and the right lingual artery was performed, no venous flow was observed at the vena comitans. Then re-anastomosis followed by topical application of papaverine and lidocaine was attempted. However, the blood supply was not recovered. Warm saline irrigation over 30 minutes was also useless. Microvascular thromboses of donor vessels were clinically suspected, so a solution of 100,000 units of urokinase was infused once through a 26-gauge angiocatheter inserted into the recipient artery just at the arterial anastomotic site, until the solution gushed out through the flap vena comitans. Immediately after the application of urokinase, arterial flow and venous return were restored. There were no complications during the follow-up period of 11 months. We believe that vibrating injuries from the reciprocating saw during osteotomies and flap insetting might be the cause of microvascular thromboses. The use of urokinase may provide a viable option for the treatment of suspicious intraoperative arterial thrombosis.

  6. Design and Testing of a 2-Hour Oxygen Prebreathe Protocol for Space Walks from the International Space Station

    Science.gov (United States)

    Gernhardt, Michael L.; Conkin, J.; Foster, P. P.; Pilmanis, A. A.; Butler, B. D.; Beltran, E.; Fife, C. E.; Vann, R. D.; Gerth, W. A.; Loftin, K. C.; hide

    2000-01-01

    To develop and test a 2-hour prebreathe protocol for performing extravehicular activities (EVAs) from the International Space Station (ISS). Combinations of adynamia (non-walking), prebreathe exercise, and space suit donning options (10.2 vs. 14.7 psi) were evaluated, against timeline and consumable contraints to develop an operational 2- hour prebreathe protocol. Prospective accept/reject criteria were defined for decompression sickness (DCS) and venous gas emboli (VGE) from analysis of historical DCS data, combined with risk management of DCS under ISS mission circumstances. Maximum operational DCS levels were defined based on protecting for EVA capability with two crew-members at 95% confidence, throughout ISS lifetime (within the constraints of NASA DCS disposition policy JPG 1800.3). The accept/reject limits were adjusted for greater safety based on analysis of related medical factors. Monte-Carlo simulation was performed to design a closed sequential, multi-center human trial. Protocols were tested with 4 different prebreathe exercises (Phases I-IV), prior to exposure to 4.3 psi for 4 hrs. Subject selection, Doppler monitoring for VGE, test termination criteria, and DCS definitions were standardized. Phase I: upper and lower body exercises using dual-cycle ergometry (75% VO2 max for 10 min). Phase II: ergometry plus 24 min of light exercise (simulating space-suit preparations). Phase III: same 24 min of light exercise but no ergometry, and Phase IV: 56 min of light exercise without ergometry. A prebreathe procedure was accepted if, at 95% confidence, the incidence of DCS was less than 15% (with no Type II DCS), and Grade IV VGE was less than 20%.

  7. Sustainable urban regime adjustments

    DEFF Research Database (Denmark)

    Quitzau, Maj-Britt; Jensen, Jens Stissing; Elle, Morten

    2013-01-01

    The endogenous agency that urban governments increasingly portray by making conscious and planned efforts to adjust the regimes they operate within is currently not well captured in transition studies. There is a need to acknowledge the ambiguity of regime enactment at the urban scale. This directs...... attention to the transformative implications of conscious strategic maneuvering by incumbent regime actors, when confronting regime structurations. This article provides insight to processes of regime enactment performed by local governments by applying a flow-oriented perspective on regime dynamics...

  8. Thrombin inhibitory and clot-specific fibrinolytic activities of the urokinase variant, M23 (rscu-PA-40 kDa/Hir)

    NARCIS (Netherlands)

    Schneider, J; Wnendt, S; Saunders, D; HeinzelWieland, R; Wilffert, B; Steffens, G

    1996-01-01

    The recombinant bifunctional urokinase variant, M23 (rscu-PA-40 kDA/Hir), comprising the kringle and protease domain of single-chain urokinase-type plasminogen activator and a C-terminal fragment of hirudin in one single-chain molecule, was evaluated for its thrombin-inhibitory and fibrinolytic

  9. The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau

    DEFF Research Database (Denmark)

    Eugen-Olsen, J; Gustafson, P; Sidenius, Niels Chr.

    2002-01-01

    To investigate whether the serum level of soluble urokinase plasminogen activator receptor (suPAR) carries prognostic information in individuals infected with Mycobacterium tuberculosis.......To investigate whether the serum level of soluble urokinase plasminogen activator receptor (suPAR) carries prognostic information in individuals infected with Mycobacterium tuberculosis....

  10. Structure, function and expression on blood and bone marrow cells of the urokinase-type plasminogen activator receptor, uPAR

    DEFF Research Database (Denmark)

    Plesner, T; Behrendt, N; Ploug, M

    1997-01-01

    Several important functions have been assigned to the receptor for urokinase-type plasminogen activator, uPAR. As implied by the name, uPAR was first identified as a high affinity cellular receptor for urokinase plasminogen activator (uPA). It mediates the binding of the zymogen, pro-uPA, to the ...

  11. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in early focal cerebral infarction following urokinase thrombolysis in rats

    Institute of Scientific and Technical Information of China (English)

    Yuqiang Song; Hongli Zou; Guofeng Wang; Hongxia Yang; Zhaohong Xie; Jianzhong Bi

    2012-01-01

    Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and brain edema. Matrix metalloproteinase-9 also likely participates in thrombolysis. A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery. At 3 hours following model induction, urokinase was injected into the caudal vein. Decreased neurological severity score, reduced infarct volume, and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis. These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.

  12. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    DEFF Research Database (Denmark)

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R;

    2007-01-01

    reorganization in mature osteoclasts. INTRODUCTION: Urokinase receptor (uPAR) is actively involved in the regulation of important cell functions, such as proliferation, adhesion, and migration. It was previously shown that the major players in bone remodeling, osteoblasts and osteoclasts, express u...... with other osteoblasts markers. On the resorptive side, the number of osteoclasts formed in vitro from uPAR KO monocytes was decreased. Podosome imaging in uPAR KO osteoclasts revealed a defect in actin ring formation. CONCLUSIONS: The defective proliferation and differentiation of bone cells, coincident...

  13. Comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Urochinasi per via Sistemica nell'Infarto Miocardico (USIM) Collaborative Group.

    Science.gov (United States)

    Rossi, P; Bolognese, L

    1991-09-01

    In a randomized trial of the effects on in-hospital mortality of intravenous urokinase plus heparin versus heparin alone, 2,531 patients with acute myocardial infarction in 89 coronary care units were enrolled for greater than 30 months. Patients admitted within 4 hours of the onset of pain were randomized to receive either intravenous urokinase (a bolus dose of 1 million U repeated after 60 minutes) plus heparin (a bolus dose of 10,000 U followed by 1,000 IU/hour for 48 hours) or heparin alone (infused at the same rate). Complete data were obtained in 2,201 patients (1,128 taking urokinase and 1,073 taking heparin). At 16 days, overall hospital mortality was 8% in the urokinase and 8.3% in the heparin group (p = not significant). Among patients with anterior infarction, mortality was 10.3% in the urokinase and 13.9% in the heparin group (p = 0.09; relative risk = 0.73). The incidence of major bleeding (urokinase 0.44%, heparin 0.37%) as well as the overall incidence of stroke (urokinase 0.35%, heparin 0.20%) was similar in the 2 groups. The rates of major in-hospital cardiac complications (reinfarction, postinfarction angina) were also similar.

  14. Soluble urokinase plasminogen activator receptor and hypertension among black South Africans after 5 years

    DEFF Research Database (Denmark)

    Botha, Shani; Fourie, Carla Mt; Schutte, Rudolph;

    2015-01-01

    Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker that links inflammation with cardiovascular risk. However, studies linking suPAR and hypertension are scant. First, we determined whether baseline suPAR is elevated in normotensive black South Africans who developed hypertens......Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker that links inflammation with cardiovascular risk. However, studies linking suPAR and hypertension are scant. First, we determined whether baseline suPAR is elevated in normotensive black South Africans who developed...... hypertension over 5 years, compared with those who remained normotensive; and second, whether hypertension is associated with suPAR. This substudy is embedded in the South African leg of the Prospective Urban and Rural Epidemiology study, performed in the North West Province. We investigated 429 normotensive......PAR with hypertensive status. This study highlights the need for more research on the role of suPAR in hypertension and cardiovascular disease development in black South Africans....

  15. The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality

    DEFF Research Database (Denmark)

    Wittenhagen, p; Kronborg, Gitte; Nielsen, H

    2004-01-01

    This multicentre prospective study was conducted to investigate whether the level of the soluble form of urokinase-type plasminogen activator receptor (suPAR) is elevated during pneumococcal bacteraemia and is of predictive value in the early stage of the disease. Plasma levels of suPAR were incr...

  16. A sensitive bioimmunoassay for thrombin-cleaved two-chain urokinase-type plasminogen activator in human body fluids

    NARCIS (Netherlands)

    Braat, E.A.M.; Nauland, U.; Dooijewaard, G.; Rijken, D.C.

    1996-01-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a two-chain form (tcu-PA/T), which is virtually inactive in plasminogen activator assays. Little is known about the physiological importance of tcu-PA/T. To examine the occurrence of tcu-PA/T in vivo, we developed a sen

  17. Quantitative PET of human urokinase-type plasminogen activator receptor with 64Cu-DOTA-AE105

    DEFF Research Database (Denmark)

    Persson, Morten; Madsen, Jacob; Østergaard, Søren

    2012-01-01

    Expression levels of the urokinase-type plasminogen activator receptor (uPAR) represent an established biomarker for poor prognosis in a variety of human cancers. The objective of the present study was to explore whether noninvasive PET can be used to perform a quantitative assessment of expressi...

  18. The urokinase receptor (uPAR) and the uPAR-associated protein (uPARAP/Endo180)

    DEFF Research Database (Denmark)

    Behrendt, Niels

    2004-01-01

    processes involve a highly organized interplay between proteases and their cellular binding sites as well as specific substrates and internalization receptors. This review article is focused on two components, the urokinase plasminogen activator receptor (uPAR) and the uPAR-associated protein (uPARAP, also...

  19. Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV-infected patients receiving highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Andersen, Ove; Eugen-Olsen, Jesper; Kofoed, Kristian;

    2008-01-01

    Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV-infected...

  20. Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome

    DEFF Research Database (Denmark)

    Ostergaard, Christian; Benfield, Thomas; Lundgren, Jens D;

    2004-01-01

    The urokinase-type plasminogen activator system has been suggested to play a pathophysiological role in brain damage. The aim of this study was to evaluate CSF levels of suPAR in 183 patients clinically suspected of having meningitis on admission. Of these, 54 patients were found to have purulent...

  1. A sensitive bioimmunoassay for thrombin-cleaved two-chain urokinase-type plasminogen activator in human body fluids

    NARCIS (Netherlands)

    Braat, E.A.M.; Nauland, U.; Dooijewaard, G.; Rijken, D.C.

    1996-01-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a two-chain form (tcu-PA/T), which is virtually inactive in plasminogen activator assays. Little is known about the physiological importance of tcu-PA/T. To examine the occurrence of tcu-PA/T in vivo, we developed a

  2. Genetic association of urokinase-type plasminogen activator gene rs2227564 site polymorphism with sporadic Alzheimer's disease in the Han Chinese population

    Institute of Scientific and Technical Information of China (English)

    Xuelian Ji; Longfei Jia; Jianping Jia; Li Qi

    2012-01-01

    A missense C/T polymorphism in exon 6 (the NCBI rsID is rs2227564) of the urokinase-type plasminogen activator gene has been identified as a possible hot spot for Alzheimer's disease risk.The present study analyzed urokinase-type plasminogen gene polymorphisms of rs2227564 with sporadic Alzheimer's disease by PCR-restriction fragment length polymorphism.Results showed that CC,CT and TT genotype distribution frequencies had significant differences between sporadic Alzheimer's disease patients and healthy controls.In-depth analysis of the association between urokinase-type plasminogen gene rs2227564 polymorphisms and sporadic Alzheimer's disease indicated that people with the C-positive genotype CC + CT were at a higher risk for developing sporadic Alzheimer's disease.These results support the contribution of the polymorphisms of rs2227564 in the urokinase-type plasminogen gene to the pathogenesis of sporadic Alzheimer's disease in the Han Chinese population.

  3. Measuring autocratic regime stability

    Directory of Open Access Journals (Sweden)

    Joseph Wright

    2016-01-01

    Full Text Available Researchers measure regime stability in autocratic contexts using a variety of data sources that capture distinct concepts. Often this research uses concepts developed for the study of democratic politics, such as leadership change or institutionalized authority, to construct measures of regime breakdown in non-democratic contexts. This article assesses whether the measure a researcher chooses influences the results they obtain by examining data on executive leadership, political authority, and autocratic regimes. We illustrate the conceptual differences between these variables by extending recent studies in the literature on the political consequences of non-tax revenue and unearned foreign income.

  4. Exchange rate regime choice

    Directory of Open Access Journals (Sweden)

    Beker Emilija

    2006-01-01

    Full Text Available The choice of an adequate exchange rate regime proves to be a highly sensitive field within which the economic authorities present and confirm themselves. The advantages and disadvantages of fixed and flexible exchange rate regimes, which have been quite relativized from the conventional point of view, together with simultaneous, but not synchronized effects of structural and external factors, remain permanently questioned throughout a complex process of exchange rate regime decision making. The paper reflects the attempt of critical identification of the key exchange rate performances with emphasis on continuous non-uniformity and (uncertainty of shelf life of a relevant choice.

  5. Identification and characterization of the murine cell surface receptor for the urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Solberg, H.; Løber, D.; Eriksen, J

    1992-01-01

    Cell-binding experiments have indicated that murine cells on their surface have specific binding sites for mouse urokinase-type plasminogen activator (u-PA). In contrast to the human system, chemical cross-linking studies with an iodinated ligand did not yield any covalent adducts in the murine...... system, but in ligand-blotting analysis, two mouse u-PA-binding proteins could be visualized. To confirm that these proteins are the murine counterpart of the human u-PA receptor (u-PAR), a peptide was derived from the murine cDNA clone assigned to represent the murine u-PAR due to cross......-hybridization and pronounced sequence similarity with human u-PAR cDNA [Kristensen, P., Eriksen, J., Blasi, F. & Danø, K. (1991) J. Cell Biol. 115, 1763-1771]. A rabbit antiserum raised against this peptide specifically recognized two polypeptide bands with electrophoretic mobilities identical to those identified by ligand...

  6. Urokinase plasminogen activator receptor: a functional integrator of extracellular proteolysis, cell adhesion, and signal transduction.

    Science.gov (United States)

    Ferraris, Gian Maria Sarra; Sidenius, Nicolai

    2013-06-01

    The urokinase plasminogen activator receptor (uPAR) is a cell surface receptor involved in a multitude of physiologic and pathologic processes. uPAR regulates simultaneously a branch of the plasminogen activator system and modulates cell adhesion and intracellular signaling by interacting with extracellular matrix components and signaling receptors. The multiple uPAR functions are deeply interconnected, and their integration determines the effects that uPAR expression triggers in different contexts. The proteolytic function of uPAR affects both the signaling and the adhesive functions of the receptor, whereas these latter two are closely interconnected. This review focuses on the molecular mechanisms that connect and mutually regulate the different uPAR functions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  7. Soluble Urokinase-Type Plasminogen Activator Receptor Levels in Patients With Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Røge, Rasmus; Pristed, Sofie Gry;

    2015-01-01

    BACKGROUND: The etiology of schizophrenia remains largely unknown but alterations in the immune system may be involved. In addition to the psychiatric symptoms, schizophrenia is also associated with up to 20 years reduction in life span. Soluble urokinase-type plasminogen activator receptor (su......PAR) is a protein that can be measured in blood samples and reflects the levels of inflammatory activity. It has been associated with mortality and the development of type 2 diabetes and cardiovascular disease. METHODS: suPAR levels in patients with schizophrenia were compared to healthy controls from the Danish...... Blood Donor Study. SuPAR levels were dichotomized at >4.0 ng/ml, which is considered the threshold for low grade inflammation. A multiple logistic regression model was used and adjusted for age, sex, and current smoking. RESULTS: In total we included 1009 subjects, 105 cases with schizophrenia (10...

  8. Activation of pro-urokinase and plasminogen on human sarcoma cells

    DEFF Research Database (Denmark)

    Stephens, R W; Pöllänen, J; Tapiovaara, H

    1989-01-01

    Human HT-1080 fibrosarcoma cells produce urokinase-type plasminogen activator (u-PA) and type 1 plasminogen activator inhibitor (PAI-1). We found that after incubation of monolayer cultures with purified native human plasminogen in serum-containing medium, bound plasmin activity could be eluted...... from the cells with tranexamic acid, an analogue of lysine. The bound plasmin was the result of plasminogen activation on the cell surface; plasmin activity was not taken up onto cells after deliberate addition of plasmin to the serum-containing medium. The cell surface plasmin formation was inhibited...... to inhibition by endogenous PAI-1 and by added PAI-2, while the cell-bound plasmin was inaccessible to serum inhibitors, but accessible to added aprotinin and an anticatalytic monoclonal antibody. A model for cell surface plasminogen activation is proposed in which plasminogen binding to cells from serum medium...

  9. Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

    DEFF Research Database (Denmark)

    Hansen, Line; Unmack Larsen, Esben Kjær; Nielsen, Erik Holm

    2013-01-01

    Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted...... towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor...... to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient...

  10. The soluble urokinase plasminogen activator receptor and its fragments in venous ulcers

    DEFF Research Database (Denmark)

    Ahmad, Anwar; Saha, Prakash; Evans, Colin

    2015-01-01

    OBJECTIVE: Activation of proteolytic mechanisms at the cell surface through the activity of urokinase-type plasminogen activator (uPA) bound to its receptor, uPAR, is an important process in wound healing. The soluble forms of uPAR (suPAR and its fragments I, II, and III) have nonproteolytic...... functions that include chemotaxis, adhesion, and proliferation, which also have a role in wound healing. The aim of this study was to determine whether suPAR and its cleaved fragments are present in venous ulcers and whether their levels are associated with healing. METHODS: Ulcer exudates were collected...... from patients with venous leg ulcers (n = 30). Healing was defined as complete re-epithelialization within 6 months of compression therapy. Time-resolved fluorescence immunoassays were validated for quantification of suPAR and its fragments in ulcer exudates. The effect of exudates on keratinocyte...

  11. Quantitation of the receptor for urokinase plasminogen activator by enzyme-linked immunosorbent assay

    DEFF Research Database (Denmark)

    Rønne, E; Behrendt, N; Ploug, M;

    1994-01-01

    variant of uPAR, suPAR, has been constructed by recombinant technique and the protein content of a purified suPAR standard preparation was determined by amino acid composition analysis. The sensitivity of the assay (0.6 ng uPAR/ml) is strong enough to measure uPAR in extracts of cultured cells and cancer......Binding of the urokinase plasminogen activator (uPA) to a specific cell surface receptor (uPAR) plays a crucial role in proteolysis during tissue remodelling and cancer invasion. An immunosorbent assay for the quantitation of uPAR has now been developed. This assay is based on two monoclonal...... tissue. Recent studies have shown that a high uPA level in tumor extracts is in some cancers associated with poor prognosis. The present assay will now allow similar prognostic studies of uPAR levels....

  12. Soluble urokinase plasminogen activator receptor (suPAR) in acute care

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Ladelund, Steen; Haupt, Thomas Huneck

    2016-01-01

    with age, admission time, admission to intensive care unit and Charlson score. CONCLUSIONS: In this large unselected population of acute medical patients, suPAR is strongly associated with disease severity, readmission and mortality after adjusting for all other risk factors, indicating that suPAR adds....... METHODS: This registry-based retrospective cohort study included 4343 consecutively admitted patients from the Acute Medical Unit at a large Danish university hospital. Time to readmission and death were analysed by multiple Cox regression. Results were reported as HRs for 30-day and 90-day follow......OBJECTIVE: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker associated with presence and progression of disease and with increased risk of mortality. We aimed to evaluate the unspecific biomarker suPAR as a prognostic marker in patients admitted to acute care...

  13. Activation of pro-urokinase and plasminogen on human sarcoma cells

    DEFF Research Database (Denmark)

    Stephens, R. W.; Pöllänen, J.; Tapiovaara,, Hannele

    1989-01-01

    Human HT-1080 fibrosarcoma cells produce urokinase-type plasminogen activator (u-PA) and type 1 plasminogen activator inhibitor (PAI-1). We found that after incubation of monolayer cultures with purified native human plasminogen in serum-containing medium, bound plasmin activity could be eluted...... from the cells with tranexamic acid, an analogue of lysine. The bound plasmin was the result of plasminogen activation on the cell surface; plasmin activity was not taken up onto cells after deliberate addition of plasmin to the serum-containing medium. The cell surface plasmin formation was inhibited...... by an anticatalytic monoclonal antibody to u-PA, indicating that this enzyme was responsible for the activation. Preincubation of the cells with diisopropyl fluorophosphate-inhibited u-PA led to a decrease in surface-bound plasmin, indicating that a large part, if not all, of the cell surface plasminogen activation...

  14. [Thrombolytic efficacy of a Lys-plasminogen-urokinase combination: studies in experimental animals and humans].

    Science.gov (United States)

    Latorre, J; Foncuberta, J; Rosendo, A; Elez, J

    1990-01-01

    During animal experimental phase, lis-pg combined with UK produced a thrombolysis of about a 62.5%. This effect is accompanied by an important fibrinolytic system activation, a decrease in fibrinogen levels (0.37 +/- 0.2 gr/l) and an increase PDF/Fg (120.5 +/- 30 ng/ml). Such thrombolytic stage produced diverse hemorrhagic complications in experimental animals. During human clinical trial stage, then patients with Deep Venous Thrombosis (DVT) at proximal lower limbs level were submitted to diverse treatment protocols with Lis-Plasminogen (Lis-plg) and Urokinase (UK). After preliminary outcomes we can conclude that administration of Lis-plg followed by UK increases the fibrinolytic activity but also increases the risk of hemorrhagic complications. This second effect is not probably caused by an specific absorption on the thrombo surface, but by an increase of circulating plasminogen levels Lis-plg exogenous-induced.

  15. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    DEFF Research Database (Denmark)

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R;

    2007-01-01

    reorganization in mature osteoclasts. INTRODUCTION: Urokinase receptor (uPAR) is actively involved in the regulation of important cell functions, such as proliferation, adhesion, and migration. It was previously shown that the major players in bone remodeling, osteoblasts and osteoclasts, express u...... to mechanical tests. UPAR KO calvaria osteoblasts were characterized by proliferation assays, RT-PCR for important proteins secreted during differentiation, and immunoblot for activator protein 1 (AP-1) family members. In vitro osteoclast formation was tested with uPAR KO bone marrow monocytes in the presence...... a proliferative advantage with no difference in apoptosis, higher matrix mineralization, and earlier appearance of alkaline phosphatase (ALP). Surface RANKL expression at different stages of differentiation was not altered. AP-1 components, such as JunB and Fra-1, were upregulated in uPAR KO osteoblasts, along...

  16. Ligand binding alters dimerization and sequestering of urokinase receptors in raft-mimicking lipid mixtures.

    Science.gov (United States)

    Ge, Yifan; Siegel, Amanda P; Jordan, Rainer; Naumann, Christoph A

    2014-11-01

    Lipid heterogeneities, such as lipid rafts, are widely considered to be important for the sequestering of membrane proteins in plasma membranes, thereby influencing membrane protein functionality. However, the underlying mechanisms of such sequestration processes remain elusive, in part, due to the small size and often transient nature of these functional membrane heterogeneities in cellular membranes. To overcome these challenges, here we report the sequestration behavior of urokinase receptor (uPAR), a glycosylphosphatidylinositol-anchored protein, in a planar model membrane platform with raft-mimicking lipid mixtures of well-defined compositions using a powerful optical imaging platform consisting of confocal spectroscopy XY-scans, photon counting histogram, and fluorescence correlation spectroscopy analyses. This methodology provides parallel information about receptor sequestration, oligomerization state, and lateral mobility with single molecule sensitivity. Most notably, our experiments demonstrate that moderate changes in uPAR sequestration are not only associated with modifications in uPAR dimerization levels, but may also be linked to ligand-mediated allosteric changes of these membrane receptors. Our data show that these modifications in uPAR sequestration can be induced by exposure to specific ligands (urokinase plasminogen activator, vitronectin), but not via adjustment of the cholesterol level in the planar model membrane system. Good agreement of our key findings with published results on cell membranes confirms the validity of our model membrane approach. We hypothesize that the observed mechanism of receptor translocation in the presence of raft-mimicking lipid mixtures is also applicable to other glycosylphosphatidylinositol-anchored proteins.

  17. Mis-trafficking of endosomal urokinase proteins triggers drug-induced glioma nonapoptotic cell death.

    Science.gov (United States)

    Pasupuleti, Nagarekha; Grodzki, Ana Cristina; Gorin, Fredric

    2015-04-01

    5-Benzylglycinyl-amiloride (UCD38B) is the parent molecule of a class of anticancer small molecules that kill proliferative and nonproliferative high-grade glioma cells by programmed necrosis. UCD38B intracellularly triggers endocytosis, causing 40-50% of endosomes containing proteins of the urokinase plasminogen activator system (uPAS) to relocate to perinuclear mitochondrial regions. Endosomal "mis-trafficking" caused by UCD38B in human glioma cells corresponds to mitochondrial depolarization with the release and nuclear translocation of apoptotis-inducing factor (AIF) followed by irreversible caspase-independent cell demise. High-content quantification of immunocytochemical colocalization studies identified that UCD38B treatment increased endocytosis of the urokinase plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1) into the early and late endosomes by 4- to 5-fold prior to AIF nuclear translocation and subsequent glioma demise. PAI-1 was found to comparably relocate with a subset of early and late endosomes in four different human glioma cell lines after UCD38B treatment, followed by caspase-independent, nonapoptotic cell death. Following UCD38B treatment, the receptor guidance protein LRP-1, which is required for endosomal recycling of the uPA receptor to the plasmalemma, remained abnormally associated with PAI-1 in early and late endosomes. The resultant aberrant endosomal recycling increased the total cellular content of the uPA-PAI-1 protein complex. Reversible inhibition of cellular endocytosis demonstrated that UCD38B bypasses the plasmalemmal uPAS complex and directly acts intracellularly to alter uPAS endocytotic trafficking. UCD38B represents a class of small molecules whose anticancer cytotoxicity is a consequence of causing the mis-trafficking of early and late endosomes containing uPAS cargo and leading to AIF-mediated necrotic cell death. Copyright © 2015 by The American Society for Pharmacology and

  18. Immunohistochemical localization of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and α2-antiplasmin in human corneal perforation: a case report

    Directory of Open Access Journals (Sweden)

    Sugioka Koji

    2012-11-01

    Full Text Available Abstract Background Corneal ulceration leading to perforation is associated with infectious and non-infectious destructive conditions in the cornea. The fibrinolytic (plasminogen/plasmin system is considered to contribute to tissue remodeling in the wound healing process and it is believed to play an important role in proteolysis and fibrosis. To determine the localization of urokinase-type plasminogen activator (u-PA, u-PA receptor (u-PAR and α2-antiplasmin (α2AP in the tissue of a corneal perforation, we investigated immunohistochemical expressions of u-PA, u-PAR, α2AP, CD68, and α-smooth muscle actin (α-SMA in a patient with corneal perforation that developed from an ulcer of no clear cause. Case presentation The patient was a 77-year-old woman who presented with a perforated corneal ulcer in her right eye. The cause of her corneal ulcer was unknown. Double immunohistochemistry was performed for the combinations of u-PA with u-PAR, CD68 or α-SMA and α2AP with CD68 or α-SMA to detect the localization of u-PA and α2AP. u-PA and u-PAR co-localization was seen in the corneal ulceration area. u-PA was mainly observed in CD68-positive cells and in some α-SMA positive cells. On the other hand, α2AP was not expressed in CD68-positive cells, but was expressed in α-SMA positive cells. Conclusion We identified expression of the u-PA/u-PAR complex and α2AP in a patient with a corneal ulcer. These two molecules are believed to play a crucial role in inflammatory cell recruitment, ECM synthesis and degradation during corneal wound healing.

  19. Intact and cleaved plasma soluble urokinase receptor in patients with metastatic colorectal cancer treated with oxaliplatin with or without cetuximab

    DEFF Research Database (Denmark)

    Tarpgaard, Line Schmidt; Christensen, Ib Jarle; Høyer-Hansen, Gunilla

    2015-01-01

    Circulating forms of the urokinase plasminogen activator receptor (uPAR) are associated with prognosis in patients with colorectal cancer. Preclinical studies have shown that uPAR can influence the state of phosphorylation and signalling activity of the epidermal growth factor receptor (EGFR...... with FLOX + cetuximab as compared to patients with KRAS wild-type and high levels of suPAR. These results thus support the preclinical findings and should be further tested in an independent clinical data set....

  20. Administration of Recombinant Soluble Urokinase Receptor Per Se Is Not Sufficient to Induce Podocyte Alterations and Proteinuria in Mice

    DEFF Research Database (Denmark)

    Cathelin, Dominique; Placier, Sandrine; Ploug, Michael

    2014-01-01

    Circulating levels of soluble forms of urokinase-type plasminogen activator receptor (suPAR) are generally elevated in sera from children and adults with FSGS compared with levels in healthy persons or those with other types of kidney disease. In mice lacking the gene encoding uPAR, forced increa...... in increased glomerular proteinuria or altered podocyte architecture. Our findings suggest that glomerular deposits of suPAR caused by elevated plasma levels are not sufficient to engender albuminuria....

  1. A novel, specific pro-urokinase complex on monocyte-like cells, detected by transglutaminase-catalyzed cross-linking

    DEFF Research Database (Denmark)

    Behrendt, N; Rønne, E; Danø, K

    1993-01-01

    Radiolabeled pro-urokinase plasminogen activator (pro-uPA) was cross-linked to a specific protein on the surface of human monocyte-like U937 cells in a reaction catalyzed by tissue transglutaminase. The conjugate formed with this unknown component had a much higher molecular weight (apparent M(r)...... antibody abolished the formation of the conjugate, thus showing a role of uPAR in this process....

  2. Altered expression of urokinase-type plasminogen activator and plasminogen activator inhibitor in high-risk soft tissue sarcomas

    OpenAIRE

    Benassi, M S; Ponticelli, F.; Azzoni, E.; Gamberi, G.; Pazzaglia, L.; Chiechi, A.; Conti, A; Spessotto, P.; Scapolan, M; Pignotti, E; P Bacchini; Picci, P.

    2007-01-01

    In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines a...

  3. Urokinase-targeted recombinant bacterial protein toxins-a rationally designed and engineered anticancer agent for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Yizhen LIU; Shi-Yan LI

    2009-01-01

    Urokinase-targeted recombinant bacterial protein toxins are a sort of rationally designed and engineered anticancer recombinant fusion proteins representing a novel class of agents for cancer therapy.Bacterial protein toxins have long been known as the primary virulence factor(s) for a variety of pathogenic bacteria and are the most powerful human poisons.On the other hand,it has been well documented that urokinase-type plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR),making up the uPA system,are overexpressed in a variety of human tumors and tumor cell lines.The expression of uPA system is highly correlated with tumor invasion and metastasis.To exploit these characteristics in the design of tumor cell-selective cytotoxins,two prominent bacterial protein toxins,i.e.,the diphtheria toxin and anthrax toxin are deliberately engineered through placing a sequence targeted specifically by the uPA system to form anticancer recombinant fusion proteins.These uPA system-targeted bacterial protein toxins are activated selectively on the surface of uPA systemexpressing tumor cells,thereby killing these cells.This article provides a review on the latest progress in the exploitation of these recombinant fusion proteins as potent tumoricidal agents.It is perceptible that the strategies for cancer therapy are being innovated by this novel therapeutic approach.

  4. World Nonproliferation Regime

    Institute of Scientific and Technical Information of China (English)

    Ouyang Liping; Wu Xingzuo

    2007-01-01

    2006 witnessed an intense struggle between nuclear proliferation and nonproliferation. Iran's nuclear issue and North Korea's nuclear test have cast a deep shadow over the current international nonproliferation regime. The international contest for civil nuclear development became especially fierce as global energy prices went up. Such a situation , to some extent, accelerated the pace of nuclear proliferation. Furthermore, the existing international nonproliferation regime, based upon the Nuclear Nonproliferation Treaty (NPT), was affected by loopholes, and the U.S. failed in its ambition to unite other forces to mend fences. The international community needs to come up with a comprehensive and long-term strategy to meet the demand for an effective future nonproliferation regime in a healthy nuclear order.

  5. 纳米尿激酶的性状研究%Characterization of urokinase chitosan nanoparticles

    Institute of Scientific and Technical Information of China (English)

    金海将; 张皓; 张柏根; 孙敏莉

    2011-01-01

    背景:尿激酶半衰期短,需持续大量给药,并发症也不小,故有必要研制具有缓释作用的溶栓药物.目的:了解包载尿激酶的水溶性壳聚糖纳米粒子的性状.方法:将壳聚糖和三聚磷酸钠以离子凝集法制备尿激酶纳米粒子后,用透射电镜观察其形态,采用粒径仪测纳米粒子粒径,酶标仪比色法测粒子包封率,纳米粒子冻干法测其载药量,并检测体内外纳米粒子缓释特性.结果与结论:当壳聚糖、三聚磷酸钠、尿激酶的质量比为7∶1∶1时,不仅溶液稳定,形成的纳米粒子粒径小,而且包封率和载药量均合适.制备出包封率最高达94.8%的尿激酶纳米粒子,载药量为14.5%,此时平均粒径236 nm,透射电镜观察示粒子形态较规则,呈球形;粒子具有较好的缓释性能;表明将尿激酶包被于纳米粒子中,避免了消化酶的直接作用,延长了半衰期,不仅在体内能保持较长时间的活性,而且具有明显的缓释效果.%BACKGROUND: Because urokinase has a short half-life, and has a sustained large dose, resulting in in negligible complications,it is necessary to develops low- release thrombolytic drugs .OBJECTIVE: To study the characterization of urokinase chitosan nanoparticles.METHODS: The nanoparticles were prepared via the self-assembly of chitosan and sodium tripolyphosphate. Themorphololywas observed by transmission electron microscopy (TEM). Particle size was measured with particle size instrument Theencapsulation efficiency was tested by ELISA Reader. Drug loading efficiency was measured by the way of weighing lyophiizedpowder. Release characteristics of the nanoparticles were investigated both in vitro and in vivo.RESULT SAND CONCLUSION: When the mass ratio of chitosan, sodium trip olyphosph ate, and ur ok in as was 7:1:1, the solutionwas stable, the nanoparticle size was small, and drug encapsulation efficiency and loading efficiency were appropriate. When thehighest encapsulation

  6. Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

    Science.gov (United States)

    Hansen, Line; Unmack Larsen, Esben Kjær; Nielsen, Erik Holm; Iversen, Frank; Liu, Zhuo; Thomsen, Karen; Pedersen, Michael; Skrydstrup, Troels; Nielsen, Niels Chr.; Ploug, Michael; Kjems, Jørgen

    2013-08-01

    Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific

  7. Regimes of justification

    NARCIS (Netherlands)

    Arts, Irma; Buijs, A.E.; Verschoor, G.M.

    2017-01-01

    Legitimacy of environmental management and policies is an important topic in environmental research. Based on the notion of ‘regimes of justification’, we aim to analyse the dynamics in argumentations used to legitimize and de-legitimize Dutch nature conservation practices. Contrary to prior

  8. Involvement of urokinase-type plasminogen activator system in cancer: an overview.

    Science.gov (United States)

    Mekkawy, Ahmed H; Pourgholami, Mohammad H; Morris, David L

    2014-09-01

    Currently, there are several studies supporting the role of urokinase-type plasminogen activator (uPA) system in cancer. The association of uPA to its receptor triggers the conversion of plasminogen into plasmin. This process is regulated by the uPA inhibitors (PAI-1 and PAI-2). Plasmin promotes degradation of basement membrane and extracellular matrix (ECM) components as well as activation of ECM latent matrix metalloproteases. Degradation and remodeling of the surrounding tissues is crucial in the early steps of tumor progression by facilitating expansion of the tumor mass, release of tumor growth factors, activation of cytokines as well as induction of tumor cell proliferation, migration, and invasion. Hence, many tumors showed a correlation between uPA system component levels and tumor aggressiveness and survival. Therefore, this review summarizes the structure of the uPA system, its contribution to cancer progression, and the clinical relevance of uPA family members in cancer diagnosis. In addition, the review evaluates the significance of uPA system in the development of cancer-targeted therapies.

  9. Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View

    Directory of Open Access Journals (Sweden)

    Andreas Kronbichler

    2016-01-01

    Full Text Available Focal segmental glomerulosclerosis (FSGS is one of the primary glomerular disorders in both children and adults which can progress to end-stage renal failure. Although there are genetic and secondary causes, circulating factors have also been regarded as an important factor in the pathogenesis of FSGS, because about 40% of the patients with FSGS have recurrence after renal transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR is a soluble form of uPAR, which is a membrane-bound protein linked to GPI in various immunologically active cells, including podocytes. It has recently been suggested as a potential circulating factor in FSGS by in vitro podocyte experiments, in vivo mice models, and human studies. However, there have also been controversies on this issue, because subsequent studies showed conflicting results. suPAR levels were also increased in patients with other glomerular diseases and were inversely correlated with estimated glomerular filtration rate. Nevertheless, there has been no balanced review on this issue. In this review, we compare the conflicting data on the involvement of suPAR in the pathogenesis of FSGS and shed light on interpretation by taking into account many points and the potential variables and confounders influencing serum suPAR levels.

  10. EXPRESSION AND SIGNIFICANCE OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    XIAO Jiping; ZHANG Guangde; XIA Wenhua; CHENG Deji

    1999-01-01

    Objective: To study the expression and clinical significance of urokinase-type plasminogen activator (uPA) in breast cancer. Methods: Applying streptavidin-biotin complex (SABC) immunohistochemical technique, expression of uPA was studied in 100 patients with primary breast cancer. Results: There were 55 patients with high uPA expression, and 45 with lower expression. There was significant correlation between uPA expression and TNM stage, lymph node status, and the tumor size. Neither age, menopausal status, nor ER status was significantly related with level of uPA expression. The patients with high expression of uPA had significantly shorter disease-free survival (DFS)and overall survival (OS) than did those with low expression of uPA. Univariate analysis showed that uPA as a prognostic factor was of similar magnitude to lymph node status and TNM stage, but stronger than that of ER status and tumor size. UPA was an independent prognostic factor affecting disease-free survival and overall survival. Conclusion: uPA appears to be a strong and independent biologic marker for predicting prognosis of breast cancer.

  11. Computer-assisted mutagenesis of ecotin to engineer its secondary binding site for urokinase inhibition.

    Science.gov (United States)

    Laboissière, Martha C A; Young, Malin M; Pinho, Rilva G; Todd, Stephen; Fletterick, Robert J; Kuntz, Irwin; Craik, Charles S

    2002-07-19

    Inhibitors of urokinase-type plasminogen activator (uPA) were selected in vitro from two ecotin phage-display libraries to study the effect on binding of amino acid substitutions at critical positions 108, 110, 112, and 113 within the 100s loop (RNKL, respectively, in wild type ecotin). The first, a focused library, was the result of a computation-assisted approach using the three-dimensional structure of the ecotin-trypsin complex to guide the modeling of amino acid substitutions predicted to increase affinity for uPA. The second, a complete library, allowed for all substitutions at the above identified positions. The consensus sequences selected from the focused, and complete libraries were RRWS and R(R/N)QL, respectively. Inhibition constant determinations showed ecotin variants containing these sequences to be similarly potent (K(i) = 1-2 nm). These substitutions were combined with previously identified substitutions in another critical region of ecotin. One of these combinations (D70R/M84R/RRQL) is the tightest (K(i) = 50 pm) ecotin variant inhibitor of uPA. The blending of combinatorial methods and computer algorithms designed to predict stronger binders has allowed us to obtain protein derivatives that exhibit greatly increased affinity for a predetermined target. This technology can be applied to select for enhanced binding interactions at protein-protein interfaces and accelerate the process of protease inhibitor development.

  12. Retro-inverso Urokinase Receptor Antagonists for the Treatment of Metastatic Sarcomas.

    Science.gov (United States)

    Carriero, Maria Vincenza; Bifulco, Katia; Ingangi, Vincenzo; Costantini, Susan; Botti, Giovanni; Ragone, Concetta; Minopoli, Michele; Motti, Maria Letizia; Rea, Domenica; Scognamiglio, Giosuè; Botti, Gerardo; Arra, Claudio; Ciliberto, Gennaro; Pessi, Antonello

    2017-05-02

    The development of metastases is a multistep process that requires the activation of physiological and biochemical processes that govern migration, invasion and entry of metastatic cells into blood vessels. The urokinase receptor (uPAR) promotes cell migration by interacting with the Formyl Peptide Receptors (FPRs). Since both uPAR and FPR1 are involved in tumor progression, the uPAR-FPR1 interaction is an attractive therapeutic target. We previously described peptide antagonists of the uPAR-FPR1 interaction that inhibited cell migration and angiogenesis. To develop enzyme-resistant analogues, we applied here the Retro-Inverso (RI) approach, whereby the topology of the side chains is maintained by inverting the sequence of the peptide and the chirality of all residues. Molecular dynamics suggests that peptide RI-3 adopts the turn structure typical of uPAR-FPR1 antagonists. Accordingly, RI-3 is a nanomolar competitor of N-formyl-Met-Leu-Phe for binding to FPR1 and inhibits migration, invasion, trans-endothelial migration of sarcoma cells and VEGF-triggered endothelial tube formation. When sarcoma cells were subcutaneously injected in nude mice, tumor size, intra-tumoral microvessel density, circulating tumor cells and pulmonary metastases were significantly reduced in animals treated daily with 6 mg/Kg RI-3 as compared to animals treated with vehicle only. Thus, RI-3 represents a promising lead for anti-metastatic drugs.

  13. The modified pulse-spray method using Urokinase in subacute and chronic thrombotic arterial occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Youn Kil; Hahn, Seong Tae; Baek, Jee Hee; Kim, Choon Yul; Shinn, Kyung Sub [The Catholic Univ. College of Medicine, Seoul (Korea, Republic of)

    1996-01-01

    To evaluate the effectiveness and safety of the modified pulse-spray method using Urokinase(UK) in subacute and chronic thrombotic arterial occlusion. Modified pulse-spray methods using UK were performed in seven patients with subacute (1 week-1month) to chronic (1month-5years) occlusive symptoms such as limb pain, claudication and impotence. Angiographic examination revealed thrombotic occlusion of the aorta, common iliac arteries, brachial arterio-venous hemodialysis graft and femoro-popliteal bypass graft. The patients underwent thrombolysis using modified pulse-spray and additional constant infusion of UK. In the presence of underlying stenosis or organized clots, balloon angioplasty or stent placement was performed. Complete lysis was obtained in five of seven patients. For initial lysis, the mean dose of UK was 420,000 units, and the mean modified pulse-spray time was 50 minutes. Mean total dose of UK and mean total time for complete lysis were 800,000 units and 161 minutes, respectively. Thrombolysis of the femoro-popliteal bypass graft failed due to severe occlusion of the distal anastomosis. Partial lysis was achieved in one patient with aorto-illac occlusion, but further thrombolysis was stopped due to bleeding at the puncture site. The modified pulse-spray method using UK is effective in treating subacute and chronic arterial thrombotic occlusion. It augments the speed, safety and efficacy of thrombolysis. When underlying stenosis or organized clots remain after thrombolysis, ballon angioplasty or stent placement would be helpful.

  14. Endovascular Treatment of Left Iliofemoral Deep Vein Thrombosis Using Urokinase Thrombolysis and Adjunctive Aspiration Thrombectomy

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Sang Hyun; Lee, Do Yun; Won, Jong Yun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2010-02-15

    To evaluate the efficacy of adjunctive aspiration thrombectomy for the treatment of iliofemoral deep vein thrombosis (DVT). 24 patients (9 males and 15 females; mean age, 53 years), treated by aspiration thrombectomy were enrolled in this study. The day after undergoing urokinase (UK) thrombolysis, any residual thrombus over a long segment was treated by aspiration thrombectomy using a 12 Fr long sheath. Residual short-segment (< 10 cm) iliac vein thrombus and/or stenosis were treated with a stent. The evaluation of venous patency was conducted by color Doppler ultrasonography, venography and/or computed tomography. The technical and clinical success rates were 100% and 92%, respectively. Twenty-three patients were treated by UK thrombolysis and iliac stent. The overall patency rate at 1, 2 and 3 years was 85%, 82% and 81%, respectively. Over the course of the follow-up period, occlusion was observed in 4 cases (1 acute and 3 chronic cases). Periprocedural complication occurred in 4 cases (17%) in the form of a minimal hematoma or pain on the puncture site as well as a case of pulmonary embolism at one month after treatment. The adjunctive aspiration thrombectomy with conventional thrombolysis and stent placement can be an effective and safe method in the treatment of left iliofemoral DVT

  15. Soluble urokinase plasminogen activator receptor as a marker for use of antidepressants.

    Directory of Open Access Journals (Sweden)

    Eva Haastrup

    Full Text Available OBJECTIVES: Inflammation is involved in the pathogenesis of depression. A few cross-sectional population-based studies have found that depression is associated with increased levels of inflammatory markers. Soluble urokinase plasminogen activation receptor (suPAR is known to be a stable marker for inflammation. We investigated the bidirectional association between suPAR levels and use of antidepressants. METHODS: suPAR level was measured in 9305 blood donors and analysed in relation to 5-years follow-up data on purchase of antidepressants and hospital diagnoses of depression from a nationwide Danish register. RESULTS: For men and women without prior use of antidepressants we found a significantly higher risk for incident use of antidepressants with higher suPAR values. For men, the risk of first use of antidepressants increased by 72% from the 1st to the 4th quartile (HR = 1.72, 95% CI: 1.11-2.69. For women, it increased by 108% from the 1st to the 4th quartile (HR = 2.08, 95% CI: 1.45-2.98. Previous use of antidepressants was also significantly associated with higher suPAR levels (p = 0.002. CONCLUSIONS: High suPAR levels are associated with an increased risk for both previous and future use of antidepressants in healthy men and women. High suPAR are also associated with increased risk for a hospital diagnosis of depression.

  16. EFFECT OF GLYCOSYLATION AT ASN302 OF PRO-UROKINASE ON ITS STABILITY IN CULTURE SUPERNATANT

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the effect of glycosylation at Asn302 of pro-urokinase (pro-UK) on the stability in culture supernatant.Methods Nonglycosylated pro-UK was constructed by site-directed mutagenesis of Asn302 to Ala302. The proUK mutant and native pro-UK were transfected into dhfr-CHO cells, and serum-free culture supernatant was harvested and incubated at 4℃ and 37℃, respectively. The pro-UK activity in culture supernatant was measured by the optical density (OD) increase with time ( 12 hours) at 405 nm. Without thermolysin activation, the percentage of single chain pro-UK was measured.Results After 48 hours of incubation at 4℃, the activities of pro-UK mutant and native pro-UK decreased 3.7%and 2. 9% respectively, and at 37℃ decreased 37.9 % and 23.5 %, respectively. The total activity of native pro-UK was significantly higher than that of nonglycosylated mutant at 37℃. The single-chain percentage of native pro-UK was higher than that of nonglycosylated mutant at both 4℃ and 37℃.Conclusion Higher temperature increases the proteolysis of pro-UK. The glycosylation site on Asn302 is beneficial to pro-UK stability in culture supernatant.

  17. Interferon-alpha (Intron A) upregulates urokinase-type plasminogen activator receptor gene expression.

    Science.gov (United States)

    Wu, Shanshan; Murrell, George A C; Wang, Yao

    2002-07-01

    The regulation of urokinase plasminogen activator receptor (uPAR) gene expression by interferon-alpha (IFN-alpha, or Intron A) and interferon-gamma (IFN-gamma) was studied in a HCT116 colon cancer cell line. uPAR mRNA levels were increased in a dose- and time-dependent manner in cells stimulated with IFN-alpha or IFN-gamma. uPAR protein levels reflected IFN-alpha and IFN-gamma induction of uPAR mRNA production. Cycloheximide, a protein synthesis inhibitor, also induced uPAR mRNA accumulation either alone or in combination with IFN-alpha or IFN-gamma, suggesting that the effect on uPAR mRNA levels activated by IFN-alpha or IFN-gamma does not require de novo protein synthesis. Both sodium butyrate and amiloride inhibited the uPAR mRNA levels induced by IFN-alpha or IFN-gamma. These results may provide useful information for the treatment of patients receiving IFN-alpha or IFN-gamma.

  18. Augmented expression of urokinase plasminogen activator and extracellular matrix proteins associates with multiple myeloma progression.

    Science.gov (United States)

    Khan, Rehan; Gupta, Nidhi; Kumar, Raman; Sharma, Manoj; Kumar, Lalit; Sharma, Alpana

    2014-06-01

    Multiple myeloma (MM) represents a B cell malignancy, characterized by a monoclonal proliferation of malignant plasma cells. Interactions between tumor cells and extracellular matrix (ECM) are of importance for tumor invasion and metastasis. Protein levels of urokinase plasminogen activator (uPA) and fibulin 1, nidogen and laminin in plasma and serum respectively and mRNA levels of these molecules in peripheral blood mononuclear cells were determined in 80 subjects by using ELISA and quantitative PCR and data was analyzed with severity of disease. Pearson correlation was determined to observe interrelationship between different molecules. A statistical significant increase for ECM proteins (laminin, nidogen and fibulin 1) and uPA at circulatory level as well as at mRNA level was observed compared to healthy controls. The levels of these molecules in serum might be utilized as a marker of active disease. Significant positive correlation of all ECM proteins with uPA was found and data also correlates with severity of disease. Strong association found between ECM proteins and uPA in this study supports that there might be interplay between these molecules which can be targeted. This study on these molecules may help to gain insight into processes of growth, spread, and clinical behavior of MM.

  19. Inhibition of tumor growth and metastasis by ATF-Fc, an engineered antibody targeting urokinase receptor.

    Science.gov (United States)

    Hu, Xian-Wen; Duan, Hai-Feng; Gao, Li-Hua; Pan, Shu-Yuan; Li, Yong-Mei; Xi, Yongyi; Zhao, Su-Rong; Yin, Liang; Li, Jin-Feng; Chen, Hui-Peng; Wu, Chu-Tse

    2008-05-01

    Urokinase (uPA) and its receptor (uPAR) play an important role in tumor growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumors. In this study, ATF-Fc, an antibody-like molecule comprising the amino-terminal fragment of human uPA (ATF) linked to the Fc fragment of human IgG1 via a flexible linker was developed. Its antitumor activities were evaluated in vitro and in vivo. The results showed that ATF-Fc had obvious cytotoxic effect on several types of tumor cells, which is dependent on cellular expression of uPAR and its Fc fragment. Treatment with ATF-Fc caused a significant suppression on tumor growth and metastasis of xenograft human tumors (MCF-7 breast cancer and BGC-823 gastric cancer) in athymic nude mice. Furthermore, we demonstrated that ATF-Fc had an anti-angiogenesis activity both in vitro and in vivo. In conclusion, we provided a novel therapeutic antibody-like molecule in the management of a variety of solid tumors by disrupting the uPA/uPAR interaction.

  20. Homocysteine and its thiolactone impair plasmin activity induced by urokinase or streptokinase in vitro.

    Science.gov (United States)

    Kolodziejczyk-Czepas, Joanna; Talar, Beata; Nowak, Pawel; Olas, Beata; Wachowicz, Barbara

    2012-04-01

    Mechanisms of homocysteine (Hcy) contribution to thrombosis are complex and only partly recognized. The available data suggest that the prothrombotic activity of homocysteine may be not only a result of the changes in coagulation process and endothelial dysfunction, but also the dysfunction of fibrinolysis. The aim of the present work was to assess the effects of homocysteine (10-100 μM mM) and its thiolactone (HTL, 0.1-1 μM) on plasminogen and plasmin functions in vitro. The amidolytic activity of generated plasmin in Hcy or HTL-treated plasminogen and plasma samples was measured by the hydrolysis of chromogenic substrate. Effects of Hcy and HTL on proteolytic activity of plasmin were monitored electrophoretically, by using of fibrinogen as a substrate. The exposure of human plasma and purified plasminogen to Hcy or HTL resulted in the decrease of urokinase-induced plasmin activity. In plasminogen samples treated with the highest concentration of homocysteine (100 μM) or thiolactone (1 μM), the activity of plasmin was inhibited by about 50%. In plasma samples, a reduction of amidolytic activity by about 30% (for 100 μM Hcy) and 40% (for 1 μM HTL), was observed. Both Hcy and HTL were also able to diminish the streptokinase-induced proteolytic activity of plasmin. In conclusion, the results obtained in this study demonstrate that Hcy and HTL may affect fibrinolytic properties of plasminogen and plasma, leading to the decrease of plasmin activity.

  1. Monocyte-expressed urokinase regulates human vascular smooth muscle cell migration in a coculture model.

    Science.gov (United States)

    Kusch, Angelika; Tkachuk, Sergey; Lutter, Steffen; Haller, Hermann; Dietz, Rainer; Lipp, Martin; Dumler, Inna

    2002-01-01

    Interactions of vascular smooth muscle cells (VSMC) with monocytes recruited to the arterial wall at a site of injury, with resultant modulation of VSMC growth and migration, are central to the development of vascular intimal thickening. Urokinase-type plasminogen activator (uPA) expressed by monocytes is a potent chemotactic factor for VSMC and might serve for the acceleration of vascular remodeling. In this report, we demonstrate that coculture of human VSMC with freshly isolated peripheral blood-derived human monocytes results in significant VSMC migration that increases during the coculture period. Accordingly, VSMC adhesion was inhibited with similar kinetics. VSMC proliferation, however, was not affected and remained at the same basal level during the whole period of coculture. The increase of VSMC migration in coculture was equivalent to the uPA-induced migration of monocultured VSMC and was blocked by addition into coculture of soluble uPAR (suPAR). Analysis of uPA and uPAR expression in cocultured cells demonstrated that monocytes are a major source of uPA, whose expression increases in coculture five-fold, whereas VSMC display an increased expression of cell surface-associated uPAR. These findings indicate that upregulated uPA production by monocytes following vascular injury acts most likely as an endogenous activator of VSMC migration contributing to the remodeling of vessel walls.

  2. Electroanalysis of pM-levels of urokinase plasminogen activator in serum by phosphorothioated RNA aptamer.

    Science.gov (United States)

    Jarczewska, Marta; Kékedy-Nagy, László; Nielsen, Jesper S; Campos, Rui; Kjems, Jørgen; Malinowska, Elżbieta; Ferapontova, Elena E

    2015-06-01

    Protein biomarkers of cancer allow a dramatic improvement in cancer diagnostics as compared to the traditional histological characterisation of tumours by enabling a non-invasive analysis of cancer development and treatment. Here, an electrochemical label-free assay for urokinase plasminogen activator (uPA), a universal biomarker of several cancers, has been developed based on the recently selected uPA-specific fluorinated RNA aptamer, tethered to a gold electrode via a phosphorothioated dA tag, and soluble redox indicators. The binding properties of the uPA-aptamer couple and interference from the non-specific adsorption of bovine serum albumin (BSA) were modulated by the electrode surface charge. A nM uPA electroanalysis at positively charged surfaces, complicated by the competitive adsorption of BSA, was tuned to the pM uPA analysis at negative surface charges of the electrode, being improved in the presence of negatively charged BSA. The aptamer affinity for uPA displayed via the binding/dissociation constant relationship correspondingly increased, ca. three orders of magnitude, from 0.441 to 367. Under optimal conditions, the aptasensor allowed 10(-12)-10(-9) M uPA analysis, also in serum, being practically useful for clinical applications. The proposed strategy for optimization of the electrochemical protein sensing is of particular importance for the assessment and optimization of in vivo protein ligand binding by surface-tethered aptamers.

  3. Mutation of Arg154 to Gly154 in urokinase augments its fibrin-specificity.

    Science.gov (United States)

    Peng, G; Ma, Z; Kuai, L; Zhu, D

    1997-04-01

    Rscu-PA and its mutant constructed by in vitro site specific mutagenesis of Arg154 in rscu-PA to Gly154 (mscu-PA) were both expressed in Escherichia coli. After in vitro denaturation and renaturation, the rscu-PA and mscu-PA were purified to homogeneity by Zn2+ selective precipitation, anti-u-PA IgG-sepharose CL 4B affinity chromatography. After activation by plasmin, the kinetic constants for the resultant mtcu-PA against synthetic substrate S2444 hydrolysis were found to be essentially identical to rtcu-PA, suggesting that no impairment had been exerted on the catalytic active site of mtcu-PA. However, both 125I-fibrin plasma-clot lysis and fibrinogenolysis showed that mtcu-PA possessed a higher fibrinolytic activity but hardly any degradation of fibrinogen in plasma compared to rtcu-PA and rscu-PA. It was concluded that the substitution of Arg154 by Gly154 in tcu-PA promoted the fibrin-specificity of urokinase.

  4. Construction of Urokinase Mutant Glu154-mtcu-PA and Characterization of Its Properties.

    Science.gov (United States)

    Peng, Gui-Hong; Ma, Zhong; Xue, Yu-Ming; Chen, Yu-Hong; Zhu, De-Xu

    1997-01-01

    The recombinant single chain urokinase-type plasminogen activator (rscu-PA) and a mutant constructed by in vitro site-specific mutagenesis of Argl54 in rscu-PA to Glul54 (Glul54-mscu-PA) were both expressed in E. coli. The expressed products were both purified to homogeneity by in vitro denaturation and renaturation, followed by Zn(2+) selective precipitation and immuno-affinity chromatography. The plasmin sensitivity assay indicated that the activation of this single chain Glul54-mscu-PA by plasmin was essentially identical to that of rscu-PA. After activation by plasmin, the kinetic constants against synthetic substrate S2444 of the resulted two chain form of Glul54-mscu-PA (Glul54-mtcu-PA) and that of rscu-PA (rtcu-PA) were 87 &mgr;M and 80 &mgr;M, respectively, which indicated that the catalytic active site of the Glul54-mtcu-PA was not changed by the mutation. Whereas, both (125)I-fibrin plasma-clot lysis and fibrinogenolysis in plasma showed that the Glul54-mtcu-PA possessed a better affinity and selectivity for fibrin than rtcu-PA, even better than rscu-PA.

  5. Matrix metalloproteinase-9 and urokinase plasminogen activator mediate interleukin-1-induced neurotoxicity.

    Science.gov (United States)

    Thornton, Peter; Pinteaux, Emmanuel; Allan, Stuart M; Rothwell, Nancy J

    2008-01-01

    Matrix metalloproteinases (MMPs) are endopeptidases known to mediate acute neuronal injury, but it is unclear whether these proteases are induced by the primary insult or by inflammation associated with injury. We have reported recently that interleukin-1 (IL-1) induces neurotoxicity by an astrocyte-dependent mechanism. The aim of the present study was to test the hypothesis that MMPs mediate IL-1 neurotoxicity in rat, glial-neuronal cocultures. IL-1beta induced the release of astrocytic MMP-9 in cocultures, whilst an antagonist of MMP-9 inhibited IL-1beta-induced neuronal death. Urokinase plasminogen activator (uPA) was constitutively expressed on neuronal membrane fractions, and amiloride (an antagonist of uPA) or plasminogen activator inhibitor (PAI)-1 significantly reduced IL-1beta-induced neurotoxicity. Thus, neuronal uPA contributes to IL-1 neurotoxicity, and may be responsible for activating MMP-9 released from IL-1-primed astrocytes. In summary, IL-1-induced neurotoxicity is dependent on extracellular protease activity, and these mechanisms may contribute to neuronal cell death in CNS diseases.

  6. Regimes Of Helium Burning

    CERN Document Server

    Timmes, F X

    2000-01-01

    The burning regimes encountered by laminar deflagrations and ZND detonations propagating through helium-rich compositions in the presence of buoyancy-driven turbulence are analyzed. Particular attention is given to models of X-ray bursts which start with a thermonuclear runaway on the surface of a neutron star, and the thin shell helium instability of intermediate-mass stars. In the X-ray burst case, turbulent deflagrations propagating in the lateral or radial directions encounter a transition from the distributed regime to the flamlet regime at a density of 10^8 g cm^{-3}. In the radial direction, the purely laminar deflagration width is larger than the pressure scale height for densities smaller than 10^6 g cm^{-3}. Self-sustained laminar deflagrations travelling in the radial direction cannot exist below this density. Similarily, the planar ZND detonation width becomes larger than the pressure scale height at 10^7 g cm^{-3}, suggesting that a steady-state, self-sustained detonations cannot come into exista...

  7. The immune marker soluble urokinase plasminogen activator receptor is associated with new-onset diabetes in non-smoking women and men

    DEFF Research Database (Denmark)

    Haugaard, S B; Andersen, O; Hansen, T W

    2012-01-01

    Aim: To explore the putative association of new-onset diabetes and the soluble urokinase plasminogen activator receptor (suPAR), which is a new and stable plasma marker of immune function and low-grade inflammation. This association has been previously suggested by using the less sensitive...... International Classification of Disease system to detect incident diabetes in the Danish MONICA 10 cohort. Methods: The Danish National Diabetes Register enabled more accurate identification of incident diabetes during a median follow-up of 13.8 years in the Danish MONICA 10 cohort (n = 2353 generally healthy...... individuals). The soluble urokinase plasminogen activator receptor was measured by the ELISA method. To fulfil model assumptions, outcome analyses were stratified by age, and further by smoking, owing to the interaction between the soluble urokinase plasminogen activator receptor and smoking on new...

  8. Fibrin sheaths in central venous port catheters: treatment with low-dose, single injection of urokinase on an outpatient basis

    Science.gov (United States)

    Chang, De-Hua; Mammadov, Kamal; Hickethier, Tilman; Borggrefe, Jan; Hellmich, Martin; Maintz, David; Kabbasch, Christoph

    2017-01-01

    Purpose Evaluation of the efficacy of single-shot, low-dose urokinase administration for the treatment of port catheter-associated fibrin sheaths. Methods Forty-six patients were retrospectively evaluated for 54 episodes of port catheter dysfunction. The presence of a fibrin sheath was detected by angiographic contrast examinations. On an outpatient basis, patients subsequently received thrombolysis consisting of a single injection of urokinase (15.000 IU in 1.5 mL normal saline) through the port system. A second attempt was made in cases of treatment failure. Patients were followed up for technical success, complications and long-term outcome. Results Port dysfunction occurred at a median of 117 days after implantation (range: 7–825 days). The technical success after first port dysfunction by thrombolysis was 87% (40/46); thereof, initial thrombolysis was effective in 78% (36/46). Nine patients (20%) received a second dose of urokinase after previous treatment failure. Follow-up was available for 26 of 40 patients after successful thrombolysis. In 8 of these, rethrombosis occurred after a median of 98 days (range: 21–354 days), whereby rethrombolysis was effective in 5 of 7 (63%) patients. The overall success of all thrombolyses performed was 70% (45/64). No procedure-related technical or clinical complications occurred. After first favorable thrombolysis, a Kaplan–Meier analysis yielded a 30-, 90- and 180-day probability of patency of 96%, 87% and 81%. Conclusion Thrombolytic therapy on an outpatient basis appears to be a safe and efficient. Three-month patency rates are comparable to more invasive treatment options, including catheter exchange over a guide wire and percutaneous fibrin sheath stripping. PMID:28182117

  9. Involvement of urokinase receptor in the cross-talk between human hematopoietic stem cells and bone marrow microenvironment

    DEFF Research Database (Denmark)

    Selleri, Carmine; Montuori, Nunzia; Salvati, Annamaria

    2016-01-01

    microenvironment.uPAR is a three domain receptor (DIDIIDIII) which binds urokinase, vitronectin, integrins. uPAR can be cleaved and shed from the cell surface generating full-length and cleaved soluble forms (suPAR and DIIDIII-suPAR). DIIDIII-suPAR can bind fMLF receptors through the SRSRY sequence (residues 88......, is indeed down-regulated by pre-transplant conditioning, probably to favour HSC homing. BM full-length suPAR and DIIDIII-suPAR may be involved in HSC lodgement within the BM by contributing to a suitable microenvironment....

  10. A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene

    DEFF Research Database (Denmark)

    Soravia, E; Grebe, A; De Luca, P

    1995-01-01

    The urokinase-type plasminogen activator receptor (uPAR) focuses at the cell surface the activation of pro-uPA and, hence, the formation of plasmin, thus enhancing directional extracellular proteolysis. To characterize the transcriptional regulatory mechanisms that control receptor expression, we...... have cloned an uPAR DNA segment containing upstream regulatory sequences from both the human and murine genomes. We report that a proximal promoter, contained within 180 bp from the major transcription start sites of the human uPAR gene, drives basal transcription. This region lacks TATA and CAAT boxes...

  11. Antibody-mediated targeting of the urokinase-type plasminogen activator proteolytic function neutralizes fibrinolysis in vivo

    DEFF Research Database (Denmark)

    Lund, Ida K; Jögi, Annika; Rønø, Birgitte

    2008-01-01

    Urokinase-type plasminogen activator (uPA) plays a central role in tissue remodeling processes. Most of our understanding of the role of uPA in vivo is derived from studies using gene-targeted uPA-deficient mice. To enable in vivo studies on the specific interference with uPA functionality in mouse...... models, we have now developed murine monoclonal antibodies (mAbs) directed against murine uPA by immunization of uPA-deficient mice with the recombinant protein. Guided by enzyme-linked immunosorbent assay, Western blotting, surface plasmon resonance, and enzyme kinetic analyses, we have selected two...

  12. Serum soluble urokinase-type plasminogen activator receptor levels in male patients with acute exacerbation of schizophrenia.

    Science.gov (United States)

    Genc, Abdullah; Kalelioglu, Tevfik; Karamustafalioglu, Nesrin; Tasdemir, Akif; Genc, Esra Sena; Akkus, Mustafa; Emul, Murat

    2016-02-28

    Inflammatory abnormalities have been shown in the pathogenesis of schizophrenia. Soluble urokinase-type plasminogen activator receptor (suPAR) is a protein that is measurable in the circulating blood and reflects the inflammation in the body. We aimed to investigate serum suPAR levels in patients with schizophrenia who were in acute state and to compare with healthy controls. Forty five patients and 43 healthy controls were included in the study. We found no significant difference in suPAR levels between patients and controls, suggesting that suPAR as an inflammatory marker does not have a role in the inflammatory process of acute schizophrenia.

  13. East Asian welfare regime

    DEFF Research Database (Denmark)

    Abrahamson, Peter

    2017-01-01

    . Political science studies tend to conclude that the region has left the old legacies behind and are now welfare states comparable to European states including them either in the conservative type (e.g. Japan), the liberal type (e.g. Korea) or even as a tendency in the Nordic type (e.g. China), while studies......The paper asks if East Asian welfare regimes are still productivist and Confucian? And, have they developed public care policies? The literature is split on the first question but (mostly) confirmative on the second. Care has to a large, but insufficient extent, been rolled out in the region...

  14. Benefits of maltodextrin intake 2 hours before cholecystectomy by laparotomy in respiratory function and functional capacity: a prospective randomized clinical trial.

    Science.gov (United States)

    Zani, Fabiana Vieira Breijão; Aguilar-Nascimento, José Eduardo; Nascimento, Diana Borges Dock; Silva, Ageo Mário Cândido da; Caporossi, Fernanda Stephan; Caporossi, Cervantes

    2015-01-01

    To evaluate the change in respiratory function and functional capacity according to the type of preoperative fasting. Randomized prospective clinical trial, with 92 female patients undergoing cholecystectomy by laparotomy with conventional or 2 hours shortened fasting. The variables measured were the peak expiratory flow, forced expiratory volume in the first second, forced vital capacity, dominant handgrip strength, and non-dominant handgrip strength. Evaluations were performed 2 hours before induction of anesthesia and 24 hours after the operation. The two groups were similar in preoperative evaluations regarding demographic and clinical characteristics, as well as for all variables. However, postoperatively the group with shortened fasting had higher values than the group with conventional fasting for lung function tests peak expiratory flow (128.7±62.5 versus 115.7±59.9; p=0.040), forced expiratory volume in the first second (1.5±0.6 versus 1.2±0.5; p=0.040), forced vital capacity (2.3±1.1 versus 1.8±0.9; p=0.021), and for muscle function tests dominant handgrip strength (24.9±6.8 versus 18.4±7.7; p=0.001) and non-dominant handgrip strength (22.9±6.3 versus 17.0±7.8; p=0.0002). In the intragroup evaluation, there was a decrease in preoperative compared with postoperative values, except for dominant handgrip strength (25.2±6.7 versus 24.9±6.8; p=0.692), in the shortened fasting group. Abbreviation of preoperative fasting time with ingestion of maltodextrin solution is beneficial to pulmonary function and preserves dominant handgrip strength.

  15. Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence.

    Science.gov (United States)

    Bifulco, Katia; Votta, Giuseppina; Ingangi, Vincenzo; Di Carluccio, Gioconda; Rea, Domenica; Losito, Simona; Montuori, Nunzia; Ragno, Pia; Stoppelli, Maria Patrizia; Arra, Claudio; Carriero, Maria Vincenza

    2014-06-30

    The clinical relevance of the urokinase receptor (uPAR) as a prognostic marker in ovarian cancer is well documented. We had shown that the uPAR sequence corresponding to 84-95 residues, linking D1 and D2 domains (uPAR84-95), drives cell migration and angiogenesis in a protease-independent manner. This study was aimed at defining the contribution of uPAR84-95 sequence to invasion of ovarian cancer cells. Now, we provide evidence that the ability of uPAR-expressing ovarian cancer cells to cross extra-cellular matrix and mesothelial monolayers is prevented by specific inhibitors of the uPAR84-95 sequence. To specifically investigate uPAR84-95 function, uPAR-negative CHO-K1 cells were stably transfected with cDNAs coding for uPAR D2 and D3 regions exposing (uPARD2D3) or lacking (uPAR∆D2D3) the 84-95 sequence. CHO-K1/D2D3 cells were able to cross matrigel, mesothelial and endothelial monolayers more efficiently than CHO-K1/∆D2D3 cells, which behave as CHO-K1 control cells. When orthotopically implanted in nude mice, tumor nodules generated by CHO-K1/D2D3 cells spreading to peritoneal cavity were more numerous as compared to CHO-K1/∆D2D3 cells. Ovarian tumor size and intra-tumoral microvessel density were significantly reduced in the absence of uPAR84-95. Our results indicate that cell associated uPAR promotes growth and abdominal dissemination of ovarian cancer cells mainly through its uPAR84-95 sequence.

  16. Probing binding and cellular activity of pyrrolidinone and piperidinone small molecules targeting the urokinase receptor.

    Science.gov (United States)

    Mani, Timmy; Liu, Degang; Zhou, Donghui; Li, Liwei; Knabe, William Eric; Wang, Fang; Oh, Kyungsoo; Meroueh, Samy O

    2013-12-01

    The urokinase receptor (uPAR) is a cell-surface protein that is part of an intricate web of transient and tight protein interactions that promote cancer cell invasion and metastasis. Here, we evaluate the binding and biological activity of a new class of pyrrolidinone and piperidinone compounds, along with derivatives of previously-identified pyrazole and propylamine compounds. Competition assays revealed that the compounds displace a fluorescently labeled peptide (AE147-FAM) with inhibition constant (Ki ) values ranging from 6 to 63 μM. Structure-based computational pharmacophore analysis followed by extensive explicit-solvent molecular dynamics (MD) simulations and free energy calculations suggested the pyrazole-based and piperidinone-based compounds adopt different binding modes, despite their similar two-dimensional structures. In cells, pyrazole-based compounds showed significant inhibition of breast adenocarcinoma (MDA-MB-231) and pancreatic ductal adenocarcinoma (PDAC) cell proliferation, but piperidinone-containing compounds exhibited no cytotoxicity even at concentrations of 100 μM. One pyrazole-based compound impaired MDA-MB-231 invasion, adhesion, and migration in a concentration-dependent manner, while the piperidinone inhibited only invasion. The pyrazole derivative inhibited matrix metalloprotease-9 (gelatinase) activity in a concentration-dependent manner, while the piperidinone showed no effect suggesting different mechanisms for inhibition of cell invasion. Signaling studies further highlighted these differences, showing that pyrazole compounds completely inhibited ERK phosphorylation and impaired HIF1α and NF-κB signaling, while pyrrolidinones and piperidinones had no effect. Annexin V staining suggested that the effect of the pyrazole-based compound on proliferation was due to cell killing through an apoptotic mechanism. The compounds identified represent valuable leads in the design of further derivatives with higher affinities and

  17. Chemotactic effect of urokinase-type plasminogen activator on mouse spermatozoa in vitro

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The aim of this study is to investigate the chemotactic effect of urokinase-type plasminogen activator (uPA)on mouse spermatozoa.Capillary assays were applied to study the chemotactic activity of ascending and descending gradients of uPA.Firstly,the chemotactic effect of an ascending gradient of uPA on mouse spermatozoa was observed by counting the number of spermatozoa that migrated into the capillary after incubation with uPA for 5,10,20,and 30 min,respectively,compared with that after incubation with F10.Twenty minutes was a suitable incubation time to obtain a plateau of sperm accumulation.Meanwhile,to confirm the specific effect of uPA on mouse sperm chemotaxis,uPA inhibitor (PAI-1)and anti-uPAR rabbit IgG were added to the test solution containing 20 U/mL uPA,respectively.To exclude the possibility that PAI-1 and anti-uPAR rabbit IgG may affect sperm accumulation nonspecifically,PAIl and anti-uPAR rabbit IgG were added to F10,respectively.It was found that the chemotactic effect of uPA was neutralized completely by PAI-1 and anti-uPAR rabbit IgG.PAI-1 and anti-uPAR rabbit IgG had no neutralizing effect on the sperm chemotactic effect.Lastly,the sperm chemotaxis response to a descending gradient of uPA was also observed.Taken together,the results suggest that uPA can induce sperm chemotaxis in vitro by binding to its receptor on the sperm membrane and may act as a chemoattractant in precontacting sperm-egg communication thereby increasing the chance encounter of spermatozoa and eggs.

  18. The urokinase receptor (uPAR facilitates clearance of Borrelia burgdorferi.

    Directory of Open Access Journals (Sweden)

    Joppe W R Hovius

    2009-05-01

    Full Text Available The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR; however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or independently of ligation to uPA, directly affect leukocyte function. We here demonstrate that uPAR is upregulated on murine and human leukocytes upon exposure to B. burgdorferi both in vitro as well as in vivo. Notably, B. burgdorferi-inoculated C57BL/6 uPAR knock-out mice harbored significantly higher Borrelia numbers compared to WT controls. This was associated with impaired phagocytotic capacity of B. burgdorferi by uPAR knock-out leukocytes in vitro. B. burgdorferi numbers in vivo, and phagocytotic capacity in vitro, were unaltered in uPA, tPA (low fibrinolytic activity and PAI-1 (high fibrinolytic activity knock-out mice compared to WT controls. Strikingly, in uPAR knock-out mice partially backcrossed to a B. burgdorferi susceptible C3H/HeN background, higher B. burgdorferi numbers were associated with more severe carditis and increased local TLR2 and IL-1beta mRNA expression. In conclusion, in B. burgdorferi infection, uPAR is required for phagocytosis and adequate eradication of the spirochete from the heart by a mechanism that is independent of binding of uPAR to uPA or its role in the fibrinolytic system.

  19. Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus.

    Science.gov (United States)

    Enocsson, Helena; Wetterö, Jonas; Skogh, Thomas; Sjöwall, Christopher

    2013-11-01

    Assessments of disease activity and organ damage in systemic lupus erythematosus (SLE) remain challenging because of the lack of reliable biomarkers and disease heterogeneity. Ongoing inflammation can be difficult to distinguish from permanent organ damage caused by previous flare-ups or medication side effects. Circulating soluble urokinase plasminogen activator receptor (suPAR) has emerged as a potential marker of inflammation and disease severity, and an outcome predictor in several disparate conditions. This study was done to evaluate suPAR as a marker of disease activity and organ damage in SLE. Sera from 100 healthy donors and 198 patients with SLE fulfilling the 1982 American College of Rheumatology classification criteria and/or the Fries criteria were analyzed for suPAR by enzyme immunoassay. Eighteen patients with varying degree of disease activity were monitored longitudinally. Disease activity was assessed by the SLE disease activity index 2000 and the physician's global assessment. Organ damage was evaluated by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). Compared with healthy control subjects, serum suPAR levels were elevated significantly in patients with SLE. No association was recorded regarding suPAR levels and SLE disease activity in cross-sectional or consecutive samples. However, a strong association was observed between suPAR and SDI (P < 0.0005). Considering distinct SDI domains, renal, neuropsychiatric, ocular, skin, and peripheral vascular damage had a significant effect on suPAR levels. This study is the first to demonstrate an association between serum suPAR and irreversible organ damage in SLE. Further studies are warranted to evaluate suPAR and other biomarkers as predictors of evolving organ damage.

  20. Uncharged isocoumarin-based inhibitors of urokinase-type plasminogen activator

    Directory of Open Access Journals (Sweden)

    Deck Lorraine M

    2006-02-01

    Full Text Available Abstract Background Urokinase-type plasminogen activator (uPA plays a major role in extracellular proteolytic events associated with tumor cell growth, migration and angiogenesis. Consequently, uPA is an attractive target for the development of small molecule active site inhibitors. Most of the recent drug development programs aimed at nonpeptidic inhibitors targeted at uPA have focused on arginino mimetics containing amidine or guanidine functional groups attached to aromatic or heterocyclic scaffolds. There is a general problem of limited bioavailability of these charged inhibitors. In the present study, uPA inhibitors were designed on an isocoumarin scaffold containing uncharged substituents. Results 4-Chloro-3-alkoxyisocoumarins were synthesized in which the 3-alkoxy group contained a terminal bromine; these were compared with similar inhibitors that contained a charged terminal functional group. Additional variations included functional groups attached to the seven position of the isocoumarin scaffold. N- [3-(3-Bromopropoxy-4-chloro-1-oxo-1H-isochromen-7-yl]benzamide was identified as an uncharged lead inhibitor of uPA, Ki = 0.034 μM. Molecular modeling of human uPA with these uncharged inhibitors suggests that the bromine occupies the same position as positively charged arginino mimetic groups. Conclusion This study demonstrates that potent uncharged inhibitors of uPA can be developed based upon the isocoumarin scaffold. A tethered bromine in the three position and an aromatic group in the seven position are important contributors to binding. Although the aim was to develop compounds that act as mechanism-based inactivators, these inhibitors are competitive reversible inhibitors.

  1. Soluble urokinase-type plasminogen activator receptor levels in patients with schizophrenia.

    Science.gov (United States)

    Nielsen, Jimmi; Røge, Rasmus; Pristed, Sofie Gry; Viuff, Anne Grethe; Ullum, Henrik; Thørner, Lise Wegner; Werge, Thomas; Vang, Torkel

    2015-05-01

    The etiology of schizophrenia remains largely unknown but alterations in the immune system may be involved. In addition to the psychiatric symptoms, schizophrenia is also associated with up to 20 years reduction in life span. Soluble urokinase-type plasminogen activator receptor (suPAR) is a protein that can be measured in blood samples and reflects the levels of inflammatory activity. It has been associated with mortality and the development of type 2 diabetes and cardiovascular disease. suPAR levels in patients with schizophrenia were compared to healthy controls from the Danish Blood Donor Study. SuPAR levels were dichotomized at >4.0 ng/ml, which is considered the threshold for low grade inflammation. A multiple logistic regression model was used and adjusted for age, sex, and current smoking. In total we included 1009 subjects, 105 cases with schizophrenia (10.4%) and 904 controls (89.6%). The mean suPAR values were 4.01 ng/ml (SD = 1.43) for the cases vs 1.91 ng/ml (SD = 1.35) for the controls (P 4.0 ng/ml yielded: schizophrenia, OR: 46.15 95% CI 22.69-93.87, P schizophrenia had significantly higher suPAR levels than healthy controls. Further studies are warranted to clarify if elevated suPAR levels are involved in the pathophysiology of schizophrenia and/or the increased mortality found in patients with schizophrenia. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Safety and Efficacy of Low Dosage of Urokinase for Catheter-directed Thrombolysis of Deep Venous Thrombosis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Long Du; Ling-Shang Kong; Qing-You Meng; Aimin Qian; Wen-Dong Li; Hong Chen; Xiao-Qiang Li

    2015-01-01

    Background:Catheter-directed thrombolysis (CDT) has been a mainstay in treating deep venous thrombosis (DVT).However,the optimal dosage of a thrombolytic agent is still controversial.The goal of this study was to evaluate the safety and efficacy of low dosage urokinase with CDT for DVT.Methods:A retrospective analysis was performed using data from a total of 427 patients with DVT treated with CDT in our single center between July 2009 and December 2012.Early efficacy of thrombolysis was assessed with a thrombus score based on daily venography.The therapeutic safety was evaluated by adverse events.A venography or duplex ultrasound was performed to assess the outcome at 6 months,1 year and 2 years postoperatively.Results:The mean total dose of 3.34 (standard deviation [SD] 1.38) million units of urokinase was administered during a mean of 5.18 (SD 2.28) days.Prior to discharge,Grade Ⅲ (complete lysis) was achieved in 154 (36%) patients;Grade Ⅱ (50-99% lysis) in 222 (52%);and Grade Ⅰ (50% lysis) in 51 (12%).The major complications included one intracranial hemorrhage,one hematochezia,five gross hematuria,and one pulmonary embolism.Moreover,no death occurred in the study.Conclusions:Treatment of low-dose catheter-directed thrombosis is an efficacious and safe therapeutic approach in patients with DVT offering good long-term outcomes and minimal complications.

  3. Design, synthesis, biochemical studies, cellular characterization, and structure-based computational studies of small molecules targeting the urokinase receptor.

    Science.gov (United States)

    Wang, Fang; Eric Knabe, W; Li, Liwei; Jo, Inha; Mani, Timmy; Roehm, Hartmut; Oh, Kyungsoo; Li, Jing; Khanna, May; Meroueh, Samy O

    2012-08-01

    The urokinase receptor (uPAR) serves as a docking site to the serine protease urokinase-type plasminogen activator (uPA) to promote extracellular matrix (ECM) degradation and tumor invasion and metastasis. Previously, we had reported a small molecule inhibitor of the uPAR·uPA interaction that emerged from structure-based virtual screening. Here, we measure the affinity of a large number of derivatives from commercial sources. Synthesis of additional compounds was carried out to probe the role of various groups on the parent compound. Extensive structure-based computational studies suggested a binding mode for these compounds that led to a structure-activity relationship study. Cellular studies in non-small cell lung cancer (NSCLC) cell lines that include A549, H460 and H1299 showed that compounds blocked invasion, migration and adhesion. The effects on invasion of active compounds were consistent with their inhibition of uPA and MMP proteolytic activity. These compounds showed weak cytotoxicity consistent with the confined role of uPAR to metastasis.

  4. Altered expression of urokinase-type plasminogen activator and plasminogen activator inhibitor in high-risk soft tissue sarcomas.

    Science.gov (United States)

    Benassi, M S; Ponticelli, F; Azzoni, E; Gamberi, G; Pazzaglia, L; Chiechi, A; Conti, A; Spessotto, P; Scapolan, M; Pignotti, E; Bacchini, P; Picci, P

    2007-09-01

    In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant up-regulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered. Clearly, the controversial role of PAI-1 protein requires further biological analyses, but evident involvement of uPA/PAI-1 gene overexpression in STS malignancy may highlight a molecular defect useful in discriminating STS high-risk patients.

  5. Interleukin-6 infusion during human endotoxaemia inhibits in vitro release of the urokinase receptor from peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Ostrowski, S R; Plomgaard, P; Fischer, C P

    2005-01-01

    Leucocyte expression of the urokinase receptor [urokinase-type plasminogen activator receptor (uPAR)] is regulated by inflammatory mediators. This study investigated the in vivo effect of endotoxin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha on uPAR-release in vivo and in vitro...... in humans. Healthy subjects received intravenous endotoxin injection [high-dose, 2 ng/kg (n=8) and low-dose, 0.06 ng/kg (n=7)], coadministration of 0.06 ng/kg endotoxin and 3 h recombinant human (rh)IL-6 infusion (n=7) or 3 h infusion of rhIL-6 (n=6), rhTNF-alpha (n=6) or NaCl (n=5). Soluble uPAR (su......PAR) was measured by enzyme-linked immunosorbent assay in plasma and supernatants from unstimulated and phytohaemagglutinin and lipopolysaccharide-stimulated peripheral blood mononuclear cell (PBMC) cultures incubated for 24 h. The spontaneous and stimulated uPAR-release from PBMC cultures was enhanced 5 h after...

  6. Significantly increased concentration of soluble urokinase-type plasminogen activator receptor in the blood of patients with pelvic inflammatory disease.

    Science.gov (United States)

    Yeh, Yuan-Hung; Wang, Po-Hui; Lin, Long-Yau; Tee, Yi-Torng; Chou, Ming-Chih; Yang, Shun-Fa; Tsai, Hsiu-Ting

    2013-01-16

    To determine expression levels of urokinase-type plasminogen activator (uPA), soluble urokinase-type plasminogen activator receptor (suPAR), plasminogen activator inhibitor-1 (PAI-1) in plasma and to identify gene polymorphisms specific to patients with pelvic inflammatory disease (PID) and healthy controls. Enzyme-linked immunosorbent assay and polymerase chain reaction-restriction fragment length polymorphism were used to measure plasma levels and polymorphisms in uPA, suPAR, and PAI-1 among seventy healthy controls and 64 PID patients before and after they received routine treatment protocols. The levels of plasma uPA (ng/ml) and soluble suPAR (pg/ml) were significantly increased in PID patients (uPA: 0.57±0.03; suPAR: 1372.04±68.20) when compared to that in normal controls (uPA: 0.55±0.06, p=0.002; suPAR: 1192.46±51.98, p=0.04); moreover, suPAR decreased significantly after treatment when compared to levels noted in the same patients (1220.06±58.14; p=0.003) after they received treatment. The increased expression of suPAR was significantly correlated with WBC counts (r=0.382, p=0.002, n=64) in blood as well as the plasma levels of CRP (r=0.441, ppelvic inflammatory disease. Copyright © 2012. Published by Elsevier B.V.

  7. ELISA for complexes between urokinase-type plasminogen activator and its receptor in lung cancer tissue extracts

    DEFF Research Database (Denmark)

    de Witte, H; Pappot, H; Brünner, N

    1997-01-01

    A sandwich-type ELISA has been developed for the assessment of complexes between urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in extracts of squamous cell lung carcinomas. The assay is based on a combination of rabbit polyclonal anti-uPA antibodies and a biotinylated mouse a......PA:uPAR complexes in lung tumor tissue as well as other types of cancer.......A sandwich-type ELISA has been developed for the assessment of complexes between urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in extracts of squamous cell lung carcinomas. The assay is based on a combination of rabbit polyclonal anti-uPA antibodies and a biotinylated mouse...... indicate that de novo complex formation is a major factor to consider and that complexes analyzed in the presence of this antagonist represent original uPA:uPAR complexes present prior to tumor tissue processing. The present ELISA appears suitable for studying the potential prognostic impact of u...

  8. Supply regimes in fisheries

    DEFF Research Database (Denmark)

    Nielsen, Max

    2006-01-01

    Supply in fisheries is traditionally known for its backward bending nature, owing to externalities in production. Such a supply regime, however, exist only for pure open access fisheries. Since most fisheries worldwide are neither pure open access, nor optimally managed, rather between the extremes......-economic supply model with mesh sizes is developed. It is found that in the presence of realistic management schemes, the supply curves are close to vertical in the relevant range. Also, the supply curve under open access with mesh size limitations is almost vertical in the relevant range, owing to constant...... recruitment. The implications are that the effects on supply following from e.g. trade liberalisation and reductions of subsidies are small in several and probably most fisheries worldwide. Keywords: backward-bending supply, regulated open access, regulated restricted access, mesh size regulation, Beverton...

  9. Exploring soluble urokinase plasminogen activator receptor and its relationship with arterial stiffness in a bi-ethnic population: the SAfrEIC-study

    DEFF Research Database (Denmark)

    Schutte, Aletta E; Myburgh, Anélda; Olsen, Michael Hecht;

    2012-01-01

    INTRODUCTION: Elevated soluble urokinase-type plasminogen activator receptor (suPAR) indicates an inflammatory state caused by conditions such as HIV and cancer. Recently suPAR was identified as an indicator of cardiovascular disease (CVD). CVD is highly prevalent in black South Africans, but the...

  10. MMP-9 and MMP-2 activities in stomach and breast tumours, as measured by a novel MMP activity assay using modified urokinase as a substrate

    NARCIS (Netherlands)

    Hanemaaijer, R.; Visser, H.; Duffy, J.; Verspaget, H.W.; Verheijen, J.H.; Maguire, T.

    1998-01-01

    Matrix metalloproteinases (MMPs) play an important role in many pathological processes. However, MMP activities are difficult to determine since no simple specific and/or chromogenic substrates exist. Therefore, we have developed a novel MMP activity assay using a modified urokinase as a substrate.

  11. Renin angiotensin system blockade reduces urinary levels of soluble urokinase plasminogen activator receptor (suPAR) in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, Frederik; Theilade, Simone; Eugen-Olsen, Jesper;

    2016-01-01

    Soluble urokinase plasminogen activator receptor (suPAR) is associated with faster decline in kidney function and the pathogenesis of diabetic nephropathy. However, little is known about the impact of treatment on plasma and urinary levels of suPAR. We aimed to investigate the impact of renin ang...

  12. Extracellular matrix biomarker, fibulin-1, is closely related to NT-proBNP and soluble urokinase plasminogen activator receptor in patients with aortic valve stenosis (the SEAS study)

    DEFF Research Database (Denmark)

    Kruger, Ruan; Rasmussen, Lars M; Argraves, William S;

    2014-01-01

    BACKGROUND: Fibulin-1, a circulating extracellular matrix glycoprotein, has been associated with arterial disease and elevated N-terminal prohormone B-type natriuretic peptide (NT-proBNP) in diabetes. Soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation, has been ass...

  13. Domain interplay in the urokinase receptor. Requirement for the third domain in high affinity ligand binding and demonstration of ligand contact sites in distinct receptor domains

    DEFF Research Database (Denmark)

    Behrendt, N; Ronne, E; Dano, K

    1996-01-01

    The urokinase plasminogen activator receptor (uPAR) is a membrane protein comprised of three extracellular domains. In order to study the importance of this domain organization in the ligand-binding process of the receptor we subjected a recombinant, soluble uPAR (suPAR) to specific proteolytic c...

  14. Comparison of the inhibition of urokinase-type plasminogen activator (u-PA) activity by monoclonal antibodies specific for u-PA as assessed by different assays

    NARCIS (Netherlands)

    Boheemen, P.A. van; Hoogen, N.M. van den; Koolwijk, N.

    1995-01-01

    Six murine monoclonal antibodies (MAbs) specific for urokinase-type plasminogen activator (u-PA) were tested for their ability to inhibit u-PA activity in three different assays with respect to amidolytic activity, plasminogen activation and fibrinolytic activity. Two of the MAbs were able to inhibi

  15. Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Sidenius, N; Sier, C.F.M.; Ullum, H

    2000-01-01

    Human immunodeficiency virus-1 (HIV-1) infection has been shown to result in up-regulation of the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes in vitro and in vivo. The objective of this study was to investigate whether this up-regulation is paralleled by higher serum l...

  16. A new tagging system for production of recombinant proteins in Drosophila S2 cells using the third domain of the urokinase receptor

    DEFF Research Database (Denmark)

    Gårdsvoll, Henrik; Hansen, Line V.; Jørgensen, Thomas J D

    2007-01-01

    The use of protein fusion tag technology greatly facilitates detection, expression and purification of recombinant proteins, and the demands for new and more effective systems are therefore expanding. We have used a soluble truncated form of the third domain of the urokinase receptor as a conveni...

  17. Prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) in Danish patients with recurrent epithelial ovarian cancer (REOC)

    DEFF Research Database (Denmark)

    Begum, Farah Diba; Høgdall, Estrid V S; Riisbo, Rikke

    2006-01-01

    The level of the soluble urokinase plasminogen activator receptor (suPAR) is elevated in tumour tissue from several types of cancer. This is the first study aiming to predict the prognosis for survival by the use of a pre-chemotherapeutic plasma suPAR value in 71 patients with recurrent epithelial...

  18. The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose

    Science.gov (United States)

    Malavazos, Alexis Elias; Cereda, Emanuele; Ermetici, Federica; Caccialanza, Riccardo; Briganti, Silvia; Rondanelli, Mariangela; Morricone, Lelio

    2015-01-01

    “Lipid accumulation product” (LAP) is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT) abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR) in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23%) adult (age: 18–70 years) overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2) having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT) and type-2 diabetes mellitus (T2-DM). According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM) and composite (IGT + T2-DM) abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P = 0.006 and P = 0.007, resp.). LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose. PMID:25792981

  19. The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose

    Directory of Open Access Journals (Sweden)

    Alexis Elias Malavazos

    2015-01-01

    Full Text Available “Lipid accumulation product” (LAP is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23% adult (age: 18–70 years overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2 having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT and type-2 diabetes mellitus (T2-DM. According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM and composite (IGT + T2-DM abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P=0.006 and P=0.007, resp.. LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose.

  20. Resilience of river flow regimes.

    Science.gov (United States)

    Botter, Gianluca; Basso, Stefano; Rodriguez-Iturbe, Ignacio; Rinaldo, Andrea

    2013-08-06

    Landscape and climate alterations foreshadow global-scale shifts of river flow regimes. However, a theory that identifies the range of foreseen impacts on streamflows resulting from inhomogeneous forcings and sensitivity gradients across diverse regimes is lacking. Here, we derive a measurable index embedding climate and landscape attributes (the ratio of the mean interarrival of streamflow-producing rainfall events and the mean catchment response time) that discriminates erratic regimes with enhanced intraseasonal streamflow variability from persistent regimes endowed with regular flow patterns. Theoretical and empirical data show that erratic hydrological regimes typical of rivers with low mean discharges are resilient in that they hold a reduced sensitivity to climate fluctuations. The distinction between erratic and persistent regimes provides a robust framework for characterizing the hydrology of freshwater ecosystems and improving water management strategies in times of global change.

  1. Inhibition of establishment of primary and micrometastatic tumors by a urokinase plasminogen activator receptor antagonist.

    Science.gov (United States)

    Ignar, D M; Andrews, J L; Witherspoon, S M; Leray, J D; Clay, W C; Kilpatrick, K; Onori, J; Kost, T; Emerson, D L

    1998-01-01

    Tumor establishment and metastasis are dependent on extracellular matrix proteolysis, tumor cell migration, and angiogenesis. Urokinase plasminogen activator (uPA) and its receptor are essential mediators of these processes. The purpose of this study was to investigate the effect of a recombinant human uPAR antagonist on growth, establishment, and metastasis of tumors derived from human cancer cell lines. A noncatalytic recombinant protein, consisting of amino acids 1-137 of human uPA and the CH2 and CH3 regions of mouse IgG1 (uPA-IgG), was expressed, purified, and shown to bind specifically to human uPAR and to saturate the surface of human tumor cells which express uPAR. Daily i.p. administration of uPA-IgG to nude mice extended latencies of unstaged tumors derived from Lox melanoma and SW48 colon carcinoma cells by 7.7 and 5.5 days, respectively. uPA-IgG treatment did not affect the growth of Lox or KB tumors staged to 200 mg before antagonist treatment commenced. The effect of uPA-IgG on the establishment of micrometastases was assessed in SCID mice. KB head/neck tumor cells were injected in the tail vein and allowed to seed for 48 h before initiation of daily i.p. injections of uPA-IgG for 24 days. The number of lung colonies ranged between 5 and 30% of vehicle-treated mice in two separate experiments. Furthermore, a single 800 microg dose of uPA-IgG administered 1 h prior to tail vein injection of KB cells reduced lung colony formation to just 3.5% of vehicle-treated SCID mice. These data demonstrate that antagonism of uPAR arrested metastasis and inhibited the establishment of primary tumors and micrometastases. Thus, small molecule uPAR antagonists may serve as useful adjuvant agents in combination with existing cancer chemotherapy.

  2. Opposite modulation of cell migration by distinct subregions of urokinase connecting peptide.

    Science.gov (United States)

    Franco, Paola; Carotenuto, Alfonso; Marcozzi, Cristina; Votta, Giuseppina; Sarno, Ciro; Iaccarino, Ingram; Brancaccio, Diego; De Vincenzo, Anna; Novellino, Ettore; Grieco, Paolo; Stoppelli, Maria Patrizia

    2013-05-10

    Functional analysis of isolated protein domains may uncover cryptic activities otherwise missed. The serine protease urokinase (uPA) has a clear-cut motogen activity that is catalytically independent and resides in its amino-terminal growth factor domain (GFD, residues 1-49) and connecting peptide region (CP, residues 132-158). To functionally dissect the CP region, we analysed the biological activity of two synthetic peptides corresponding to the N-terminal [uPA-(135-143), residues 135-143] and C-terminal [uPA-(144-158), residues 144-158] CP subregions. Most of the chemotactic activity of connecting peptide-derived peptide (CPp, [uPA-(135-158)]) for embryonic kidney HEK293/uPAR-25 cells is retained by uPA-(144-158) at nanomolar concentrations. In contrast, uPA-(135-143) inhibits basal, CPp -, vitronectin- and fibronectin-induced cell migration. Radioreceptor binding assays on intact HEK293 cells revealed that uPA-(135-143) and uPA-(144-158) are both able to compete with [(125)I]-CPp, albeit with different binding affinities. The consequences of phospho-mimicking, S138E substitution, were studied using [138E]uPA-(135-158) and [138E]uPA-(135-143) peptides. Unlike CPp, [138E]uPA-(135-158) and [138E]uPA-(135-143) exhibit remarkable inhibitory properties. Finally, analysis of the conformational preferences of the peptides allowed to identify secondary structure elements exclusively characterising the stimulatory CPp and uPA-(144-158) versus the inhibitory uPA-(135-143), [138E]uPA-(135-158) and [138E]uPA-(135-143) peptides. In conclusion, these data shed light on the cryptic activities of uPA connecting peptide, revealing the occurrence of two adjacent regions, both competing for binding to cell surface but conveying opposite signalling on cell migration.

  3. Characterisation of urokinase plasminogen activator receptor variants in human airway and peripheral cells

    Directory of Open Access Journals (Sweden)

    Sayers Ian

    2009-07-01

    Full Text Available Abstract Background Expression of the urokinase plasminogen activator receptor (UPAR has been shown to have clinical relevance in various cancers. We have recently identified UPAR as an asthma susceptibility gene and there is evidence to suggest that uPAR may be upregulated in lung diseases such as COPD and asthma. uPAR is a key receptor involved in the formation of the serine protease plasmin by interacting with uPA and has been implicated in many physiological processes including proliferation and migration. The current aim was to determine key regulatory regions and splice variants of UPAR and quantify its expression in primary human tissues and cells (including lung, bronchial epithelium (HBEC, airway smooth muscle (HASM and peripheral cells. Results Using Rapid Amplification of cDNA Ends (RACE a conserved transcription start site (-42 to -77 relative to ATG was identified and multiple transcription factor binding sites predicted. Seven major splice variants were identified (>5% total expression, including multiple exon deletions and an alternative exon 7b (encoding a truncated, soluble, 229aa protein. Variants were differentially expressed, with a high proportion of E7b usage in lung tissue and structural cells (55–87% of transcripts, whereas classical exon 7 (encoding the GPI-linked protein was preferentially expressed in peripheral cells (~80% of transcripts, often with exon 6 or 5+6 deletions. Real-time PCR confirmed expression of uPAR mRNA in lung, as well as airway and peripheral cell types with ~50–100 fold greater expression in peripheral cells versus airway cells and confirmed RACE data. Protein analysis confirmed expression of multiple different forms of uPAR in the same cells as well as expression of soluble uPAR in cell supernatants. The pattern of expression did not directly reflect that seen at the mRNA level, indicating that post-translational mechanisms of regulation may also play an important role. Conclusion We have

  4. Combined use of serum adiponectin and tumor necrosis factor-alpha receptor 2 levels was comparable to 2-hour post-load glucose in diabetes prediction.

    Directory of Open Access Journals (Sweden)

    Yu-Cho Woo

    Full Text Available BACKGROUND: Adipose tissue inflammation and dysregulated adipokine secretion are implicated in obesity-related insulin resistance and type 2 diabetes. We evaluated the use of serum adiponectin, an anti-inflammatory adipokine, and several proinflammatory adipokines, as biomarkers of diabetes risk and whether they add to traditional risk factors in diabetes prediction. METHODS: We studied 1300 non-diabetic subjects from the prospective Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS. Serum adiponectin, tumor necrosis factor-alpha receptor 2 (TNF-α R2, interleukin-6 (IL-6, adipocyte-fatty acid binding protein (A-FABP and high-sensitivity C-reactive protein (hsCRP were measured in baseline samples. RESULTS: Seventy-six participants developed diabetes over 5.3 years (median. All five biomarkers significantly improved the log-likelihood of diabetes in a clinical diabetes prediction (CDP model including age, sex, family history of diabetes, smoking, physical activity, hypertension, waist circumference, fasting glucose and dyslipidaemia. In ROC curve analysis, "adiponectin + TNF-α R2" improved the area under ROC curve (AUC of the CDP model from 0.802 to 0.830 (P = 0.03, rendering its performance comparable to the "CDP + 2-hour post-OGTT glucose" model (AUC = 0.852, P = 0.30. A biomarker risk score, derived from the number of biomarkers predictive of diabetes (low adiponectin, high TNF-α R2, had similar performance when added to the CDP model (AUC = 0.829 [95% CI: 0.808-0.849]. CONCLUSIONS: The combined use of serum adiponectin and TNF-α R2 as biomarkers provided added value over traditional risk factors for diabetes prediction in Chinese and could be considered as an alternative to the OGTT.

  5. Unitary Housing Regimes in Transition

    DEFF Research Database (Denmark)

    Bengtsson, Bo; Jensen, Lotte

    2013-01-01

    to the Danish and Swedish housing regimes are analysed and the responses and outcomes in terms of policy change and/or institutional continuity (path dependence) are compared. Overall, the more decentralized Danish housing regime seems to have resisted pressures for change and retrenchment better so far than...

  6. Regime shifts in resource management

    NARCIS (Netherlands)

    de Zeeuw, A.J.

    2014-01-01

    Resource management has to take account of the possibility of tipping points and regime shifts in ecological systems that provide the resources. This article focuses on the typical model of regime shifts in the ecological literature and analyzes optimal management and common-property issues when tra

  7. Examination Regimes and Student Achievement

    Science.gov (United States)

    Cosentino de Cohen, Clemencia

    2010-01-01

    Examination regimes at the end of secondary school vary greatly intra- and cross-nationally, and in recent years have undergone important reforms often geared towards increasing student achievement. This research presents a comparative analysis of the relationship between examination regimes and student achievement in the OECD. Using a micro…

  8. 'Regime shopping' across (blurring) boundaries

    NARCIS (Netherlands)

    Houwerzijl, M.S.; Evju, Stein

    2014-01-01

    This book chapter identifies and explores the (blurring) boundaries between the legal regimes for labour mobility across the EU. In the context of - what is sometimes called - 'regime shopping' a close look is taken into the law on freedom of movement within the EU. Several categories of transnation

  9. 'Regime shopping' across (blurring) boundaries

    NARCIS (Netherlands)

    Houwerzijl, M.S.; Evju, Stein

    2014-01-01

    This book chapter identifies and explores the (blurring) boundaries between the legal regimes for labour mobility across the EU. In the context of - what is sometimes called - 'regime shopping' a close look is taken into the law on freedom of movement within the EU. Several categories of

  10. The complex between urokinase (uPA) and its type-1 inhibitor (PAI-1) in pulmonary adenocarcinoma: Relation to prognosis

    DEFF Research Database (Denmark)

    Pappot, Helle; Pedersen, Anders N; Brünner, Nils

    2006-01-01

    In a lung cancer population comprising tumor tissue from 99 pulmonary adenocarcinoma patients, the relationship between tumor tissue level of the complex formed of urokinase (uPA) and its type-1 inhibitor (PAI-1) and survival was studied. The study included patient material previously investigated....... The amounts of uPA-PAI-1 complex measured in pulmonary adenocarcinoma tissue were within the same range as previously reported in breast cancer tissue (0.11-5.74 ng/mg protein). uPA and PAI-1 levels were weakly correlated to the uPA-PAI-1 complex, r = 0.52 and r = 0.47, respectively, and no relation was found...... these interactions and the clinical importance of the tissue levels of uPA, PAI-1 and uPA-PAI-1 complex, the results suggest further exploratory studies of the components in pulmonary adenocarcinomas and other cancers....

  11. The complex between urokinase (uPA) and its type-1 inhibitor (PAI-1) in pulmonary adenocarcinoma

    DEFF Research Database (Denmark)

    Pappot, Helle; Pedersen, Anders N.; Brünner, Nils

    2006-01-01

    In a lung cancer population comprising tumor tissue from 99 pulmonary adenocarcinoma patients, the relationship between tumor tissue level of the complex formed of urokinase (uPA) and its type-1 inhibitor (PAI-1) and survival was studied. The study included patient material previously investigated....... The amounts of uPA-PAI-1 complex measured in pulmonary adenocarcinoma tissue were within the same range as previously reported in breast cancer tissue (0.11-5.74 ng/mg protein). uPA and PAI-1 levels were weakly correlated to the uPA-PAI-1 complex, r = 0.52 and r = 0.47, respectively, and no relation was found...... these interactions and the clinical importance of the tissue levels of uPA, PAI-1 and uPA-PAI-1 complex, the results suggest further exploratory studies of the components in pulmonary adenocarcinomas and other cancers....

  12. The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality

    DEFF Research Database (Denmark)

    Wittenhagen, P; Kronborg, G; Weis, N;

    2004-01-01

    This multicentre prospective study was conducted to investigate whether the level of the soluble form of urokinase-type plasminogen activator receptor (suPAR) is elevated during pneumococcal bacteraemia and is of predictive value in the early stage of the disease. Plasma levels of suPAR were...... (n = 117; p cerebral symptoms and high serum concentrations of protein YKL-40 and suPAR were associated significantly with mortality (p ....05). In multivariate analysis, only suPAR remained a significant predictor of death (mortality rate of 13 for suPAR levels of > 10 ng/mL; 95% CI: 1.1-158). The increase in suPAR levels may reflect increased expression by vascular or inflammatory cells in the setting of pneumococcal sepsis. This plasma protein may...

  13. Urokinase plasminogen activator receptor is expressed in invasive cells in gastric carcinomas from high- and low-risk countries

    DEFF Research Database (Denmark)

    Alpizar Alpizar, Warner Enrique; Nielsen, Boye Schnack; Sierra, Rafaela

    2010-01-01

    Gastric cancer is the second cancer causing death worldwide. Both incidence and mortality rates vary according to geographical regions. The receptor for urokinase plasminogen activator (uPAR) is involved in extracellular matrix degradation by mediating cell surface associated plasminogen activation......, and its presence on gastric cancer cells is linked to micro-metastasis and poor prognosis. Immunohistochemical analyses of a set of 44 gastric cancer lesions from Costa Rica showed expression of uPAR in cancer cells in both intestinal subtype (14 of 27) and diffuse subtype (10 of 17). We compared...... the expression pattern of uPAR in gastric cancers from a high-risk country (Costa Rica) with a low-risk country (Norway). We found uPAR on gastric cancer cells in 24 of 44 cases (54%) from Costa Rica and in 13 of 23 cases (56%) from Norway. uPAR was seen in macrophages and neutrophils in all cases. We also...

  14. Soluble urokinase receptor levels in plasma during 5 years of highly active antiretroviral therapy in HIV-1-infected patients

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Katzenstein, Terese L; Piironen, Timo;

    2004-01-01

    High blood levels of the soluble urokinase receptor (suPAR) strongly predict increased mortality in human immunodeficiency virus-1 (HIV-1)-infected patients. This study investigated the plasma concentration of suPAR in 29 treatment-naive HIV-1-infected patients during 5 years treatment with highly...... active antiretroviral therapy (HAART). Plasma suPAR decreased after introducing HAART, most pronounced during the first treatment year. The change in plasma suPAR was independent of changes in viral replication and CD4+ cells but it was strongly correlated with plasma levels of the soluble TNF receptor...... is linked to inflammation in untreated as well as HAART-treated HIV-1-infected patients....

  15. Inhibition of migration and invasion of carcinoma cells by urokinase-derived antagonists of alphavbeta5 integrin activation.

    Science.gov (United States)

    Vocca, Immacolata; Franco, Paola; Alfano, Daniela; Votta, Giuseppina; Carriero, Maria Vincenza; Estrada, Yeriel; Caputi, Mario; Netti, Paolo A; Ossowski, Liliana; Stoppelli, Maria Patrizia

    2009-01-15

    We previously showed that, while binding to urokinase receptor (uPAR) through its growth factor domain (GFD, residues 1-49), urokinase (uPA) can engage alphavbeta5 integrin through an internal domain (CP, residues 132-158). This novel uPA/alphavbeta5 interaction promotes cytoskeletal rearrangements and directional cell migration (Franco et al., J Cell Sci 2006;119:3424-34). We now show that treatment of cells with phosphomimic uPA (uPA138E/303E, serine 138 and 303 substituted with glutamic acid) strongly inhibits matrix-induced cell migration. Unlike uPA, binding of uPA138E/303E to cell surface did not induce F-actin enriched protruding structures and caused a 5-fold reduction in cell translocation speed, as determined by video tracking of living cells. Inhibition of migration was found to be independent of uPAR, since uPA variants lacking the GFD domain, but carrying the relevant Ser to Glu substitutions were as effective inhibitor as uPA138E/303E. Through several independent approaches, we established that the phosphomimics specifically bind to alphavbeta5 integrin through the CP region carrying the S138E mutation. This interaction blocks integrin activation, as determined by a decreased affinity of alphavbeta5 to vitronectin and a reduced association of the beta5 cytoplasmic tail with talin. Finally, stable expression of uPA138E/303E in human squamous carcinoma cells prevented tumor cell invasion in vivo. Thus, when expressed in cancer cells, the inhibitory phosphomimic effect was dominant over the effect of endogenously produced uPA. These results shed light on the regulation of cell migration by uPA phosphorylation and provide a realistic opportunity for a novel antiinvasive/metastatic therapeutic intervention.

  16. Influential factors of clinical outcome of local intra-arterial thrombolysis using urokinase in patients with hyperacute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jae Min; Yoon, Woong; Kim, Jae Kyu; Seo, Jeong Jin; Heo, Sook Hee; Park, Jin Gyoon; Jeong, Yoon Yeon; Kang, Heoung Keun [Chonam University Hospital, Kwangju (Korea, Republic of)

    2002-10-01

    To evaluate the clinical outcome and other relevant factors in cases where local intra-arterial thrombolysis (LIT) is used for the treatment of hyperacute ischemic stroke. Forty-eight hyperacute ischemic stroke patients were treated by LIT, using urokinase, within six hours of ictus, and for evaluation of their neurological status, the national institutes of health stroke scale (NIHSS) score was used. Angiography recanalization was classified according to Mori recanalization grades. Three months after LIT, the outcome was assessed by clinical examination using the modified rankin scale (good outcome: RS=0-3; poor outcome: RS=4-6). In all patients, the findings of pre- and post- LIT CT, and angiography, as well as neurological status and hemorrhagic complications, were also analysed. Thirty-three patients had occlusions of the middle cerebral artery (MCA), and 15, of the internal carotid artery (ICA). The NIHSS score averaged 16.9 at the onset of therapy and 13.5 at 24 hours later. Successful recanalization (Mori grade 3,4) was achieved in 28 (58.3%) of 48 patients, but in 20 (41.7%) the attempt failed. Twenty-two (45.8%) of the 48 patients had a good outcome, but in (54.2%) the outcome was poor. Thirteen (40.6%) of 32 patients with MCA occlusions and 13 (81.2%) of 16 with ICA occlusions had a poor outcome. Eight patients (16.7%) died. Overall, hemorrhages occured in 20 (41.7%) of 48 patients, with symptomatic hemorrhage in ten. Five (50%) of these ten died. LIT using urokinase for hyperacute ischemic stroke is feasible; patients with MCA occlusions had better outcomes than those with ICA occlusions. Hemorrhagic complications of LIT were frequent, and in cases of symptomatic hemorrhage a fatal outcome may be expected.

  17. Construction, Expression, and Characterization of a Recombinant Annexin B1-Low Molecular Weight Urokinase Chimera in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    Hong-Li YAN; Wei-Ting WANG; Yan HE; Zhuan-You ZHAO; Yuan-Jian GAO; Yi ZHANG; Shu-Han SUN

    2004-01-01

    To produce a thrombi-targeting plasminogen activator,low molecular weight single-chain urokinase gene(scuPA32k)was spliced with the full-length cDNA of annexin B 1 gene(anxB1)by overlap extension method.The fused gene anxBlscuPA was ligated into pET28a vector,transformed into E.coli BL21-RIL,and then induced to express under the control of T7 promoter.The AnxB 1ScuPA protein expressed amounted to 22% of the total bacterial proteins.The product was refolded,and then purified by using DEAE Sepharose fast flow ion-exchange column and Superdex S-200 gel-filtration column.HPLC analysis revealed that the final purity is about 95%.The specific activity ofAnxB 1ScuPA,measured as amidolytic activity,reached 100,000 IU/mg.It had a similar S2444 catalytic efficiency(kcat/Km)to ScuPA32k,and also showed high activated-platelet membrane-binding activity and anticoagulant activity,indicating that the chimera fully retained the components of enzymatic and membrane-binding activities of the parent molecules.In vivo test revealed that,the dogs administered with AnxB 1ScuPA had less reperfusion time,higher reperfusion ratio,and less bleeding effects than those with urokinase.These findings indicated that AnxB 1ScuPAmight have advantages over current available thrombolytic agents.

  18. Effect of low-molecular-weight heparin and urokinase on pulmonary arteries involved in pulmonary embolism

    Institute of Scientific and Technical Information of China (English)

    WU Jun-ping; SUN Xin; WU Qi; DU Zhong-zhen; LI Li; WU Qian; SUN Hong-fen

    2013-01-01

    Background Pulmonary embolism (PE) is a common and often fatal disease.Early after pulmonary thromboembolism,inflammation and associated intimal hyperplasia occur within the pulmonary arteries,similar to what is observed with chronic thromboembolic pulmonary hypertension.This study tested the hypothesis that thrombolytic and anticoagulant agents would have anti-inflammatory effects or inhibit intimal hyperplasia of involved pulmonary arteries.Methods Seventy-two male New Zealand white rabbits were randomly divided into two groups (54 rabbits in the PE group and 18 in the sham group).Experimental PE was induced in 54 rabbits by femoral vein injection of autologous blood clots and confirmed with pulmonary angiography,and other 18 rabbits underwent sham operations.Fifty-four rabbits in the PE group were randomly divided into three groups:a control group (treated with normal saline),a low-molecularweight heparin (LMWH) group (treated with LMWH),and a urokinase (UK) group (treated with UK).Arterial blood gas was analyzed at 2,7,and 28 days (n=6 per time point by random group division),then lung tissues were removed and were analyzed for pro-inflammatory cytokines and chemokines,and were stained for intimal hyperplasia.Results The overall survival of rabbits undergoing PE was 100%.PE distribution detected on digital signal angiography (DSA) and histopathology was shown in 67% of rabbits (36/54) in the bilateral low lobar pulmonary arteries (PAs).The results showed that alveolar-arterial partial pressure of oxygen (PO2) difference (PA-aO2) significantly increased and PO2 decreased in the control group compared with the sham group.Compared with controls,the UK group had a decreased level of PA-aO2 on day 2 (P <0.05),however,there was no significant difference in the LMWH group.Compared with controls,the LMWH group had a decreased level of monocyte chemoattractant protein-1 (MCP-1) in affected tissue and serum samples on days 7 and 28 (P <0.05),and the UK group had

  19. Preclinical evaluation of a urokinase plasminogen activator receptor-targeted nanoprobe in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Chen Y

    2015-10-01

    Full Text Available Yushu Chen,1 Li Gong,2 Ning Gao,3 Jichun Liao,1 Jiayu Sun,1 Yuqing Wang,1 Lei Wang,1 Pengjin Zhu,1 Qing Fan,1 Yongqiang Andrew Wang,4 Wen Zeng,2 Hui Mao,3 Lily Yang,5 Fabao Gao11Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, 2Sichuan Primed Bio-Tech Group Co, Ltd, Chengdu, People’s Republic of China; 3Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, 4Ocean NanoTech, LLC, San Diego, CA, 5Department of Surgery, Emory University School of Medicine, Atlanta, GA, USAPurpose: To translate a recombinant peptide containing the amino-terminal fragment (ATF of urokinase plasminogen activator receptor-targeted magnetic iron oxide (IO nanoparticles (uPAR-targeted human ATF-IONPs into clinical applications, we conducted a pilot study to evaluate the toxicity and pharmacokinetics of this nanoparticle in normal rhesus monkeys.Methods: We assessed the changes in the following: magnetic resonance imaging (MRI signals from pretreatment stage to 14 days posttreatment, serum iron concentrations from 5 minutes posttreatment to 12 weeks posttreatment, routine blood examination and serum chemistry analysis results from pretreatment stage to 12 weeks after administration, and results of staining of the liver with Perls’ Prussian Blue and hematoxylin–eosin at 24 hours and 3 months posttreatment in two rhesus monkeys following an intravenous administration of the targeted nanoparticles either with a polyethylene glycol (ATF-PEG-IONP or without a PEG (ATF-IONP coating.Results: The levels of alkaline phosphatase, alanine transaminase, and direct bilirubin in the two monkeys increased immediately after the administration of the IONPs but returned to normal within 20 days and stayed within the normal reference range 3 months after the injection. The creatinine levels of the two monkeys stayed within the normal range during the study. In addition, red blood cells

  20. The Choice of Monetary Regime

    DEFF Research Database (Denmark)

    Østrup, Finn

    , a comparisonbetween monetary regimes suggests that welfare is highest under nominalincome targeting where the nominal income target is determined to bring aboutprice stability.Keywords: Monetary regimes; fiscal policy; monetary non-neutrality.JEL classicification: E42, E61, E62.......The article examines how government spending is determined in a closedeconomy where the nominal wage is pre-set through contracts and the wage settershave perfect foresight regarding subsequent policy decisions. The monetaryregime affects government spending because: (i) with a pre-set nominal wage......, agiven change in government spending has different effects on employment andinflation under different monetary regimes, and (ii) the authorities' inclinationto expand government spending is affected by the inflation rate which dependson the monetary regime. If the costs related to inflation are high...

  1. THE ETHIOPIAN ENVIRONMENTAL REGIME VERSUS ...

    African Journals Online (AJOL)

    Haramaya Law Review ... ozone layer and climate change regimes, among others, to succeed. Id. ... international act dealing with general aspects of air pollution. ..... environmental and developmental decisions that affect their interests or the.

  2. Urokinase plasminogen activator (uPA and plasminogen activator inhibitor type-1 (PAI-1 in breast cancer - correlation with traditional prognostic factors

    Directory of Open Access Journals (Sweden)

    Lampelj Maja

    2015-12-01

    Full Text Available Background. Urokinase plasminogen activator (uPA and plasminogen activator inhibitor type-1 (PAI-1 play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients.

  3. 一种简易的尿激酶活性测定方法%A Simple Method for Determination of Urokinase Activity

    Institute of Scientific and Technical Information of China (English)

    李岩

    2013-01-01

    The study improved the method of plate thrombolytic enzyme screening, established a new method to test the urokinase activity. The method with agarose as carrier, activated fibrinogen into fibrin clots by thrombin, then dissolve it by urokinase, forming a transparent circle, transparent circle size was positively correlated with urokinase activity. compared with the method of bubble method in Pharmacopoeia, plate method has the superiority of low cost, simple operation, good repeatability.%本研究改良了溶栓酶筛选采用的平板法,建立了一种新的尿激酶活性测定方法。该方法以琼脂糖为载体,纤维蛋白原经凝血酶激活后转变为纤维蛋白形成凝块,再经尿激酶作用使其溶解,形成透明圈,透明圈的面积与尿激酶的活性大小呈正相关。与《药典》中使用的气泡法测定尿激酶活性相比该方法成本低、操作简单、重复性好。

  4. A region in urokinase plasminogen receptor domain III controlling a functional association with alpha5beta1 integrin and tumor growth

    DEFF Research Database (Denmark)

    Chaurasia, Pratima; Aguirre-Ghiso, Julio; Liang, Olin D

    2006-01-01

    Highly expressed urokinase plasminogen activator receptor (uPAR) can interact with alpha5beta1 integrin leading to persistent ERK activation and tumorigenicity. Disrupting this interaction reduces ERK activity, forcing cancer cells into dormancy. We identified a site in uPAR domain III that is in......Highly expressed urokinase plasminogen activator receptor (uPAR) can interact with alpha5beta1 integrin leading to persistent ERK activation and tumorigenicity. Disrupting this interaction reduces ERK activity, forcing cancer cells into dormancy. We identified a site in uPAR domain III...... that is indispensable for these effects. A 9-mer peptide derived from a sequence in domain III (residues 240-248) binds purified alpha5beta1 integrin. Substituting a single amino acid (S245A) in this peptide, or in full-length soluble uPAR, impairs binding of the purified integrin. In the recently solved crystal...... structure of uPAR the Ser-245 is confined to the large external surface of the receptor, a location that is well separated from the central urokinase plasminogen binding cavity. The impact of this site on alpha5beta1 integrin-dependent cell functions was examined by comparing cells induced to express u...

  5. MULTILATERAL DIPLOMACY AND INTERNATIONAL REGIMES

    Directory of Open Access Journals (Sweden)

    BENEA Ciprian-Beniamin

    2014-12-01

    Full Text Available The history of diplomacy can by divided in three main periods: one is that of occasional diplomacy peculiar to Middle Ages, while other belong to permane diplomacy, peculiar to modern times. But this one can be divided in two parts, too: one with a bilateral character, previos to 1st World War, and one with a multilateral character, manifested especially after the end on 1st World War. This third type is the focus of present paper. And it cannot be separated from the newly international constructs: international regimes, and international organizations. International instritutions the area where international regimes are belonging to – are legal constructs which provide the formal (and legal framework for continous negotiations. They are the most visible part of the new diplomacy – the one which has a permanent character, and it has an more open face. Anyway, the most important connection has to do with the international institutions, international regimes, and multilateral international negotiations. In the era of the new diplomacy, they all have a permanent character. International institutions help international negotiations carring on; while in their turn, they provide the base for international regimes’ creation, and especially for their evolution. The international regimes’ evolution is an inseparable part of a permanent international framework. And if there is missing a permanent international framework (international organization connected to a specific regime, this regime is a difuse one, its members have only informal relations among them, while they survey each other, looking at their behavior, but they don’t have a formal relationship among them, which could help them solving their future common interests, and protect them from their common fears. International regimes are very important in the era when evrithing touches, and influences everything. In the same time, the complexity of our present world can be successfully

  6. Great Lakes' regional climate regimes

    Science.gov (United States)

    Kravtsov, Sergey; Sugiyama, Noriyuki; Roebber, Paul

    2016-04-01

    We simulate the seasonal cycle of the Great Lakes' water temperature and lake ice using an idealized coupled lake-atmosphere-ice model. Under identical seasonally varying boundary conditions, this model exhibits more than one seasonally varying equilibrium solutions, which we associate with distinct regional climate regimes. Colder/warmer regimes are characterized by abundant/scarce amounts of wintertime ice and cooler/warmer summer temperatures, respectively. These regimes are also evident in the observations of the Great Lakes' climate variability over recent few decades, and are found to be most pronounced for Lake Superior, the deepest of the Great Lakes, consistent with model predictions. Multiple climate regimes of the Great Lakes also play a crucial role in the accelerated warming of the lakes relative to the surrounding land regions in response to larger-scale global warming. We discuss the physical origin and characteristics of multiple climate regimes over the lakes, as well as their implications for a longer-term regional climate variability.

  7. Friction Regimes in the Lubricants Solid-State Regime

    NARCIS (Netherlands)

    Schipper, D.J.; Maathuis, O.; Dowson, D.; Taylor, C.M.; Childs, T.H.C.; Dalmaz, G.

    1995-01-01

    Friction measurements were performed in the lubricant's solid-state regime to study the transition from full-film lubrication, in which the separation is maintained by a solidified lubricant, to mixed lubrication. Special attention is paid to the influence of temperature (inlet viscosity) and roughn

  8. On the regimes of premixing

    Energy Technology Data Exchange (ETDEWEB)

    Angelini, S.; Theofanous, T.G.; Yuen, W.W. [California Univ., Santa Barbara, CA (United States). Center for Risk Studies and Safety

    1998-01-01

    The conditions of the MAGICO-2000 experiment are extended to more broadly investigate the regimes of premixing, and the corresponding internal structures of mixing zones. With the help of the data and numerical simulations using the computer code PM-ALPHA, we can distinguish extremes of behavior dominated by inertia and thermal effects - we name these the inertia and thermal regimes, respectively. This is an important distinction that should guide future experiments aimed at code verification in this area. Interesting intermediate behaviors are also delineated and discussed. (author)

  9. Monetary regimes in open economies

    NARCIS (Netherlands)

    Korpos, A.

    2006-01-01

    This thesis presents a two-country open economy framework for the analysis of strategic interactions among monetary authorities and wage bargaining institutions. From this perspective, the thesis investigates the economic consequences of replacing flexible and fixed exchange rate regimes with a mone

  10. Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel

    Science.gov (United States)

    Wein, Alexander N.; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T.; Leppla, Stephen H.

    2013-01-01

    PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wild-type lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6, paclitaxel showed a dose response in vitro, but cells remained resistant to PA-U2/LF even in the presence of paclitaxel. In vivo, each therapy slowed tumor progression, and an additive effect between the two was observed. Since LF targets tumor vasculature while paclitaxel is an anti-mitotic, it is possible the agents were acting against different cells in the stroma, precluding a synergistic effect. The engineered anthrax toxin PA-U2/LF warrants further development and testing, possibly in combination with an anti-angiogenesis therapy such as sunitinib or sorafinib. PMID:22843210

  11. The co-operative action of hyaluronidase and urokinase on the isoproterenol-induced myocardial infarction in rats.

    Science.gov (United States)

    Borrelli, F; Antonetti, F; Martelli, F; Caprino, L

    1986-04-15

    The effects of the intravenous administration of hyaluronidase (HY; 2,500 IU/kg) and urokinase (UK; 20,000 and 40,000 IU/kg), alone or in combination, on the isoproterenol (ISP) induced myocardial infarction (MI) in rats, were studied. The severity of infarction was determined by measuring the levels of serum enzymes (CPK, GOT, LDH) and by evaluating the extent of the injured areas and the incidence of mortality. Plasma thromboxane B2 (TXB2) levels were also determined. All the treatments reduced the infarction area and the enzyme levels (increased by ISP) to a varying degree. However, a definite potentiating activity was obtained when HY was combined with the highest dose of UK. This combination was also capable of reducing the mortality rate. Finally, both HY and UK or the combined preparation brought the plasma TXB2 levels back to normal. These findings suggest the possibility of complementary activities of HY and UK in the treatment of experimental MI.

  12. ELISA for complexes between urokinase-type plasminogen activator and its receptor in lung cancer tissue extracts

    DEFF Research Database (Denmark)

    de Witte, H; Pappot, H; Brünner, N;

    1997-01-01

    A sandwich-type ELISA has been developed for the assessment of complexes between urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in extracts of squamous cell lung carcinomas. The assay is based on a combination of rabbit polyclonal anti-uPA antibodies and a biotinylated mouse...... extraction of uPAR yields the highest amounts of uPA:uPAR complexes. Absorption of tumor extracts with anti-uPA or anti-uPAR MAbs results in a complete disappearance of the ELISA signal, demonstrating the specificity of the ELISA. The recovery of chemically cross-linked uPA:uPAR complexes added to tumor...... extracts varies between 80% and 105%. The intra- and inter-assay variation coefficients are 5.3% and 9.8%, respectively. Furthermore, a peptide antagonist for uPAR was employed to evaluate de novo uPA:uPAR complex formation during tumor tissue extraction and the immunoassay procedure. Our results strongly...

  13. Urokinase Gene 3′-UTR T/C Polymorphism Is Associated with Malignancy and ESRD in Idiopathic Membranous Nephropathy

    Directory of Open Access Journals (Sweden)

    Cheng-Hsu Chen

    2014-01-01

    Full Text Available Idiopathic membranous nephropathy (MN is one of the most common causes of nephrotic syndrome in adults, and 25% of MN patients proceed to ESRD. Urokinase plasminogen activator (uPA may play an important role in reducing renal fibrosis. This study was conducted to clarify the relationship between uPA gene polymorphisms and clinical manifestations of MN. We recruited 91 biopsy-diagnosed MN patients and 105 healthy subjects. Genotyping of uPA gene 3′-UTR T/C polymorphism was performed by polymerase chain reaction methods. The genotype distribution had no effect on the development of MN. Thirteen patients (15.9%; P=0.008 acquired malignancies and seventeen (20.7%; P=0.006 patients progressed to ESRD with the C/C genotype, but no patients with the T/C genotype did. In conclusion, we demonstrated that the presence of the uPA gene 3′-UTR C/C genotype was associated with ESRD as well as acquired malignancies in MN patients. These findings should prompt specific considerations for the treatment of MN patients to maintain a balance between treating disease entities and protecting the immune system from cancers.

  14. The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells.

    Science.gov (United States)

    Ingangi, Vincenzo; Bifulco, Katia; Yousif, Ali Munaim; Ragone, Concetta; Motti, Maria Letizia; Rea, Domenica; Minopoli, Michele; Botti, Giovanni; Scognamiglio, Giuseppe; Fazioli, Flavio; Gallo, Michele; De Chiara, Annarosaria; Arra, Claudio; Grieco, Paolo; Carriero, Maria Vincenza

    2016-08-23

    The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration and uPAR88-92 is the minimal sequence required to induce cell motility and angiogenesis by interacting with the formyl peptide receptor type 1 (FPR1). In this study, we present evidence that the cyclization of the uPAR88-92 sequence generates a new potent inhibitor of migration, and extracellular matrix invasion of human osteosarcoma and chondrosarcoma cells expressing comparable levels of FPR1 on cell surface. In vitro, the cyclized peptide [SRSRY] prevents formation of capillary-like tubes by endothelial cells co-cultured with chondrosarcoma cells and trans-endothelial migration of osteosarcoma and chondrosarcoma cells. When chondrosarcoma cells were subcutaneously injected in nude mice, tumor size, intra-tumoral microvessel density and circulating tumor cells in blood samples collected before the sacrifice, were significantly reduced in animals treated daily with i.p-administration of 6 mg/Kg [SRSRY] as compared to animals treated with vehicle only. Our findings indicate that [SRSRY] prevents three key events occurring during the metastatic process of osteosarcoma and chondrosarcoma cells: the extracellular matrix invasion, the formation of a capillary network and the entry into bloodstream.

  15. Soluble urokinase receptor (suPAR) predicts microalbuminuria in patients at risk for type 2 diabetes mellitus

    Science.gov (United States)

    Guthoff, Martina; Wagner, Robert; Randrianarisoa, Elko; Hatziagelaki, Erifili; Peter, Andreas; Häring, Hans-Ulrich; Fritsche, Andreas; Heyne, Nils

    2017-01-01

    Early identification of patients at risk of developing diabetic nephropathy is essential. Elevated serum concentrations of soluble urokinase receptor (suPAR) associate with diabetes mellitus and predict onset and loss of renal function in chronic kidney disease. We hypothesize, that suPAR may be an early risk indicator for diabetic nephropathy, preceding microalbuminuria. The relationship of baseline suPAR and incident microalbuminuria was assessed in a prospective long-term cohort of subjects at increased risk for type 2 diabetes (TULIP, n = 258). Association with albuminuria at later stages of disease was studied in a cross-sectional cohort with manifest type 2 diabetes (ICEPHA, n = 266). A higher baseline suPAR was associated with an increased risk of new-onset microalbuminuria in subjects at risk for type 2 diabetes (hazard ratio 5.3 (95% CI 1.1–25.2, p = 0.03) for the highest vs. lowest suPAR quartile). The proportion of subjects with prediabetes at the end of observation was higher in subjects with new-onset microalbuminuria. suPAR consistently correlated with albuminuria in a separate cohort with manifest type 2 diabetes. Elevated baseline suPAR concentrations independently associate with new-onset microalbuminuria in subjects at increased risk of developing type 2 diabetes. suPAR may hence allow for earlier risk stratification than microalbuminuria. PMID:28091558

  16. Comparison of Video-Assisted Thoracoscopic Surgery and Intrapleural Urokinase as an Initial Treatment for Parapneumonic Effusion and Thoracic Empyema

    Directory of Open Access Journals (Sweden)

    Shungo Yukumi

    2014-05-01

    Full Text Available Introduction: The treatment of complicated parapneumonic effusion (PPE and thoracic empyema (TE is controversial; and the choice of treatment after confirming the failure of simple drainage remains unclear. The purpose of this study was to compare the outcomes of intrapleural urokinase (UK administration and video-assisted thoracoscopic surgery (VATS as initial treatment options for PPE and TE. Materials and Methods: We retrospectively reviewed and compared the data of 20 patients with PPE and TE diagnosed between January 2010 and December 2012 at our hospital, dividing them on the basis of the initial treatment into a video-assisted thoracoscopic surgery (VATS group (n=9 and UK group (n=11. Results: Age was the only statistically different parameter between both groups (P=0.025; with the mean age of the VATS and UK groups being 64 and 76 years, respectively. There was no significant difference in the duration of drainage or success rate between the UK or VATS groups. Although no statistically significant differences (P=0.20 were observed, duration of hospital stay was longer in the UK group (21 and 28 day for VATS and UK, respectively. Conclusion: VATS for PPE and TE may shorten the duration of hospital stay.However, UK administration may be used for selective patients because it is considered to yield outcomes similar to VATS.

  17. Ab initio molecular simulations for proposing novel peptide inhibitors blocking the ligand-binding pocket of urokinase receptor.

    Science.gov (United States)

    Mizushima, Tatsuroh; Sugimoto, Takuya; Kasumi, Tomoyo; Araki, Kohta; Kobayashi, Hiroshi; Kurita, Noriyuki

    2014-06-01

    Recent biochemical experiments have revealed that a variety of proteases play important roles in cancer invasion and metastasis. Among these proteases, urokinase-type plasminogen activator (uPA) is particularly important, since its specific binding to the receptor (uPAR) existing on the surface of a cancer cell is considered to be a trigger for cancer invasion. It is thus expected that the blocking of the binding can inhibit cancer invasion in the cancer patients and improve their prognosis dramatically. To develop a potent inhibitor for the binding, many types of peptides of amino acids were produced and their effect on the cancer invasion was investigated in the previous biochemical experiments. On the other hand, our previous ab initio molecular simulations have clarified that some amino acid residues of uPA play important roles in the specific binding between uPA and uPAR. In the present study, we propose some peptides composed of these important residues and investigate the specific interactions and the binding affinity between uPAR and the peptides at an electronic level, using ab initio molecular simulations. Base on the results simulated, we elucidate which peptide can bind more strongly to uPAR and propose a novel potent peptide which can inhibit the binding between uPAR and uPA efficiently.

  18. Exchange rate regimes and monetary arrangements

    Directory of Open Access Journals (Sweden)

    Ivan Ribnikar

    2005-06-01

    Full Text Available There is a close relationship between a country’s exchange rate regime and monetary arrangement and if we are to examine monetary arrangements then exchange rate regimes must first be analysed. Within the conventional and most widely used classification of exchange rate regimes into rigid and flexible or into polar regimes (hard peg and float on one side, and intermediate regimes on the other there, is a much greater variety among intermediate regimes. A more precise and, as will be seen, more useful classification of exchange rate regimes is the first topic of the paper. The second topic is how exchange rate regimes influence or determine monetary arrangements and monetary policy or monetary policy regimes: monetary autonomy versus monetary nonautonomy and discretion in monetary policy versus commitment in monetary policy. Both topics are important for countries on their path to the EU and the euro area

  19. The Concept of Truth Regime

    Directory of Open Access Journals (Sweden)

    Lorna Weir

    2008-07-01

    Full Text Available “Truth regime” is a much used but little theorized concept, with the Foucauldian literature presupposing that truth in modernity is uniformly scientific/quasi-scientific and enhances power. I argue that the forms of truth characteristic of our present are wider than Foucault recognized, their relations to power more various, and their historicity more complex. The truth regime of advanced modernity is characterized by multiple, irreducible truth formulae that co-exist and sometimes vie for dominance. A truth formula stabilizes a network of elements: a relation between representation and presentation (words and things, truth and non-truth, and the place of the subject in discourse. Our contemporary truth regime comprises radically heterogeneous truthful knowledges – science, governance, religion/politics, and common culture – that have distinct histories and relations to power.

  20. Gene expression changes of urokinase plasminogen activator and urokinase receptor in rat testes at postnatal stages%出生后不同发育阶段大鼠睾丸uPA/uPAR基因表达的变化

    Institute of Scientific and Technical Information of China (English)

    D.H. Huang; H. Zhao; Y.H.Tian; H. G.Li; X. F. Ding; C. L.Xiong

    2007-01-01

    目的:为探讨uPA/uPAR系统在大鼠精子发生中的作用,研究出生后不同发育阶段大鼠睾丸组织中uPA/uPARmRNA表达的变化.方法:分别取出生后0、5、10、15、21、28、35、42、49、56天大鼠的睾丸组织,用实时定量聚合酶链反应法(PCR)检测各年龄组uPA/uPAR mRNA的表达变化.结果:除了出生后0天外,在其它大多数时间点uPA与uPAR mRNA表达趋势很相似.在出生后0天,大鼠睾丸组织中uPAR mRNA表达水平相对来说高于uPA mRNA表达水平,后逐渐减少,在出生后21天表达水平最低,到28天急剧增加,35天到达高峰,42天迅速下降,之后维持一个低表达水平.结论:uPA/uPAR系统可能通过调节生精细胞迁移及增殖、促进精子排放及残余胞体从成熟精子中脱落等方式与精子排放和精子发生密切相关.%Aim: To investigate the gene expression changes of urokinase plasminogen activator (uPA)/urokinase receptor (uPAR)in rat testes at postnatal stages and explore the effects of uPA/uPAR system on the rat spermatogenesis. Methods:The mRNAs of uPA and uPAR in rat testes were measured by using real-time quantitative polymerase chain reaction (PCR) at postnatal days 0, 5, 10, 15, 21, 28, 35, 42, 49 and 56, respectively. Results: The tendencies of uPA and uPAR mRNA expression were similar at most postnatal stages except for D0. The expression of uPAR mRNA in rats testes was relatively higher than that of uPA at postnatal D0, and both were decreased until D21, increased obviously at postnatal D28, reached a peak at postnatal D35, then declined sharply at postnatal D42 and retained at a low level afterwards. Conclusion: The uPA/uPAR system may be strongly linked to spermiation and spermatogenesis via regulating germ cell migration and proliferation, as well as promoting the spermiation and detached residual bodies from the mature spermatids. (Asian J Androl 2007 Sep; 9: 679-683)

  1. Detecting spatial regimes in ecosystems

    Science.gov (United States)

    Sundstrom, Shana M.; Eason, Tarsha; Nelson, R. John; Angeler, David G.; Barichievy, Chris; Garmestani, Ahjond S.; Graham, Nicholas A.J.; Granholm, Dean; Gunderson, Lance; Knutson, Melinda; Nash, Kirsty L.; Spanbauer, Trisha; Stow, Craig A.; Allen, Craig R.

    2017-01-01

    Research on early warning indicators has generally focused on assessing temporal transitions with limited application of these methods to detecting spatial regimes. Traditional spatial boundary detection procedures that result in ecoregion maps are typically based on ecological potential (i.e. potential vegetation), and often fail to account for ongoing changes due to stressors such as land use change and climate change and their effects on plant and animal communities. We use Fisher information, an information theory-based method, on both terrestrial and aquatic animal data (U.S. Breeding Bird Survey and marine zooplankton) to identify ecological boundaries, and compare our results to traditional early warning indicators, conventional ecoregion maps and multivariate analyses such as nMDS and cluster analysis. We successfully detected spatial regimes and transitions in both terrestrial and aquatic systems using Fisher information. Furthermore, Fisher information provided explicit spatial information about community change that is absent from other multivariate approaches. Our results suggest that defining spatial regimes based on animal communities may better reflect ecological reality than do traditional ecoregion maps, especially in our current era of rapid and unpredictable ecological change.

  2. Urokinase-type plasminogen activator deficiency has little effect on seizure susceptibility and acquired epilepsy phenotype but reduces spontaneous exploration in mice.

    Science.gov (United States)

    Rantala, J; Kemppainen, S; Ndode-Ekane, X E; Lahtinen, L; Bolkvadze, Tamuna; Gurevicius, K; Tanila, H; Pitkänen, A

    2015-01-01

    Urokinase-type plasminogen activator (uPA), a serine protease, converts plasminogen to plasmin. Activation of plasmin leads to degradation of the extracellular matrix, which is critical for tissue recovery, angiogenesis, cell migration, and axonal and synaptic plasticity. We hypothesized that uPA deficiency would cause an abnormal neurophenotype and would lead to exacerbated epileptogenesis after brain injury. Wild-type (Wt) and uPA-/- mice underwent a battery of neurologic behavioral tests evaluating general reactivity, spontaneous exploratory activity, motor coordination, pain threshold, fear and anxiety, and memory. We placed particular emphasis on the effect of uPA deficiency on seizure susceptibility, including the response to convulsants (pentylenetetrazol, kainate, or pilocarpine) and kainate-induced epileptogenesis and epilepsy. The uPA-/- mice showed no motor or sensory impairment compared with the Wt mice. Hippocampus-dependent spatial memory also remained intact. The uPA-/- mice, however, exhibited reduced exploratory activity and an enhanced response to a tone stimulus (p<0.05 compared with the Wt mice). The urokinase-type plasminogen activator deficient mice showed no increase in spontaneous or evoked epileptiform electrographic activity. Rather, the response to pilocarpine administration was reduced compared with the Wt mice (p<0.05). Also, the epileptogenesis and the epilepsy phenotype after intrahippocampal kainate injection were similar to those in the Wt mice. Taken together, uPA deficiency led to diminished interest in the environmental surroundings and enhanced emotional reactivity to unexpected aversive stimuli. Urokinase-type plasminogen activator deficiency was not associated with enhanced seizure susceptibility or worsened poststatus epilepticus epilepsy phenotype.

  3. Elevated soluble urokinase receptor values in CSF, age and bacterial meningitis infection are independent and additive risk factors of fatal outcome

    DEFF Research Database (Denmark)

    Tzanakaki, G; Paparoupa, M; Kyprianou, M;

    2012-01-01

    outcome. Patients with levels of suPAR above the cut-off values and age ≥51 years, or patients in which either Neisseria meningitis or Streptococcus pneumoniae were detected were categorized as high risk patients. The combination of the above three predictors (suPAR, age and infectious agent......The aim of the present study was to evaluate the potential role of cerebrospinal fluid soluble urokinase receptor (suPAR) level, infection and age as risk factors for fatal outcome in patients suspected of having meningitis and/or bacteraemia on admission to hospital. A total of 545 cerebrospinal...

  4. 重组人尿激酶原的体外变复性研究%In vitro renaturation of recombinant human pro-urokinase expressed in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    朱慧; 刘伟; 史蔚; 薛宇鸣; 蒯乐天; 马忠

    2001-01-01

    Objective Recombinant human pro-urokinase forms insoluble inclusion body when overexpressed in Escherichia coli. It must be denatured and renatured in vitro so that it can acquire activity. This study aimed at increasing the renaturation yield of denaturant pro-urokinase. Methods We evaluated the basic renaturation conditions of pro-urokinase through qualitative and quantitative analysis of pH, temperature, denatured concentration, protein concentration, and the ratio of reduced and oxidized thiol reagents. We also compared the effects of nonspecific additives, step-wise dilution and urea gradient dialysis. Results We defined the optimal conditions of pro-urokinase renaturation with a yield of about 20%-30%. Conclusion Different recombinant denatured proteins have different renaturation conditions due to their different molecular sizes, molecular constructions, disulfide bond numbers, and hydrophobicity. The renaturation yield can be increased by optimizing the renaturation conditions of a specific protein.%目的 重组人尿激酶原在大肠杆菌中过量表达时形成不溶物包涵体,需经体外变复性后才能获得生物活性。本文旨在提高包涵体中变性尿激酶原的复性效率。 方法 通过对pH、温度、变性剂种类及浓度、蛋白浓度、以及巯基氧化还原对比率等的定性定量分析,研究重组人尿激酶原体外变复性的基本条件,并比较了添加一些非特异有效成分、脉冲稀释、梯度透析等方法对提高重组人尿激酶原体外变复性效率的作用。 结果 确定了重组人尿激酶原体外变复性的基本方法,其复性效率可达30%左右。 结论 不同的包涵体蛋白的体外变复性效率因蛋白的分子大小、二巯键数目、疏水程度等而异,对特定蛋白复性条件的优化可提高其复性效率。

  5. Prognostic value of intact and cleaved forms of the urokinase plasminogen activator receptor in a retrospective study of 518 colorectal cancer patients

    DEFF Research Database (Denmark)

    Lomholt, Anne Fog; Christensen, Ib J; Høyer-Hansen, Gunilla

    2010-01-01

    The levels of the soluble urokinase plasminogen activator receptor (suPAR) in blood have been shown to correlate with prognosis in various cancers. Plasma levels of the combined suPAR forms have previously shown to be a strong prognostic marker in the present cohort of CRC patients and could...... potentially identify high-risk patients among those with early stage disease. In order to investigate whether the individual suPAR forms are stronger prognostic markers than the combined amount we measured the different uPAR forms in serum from the same cohort and evaluated their prognostic significance....

  6. Camptothecin induces urokinase-type plasminogen activator gene-expression in human RC-K8 malignant lymphoma and H69 small cell lung cancer cells.

    OpenAIRE

    Shibakura M; Niiya K; Kiguchi T; Nakata Y; Tanimoto M

    2002-01-01

    We previously reported that anthracyclines, which could generate reactive oxygen species (ROS), could induce the urokinase-type plasminogen activator (uPA) gene expression in human RC-K8 malignant lymphoma cells and in H69 small cell lung cancer (SCLC) cells. In screening other uPA-inducible anti-cancer agents, we found that camptothecin (CPT) and its derivative, SN38, could induce uPA in RC-K8 and H69 cells. CPT and SN38, which are also used for the treatment of lymphoma and SCLC, significan...

  7. Levels of plasminogen activator inhibitor type 1 and urokinase plasminogen activator receptor in non-small cell lung cancer as measured by quantitative ELISA and semiquantitative immunohistochemistry

    DEFF Research Database (Denmark)

    Pappot, Helle; Skov, Birgit Guldhammer; Pyke, Charles

    1997-01-01

    The components of the plasminogen activation system have been reported to have prognostic impact in several cancer types, e.g. breast-, colon-, gastric- and lung cancer. Most of these studies have used quantification by enzyme-linked immunosorbent assay (ELISA) on tumour tissue extracts. However...... methodology. In the present study we investigated levels of plasminogen activator inhibitor type 1 (PAI-I) and urokinase plasminogen activator receptor (uPAR), as quantitated by ELISA in tumour extracts from 64 NSCLC patients (38 squamous cell carcinomas, 26 adenocarcinomas), and compared them to staining...

  8. Domain interplay in the urokinase receptor. Requirement for the third domain in high affinity ligand binding and demonstration of ligand contact sites in distinct receptor domains

    DEFF Research Database (Denmark)

    Behrendt, N; Ronne, E; Dano, K

    1996-01-01

    . The purified suPAR was cross-linked to the radiolabeled amino-terminal fragment (ATF) of urokinase, followed by cleavage with chymotrypsin. In accordance with the cleavage pattern found for the uncomplexed receptor, this treatment led to cleavage between D1 and D(2 + 3). Analysis of the radiolabeled fragments...... revealed the expected ligand labeling of D1 but a clear labeling of D(2 + 3) was also found, indicating that this part of the molecule is also situated in close contact with ATF in the receptor-ligand complex. The latter contact site may contribute to the role of molecular regions outside D1 in high...

  9. Catheter-Directed Thrombolysis with a Continuous Infusion of Low-Dose Urokinase for Non-Acute Deep Venous Thrombosis of the Lower Extremity

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Binbin; Zhang, Jingyong; Wu, Xuejun; Han, Zonglin; Zhou, Hua; Dong, Dianning; Jin, Xing [Shandong Provincial Hospital, Shandong University, Ji' nan (China)

    2011-02-15

    We wanted to evaluate the feasibility of catheter-directed thrombolysis with a continuous infusion of low-dose urokinase for treating non-acute (less than 14 days) deep venous thrombosis of the lower extremity. The clinical data of 110 patients who were treated by catheter-directed thrombolysis with a continuous infusion of low-dose urokinase for lower extremity deep venous thrombosis was analysed. Adjunctive angioplasty or/and stenting was performed for the residual stenosis. Venous recanalization was graded by pre- and posttreatment venography. Follow-up was performed by clinical evaluation and Doppler ultrasound. A total of 112 limbs with deep venous thrombosis with a mean symptom duration of 22.7 days (range: 15-38 days) were treated with a urokinase infusion (mean: 3.5 million IU) for a mean of 196 hours. After thrombolysis, stent placement was performed in 25 iliac vein lesions and percutaneous angioplasty (PTA) alone was done in fi ve iliac veins. Clinically significant recanalization was achieved in 81% (90 of 112) of the treated limbs: complete recanalization was achieved in 28% (31 of 112) and partial recanalization was achieved in 53% (59 of 112). Minor bleeding occurred in 14 (13%) patients, but none of the patients suffered from major bleeding or symptomatic pulmonary embolism. During followup (mean: 15.2 months, range: 3-24 months), the veins were patent in 74 (67%) limbs. Thirty seven limbs (32%) showed progression of the stenosis with luminal narrowing more than 50%, including three with rethrombosis, while one revealed an asymptomatic iliac vein occlusion: 25 limbs (22%) developed mild post-thrombotic syndrome, and none had severe post-thrombotic syndrome. Valvular reflux occurred in 24 (21%) limbs. Catheter-directed thrombolysis with a continuous infusion of low-dose urokinase combined with adjunctive iliac vein stenting is safe and effective for removal of the clot burden and for restoration of the venous flow in patients with non-acute lower

  10. Plasminogen activator inhibitor-1 (PAI-1 and urokinase plasminogen activator (uPA in sputum of allergic asthma patients.

    Directory of Open Access Journals (Sweden)

    Sebastian Zukowski

    2008-06-01

    Full Text Available Urokinase plasminogen activator (uPA and its inhibitor (PAI-1 have been associated with asthma. The aim of this study was to evaluate concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs. The study was performed on 19 HDM-AAs and 8 healthy nonatopic controls (HCs. Concentration of uPA and PAI-1 was evaluated in induced sputum supernatants using ELISA method. In HDM-AAs the median sputum concentration of uPA (128 pg/ml; 95% CI 99 to 183 pg/ml and PAI-1 (4063 pg/ml; 95%CI 3319 to 4784 pg/ml were significantly greater than in HCs (17 pg/ml; 95%CI 12 to 32 pg/ml; p<0.001 and 626 pg/ml; 95%CI 357 to 961 pg/ml; p<0.001 for uPA and PAI-1 respectively. The sputum concentration of uPA correlated with sputum total cell count (r=0.781; p=0.0001 and with logarithmically transformed exhaled nitric oxide concentration (eNO (r=0.486; p=0.035 but not with FEV1 or bronchial reactivity to histamine. On the contrary, the sputum PAI-1 concentration correlated with FEV1 (r=-0,718; p=0.0005 and bronchial reactivity to histamine expressed as log(PC20 (r=-0.824; p<0.0001 but did not correlate with sputum total cell count or eNO. The results of this study support previous observations linking PAI-1 with airway remodeling and uPA with cellular inflammation. Moreover, the observed effect of uPA seems to be independent of its fibrynolytic activity.

  11. Influence of irbesartan combined with low dose urokinase on treatment effect and serologic indexes in elderlyisolated systolic hypertension patients

    Institute of Scientific and Technical Information of China (English)

    Gui-Peng Wang; Xiao-Mei Luo

    2017-01-01

    To study the influence of irbesartan combined with low dose urokinase on treatment effect and serologic indexes in elderly isolated systolic hypertension patients. Methods: One hundred and ten cases of elderly isolated systolic hypertension patients in our hospital during January 2013–January 2016 were randomly divided into observation group with 55 cases and control group with 55 cases. Patients in observation group received irbesartan combined with low dose hydrochlorothiazide treatment and those in control group received amlodipine combined with low dose hydrochlorothiazide treatment, each lasted for 4 weeks. After 4 weeks treatment, non-invasive blood pressure and blood pressure variability indexes were measured, serum endothelial function, inflammatory factors and oxidative stress indexes were measured. Results: After 4 weeks treatment, patients systolic blood pressure (SBP), 24 h mean systolic blood pressure (24 h SBP), 24 h systolic blood pressure standard deviation (24 h SSD) were significantly lower in observation group than in control group (P<0.05); serum endothelial function index EF-1 was lower in observation group than in control group, while NO and endothelial nitric oxide synthase (eNOS) were higher in observation group than in control group (P<0.05); serum high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α) contents were lower in observation group than in control group (P<0.05); serum oxidation index such as malondialdehyde (MDA) was lower in observation group than in control group, while antioxidant indexes such as total anti-oxidative capacity (TAC), superoxide dismutase (SOD), GSH were higher in observation group than in control group (P<0.05). Conclusions: Irbesartan combined with low dose hydrochlorothiazide can effectively reduce systolic hypertension and blood pressure variability in elderly isolated systolic hypertension patients, while optimizing the systemic inflammation and

  12. Cambodian Phellinus linteus inhibits experimental metastasis of melanoma cells in mice via regulation of urokinase type plasminogen activator.

    Science.gov (United States)

    Lee, Hyo-Jung; Lee, Hyo-Jeong; Lim, Eu-Soo; Ahn, Kyoo-Seok; Shim, Beom-Sang; Kim, Hyung-Min; Gong, Soo-Ja; Kim, Dae-Keun; Kim, Sung-Hoon

    2005-01-01

    Phellinus linteus (PL) is a fungus mainly found in tropical America, Africa and Asian countries including Korea, Japan and China. PL has been traditionally used for the treatment of arthritis, liver damage and cancer. However, little was known on the biological activity and characterization of Phellinus species in Cambodia. Thus, in the present study, the anti-metastatic mechanism of aqueous extract of Cambodian Phellinus linteus (CPL) was evaluated. Cambodian mushroom was identified as a Phellinus species with 99% homology of Phellinus linteus by DNA sequence analysis and comparison by the National Center for Biotechnology Information. CPL did not exhibit any significant cytotoxicity against B16BL6 cells, invasive melanoma cells at 1 mg/ml. However, CPL inhibited platelet aggregation induced by B16BL6 cells and also disrupted the adhesion to gelatin and invasion of B16BL6 cells in a concentration dependent manner. Similarly, CPL dose-dependently inhibited the pulmonary metastatic colonies in C57BL/6 mice intravenously injected by B16BL6 cells up to 55.5% at a dose of 50 mg/kg compared with untreated control. CPL also down-regulated the expression of urokinase type plasminogen activator (uPA), one of key proteins associated with invasion and metastasis of tumor cells in a concentration dependent fashion, while CPL didn't significantly affect the expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) by reverse transcriptase-polymerase chain reaction (RT-PCR). Taken together, these findings indicate that Cambodian Phellinus linteus may inhibit metastasis at least partly via regulation of uPA associated with tumor cell induced platelet aggregation (TCIPA) and also suggest a further study for isolation of active ingredients and the involvement of adhesion molecule signaling pathway.

  13. Proteomic Identification of LASP-1 Down-regulation After RNAi Urokinase Silencing in Human Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Alessandro Salvi

    2009-02-01

    Full Text Available In human hepatocellular carcinoma (HCC, the high expression of urokinase-type plasminogen activator (uPA is an unfavorable prognostic factor and a therapeutic target. To identify the downstream effects of uPA silencing by RNA interference, we studied proteome modifications of uPA-inhibited SKHep1C3 cells, an HCC-derived cell line. The study with two-dimensional difference gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry showed Lim and SH3 protein 1 (LASP-1, cytokeratin 1 (CK-1, cytokeratin 10 (CK-10, and heterogeneous nuclear ribonucleoprotein H1 down-modulation after uPA inhibition. LASP-1, CK-1, and CK-10 are involved in cytoskeleton dynamics as heterogeneous nuclear ribonucleoprotein H1 takes part in the mRNA processing and stability. We first confirmed the proteomic data by Western blot and immunoflorescence and then explored the link between uPA and LASP-1. The ectopic expression of uPA and LASP-1 supported the proteomic results and showed that uPA up-regulation increased LASP-1 expression and that both were implicated in SKHep1C3 motility. siRNA LASP-1 inhibition showed that LASP-1 was involved in actin microfilaments organization of SKHep1C3 cells. The disruption of the actin microfilaments after LASP-1 depletion increased uPA secretion and SKHep1C3 motility. Our results would suggest the hypothesis that uPA and LASP-1 expression may be coordinated in HCC-derived cells. In summary, the proteomic identification of a set of uPA downstream proteins provides new insight into the function of uPA in HCC cells.

  14. A key role for the urokinase plasminogen activator (uPA) in invasive Group A streptococcal infection.

    Science.gov (United States)

    Sanderson-Smith, Martina L; Zhang, Yueling; Ly, Diane; Donahue, Deborah; Hollands, Andrew; Nizet, Victor; Ranson, Marie; Ploplis, Victoria A; Walker, Mark J; Castellino, Francis J

    2013-01-01

    Recruitment of the serine protease plasmin is central to the pathogenesis of many bacterial species, including Group A streptococcus (GAS), a leading cause of morbidity and mortality globally. A key process in invasive GAS disease is the ability to accumulate plasmin at the cell surface, however the role of host activators of plasminogen in this process is poorly understood. Here, we demonstrate for the first time that the urokinase-type plasminogen activator (uPA) contributes to plasmin recruitment and subsequent invasive disease initiation in vivo. In the absence of a source of host plasminogen activators, streptokinase (Ska) was required to facilitate cell surface plasmin acquisition by GAS. However, in the absence of Ska, host activators were sufficient to promote cell surface plasmin acquisition by GAS strain 5448 during incubation with plasminogen or human plasma. Furthermore, GAS were able mediate a significant increase in the activation of zymogen pro-uPA in human plasma. In order to assess the contribution of uPA to invasive GAS disease, a previously undescribed transgenic mouse model of infection was employed. Both C57/black 6J, and AlbPLG1 mice expressing the human plasminogen transgene, were significantly more susceptible to invasive GAS disease than uPA-/- mice. The observed decrease in virulence in uPA-/-mice was found to correlate directly with a decrease in bacterial dissemination and reduced cell surface plasmin accumulation by GAS. These findings have significant implications for our understanding of GAS pathogenesis, and research aimed at therapeutic targeting of plasminogen activation in invasive bacterial infections.

  15. A key role for the urokinase plasminogen activator (uPA in invasive Group A streptococcal infection.

    Directory of Open Access Journals (Sweden)

    Martina L Sanderson-Smith

    Full Text Available Recruitment of the serine protease plasmin is central to the pathogenesis of many bacterial species, including Group A streptococcus (GAS, a leading cause of morbidity and mortality globally. A key process in invasive GAS disease is the ability to accumulate plasmin at the cell surface, however the role of host activators of plasminogen in this process is poorly understood. Here, we demonstrate for the first time that the urokinase-type plasminogen activator (uPA contributes to plasmin recruitment and subsequent invasive disease initiation in vivo. In the absence of a source of host plasminogen activators, streptokinase (Ska was required to facilitate cell surface plasmin acquisition by GAS. However, in the absence of Ska, host activators were sufficient to promote cell surface plasmin acquisition by GAS strain 5448 during incubation with plasminogen or human plasma. Furthermore, GAS were able mediate a significant increase in the activation of zymogen pro-uPA in human plasma. In order to assess the contribution of uPA to invasive GAS disease, a previously undescribed transgenic mouse model of infection was employed. Both C57/black 6J, and AlbPLG1 mice expressing the human plasminogen transgene, were significantly more susceptible to invasive GAS disease than uPA-/- mice. The observed decrease in virulence in uPA-/-mice was found to correlate directly with a decrease in bacterial dissemination and reduced cell surface plasmin accumulation by GAS. These findings have significant implications for our understanding of GAS pathogenesis, and research aimed at therapeutic targeting of plasminogen activation in invasive bacterial infections.

  16. The january effect across volatility regimes

    OpenAIRE

    Agnani, Betty; Aray, Henry

    2007-01-01

    Using a Markov regime switching model, this article presents evidence on the well-known January effect on stock returns. The specification allows a distinction to be drawn between two regimes, one with high volatility and other with low volatility. We obtain a time-varying January effect that is, in general, positive and significant in both volatility regimes. However, this effect is larger in the high volatility regime. In sharp contrast with most previous literature we find two major result...

  17. Implementation Regimes and Street-Level Bureaucrats

    DEFF Research Database (Denmark)

    Winter, Søren; T. Dinesen, Peter; J. May, Peter

    -government regimes foster greater policy commitment, attention to rules, and adherence among frontline workers than is the case for a local-government implementation regime. These lead to actions of street-level bureaucrats in central-government regimes that are more in line with national policies than those...

  18. Accommodating human values in the climate regime

    NARCIS (Netherlands)

    Cook, Rosalind; Tauschinsky, Eljalill

    2008-01-01

    The climate regime addresses one of the most important challenges facing humankind today. However, while the environmental and economic sides of the problem are well represented, it lacks the inclusion of social and human aspects. The human rights regime, in contrast, is a regime which has been esta

  19. Adaptation in Collaborative Governance Regimes

    Science.gov (United States)

    Emerson, Kirk; Gerlak, Andrea K.

    2014-10-01

    Adaptation and the adaptive capacity of human and environmental systems have been of central concern to natural and social science scholars, many of whom characterize and promote the need for collaborative cross-boundary systems that are seen as flexible and adaptive by definition. Researchers who study collaborative governance systems in the public administration, planning and policy literature have paid less attention to adaptive capacity specifically and institutional adaptation in general. This paper bridges the two literatures and finds four common dimensions of capacity, including structural arrangements, leadership, knowledge and learning, and resources. In this paper, we focus on institutional adaptation in the context of collaborative governance regimes and try to clarify and distinguish collaborative capacity from adaptive capacity and their contributions to adaptive action. We posit further that collaborative capacities generate associated adaptive capacities thereby enabling institutional adaptation within collaborative governance regimes. We develop these distinctions and linkages between collaborative and adaptive capacities with the help of an illustrative case study in watershed management within the National Estuary Program.

  20. Urokinase plasminogen receptor and the fibrinolytic complex play a role in nerve repair after nerve crush in mice, and in human neuropathies.

    Directory of Open Access Journals (Sweden)

    Cristina Rivellini

    Full Text Available Remodeling of extracellular matrix (ECM is a critical step in peripheral nerve regeneration. In fact, in human neuropathies, endoneurial ECM enriched in fibrin and vitronectin associates with poor regeneration and worse clinical prognosis. Accordingly in animal models, modification of the fibrinolytic complex activity has profound effects on nerve regeneration: high fibrinolytic activity and low levels of fibrin correlate with better nerve regeneration. The urokinase plasminogen receptor (uPAR is a major component of the fibrinolytic complex, and binding to urokinase plasminogen activator (uPA promotes fibrinolysis and cell movement. uPAR is expressed in peripheral nerves, however, little is known on its potential function on nerve development and regeneration. Thus, we investigated uPAR null mice and observed that uPAR is dispensable for nerve development, whereas, loss of uPAR affects nerve regeneration. uPAR null mice showed reduced nerve repair after sciatic nerve crush. This was a consequence of reduced fibrinolytic activity and increased deposition of endoneurial fibrin and vitronectin. Exogenous fibrinolysis in uPAR null mice rescued nerve repair after sciatic nerve crush. Finally, we measured the fibrinolytic activity in sural nerve biopsies from patients with peripheral neuropathies. We showed that neuropathies with defective regeneration had reduced fibrinolytic activity. On the contrary, neuropathies with signs of active regeneration displayed higher fibrinolytic activity. Overall, our results suggest that enforced fibrinolysis may facilitate regeneration and outcome of peripheral neuropathies.

  1. Structure-function relationships in the receptor for urokinase-type plasminogen activator. Comparison to other members of the Ly-6 family and snake venom alpha-neurotoxins

    DEFF Research Database (Denmark)

    Ploug, M; Ellis, V

    1994-01-01

    Plasminogen activation is regulated by the interaction between urokinase-type plasminogen activator (uPA) and its specific glycolipid-anchored cell surface receptor (uPAR). uPAR is composed of three homologous domains and is the only multi-domain member of the Ly-6 family of glycolipid-anchored m......Plasminogen activation is regulated by the interaction between urokinase-type plasminogen activator (uPA) and its specific glycolipid-anchored cell surface receptor (uPAR). uPAR is composed of three homologous domains and is the only multi-domain member of the Ly-6 family of glycolipid......-anchored membrane proteins. Recent evidence has highlighted similarities between the individual domains of uPAR and the large family of secreted, single domain snake venom alpha-neurotoxins, suggesting that uPAR may adopt the same gross folding pattern as these structurally well characterized proteins. Structural...... aspects of the binding between alpha-neurotoxins and the acetylcholine receptor may have a major influence on future studies of the interaction between uPA and uPAR....

  2. Reversibility of epithelial-mesenchymal transition (EMT) induced in breast cancer cells by activation of urokinase receptor-dependent cell signaling.

    Science.gov (United States)

    Jo, Minji; Lester, Robin D; Montel, Valerie; Eastman, Boryana; Takimoto, Shinako; Gonias, Steven L

    2009-08-21

    Hypoxia induces expression of the urokinase receptor (uPAR) and activates uPAR-dependent cell signaling in cancer cells. This process promotes epithelial-mesenchymal transition (EMT). uPAR overexpression in cancer cells also promotes EMT. In this study, we tested whether uPAR may be targeted to reverse cancer cell EMT. When MDA-MB 468 breast cancer cells were cultured in 1% O(2), uPAR expression increased, as anticipated. Cell-cell junctions were disrupted, vimentin expression increased, and E-cadherin was lost from cell surfaces, indicating EMT. Transferring these cells back to 21% O(2) decreased uPAR expression and reversed the signs of EMT. In uPAR-overexpressing MDA-MB 468 cells, EMT was reversed by silencing expression of endogenously produced urokinase-type plasminogen activator (uPA), which is necessary for uPAR-dependent cell signaling, or by targeting uPAR-activated cell signaling factors, including phosphatidylinositol 3-kinase, Src family kinases, and extracellular signal-regulated kinase. MDA-MB 231 breast cancer cells express high levels of uPA and uPAR and demonstrate mesenchymal cell morphology under normoxic culture conditions (21% O(2)). Silencing uPA expression in MDA-MB-231 cells decreased expression of vimentin and Snail, and induced changes in morphology characteristic of epithelial cells. These results demonstrate that uPAR-initiated cell signaling may be targeted to reverse EMT in cancer.

  3. Urokinase Plasminogen Receptor and the Fibrinolytic Complex Play a Role in Nerve Repair after Nerve Crush in Mice, and in Human Neuropathies

    Science.gov (United States)

    Rivellini, Cristina; Dina, Giorgia; Porrello, Emanuela; Cerri, Federica; Scarlato, Marina; Domi, Teuta; Ungaro, Daniela; Carro, Ubaldo Del; Bolino, Alessandra; Quattrini, Angelo; Comi, Giancarlo; Previtali, Stefano C.

    2012-01-01

    Remodeling of extracellular matrix (ECM) is a critical step in peripheral nerve regeneration. In fact, in human neuropathies, endoneurial ECM enriched in fibrin and vitronectin associates with poor regeneration and worse clinical prognosis. Accordingly in animal models, modification of the fibrinolytic complex activity has profound effects on nerve regeneration: high fibrinolytic activity and low levels of fibrin correlate with better nerve regeneration. The urokinase plasminogen receptor (uPAR) is a major component of the fibrinolytic complex, and binding to urokinase plasminogen activator (uPA) promotes fibrinolysis and cell movement. uPAR is expressed in peripheral nerves, however, little is known on its potential function on nerve development and regeneration. Thus, we investigated uPAR null mice and observed that uPAR is dispensable for nerve development, whereas, loss of uPAR affects nerve regeneration. uPAR null mice showed reduced nerve repair after sciatic nerve crush. This was a consequence of reduced fibrinolytic activity and increased deposition of endoneurial fibrin and vitronectin. Exogenous fibrinolysis in uPAR null mice rescued nerve repair after sciatic nerve crush. Finally, we measured the fibrinolytic activity in sural nerve biopsies from patients with peripheral neuropathies. We showed that neuropathies with defective regeneration had reduced fibrinolytic activity. On the contrary, neuropathies with signs of active regeneration displayed higher fibrinolytic activity. Overall, our results suggest that enforced fibrinolysis may facilitate regeneration and outcome of peripheral neuropathies. PMID:22363796

  4. Construction and Characterization of a Mutant of Single-chain Urokinase-type Plasminogen Activator Ser(175)-His(187)-mscu-PA

    Science.gov (United States)

    Xue, Yu-Ming; Zhu, Hui; Shi, Wei; Liu, Wei; Liu, Jian-Ning; Ma, Zhong

    2000-01-01

    Single-chain urokinase-type plasminogen activator scu-PA is the precursor of double-chain urokinase tcu-PA , which has a much higher intrinsic catalytic activity than other zymogens of the serine protease family. To restore the "zymogen triad" of Asp-His-Ser in the serine protease family, the mutant gene of scu-PA mscu-PA, Ala(175)right curved arrow Ser(175), Tyr(187)right curved arrow His(187) was constructed by the method of oligonucleotide-directed, site-specific mutagenesis in order to reduce its intrinsic catalytic activity. mscu-PA was expressed in E. coli BL21. After denaturation and renaturation in vitro, the mscu-PA was purified to homogeneity by SP-Sepharose ion-exchange chromatography, Sephacryl S-200 chromatography and Benzamidine-Sepharose affinity adsorption. mscu-PA had the same activity to plasmin as scu-PA. The catalytic efficiency measured by k(cat)/K(m) to synthetic substrate S(2444) was 2.5-fold lower than that of scu-PA, and the activity against Glu-plasminogen was also reduced. After activation by plasmin, mtcu-PA and tcu-PA had similar catalytic efficiency against S(2444) and Glu-plasminogen. The results suggest that the intrinsic catalytic activity of mscu-PA be really reduced after restoring the "zymogen triad".

  5. Measuring the effectiveness of international environmental regimes

    Energy Technology Data Exchange (ETDEWEB)

    Helm, C.; Sprinz, D.F.

    1999-05-01

    While past research has emphasized the importance of international regimes for international governance, systematic assessments of regime effects are missing. This article derives a standardized measurement concept for the effectiveness of international environmental regimes by developing an operational rational choice calculus to evaluate actual policy simultaneously against a non-regime counterfactual and a collective optimum. Subsequently, the empirical feasibility of the measurement instrument is demonstrated by way of two international treaties regulating transboundary air pollution in Europe. The results demonstrate that the regimes indeed show positive effects - but fall substantially short of the collective optima. (orig.)

  6. Quantitative RT-PCR assays for the determination of urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 mRNA in primary tumor tissue of breast cancer patients: comparison to antigen quantification by ELISA.

    NARCIS (Netherlands)

    Biermann, J.C.; Holzscheiter, L.; Kotzsch, M.; Luther, T.; Kiechle-Bahat, M.; Sweep, F.C.; Span, P.N.; Schmitt, M.; Magdolen, V.

    2008-01-01

    Urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) play a key role in tumor-associated processes such as the degradation of extracellular matrix proteins, tissue remodeling, cell adhesion, migration, and invasion. High antigen levels of uPA an

  7. Ligand interaction between urokinase-type plasminogen activator and its receptor probed with 8-anilino-1-naphthalenesulfonate. Evidence for a hydrophobic binding site exposed only on the intact receptor

    DEFF Research Database (Denmark)

    Ploug, M; Ellis, V; Danø, K

    1994-01-01

    The cellular receptor for urokinase-type plasminogen activator (uPAR) is a glycolipid-anchored membrane protein thought to play a primary role in the generation of pericellular proteolytic activity, and to be involved in cancer cell invasion and metastasis. This protein is composed of three homol...

  8. Hall effect in hopping regime

    Energy Technology Data Exchange (ETDEWEB)

    Avdonin, A., E-mail: avdonin@ifpan.edu.pl [Institute of Physics, Polish Academy of Sciences, Al. Lotników 32/46, 02-668 Warszawa (Poland); Skupiński, P. [Institute of Physics, Polish Academy of Sciences, Al. Lotników 32/46, 02-668 Warszawa (Poland); Grasza, K. [Institute of Physics, Polish Academy of Sciences, Al. Lotników 32/46, 02-668 Warszawa (Poland); Institute of Electronic Materials Technology, ul. Wólczyńska 133, 01-919 Warszawa (Poland)

    2016-02-15

    A simple description of the Hall effect in the hopping regime of conductivity in semiconductors is presented. Expressions for the Hall coefficient and Hall mobility are derived by considering averaged equilibrium electron transport in a single triangle of localization sites in a magnetic field. Dependence of the Hall coefficient is analyzed in a wide range of temperature and magnetic field values. Our theoretical result is applied to our experimental data on temperature dependence of Hall effect and Hall mobility in ZnO. - Highlights: • Expressions for Hall coefficient and mobility for hopping conductivity are derived. • Theoretical result is compared with experimental curves measured on ZnO. • Simultaneous action of free and hopping conduction channels is considered. • Non-linearity of hopping Hall coefficient is predicted.

  9. Tumour microenvironments induce expression of urokinase plasminogen activator receptor (uPAR and concomitant activation of gelatinolytic enzymes.

    Directory of Open Access Journals (Sweden)

    Synnøve Magnussen

    Full Text Available The urokinase plasminogen activator receptor (uPAR is associated with poor prognosis in oral squamous cell carcinoma (OSCC, and increased expression of uPAR is often found at the invasive tumour front. The aim of the current study was to elucidate the role of uPAR in invasion and metastasis of OSCC, and the effects of various tumour microenvironments in these processes. Furthermore, we wanted to study whether the cells' expression level of uPAR affected the activity of gelatinolytic enzymes.The Plaur gene was both overexpressed and knocked-down in the murine OSCC cell line AT84. Tongue and skin tumours were established in syngeneic mice, and cells were also studied in an ex vivo leiomyoma invasion model. Soluble factors derived from leiomyoma tissue, as well as purified extracellular matrix (ECM proteins, were assessed for their ability to affect uPAR expression, glycosylation and cleavage. Activity of gelatinolytic enzymes in the tissues were assessed by in situ zymography.We found that increased levels of uPAR did not induce tumour invasion or metastasis. However, cells expressing low endogenous levels of uPAR in vitro up-regulated uPAR expression both in tongue, skin and leiomyoma tissue. Various ECM proteins had no effect on uPAR expression, while soluble factors originating from the leiomyoma tissue increased both the expression and glycosylation of uPAR, and possibly also affected the proteolytic processing of uPAR. Tumours with high levels of uPAR, as well as cells invading leiomyoma tissue with up-regulated uPAR expression, all displayed enhanced activity of gelatinolytic enzymes.Although high levels of uPAR are not sufficient to induce invasion and metastasis, the activity of gelatinolytic enzymes was increased. Furthermore, several tumour microenvironments have the capacity to induce up-regulation of uPAR expression, and soluble factors in the tumour microenvironment may have an important role in the regulation of posttranslational

  10. Prognostic value analysis of urokinase-type plasminogen activator receptor in oral squamous cell carcinoma: an immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Rocchetti Romina

    2008-08-01

    Full Text Available Abstract Background Oral squamous cell carcinoma (OSCC represents the most common oral malignancy. Despite recent advances in therapy, up to 50% of the cases have relapse and/or metastasis. There is therefore a strong need for the identification of new biological markers able to predict the clinical behaviour of these lesions in order to improve quality of life and overall survival. Among tumour progression biomarkers, already known for their involvement in other neoplasia, a crucial role is ascribed to the urokinase-type plasminogen activator receptor (uPAR, which plays a multiple role in extracellular proteolysis, cell migration and tissue remodelling not only as a receptor for the zymogen pro-uPA but also as a component for cell adhesion and as a chemoattractant. The purpose of this study was to gain information on the expression of uPAR in OSCC and to verify whether this molecule can have a role as a prognostic/predictive marker for this neoplasia. Methods In a retrospective study, a cohort of 189 OSCC patients was investigated for uPAR expression and its cellular localization by immunohistochemistry. As standard controls, 8 normal oral mucosal tissues free of malignancy, obtained from patients with no evidence or history of oral cavity tumours, were similarly investigated. After grouping for uPAR expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G, tumour size, recurrence, TNM staging and overall survival rate. Results In our immunohistochemical study, 74 cases (39.1% of OSCC showed a mostly cytoplasmic positivity for uPAR, whereas 115 were negative. uPAR expression correlated with tumour differentiation grade and prognosis: percentage of positive cases was the greatest in G3 (70.4% and patients positives for uPAR expression had an expectation of life lower than those for uPAR negatives. Conclusion The results obtained in this study suggest a role of uPAR as a potential biomarker useful to

  11. Role of Urokinase-type Plasminogen Activator in the Precontact Sperm-egg Communication and Fertility of Mice in vitro

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To explore the role of urokinase-type plasminogen activator(uPA) in precontact sperm-egg communication and fertility of mice in vitro.Methods Firstly, sperm chemotaxis (SC) induced by uPA was assayed by measuring the sperm densities in capillaries with a descending gradient or no gradient of uPA respectively. Secondly, the role of uPAR that exists in sperm plasma membrane in SC was studied by examining the change of sperm density in capillary after incubating spermatozoa with anti-uPAR antibody. Thirdly, SC induced by eggs, which had been treated with uPA, PAI-1 and anti-uPAR beforehand respectively, was assayed to study the role of uPA in PSEC. Lastly, the fertilization capability of spermatozoa treated with uPA was examined by counting the number of fertilized eggs.Results 1)The density of spermatozoa that migrated down the gradient of uPA into the capillary was significantly lower than that into the capillary containing no-gradient uPA. 2) When uPAR of spermatozoa was inhibited by anti-uPAR antibody, the density of spermatozoa that migrated into the capillary with ascending gradient of uPA decreased correspondingly. 3) The density of spermatozoa attracted by eggs, which were treated with uPA beforehand, increased significantly than that of attracted by non-treated eggs. On the contrary, the sperm density decreased correspondingly when the egg was treated with PAI-1. 4) The number of fertilized eggs increased significantly after the spermatozoa used here was treated with uPA beforehand.Conclusion uPA could induce SC of mice sperm in vitro through the uPAR on its membrane, enhance the capability of egg inducing SC, and promote spermatozoa to fertilize eggs. Thus, uPA may act as an attractant in PSEC, increase the chance encounter of spermatozoa and eggs, therefore, enhance the fertility success correspondingly.This study, in some degree, provides an evidence that uPA may be used as a new medicine and diagnostic reagent for male infertility.

  12. Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema

    Science.gov (United States)

    Zügel, Stefanie; Schoeb, Michele; Auinger, Katja; Dehnert, Christoph; Maggiorini, Marco

    2016-01-01

    Introduction. Acute exposure to high altitude induces inflammation. However, the relationship between inflammation and high altitude related illness such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) is poorly understood. We tested if soluble urokinase-type plasminogen activator receptor (suPAR) plasma concentration, a prognostic factor for cardiovascular disease and marker for low grade activation of leukocytes, will predict susceptibility to HAPE and AMS. Methods. 41 healthy mountaineers were examined at sea level (SL, 446 m) and 24 h after rapid ascent to 4559 m (HA). 24/41 subjects had a history of HAPE and were thus considered HAPE-susceptible (HAPE-s). Out of the latter, 10/24 HAPE-s subjects were randomly chosen to suppress the inflammatory cascade with dexamethasone 8 mg bid 24 h prior to ascent. Results. Acute hypoxic exposure led to an acute inflammatory reaction represented by an increase in suPAR (1.9 ± 0.4 at SL versus 2.3 ± 0.5 at HA, p < 0.01), CRP (0.7 ± 0.5 at SL versus 3.6 ± 4.6 at HA, p < 0.01), and IL-6 (0.8 ± 0.4 at SL versus 3.3 ± 4.9 at HA, p < 0.01) in all subjects except those receiving dexamethasone. The ascent associated decrease in PaO2 correlated with the increase in IL-6 (r = 0.46, p < 0.001), but not suPAR (r = 0.27, p = 0.08); the increase in IL-6 was not correlated with suPAR (r = 0.16, p = 0.24). Baseline suPAR plasma concentration was higher in the HAPE-s group (2.0 ± 0.4 versus 1.8 ± 0.4, p = 0.04); no difference was found for CRP and IL-6 and for subjects developing AMS. Conclusion. High altitude exposure leads to an increase in suPAR plasma concentration, with the missing correlation between suPAR and IL-6 suggesting a cytokine independent, leukocyte mediated mechanism of low grade inflammation. The correlation between IL-6 and PaO2 suggests a direct effect of hypoxia, which is not the case for suPAR. However, suPAR plasma concentration measured before hypoxic exposure may predict

  13. Equilibrium yield curves under regime switching

    OpenAIRE

    García-Verdú, Santiago

    2010-01-01

    This paper studies how inflation as a macroeconomic indicator affects nominal bond prices. I consider an economy with a representative agent with Epstein- Zin preferences. Regime switching affects the state-space capturing inflation and consumption growth. Thus, the agent is concerned about the intertemporal distribution of risk, which is affected by the persistence of the variables and the regimes. Regime switching allows for structural changes in the volatility of unexpected shocks. To the ...

  14. Thermal regime of Negotinska Krajina

    Directory of Open Access Journals (Sweden)

    Živković Ljiljana

    2005-01-01

    Full Text Available Negotin Krajina geographically belongs to Mezian tablet that means it is widely open to the influences from the East but main air influences come from the West and North-West causes specific thermal characteristics. Meteorological station "Negotin" is the only one respectable station in the Krajina then we analyze results from various periods since 1901. It is important to emphasize that station "Negotin" doesn't have work continuity since the beginning of the century, thus for analyzing certain climate elements we have had to use method of analogy with station "Zaječar". A part of that, observations were not done by the same methodology so there is lack of some important indicators for this first period. To determine air thermo-regime of Negotin Krajina during 20 century, standard periods (1901-1930., 1931-1960. and 1961-1990 for analyzing climate elements suggested by WMO, were compared. Also, periods from 1925. to 1940. and from 1990. to 2000. were added to this analysis (according to data we had.

  15. Plasma soluble urokinase-type plasminogen activator receptor level is independently associated with coronary microvascular function in patients with non-obstructive coronary artery disease

    DEFF Research Database (Denmark)

    Mekonnen, Girum; Corban, Michel T; Hung, Olivia Y;

    2015-01-01

    , medications profiles and hs-CRP, suPAR remained an independent predictor of CFR (B = -0.30, p = 0.04), indicating an independent association between suPAR level and coronary microvascular function. CONCLUSIONS: In this cross-sectional study, plasma suPAR level was an independent predictor of coronary......BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) is a novel biomarker released from leukocytes and endothelial cells that has been associated with atherosclerotic cardiovascular disease. We hypothesized that plasma suPAR level is an independent predictor of coronary...... microvascular function. METHODS: Coronary blood flow velocity and plasma suPAR levels were evaluated in patients with non-obstructive coronary artery disease. Coronary flow reserve (CFR) was calculated as the ratio of hyperemic to basal average peak blood flow velocity and coronary microvascular dysfunction...

  16. Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

    DEFF Research Database (Denmark)

    Eapen, Danny J; Manocha, Pankaj; Ghasemzedah, Nima;

    2014-01-01

    (Plevel ≥3.5 ng/mL (cutoff by Youden's index) predicted future risk of MI (hazard ratio [HR]=3.2; Pstatistic......INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD......, is unknown. METHODS AND RESULTS: We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary...

  17. Aberrant glomerular filtration of urokinase-type plasminogen activator in nephrotic syndrome leads to amiloride-sensitive plasminogen activation in urine

    DEFF Research Database (Denmark)

    Staehr, Mette; Buhl, Kristian B; Andersen, René F

    2015-01-01

    (uPA) in vitro. It was hypothesized that uPA is abnormally filtered to pre-urine and is inhibited in urine by amiloride in nephrotic syndrome. This was tested by determination of Na+-balance, uPA protein and activity and amiloride concentration in urine from rats with puromycin aminonucleoside (PAN......In nephrotic syndrome, aberrant glomerular filtration of plasminogen and conversion to active plasmin in pre-urine is thought to activate proteolytically ENaC and contribute to sodium retention and edema. The ENaC blocker amiloride is an off-target inhibitor of urokinase-type plasminogen activator......) induced nephrotic syndrome. Urine samples from 6 adult and 18 pediatric patients with nephrotic syndrome were analyzed for uPA activity and protein. PAN-treatment induced significant proteinuria in rats which coincided with increased urine uPA protein and activity, increased urine protease activity...

  18. Anti-Urokinase Receptor Antisense Oligonucleotide (uPAR-aODN) to Prevent and Cure Long-Term Space Exploration-Related Retinal Pathological Angiogenesis

    Science.gov (United States)

    Lazzarano, Stefano; Lulli, Matteo; Fibbi, Gabriella; Margheri, Francesca; Papucci, Laura; Serrati, Simona; Witort, Ewa; Chilla, Anastasia; Lapucci, Andrea; Donnini, Martino; Quaglierini, Paolo; Romiti, Alice; Specogna, Rebecca; Del Rosso, Mario; Capaccioli, Sergio

    2008-06-01

    Angiogenesis underlies a variety of physiological processes and its possible deregulation during long term space exploration needs to be investigated. Angiogenesis is a multistep process of new blood capillary formation, where degradation of the extracellular matrix (ECM) by proteolytic enzymes, including uPA (urokinase plasminogen activator) and opening the way to migration of endothelial cells (EC), is critical. Plasminogen activation system regulates angiogenesis by both uPA-driven ECM degradation and uPA receptor (uPAR). Microgravity and low dose irradiations promote tissue neoangiogeenesis and neovascularization is often common occurence in ophthalmologic pathologies. We have designed and patented the uPAR antisense oligonucleotide (aODN) and evaluated its antiangiogenetic activity by EC cellular migration and capillary morphogenesis assays. The uPAR aODN treatment caused a 75% inhibition of human microvascular EC migration and a complete inhibition of capillary morphogenesis, suggesting its therapeutic application to prevent neoangiogenesis-related ophthalmologic pathologies during space exploration.

  19. The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau

    DEFF Research Database (Denmark)

    Eugen-Olsen, Jesper; Gustafson, P; Sidenius, N

    2002-01-01

    OBJECTIVE: To investigate whether the serum level of soluble urokinase plasminogen activator receptor (suPAR) carries prognostic information in individuals infected with Mycobacterium tuberculosis. DESIGN: suPAR was measured by ELISA in 262 individuals at the time of enrolment into a cohort based...... on suspicion of active tuberculosis and in 101 individuals after 8 months of follow-up. RESULTS: The suPAR levels were elevated in patients with active TB compared to TB-negative individuals (P ...-month treatment period, 23 TB cases died. In a multivariate Cox model controlling for HIV status, age, sex, CD4 count and type of TB diagnosis, the mortality increase per ng suPAR was 1.25 (95%CI 1.12-1.40). After treatment, suPAR levels had decreased to the levels of TB-negative individuals...

  20. Mapping the topographic epitope landscape on the urokinase plasminogen activator receptor (uPAR) by surface plasmon resonance and X-ray crystallography

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Gandhi, Sonu; Yuan, Cai

    2015-01-01

    as a dynamic modular protein structure composed of three homologous Ly6/uPAR domains (LU).This internally flexible protein structure of uPAR enables an allosteric regulation of the interactions with its two principal ligands: the serine protease urokinase-type plasminogen activator (uPA) and the provisional...... matrix protein vitronectin (Vn) (Mertens et al., 2012; Gårdsvoll et al., 2011; Madsen et al., 2007 [2-4]). The data presented here relates to the non-covalent trapping of one of these biologically relevant uPAR-conformations by a novel class of monoclonal antibodies (Zhao et al., 2015 [5......]) and to the general mapping of the topographic epitope landscape on uPAR. The methods required to achieve these data include: (1) recombinant expression and purification of a uPAR-hybrid protein trapped in the desired conformation [patent; WO 2013/020898 A12013]; (2) developing monoclonal antibodies with unique...

  1. Purification of c-phycocyanin from Spirulina fusiformis and its effect on the induction of urokinase-type plasminogen activator from calf pulmonary endothelial cells.

    Science.gov (United States)

    Madhyastha, H K; Radha, K S; Sugiki, M; Omura, S; Maruyama, M

    2006-09-01

    c-Phycocyanin (c-pc), a blue coloured, fluorescent protein was purified from blue-green alga, Spirulina fusiformis and its effect on fibrinolytic system in vascular endothelial cells was investigated. The c-pc consisted of two subunits, alpha and beta, whose molecular masses were 16 and 17 kDa, respectively. N-terminal sequences of both subunits were well conserved compared with other blue green algal phycobiliproteins. Fibrinolytic activity in the medium conditioned by calf pulmonary arterial endothelial cells was measured by the fibrin plate method. The c-pc increased the fibrinolytic activity in dose- and time-dependent manners. Fibrin zymographic studies indicated that c-pc-induced urokinase-type plasminogen activator in the cells. These in vitro results suggest that c-pc from S. fusiformis is a potent profibrinolytic protein in the vascular endothelial system.

  2. Soluble urokinase plasminogen activator receptor is in contrast to high-sensitive C-reactive-protein associated with coronary artery calcifications in healthy middle-aged subjects

    DEFF Research Database (Denmark)

    Sørensen, Mette Hjortdal; Gerke, Oke; Eugen-Olsen, Jesper;

    2014-01-01

    OBJECTIVE: The main objective of this study was to investigate the association between two markers of low-grade inflammation; soluble urokinase plasminogen activator receptor (suPAR) and high-sensitive C-reactive protein (hs-CRP); and coronary artery calcification (CAC) score detected by cardiac...... computed tomography (CT) scan. DESIGN: A cross sectional study of 1126 randomly sampled middle-aged men and women. METHODS: CAC score was measured by a non-contrast cardiac CT scan and total 10-year cardiovascular mortality risk was estimated using the Systematic Coronary Risk Evaluation (SCORE). Plasma...... samples were analysed for suPAR and hs-CRP. The association of suPAR and hs-CRP to CAC was evaluated by logistic regression analyses adjusting for categorised SCORE. The additive effect of suPAR to SCORE was evaluated by comparing area under curve (AUC) and net reclassification improvement (NRI). RESULTS...

  3. Extracellular collagenases and the endocytic receptor, urokinase plasminogen activator receptor-associated protein/Endo180, cooperate in fibroblast-mediated collagen degradation

    DEFF Research Database (Denmark)

    Madsen, Daniel H; Engelholm, Lars H; Ingvarsen, Signe

    2007-01-01

    The collagens of the extracellular matrix are the most abundant structural proteins in the mammalian body. In tissue remodeling and in the invasive growth of malignant tumors, collagens constitute an important barrier, and consequently, the turnover of collagen is a rate-limiting process...... in these events. A recently discovered turnover route with importance for tumor growth involves intracellular collagen degradation and is governed by the collagen receptor, urokinase plasminogen activator receptor-associated protein (uPARAP or Endo180). The interplay between this mechanism and extracellular...... collagenolysis is not known. In this report, we demonstrate the existence of a new, composite collagen breakdown pathway. Thus, fibroblast-mediated collagen degradation proceeds preferentially as a sequential mechanism in which extracellular collagenolysis is followed by uPARAP/Endo180-mediated endocytosis...

  4. Crustal stress regime in Italy

    Directory of Open Access Journals (Sweden)

    M. Cesaro

    1997-06-01

    Full Text Available In order to obtain a reliable map of the present-day stress field in Italy, needed to better understand the active tectonic processes and to contribute to the assessment of seismic hazard, in 1992 we started to collect and analyze new data from borehole breakouts in deep oil and geothermal wells and focal mechanisms of earthquakes (2.5 < M <5 occurred in Italy between 1988 and 1995. From about 200 deep wells and 300 focal mechanisms analyzed to date, we infer that: the internal (SW sector of the Northern Apenninic arc is extending with minimum compressional stress (Shmin oriented ? ENE, while the external front is thrusting over the Adriatic foreland (Shmin ? NW-SE. The entire Southern Apennine is extending in NE direction (from the Tyrrhenian margin to the Apulian foreland and compression (in the foredeep is no longer active at the outer (NE thrust front. Between these two arcs, an abrupt change in the tectonic regime is detected with directions of horizontal stress changing by as much as 90º in the external front, around latitude 430N. Along the Ionian side of the Calabrian arc the stress directions inferred from breakouts and focal mechanisms are scattered with a hint of rotation from N-S Shmin close to the Southern Apennines, to ~ E-W directions in the Messina Strait. In Sicily, a NW-SE direction of SHmax is evident in the Hyblean foreland, parallel to the direction of plate motion between Africa and Europe. A more complex pattern of stress directions is observed in the thrust belt zone, with rotations from the regional trend (NW í directed SHmax to NE oriented SHmax. A predominant NW direction of SHmax is also detected in mainland Sicily from earthquake focal mechanisms, but no well data are available in this region. In the northern part of Sicily (Aeolian Islands a ~N-S direction of SHmax is observed.

  5. Transcriptional Regulation of Urokinase-type Plasminogen Activator Receptor by Hypoxia-Inducible Factor 1 Is Crucial for Invasion of Pancreatic and Liver Cancer

    Directory of Open Access Journals (Sweden)

    Peter Büchler

    2009-02-01

    Full Text Available Angioinvasion is critical for metastasis with urokinase-type plasminogen activator receptor (uPAR and tumor hypoxia-activated hypoxia-inducible factor 1 (HIF-1 as key players. Transcriptional control of uPAR expression by HIF has never been reported. The aim of the present study, therefore, was to test whether tumor hypoxia-induced HIF expression may be linked to transcriptional activation of uPAR and dependent angioinvasion. We used human pancreatic cancer cells and a model of parental and derived HIF-1β-deficient mouse liver cancer cell lines and performed Northern blot analysis, nuclear runoff assays, electrophoretic mobility shift assay, polymerase chain reaction-generated deletion mutants, luciferase assays, Matrigel invasion assays, and in vivo angioinvasion assays in the chorioallantoic membrane of fertilized chicken eggs. Urokinase-type plasminogen activator receptor promoter analysis resulted in four putative HIF binding sites. Hypoxia strongly induced de novo transcription of uPAR mRNA. With sequential deletion mutants of the uPAR promoter, it was possible to identify one HIF binding site causing a nearly 200-fold increase in luciferase activity. Hypoxia enhanced the number of invading tumor cells in vitro and in vivo. In contrast, HIF-1β-deficient cells failed to upregulate uPAR expression, to activate luciferase activity, and to invade on hypoxia. Taken together, we show for the first time that uPAR is under transcriptional control of HIF and that this is important for hypoxia-induced metastasis.

  6. Gene expression of fibrinolytic factors urokinase plasminogen activator and plasminogen activator inhibitor-1 in rabbit temporo-mandibular joint cartilage with disc displacement

    Institute of Scientific and Technical Information of China (English)

    ZHAN Jing; GU Zhi-yuan; WU Li-qun; ZHANG Yin-kai; HU Ji-an

    2005-01-01

    Background The urokinase plasminogen activator system is believed to play an important role in degradation of the extracellular matrix associated with cartilage and bone destruction; however its precise roles in temporomandibular disorders have not yet been clarified. The aims of this study were to investigate the gene expression of fibrinolytic factors urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the articular cartilage of rabbit temporomandibular joint (TMJ) with disc displacement (DD) and to probe the relationship between fibrinolytic activity and cartilage remodeling. Methods Disc displacement of right joints was performed in 36 of 78 rabbits under investigation. The animals were sacrificed at 4 days and 1, 2, 4, 8 and 12 weeks after surgery, respectively. The right joints of these animals were harvested and processed for the examination of mRNA expression of uPA and PAI-1 in articular cartilage using in situ hybridization techniques. Results The expression of uPA and PAI-1 was co-expressed weakly in the chondrocytes from transitive zone to hypertrophic zone and mineralized zone, while no hybridizing signals were shown in proliferative zone and superficial zone in control rabbits. The most striking was the up-regulation of uPA and PAI-1 mRNA in 4-day rabbits postoperatively at the onset of cartilage degeneration. The strongest hybridizing signals for uPA and PAI-1 were seen in 2-week rabbits postoperatively. After 2 weeks, the expression of uPA and PAI-1 began to decrease and reached nearly normal level at 12 weeks. Conclusions The expression of the uPA/PAI-1 system coincides with the pathological changes in condylar cartilage after DD. The uPA/PAI-1 system may be one of the essential mediators in articular cartilage remodeling.

  7. Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.

    LENUS (Irish Health Repository)

    Killeen, S D

    2009-05-19

    Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.

  8. The construction and expression of chimeric urokinase-type plasminogen activator genes containing kringle domains of human plasminogen.

    Science.gov (United States)

    Boutaud, A; Castellino, F J

    1993-06-01

    A series of chimeric urokinase-type plasminogen activator (uPA) genes, which contain combinations of kringle domains of human plasminogen (HPg) in place of the uPA kringle (KuPA), has been constructed and expressed. Some of the resulting recombinant (r) variant uPA chimeras contain modules that potentially mediate the macroscopic binding of HPg to its activation effectors, fibrin(ogen) and 6-aminohexanoic acid (EACA). Such binding sites are not possessed by KuPA, but are present in certain of the HPg kringles, viz., kringle 1 (K1HPg), kringle 4 (K4HPg), and kringle 5 (K5HPg). The recombinant (r) chimeras constructed included molecules with replacements of KuPA with K1HPg (r-[KuPA-->K1HPg]uPA), and with KuPA replaced by double kringle combinations of K1HPgK4HPg (r-[KuPA-->K1HPgK4HPg]uPA), K2HPgK3HPg (r-[KuPA-->K2HPgK3HPg]uPA), and K4HPgK5HPg (r-[KuPA-->K4HPgK5HPg]uPA). All of these variant genes, along with their wild-type (wt) r-uPA counterparts, were expressed in human kidney 293 cells. In cases wherein EACA-binding kringles from HPg have been placed in uPA, this property has been retained in the chimeric molecule and employed as an essential part of the purification procedures for the variants. The steady state amidolytic activity of two-chain (tc) wtr-uPA toward the chromogenic substrate, H-D-pyroglutamyl-Gly-L-Arg-p-nitroanilide (S2444), is characterized by a kcat/KM (pH 7.4, 37 degrees C) of 120 s-1 mM-1. This value ranges from 92 s-1 mM-1 (tcr-[KuPA-->K1HPg]uPA) to 166 s-1 mM-1 (tcr-[KuPA-->K1HPgK4HPg]uPA) for each of the variants, demonstrating that the catalytic efficiency of the active site is altered only in a small way by changes in the noncatalytic domain of uPA. Small differences are also observed in the abilities of these tcr variants to interact with the fast-acting plasma inhibitor of uPA, viz., plasminogen activator inhibitor-1 (PAI-1). The second-order rate constant for the interaction of PAI-1 with tcr-uPA, 0.46 x 10(7) M-1s-1 (pH 7.4, 10 degrees

  9. Framing of regimes and transition strategies

    DEFF Research Database (Denmark)

    Jensen, Jens Stissing

    2012-01-01

    This article suggests that transition strategies are always formulated in the context of specific representations of the regime and the challenges it faces. It is argued that the framing of a regime affects the envisioning of transition strategies. An analysis of the current development agenda...

  10. Multiscale regime shifts and planetary boundaries

    NARCIS (Netherlands)

    Hughes, T.P.; Carpenter, S.; Rockstrom, J.; Scheffer, M.; Walker, B.

    2013-01-01

    Life on Earth has repeatedly displayed abrupt and massive changes in the past, and there is no reason to expect that comparable planetary-scale regime shifts will not continue in the future. Different lines of evidence indicate that regime shifts occur when the climate or biosphere transgresses a ti

  11. LEGAL MATRIMONIAL REGIME IN B&H

    Directory of Open Access Journals (Sweden)

    Boris Krešić

    2011-12-01

    Full Text Available Matrimonial regime between spouses or between extramarital partners, and between parents and children is regulated by the Family Law Act of Bosnia and Herzegovina Federation, hereinafter FLA B&HF (SG FBiH 35/05, 41/05, Family Law Act of the Republic of Srpska, hereinafter FLA RS (SG RS”54/02, 41/08 and the Family Law Act of Brčko District, hereinafter FLA BD (SG RS, 66/07. Legal rules used for the regulation of the matrimonial regime between spouses, as well as between spouses and third parties make matrimonial regime (Ponjavić, 2005, p. 361. Matrimonial regime between spouses in family legislation in Bosnia and Herzegovina (B&H is regulated in two following ways: as legal matrimonial regime and as contract matrimonial regime. Legal regime is the one which applies on spouses if not arranged otherwise prior to contracting marriage or during marriage. In this paper the author indicates the differences between the legal matrimonial regimes of the two entities as well as those between the entities and Brčko District of Bosnia and Herzegovina.

  12. LOW DOSE MAGNESIUM SULPHATE REGIME FOR ECLAMPSIA

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    Bangal V

    2009-09-01

    Full Text Available Pre- eclampsia is one of the commonest medical complications seen during pregnancy. It contributes significantly to maternal and perinatal morbidity and mortality. Dr.J.A.Pritchard in 1955, introduced magnesium sulphate for control of convulsions in eclampsia and is used worldwide. Considering the low body mass index of indian women, a low dose magnesium sulphate regime has been introduced by some authors. Present study was carried out at tertiary care centre in rural area. Fifty cases of eclampsia were randomly selected to find out the efficacy of low dose magnesium sulphate regime to control eclamptic convulsions. Maternal and perinatal outcome and magnesium toxicity were analyzed. It was observed that 86% cases responded to initial intravenous dose of 4 grams of 20% magnesium sulphate . Eight percent cases, who got recurrence of convulsion, were controlled by additional 2 grams of 20% magnesium sulphate. Six percent cases required shifting to standard Pritchard regime, as they did not respond to low dose magnesium sulphate regime. The average total dose of magnesium sulphate required for control of convulsions was 20 grams ie. 54.4% less than that of standard Pritchard regime. The maternal and perinatal morbidity and mortality in the present study werecomparable to those of standard Pritchard regime. The study did not find a single case of magnesium related toxicity with low dose magnesium sulphate regime. Low dose magnesium sulphate regime was found to be safe and effective in eclampsia.

  13. High-dose urokinase via minimally invasive approach for the treatment of 90 cases of ventricular hemorrhage%微创大剂量尿激酶治疗脑室出血90例临床分析

    Institute of Scientific and Technical Information of China (English)

    左毅; 王海燕; 陈尚军

    2013-01-01

    Objective To analyze the clinical effect of high-dose urokinase via minimally invasive approach for the treatment of ventricular hemorrhage.Methods A total of 90 cases of ventricular hemorrhage were divided into control group and treatment group randomly.Lateral ventricular injection of urokinase after external ventricular drainage plus drainage of lumbar cistern were performed in control group,and lateral ventricular injection of urokinase after external ventricular drainage plus drainage of lumbar cistern with injection of urokinase were performed in treatment group.Results In treatment group,the time of lumbar cistern drainage was 6 d in average,and the time of ventricular hematoma elimination was (5 ±1.47) d.In control group,the average time of lumbar cistern drainage was 12 d and the time of ventricular hematoma elimination was (11 ±3.76) d.Conclusion Compared with control group,ventricular injection of urokinase after external ventricular drainage plus lumbar cistern injection of urokinase are helpful for the hematoma elimination and increase of survival rate.%目的 分析微创大剂量尿激酶对脑室出血的临床治疗作用.方法 90例脑室出血患者随机分为治疗组和对照组,对照组:脑室外引流术后侧脑室注入尿激酶+腰大池引流术;治疗组:脑室外引流术后侧脑室注入尿激酶+腰大池引流术后经引流管注入尿激酶.结果 治疗组腰大池置管持续引流平均时间为6d,脑室内血肿消失时间平均为(5±1.47)d.对照组腰大池置管持续引流平均时间为12 d,脑室内血肿消失时间平均为(11±3.76)d.结论 较单纯腰大池置管引流,微创超大剂量尿激酶双向治疗重度脑室出血,能显著加快脑室血肿溶解,提高生存率.

  14. FLOW REGIMES BELOW AERATORS FOR DISCHARGE TUNNELS

    Institute of Scientific and Technical Information of China (English)

    MA Fei; WU Jian-hua

    2012-01-01

    The flow regimes below an aerator influence directly the air entrainment and the cavitation damage control.Based on the theoretical considerations,the experiments of the aerator for a discharge tunnel were conducted,and the relationships between the flow regime and hydraulic and geometric parameters were investigated.The results showed that,there are two kinds of threshold values for the flow regime conversions.One is Fr1-2 standing for the conversion from the fully filled cavity to the partially filled cavity,and the other is Fr2-3 which shows the change from the partially filled cavity to the net air cavity.Two empirical expressions were obtained for the conversions of the flow regimes,which can be used in the designs of the aerators.

  15. US Forest Service LANDFIRE Historical Fire Regimes

    Data.gov (United States)

    US Forest Service, Department of Agriculture — Historical fire regimes, intervals, and vegetation conditions are mapped using the Vegetation Dynamics Development Tool (VDDT). These data support fire and landscape...

  16. Figure 1: Basal-Bolus Regime

    African Journals Online (AJOL)

    Siegal_D

    Breakfast. Lunch. Dinner. Bedtime. Plasma insulin concentrations over time with a twice daily insulin mix regime .... Hypoglycaemia. Frequency, severity, awareness, precipitants, driving, ... Post GDM, family members, IGT etc. EXAMINATION.

  17. Regimes of validity for balanced models

    Science.gov (United States)

    Gent, Peter R.; McWilliams, James C.

    1983-07-01

    Scaling analyses are presented which delineate the atmospheric and oceanic regimes of validity for the family of balanced models described in Gent and McWilliams (1983a). The analyses follow and extend the classical work of Charney (1948) and others. The analyses use three non-dimensional parameters which represent the flow scale relative to the Earth's radius, the dominance of turbulent or wave-like processes, and the dominant component of the potential vorticity. For each regime, the models that are accurate both at leading order and through at least one higher order of accuracy in the appropriate small parameter are then identified. In particular, it is found that members of the balanced family are the appropriate models of higher-order accuracy over a broad range of parameter regimes. Examples are also given of particular atmospheric and oceanic phenomena which are in the regimes of validity for the different balanced models.

  18. The Two Regimes of Postwar Shipping

    DEFF Research Database (Denmark)

    Iversen, Martin Jes; Tenold, Stig

    2014-01-01

    The aim of this article is to illustrate the most important changes in the regulatory framework of the shipping sector from the 1960s to 2010, and to analyse the basis for, and effects of, these changes. In order to explain how the transformation has occurred, we use two traditional maritime...... nations—Denmark and Norway—as case studies. First, we introduce the two regimes of Danish and Norwegian shipping: ‘the national regime’ from the early 1960s to the mid-1970s; and ‘the competitive regime’, which was fully established by the middle of the 1990s and still persists. Then, we briefly sketch...... the bargaining that accompanied the shift from the national regime to the competitive regime. Specifically, we show that the new regime primarily accommodated the interests of private actors such as shipping companies, rather than the interests of the authorities and the trade unions....

  19. Exchange rate regimes and external financial stability

    Directory of Open Access Journals (Sweden)

    Stoica Ovidiu

    2016-01-01

    Full Text Available Financial stability within the framework of the global financial crisis has become a common topic for researchers and practitioners. In order to analyse the impact of exchange rate regimes on financial stability we use both the de jure and de facto exchange rate classifications. We apply the model to a 1999-2010 annual data sample for 135 countries and territories, grouped by the level of economic development. Our second focus is the investigation of the effects of the exchange rate regimes in three economic integration areas (member countries of the European Union 27, the Southern Common Market, and the Association of Southeast Asian Nations on financial stability. Our results generally support the central banks’ concerns that the flexibility of exchange rate regimes should be reduced in order to sustain financial stability; however, the findings are not robust when using alternative regime classifications.

  20. Portfolio Selection with Jumps under Regime Switching

    Directory of Open Access Journals (Sweden)

    Lin Zhao

    2010-01-01

    Full Text Available We investigate a continuous-time version of the mean-variance portfolio selection model with jumps under regime switching. The portfolio selection is proposed and analyzed for a market consisting of one bank account and multiple stocks. The random regime switching is assumed to be independent of the underlying Brownian motion and jump processes. A Markov chain modulated diffusion formulation is employed to model the problem.

  1. International Experiences with Different Monetary Policy Regimes

    OpenAIRE

    Mishkin, Frederic S.

    1999-01-01

    In recent years a growing consensus has emerged for price stability as the overriding, long-run goal of monetary policy. However, despite this consensus, the following question still remains: how should monetary policy be conducted to achieve the price stability goal? This paper examines the experience with different monetary policy regimes currently in use in a number of countries to shed light on this question. A central feature of all of the monetary regimes discussed here is the ise of a ...

  2. Fiscal Policy and Welfare under Different Exchange Rate Regimes

    DEFF Research Database (Denmark)

    Østrup, Finn

    regime in whichthe monetary authority optimises preferences which include an employment targetand an inflation target. As government spending affects the representativeindividual's utility, the choice of exchange rate regime has an impact on welfare.Keywords: exchange rate regimes; fiscal policy...

  3. Causas estruturais e consequências dos regimes internacionais: regimes como variáveis intervenientes

    OpenAIRE

    Stephen D. Krasner

    2012-01-01

    Os regimes internacionais são definidos como princípios, normas, regras e procedimentos de tomada de decisões ao redor dos quais as expectativas dos atores convergem em uma dada área-tema. Como ponto de partida, os regimes são conceituados como variáveis intervenientes, estando entre fatores causais básicos e os resultados e comportamentos relacionados. Há três visões a respeito da importância dos regimes: as orientações estruturais convencionais desvalorizam os regimes como sendo, na melhor ...

  4. Regimes of turbulence without an energy cascade

    CERN Document Server

    Barenghi, C F; Baggaley, A W

    2016-01-01

    Experiments and numerical simulations of turbulent $^4$He and $^3$He-B have established that, at hydrodynamic length scales larger than the average distance between quantum vortices, the energy spectrum obeys the same 5/3 Kolmogorov law which is observed in the homogeneous isotropic turbulence of ordinary fluids. The importance of the 5/3 law is that it points to the existence of a Richardson energy cascade from large eddies to small eddies. However, there is also evidence of quantum turbulent regimes without Kolmogorov scaling. This raises the important questions of why, in such regimes, the Kolmogorov spectrum fails to form, what is the physical nature of turbulence without energy cascade, and whether hydrodynamical models can account for the unusual behaviour of turbulent superfluid helium. In this work we describe simple physical mechanisms which prevent the formation of Kolmogorov scaling in the thermal counterflow, and analyze the conditions necessary for emergence of quasiclassical regime in quantum tu...

  5. Interpreting MAD within multiple accretion regimes

    CERN Document Server

    Mocz, Philip

    2014-01-01

    General relativistic magnetohydrodynamic (GRMHD) simulations of accreting black holes in the radiatively inefficient regime show that systems with sufficient magnetic poloidal flux become magnetically arrested disc (MAD) systems, with a well-defined relationship between the magnetic flux and the mass accretion rate. Recently, Zamaninasab (2014) report that the jet magnetic flux and accretion disc luminosity are tightly correlated over 7 orders of magnitude for a sample of 76 radio-loud active galaxies, concluding that the data are explained by the MAD mode of accretion. Their analysis assumes radiatively efficient accretion, and their sample consists primarily of radiatively efficient sources, while GRMHD simulations of MAD thus far have been carried out in the radiatively inefficient regime. We propose a model to interpret MAD systems in the context of multiple accretion regimes, and apply it to the sample in Zamaninasab (2014), along with additional radiatively inefficient sources from archival data. We sho...

  6. Causas estruturais e consequências dos regimes internacionais: regimes como variáveis intervenientes

    Directory of Open Access Journals (Sweden)

    Stephen D. Krasner

    2012-06-01

    Full Text Available Os regimes internacionais são definidos como princípios, normas, regras e procedimentos de tomada de decisões ao redor dos quais as expectativas dos atores convergem em uma dada área-tema. Como ponto de partida, os regimes são conceituados como variáveis intervenientes, estando entre fatores causais básicos e os resultados e comportamentos relacionados. Há três visões a respeito da importância dos regimes: as orientações estruturais convencionais desvalorizam os regimes como sendo, na melhor das hipóteses, ineficazes; as orientações grocianas vêem os regimes como componentes íntimos do sistema internacional; as perspectivas estruturalistas modificadas vêem os regimes como significativos somente em certas condições restritas. Para os argumentos grociano e estruturalista modificado - que concordam com a visão de que os regimes podem influenciar resultados e comportamentos - , o desenvolvimento de regimes é visto como uma função de cinco variáveis causais básicas: auto-interesse egoísta; poder político; normas e princípios difusos; usos e costumes; conhecimento.

  7. Regimes, Non-State Actors and the State System: A 'Structurational' Regime Model

    NARCIS (Netherlands)

    Arts, B.J.M.

    2000-01-01

    Regime analysis has become a popular approach in International Relations theory and in international policy studies. However, current regime models exhibit some shortcomings with regard to (1) addressing non-state actors, and in particular nongovernmental organizations (NGOs), (2) the balancing of

  8. Regimes, Non-State Actors and the State System: A 'Structurational' Regime Model

    NARCIS (Netherlands)

    Arts, B.J.M.

    2000-01-01

    Regime analysis has become a popular approach in International Relations theory and in international policy studies. However, current regime models exhibit some shortcomings with regard to (1) addressing non-state actors, and in particular nongovernmental organizations (NGOs), (2) the balancing of a

  9. Clinical Value of Plasma Soluble Urokinase-Type Plasminogen Activator Receptor Levels in Term Neonates with Infection or Sepsis: A Prospective Study

    Directory of Open Access Journals (Sweden)

    Tania Siahanidou

    2014-01-01

    Full Text Available Background. suPAR, the soluble form of the urokinase-type plasminogen activator receptor, has been identified as a biomarker of infection in adults but its properties in neonatal infection are not known. Methods. Plasma suPAR levels were determined by ELISA in 47 term neonates with infection (19 bacterial and 28 viral and in 18 healthy neonates as controls. Thirteen out of 47 infected neonates were septic. In all infected neonates, suPAR levels were repeated at 24 hours, 48 hours, 3–5 days, and 7–10 days following admission. Results. Plasma suPAR levels were significantly increased in infected neonates upon admission, whereas they were highest in septic neonates, in comparison with controls P<0.001 and correlated positively with serum CRP levels (P=0.001. At infection subsidence, suPAR concentrations decreased significantly in comparison with baseline (P<0.001 but remained higher than in controls (P=0.01. Receiver operating characteristic analysis resulted in significant areas under the curve for detecting either infected or septic neonates, but not for discriminating between bacterial and viral cause of infection. Conclusions. suPAR is a diagnostic biomarker of infection or sepsis in term neonates; however, it cannot discriminate bacterial from viral infections and also its utility for monitoring the response to treatment is questioned.

  10. Reactive oxygen species regulate urokinase plasminogen activator expression and cell invasion via mitogen-activated protein kinase pathways after treatment with hepatocyte growth factor in stomach cancer cells

    Directory of Open Access Journals (Sweden)

    Kim Jae-Ryong

    2009-06-01

    Full Text Available Abstract Background Reactive oxygen species (ROS are closely associated with the intracellular signal cascade, thus strongly implicating involvement in tumor progression. However, the mechanism by which ROS are generated and how ROS target downstream molecules to trigger tumor metastasis is unclear. In this study, we investigated the underlying signal pathways in ROS-induced urokinase plasminogen activator (uPA expression in the human gastric cancer cells, NUGC-3 and MKN-28. Methods and Results Intracellular ROS, as determined using the fluorescent probe, 2'-7' dichlorofluorescein diacetate, decreased after treatment with hepatocyte growth factor (HGF. We confirmed that Rac-1 regulated ROS production after activation of the AKT pathway with HGF. Exogenously added H2O2 promoted the expression of HGF, but not in a dose-dependent manner and also showed negative expression of HGF after co-treatment with H2O2 and HGF. Treatment with NAC, an intracellular free radical scavenger, decreased the enhancement of uPA production and tumor invasion in both cells. We clarified the downstream pathways regulated by ROS after treatment with H2O2, which showed negative control between FRK and p38 kinase activities for uPA regulation. Conclusion HGF regulates Rac-1-induced ROS production through the Akt pathway and ROS regulates uPA production and invasion via MAP kinase, which provides novel insight into the mechanisms underlying the progression of gastric cancer.

  11. Urokinase receptor mRNA level and gene transcription are strongly and rapidly increased by phorbol myristate acetate in human monocyte-like U937 cells

    DEFF Research Database (Denmark)

    Lund, L R; Rønne, E; Roldan, A L;

    1991-01-01

    We have studied the effect of the tumor promotor phorbol myristate acetate (PMA) on the level of mRNA for the receptor for urokinase-type plasminogen activator (u-PAR) in the human monocyte-like cell line U937. PMA causes an early increase in the u-PAR mRNA level which reaches a maximal 50-fold...... enhancement after 24 h of treatment. Half-maximal stimulation occurs at approximately 5 nM PMA. The effect is observed only with phorbol esters that also act as tumor promotors. The protein synthesis inhibitor cycloheximide (10 micrograms/ml) also increases the level of u-PAR mRNA. Nuclear run-on experiments...... show a time-dependent increase in the u-PAR gene transcription rate after exposure of the cells to PMA. The PMA-induced increase in u-PAR mRNA is paralleled by a time-dependent increase in u-PAR protein as detected by cross-linking studies with radiolabeled ligand. We conclude that PMA stimulates...

  12. Signalling networks associated with urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in breast cancer tissues: new insights from protein microarray analysis.

    Science.gov (United States)

    Wolff, Claudia; Malinowsky, Katharina; Berg, Daniela; Schragner, Kerstin; Schuster, Tibor; Walch, Axel; Bronger, Holger; Höfler, Heinz; Becker, Karl-Friedrich

    2011-01-01

    The urokinase-type plasminogen activator (uPA) and the main uPA inhibitor PAI-1 play important roles in cell migration and invasion in both physiological and pathological contexts. Both factors are clinically applicable predictive markers in node-negative breast cancer patients that are used to stratify patients for adjuvant chemotherapy. In addition to their classical functions in plasmin regulation, both factors are key components in cancer-related cell signalling. Such signalling cascades are well described in cell culture systems, but a better understanding of uPA- and PAI-1-associated signalling networks in clinical tissues is needed. We examined the expression of uPA, PAI-1, and 21 signalling molecules in 201 primary breast cancer tissues using protein microarrays. Expression of uPA was significantly correlated with the expression of ERK and Stat3, while expression of PAI-1 was correlated with the uPA receptor and Akt activation, presumably via integrin and HER-receptor signalling. Analysis of uPA expression did not reveal any significant correlation with staging, grading or age of the patients. The PAI-1 expression was correlated with nodal stage. Network monitoring for uPA and PAI-1 in breast cancer reveals interactions with main signalling cascades and extends the findings from cell culture experiments. Our results reveal possible mechanisms underlying cancer development.

  13. NFkappaB-dependent regulation of urokinase plasminogen activator by proanthocyanidin-rich grape seed extract: effect on invasion by prostate cancer cells.

    Science.gov (United States)

    Uchino, Ryoji; Madhyastha, Radha; Madhyastha, Harishkumar; Dhungana, Sandra; Nakajima, Yuichi; Omura, Sayuri; Maruyama, Masugi

    2010-09-01

    Tumor invasion and metastasis present major obstacles to successful control of androgen-independent prostate cancer. Cell migration is a fundamental aspect of cancer cell metastasis. Urokinase plasminogen activator (uPA) system is implicated in cell migration and cancer metastasis and has potential to be developed as therapeutic target. In recent years, efficacy of dietary nutrients in preventing and curing cancer has gained increasing attention. One such promising candidate is proanthocyanidin-rich grape seed extract (GSE). We investigated the efficacy of GSE in regulating uPA expression and cell migration using highly metastatic androgen-independent PC3 prostate cancer cells as a model. GSE down-regulated uPA as a function of concentration. Additional studies showed that GSE inhibited DNA-binding activity of the transcription factor nuclear factor kappa B (NFkappaB), which in turn decreased NFkappaB-dependent uPA transcription. Invasion assays revealed the inhibitory effect of GSE on PC3 cell migration. These in-vitro experiments demonstrate the therapeutic property of GSE as an antimetastatic agent by targeting uPA.

  14. Camptothecin induces urokinase-type plasminogen activator gene-expression in human RC-K8 malignant lymphoma and H69 small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Shibakura M

    2002-10-01

    Full Text Available We previously reported that anthracyclines, which could generate reactive oxygen species (ROS, could induce the urokinase-type plasminogen activator (uPA gene expression in human RC-K8 malignant lymphoma cells and in H69 small cell lung cancer (SCLC cells. In screening other uPA-inducible anti-cancer agents, we found that camptothecin (CPT and its derivative, SN38, could induce uPA in RC-K8 and H69 cells. CPT and SN38, which are also used for the treatment of lymphoma and SCLC, significantly increased the uPA accumulation in the conditioned media of both cells in a dose-dependent manner. The maximum induction of uPA mRNA levels was observed 24 h after stimulation. Pretreatment with pyrrolidine dithiocarbamate (PDTC, an anti-oxidant, inhibited the CPT-induced uPA mRNA expression. Thus, CPT induces uPA through gene expression, and, therefore, CPT may influence the tumor-cell biology by up-regulating the uPA/plasmin system.

  15. Camptothecin induces urokinase-type plasminogen activator gene-expression in human RC-K8 malignant lymphoma and H69 small cell lung cancer cells.

    Science.gov (United States)

    Shibakura, Misako; Niiya, Kenji; Kiguchi, Toru; Nakata, Yasunari; Tanimoto, Mitsune

    2002-10-01

    We previously reported that anthracyclines, which could generate reactive oxygen species (ROS), could induce the urokinase-type plasminogen activator (uPA) gene expression in human RC-K8 malignant lymphoma cells and in H69 small cell lung cancer (SCLC) cells. In screening other uPA-inducible anti-cancer agents, we found that camptothecin (CPT) and its derivative, SN38, could induce uPA in RC-K8 and H69 cells. CPT and SN38, which are also used for the treatment of lymphoma and SCLC, significantly increased the uPA accumulation in the conditioned media of both cells in a dose-dependent manner. The maximum induction of uPA mRNA levels was observed 24 h after stimulation. Pretreatment with pyrrolidine dithiocarbamate (PDTC), an anti-oxidant, inhibited the CPT-induced uPA mRNA expression. Thus, CPT induces uPA through gene expression, and, therefore, CPT may influence the tumor-cell biology by up-regulating the uPA/plasmin system.

  16. The urokinase plasminogen activator receptor (UPAR) is preferentially induced by nerve growth factor in PC12 pheochromocytoma cells and is required for NGF-driven differentiation.

    Science.gov (United States)

    Farias-Eisner, R; Vician, L; Silver, A; Reddy, S; Rabbani, S A; Herschman, H R

    2000-01-01

    Nerve growth factor (NGF)-driven differentiation of PC12 pheochromocytoma cells is a well studied model used both to identify molecular, biochemical, and physiological correlates of neurotrophin-driven neuronal differentiation and to determine the causal nature of specific events in this differentiation process. Although epidermal growth factor (EGF) elicits many of the same early biochemical and molecular changes in PC12 cells observed in response to NGF, EGF does not induce molecular or morphological differentiation of PC12 cells. The identification of genes whose expression is differentially regulated by NGF versus EGF in PC12 cells has, therefore, been considered a source of potential insight into the molecular specificity of neurotrophin-driven neuronal differentiation. A "second generation" representational difference analysis procedure now identifies the urokinase plasminogen activator receptor (UPAR) as a gene that is much more extensively induced by NGF than by EGF in PC12 cells. Both an antisense oligonucleotide for the UPAR mRNA and an antibody directed against UPAR protein block NGF-induced morphological and biochemical differentiation of PC12 cells; NGF-induced UPAR expression is required for subsequent NGF-driven differentiation.

  17. High plasma levels of intact and cleaved soluble urokinase receptor reflect immune activation and are independent predictors of mortality in HIV-1-infected patients

    DEFF Research Database (Denmark)

    Ostrowski, Sisse Rye; Piironen, Timo; Høyer-Hansen, Gunilla

    2005-01-01

    ). In multivariate Cox analysis adjusting for CD4+ count, HIV RNA, beta2-microglobulin, hemoglobin and clinical stage, higher levels of suPAR(I-III) and suPAR(II-III) were independent predictors of increased mortality risk (P ...BACKGROUND: High blood levels of soluble urokinase receptor (suPAR) measured by enzyme-linked immunoassay (ELISA) (bulk measurement of 3-domain and 2-domain suPAR [suPAR(I-III), suPAR(II-III)], and suPAR(I-III) ligand complexes) strongly predict mortality in HIV-1-infected patients. This study...... investigated plasma levels of suPAR(I-III), suPAR(II-III), and 1-domain suPAR [suPAR(I)] and their predictive value for survival in HIV patients. METHODS: Plasma suPAR was measured by ELISA and 3 different time-resolved fluorescence immunoassays detecting suPAR(I-III), suPAR(I-III) plus suPAR(II-III), and su...

  18. Short-Term Catheter-Directed Thrombolysis with Low-Dose Urokinase Followed by Aspiration Thrombectomy for Treatment of Symptomatic Lower Extremity Deep Venous Thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Se Hee; Lim, Nam Yeul; Song, Jang Hyeon [Dept. of Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of); Kim, Jae Kyu; Lim, Jae Hoon [Dept. of Radiology, Hospital, Ulsan University School of Medicine, Gweangju (Korea, Republic of); Chang, Nam Kyu [Dept. of Radiology, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Choi, Soo Jin Na; Chung, Sang Young [Dept. of Radiology, Chonnam National University Hospital, Chonnam National University School of Medicine, Gwangju (Korea, Republic of)

    2011-10-15

    To evaluate the venous patency in patients treated by catheter-directed thrombolysis with low-dose urokinase (UK) for symptomatic lower extremity deep venous thrombosis (DVT). Eighty-nine consecutive patients (46 women and 43 men; mean age, 58.1 years), treated by catheter-directed thrombolysis with low-dose UK were included in this study. Immediate venous patency was evaluated in terms of technical success (successful restoration of antegrade in-line flow in the treated vein with residual stenosis rate of less than 30%) and clinical success (significant reduction of clinical symptoms before hospital discharge). Late venous patency was evaluated in terms of primary patency rate and clinical success. Immediate technical success was achieved in all patients and immediate clinical success in 80 (90%) patients. There was no major systemic bleeding complication. The primary patency rate at 6 months and 12 months was 84% and 79%, respectively. Fifty-six (63%) patients were asymptomatic after a median clinical follow-up of 18 months, eleven (12%) patients improved moderately, seven (8%) patients remained unchanged, and fifteen (17%) patients had no clinical follow-up. Short-term catheter-directed thrombolysis with low-dose UK can be an effective, safe method to manage DVT of the lower extremities.

  19. Expression of the urokinase plasminogen activator receptor (uPAR) and its ligand (uPA) in brain tissues of human immunodeficiency virus patients with opportunistic cerebral diseases.

    Science.gov (United States)

    Nebuloni, Manuela; Cinque, Paola; Sidenius, Nicolai; Ferri, Angelita; Lauri, Eleonora; Omodeo-Zorini, Elisabetta; Zerbi, Pietro; Vago, Luca

    2009-01-01

    The urokinase plasminogen activator receptor (uPAR) and its ligand (uPA) play an important role in cell migration and extracellular proteolysis. We previously described uPAR/uPA overexpression in the cerebrospinal fluid (CSF) and brain tissues of patients with human immunodeficiency virus (HIV)-related cerebral diseases. In this study, we examined uPAR/uPA expression by immunohistochemistry (IHC) in brains of HIV patients with opportunistic cerebral lesions and in HIV-positive/negative controls. uPAR was found in macrophages/microglia with the highest levels in cytomegalovirus (CMV) encephalitis, toxoplasmosis, and lymphomas; in cryptococcosis and progressive multifocal leukoencephalopathy (PML) cases, only a few positive cells were found and no positivity was observed in controls. uPA expression was demonstrated only in a few macrophages/microglia and lymphocytes in all the cases and HIV-positive controls without different pattern of distribution; no uPA immunostaining was found in cryptococcosis and HIV-negative controls. The higher expression of uPAR/uPA in most of the opportunistic cerebral lesions supports their role in these diseases, suggesting their contribution to tissue injury.

  20. The diagnostic value of soluble urokinase plasminogen activator receptor compared with C-reactive protein and procalcitonin in children with febrile neutropenia.

    Science.gov (United States)

    Sirinoglu, Melis; Soysal, Ahmet; Karaaslan, Ayşe; Kepenekli Kadayifci, Eda; Cinel, Ismail; Koç, Ahmet; Tokuç, Gülnur; Yaman, Ali; Haklar, Goncagül; Şirikçi, Önder; Turan, Serap; Altınkanat Gelmez, Gülşen; Söyletir, Güner; Bakır, Mustafa

    2016-04-01

    The aim of the present study was to determine the diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) in pediatric patients with febrile neutropenia. A prospective case-control study was performed. Patients included 29 children with febrile neutropenia (FN) and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4th to 7th days of the hospital stay. The median (minimum-maximum) serum levels of suPAR obtained on the first day of the admission were 2.08 (0.93-9.42) and 2.22 (1.08-5.13) ng/mL for the FN group and the control group, respectively. The median serum levels of suPAR in the FN and control groups were not significantly different (P = .053). The mean serum suPAR level was significantly higher in nonsurvivors than in survivors in the FN group (P febrile neutropenia; however, persistent high serum suPAR level may predict mortality in FN in children.

  1. TISSUE INHIBITOR OF METALLOPROTEINASE 1, MATRIX METALLOPROTEINASE 9, ALPHA-1 ANTITRYPSIN, METALLOTHIONEIN AND UROKINASE TYPE PLASMINOGEN ACTIVATOR RECEPTOR IN SKIN BIOPSIES FROM PATIENTS AFFECTED BY AUTOIMMUNE BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-07-01

    Full Text Available Introduction: Proteinases and proteinase inhibitors have been described to play a role in autoimmune skin blistering diseases. We studied skin lesional biopsies from patients affected by several autoimmune skin blistering diseases for proteinases and proteinase inhibitors. Methods: We utilized immunohistochemistry to evaluate biopsies for alpha-1-antitrypsin, human matrix metalloproteinase 9 (MMP9, human tissue inhibitor of metalloproteinases 1 (TIMP-1, metallothionein and urokinase type plasminogen activator receptor (uPAR. We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP, 20 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus, and 14 with dermatitis herpetiformis (DH. Results: Contrary to findings in the current literature, most autoimmune skin blistering disease biopsies were negative for uPAR and MMP9. Only some chronic patients with El Bagre-EPF were positive to MMP9 in the dermis, in proximity to telocytes. TIMP-1 and metallothionein were positive in half of the biopsies from BP patients at the basement membrane of the skin, within several skin appendices, in areas of dermal blood vessel inflammation and within dermal mesenchymal-epithelial cell junctions.

  2. Early detection of ecosystem regime shifts

    DEFF Research Database (Denmark)

    Lindegren, Martin; Dakos, Vasilis; Groeger, Joachim P.;

    2012-01-01

    methods may have limited utility in ecosystem-based management as they show no or weak potential for early-warning. We therefore propose a multiple method approach for early detection of ecosystem regime shifts in monitoring data that may be useful in informing timely management actions in the face......Critical transitions between alternative stable states have been shown to occur across an array of complex systems. While our ability to identify abrupt regime shifts in natural ecosystems has improved, detection of potential early-warning signals previous to such shifts is still very limited...

  3. Bank Liquidity and Exchange Rate Regimes

    OpenAIRE

    Bunda, Irina; Desquilbet, Jean-Baptiste

    2003-01-01

    International audience; Combining panel data on bank liquidity at the individual level and data on their macroeconomic environment, for a sample of commercial banks in emerging countries between 1995 and 2000, we show that their exists a “bank liquidity smile across exchange rate regimes”. In extreme regimes at both ends of the line, i.e. for pure floating exchange rate regimes at one end and currency boards and dollarized economies at the other end, bank assets are more liquid than in interm...

  4. Markovian quantum master equation beyond adiabatic regime

    Science.gov (United States)

    Yamaguchi, Makoto; Yuge, Tatsuro; Ogawa, Tetsuo

    2017-01-01

    By introducing a temporal change time scale τA(t ) for the time-dependent system Hamiltonian, a general formulation of the Markovian quantum master equation is given to go well beyond the adiabatic regime. In appropriate situations, the framework is well justified even if τA(t ) is faster than the decay time scale of the bath correlation function. An application to the dissipative Landau-Zener model demonstrates this general result. The findings are applicable to a wide range of fields, providing a basis for quantum control beyond the adiabatic regime.

  5. WELFARE REGIMES IN LATIN AMERICA AND CARIBBEAN

    Directory of Open Access Journals (Sweden)

    Melisa Campana-Alabarce

    2015-06-01

    Full Text Available This article provides a characterization of Latin American and Caribbean Welfare regimes in historiographical perspective. Firstly, it makes a review of the emergence conditions of Welfare States in Western Europe and its core features, with particular emphasis on its role as a method to regulate inequalities in industrial capitalism. Dialoguing with it, then stops in the specific configurations that welfare regimes have taken in Latin America during the course of the twentieth century. Finally, it provides a map of its contemporary features and the major challenges that the States of the region face in his capacity as right guarantors for the future.

  6. Light focusing in the Anderson Regime

    CERN Document Server

    Leonetti, Marco; Mafi, Arash; Conti, Claudio

    2014-01-01

    Anderson localization is a regime in which diffusion is inhibited and waves (also electromagnetic waves) get localized. Here we exploit adaptive optics to achieve focusing in disordered optical fibers in the Anderson regime. By wavefront shaping and optimization, we observe the generation of a propagation invariant beam, where light is trapped transversally by disorder, and show that Anderson localizations can be also excited by extended speckled beams. We demonstrate that disordered fibers allow a more efficient focusing action with respect to standard fibers in a way independent of their length, because of the propagation invariant features and cooperative action of transverse localizations.

  7. Convective Regimes in Crystallizing Basaltic Magma Chambers

    Science.gov (United States)

    Gilbert, A. J.; Neufeld, J. A.; Holness, M. B.

    2015-12-01

    Cooling through the chamber walls drives crystallisation in crustal magma chambers, resulting in a cumulate pile on the floor and mushy regions at the walls and roof. The liquid in many magma chambers, either the bulk magma or the interstitial liquid in the mushy regions, may convect, driven either thermally, due to cooling, or compositionally, due to fractional crystallization. We have constructed a regime diagram of the possible convective modes in a system containing a basal mushy layer. These modes depend on the large-scale buoyancy forcing characterised by a global Rayleigh number and the proportion of the chamber height constituting the basal mushy region. We have tested this regime diagram using an analogue experimental system composed of a fluid layer overlying a pile of almost neutrally buoyant inert particles. Convection in this system is driven thermally, simulating magma convection above and within a porous cumulate pile. We observe a range of possible convective regimes, enabling us to produce a regime diagram. In addition to modes characterised by convection of the bulk and interstitial fluid, we also observe a series of regimes where the crystal pile is mobilised by fluid motions. These regimes feature saltation and scouring of the crystal pile by convection in the bulk fluid at moderate Rayleigh numbers, and large crystal-rich fountains at high Rayleigh numbers. For even larger Rayleigh numbers the entire crystal pile is mobilised in what we call the snowglobe regime. The observed mobilisation regimes may be applicable to basaltic magma chambers. Plagioclase in basal cumulates crystallised from a dense magma may be a result of crystal mobilisation from a plagioclase-rich roof mush. Compositional convection within such a mush could result in disaggregation, enabling the buoyant plagioclase to be entrained in relatively dense descending liquid plumes and brought to the floor. The phenocryst load in porphyritic lavas is often interpreted as a

  8. Supercurrent in the quantum Hall regime

    Science.gov (United States)

    Amet, F.; Ke, C. T.; Borzenets, I. V.; Wang, J.; Watanabe, K.; Taniguchi, T.; Deacon, R. S.; Yamamoto, M.; Bomze, Y.; Tarucha, S.; Finkelstein, G.

    2016-05-01

    A promising route for creating topological states and excitations is to combine superconductivity and the quantum Hall (QH) effect. Despite this potential, signatures of superconductivity in the QH regime remain scarce, and a superconducting current through a QH weak link has been challenging to observe. We demonstrate the existence of a distinct supercurrent mechanism in encapsulated graphene samples contacted by superconducting electrodes, in magnetic fields as high as 2 tesla. The observation of a supercurrent in the QH regime marks an important step in the quest for exotic topological excitations, such as Majorana fermions and parafermions, which may find applications in fault-tolerant quantum computing.

  9. The oil tax regime of Azerbaijan

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Gerard

    1998-07-01

    Azerbaijan has a long history in the oil business and a chance of a spectacular future. To understand why the oil tax regime evolved into its present form and how it is likely to develop, it is necessary to know something of the country's history and the commercial environment. Consequently the presentation begins by discussing these items. It then outlines the Production Sharing Agreement regime in Azerbaijan and then deals with the Kazakh and Georgian Tax Codes, as these are likely to be the basis of a new general tax law in Azerbaijan from 1999. The presentation includes comments on the New Draft Tax Code of 1998.

  10. In Search of the Chiral Regime

    CERN Document Server

    Beane, S R

    2004-01-01

    A critical appraisal is given of a recent analysis of the quark-mass and finite-size dependence of unquenched lattice QCD data for the nucleon mass. We use this forum to estimate the boundary of the chiral regime for nucleon properties.

  11. Developmental Regimes in Africa synthesis report

    NARCIS (Netherlands)

    Booth, D.; Dietz, A.J.; Golooba-Mutebi, F.; Fuady, A.H.; Henley, D.; Kelsall, T.; Leliveld, A.H.M.; Donge, van J.K.

    2015-01-01

    Many African countries have experienced sustained economic growth, but few have achieved the type of structural change, driven by rising productivity, that has transformed mass living standards in parts of Asia. In the Developmental Regimes in Africa Synthesis Report, editor David Booth examines how

  12. Regimes of flow past a vortex generator

    DEFF Research Database (Denmark)

    Velte, Clara Marika; Okulov, V.L.; Naumov, I.V.

    2012-01-01

    A complete parametric investigation of the development of multi-vortex regimes in a wake past simple vortex generator has been carried out. It is established that the vortex structure in the wake is much more complicated than a simple monopole tip vortex. The vortices were studied by stereoscopic...

  13. Developmental Regimes in Africa synthesis report

    NARCIS (Netherlands)

    Booth, D.; Dietz, A.J.; Golooba-Mutebi, F.; Fuady, A.H.; Henley, D.; Kelsall, T.; Leliveld, A.H.M.; Donge, van J.K.

    2015-01-01

    Many African countries have experienced sustained economic growth, but few have achieved the type of structural change, driven by rising productivity, that has transformed mass living standards in parts of Asia. In the Developmental Regimes in Africa Synthesis Report, editor David Booth examines how

  14. Regime Change and the Role of Airpower

    Science.gov (United States)

    2006-08-01

    that connects the target sets with anticipated actions that lead to defeat of the regime. The theory’s mechanism relies on collective action theory as...collective action theory and Ted Gurr’s deprived actor theory to offer a theory of collective dissent. 7. Bueno de Mesquita et al., “Policy Failure

  15. A Global Classification of Contemporary Fire Regimes

    Science.gov (United States)

    Norman, S. P.; Kumar, J.; Hargrove, W. W.; Hoffman, F. M.

    2014-12-01

    Fire regimes provide a sensitive indicator of changes in climate and human use as the concept includes fire extent, season, frequency, and intensity. Fires that occur outside the distribution of one or more aspects of a fire regime may affect ecosystem resilience. However, global scale data related to these varied aspects of fire regimes are highly inconsistent due to incomplete or inconsistent reporting. In this study, we derive a globally applicable approach to characterizing similar fire regimes using long geophysical time series, namely MODIS hotspots since 2000. K-means non-hierarchical clustering was used to generate empirically based groups that minimized within-cluster variability. Satellite-based fire detections are known to have shortcomings, including under-detection from obscuring smoke, clouds or dense canopy cover and rapid spread rates, as often occurs with flashy fuels or during extreme weather. Such regions are free from preconceptions, and the empirical, data-mining approach used on this relatively uniform data source allows the region structures to emerge from the data themselves. Comparing such an empirical classification to expectations from climate, phenology, land use or development-based models can help us interpret the similarities and differences among places and how they provide different indicators of changes of concern. Classifications can help identify where large infrequent mega-fires are likely to occur ahead of time such as in the boreal forest and portions of the Interior US West, and where fire reports are incomplete such as in less industrial countries.

  16. Can Old Regimes Handle New Wars?

    DEFF Research Database (Denmark)

    Henningsen, Troels

    2017-01-01

    Research on New Wars argues that since the 1980s states and regimes have become more vulnerable to violence from non-state actors. Two developments in the Sahel region support the New Wars thesis: an increase in Islamist radicalization and new access to the global black market, both of which stre...

  17. The Forex Regime and EMU Expansion

    NARCIS (Netherlands)

    P.W. van Foreest; C.G. de Vries (Casper)

    2002-01-01

    textabstractThis paper provides empirical evidence that, irrespective of the foreign exchange rate regime, countries with high monetary volatility have lower relative output growth rates. It is argued that due to the forward looking nature of the foreign exchange market, exchange rate stability

  18. An emissions trading regime for Canada

    Energy Technology Data Exchange (ETDEWEB)

    Smith, S.L. [National Round Table on the Environment and the Economy, Ottawa, ON (Canada)

    2001-07-01

    In 1998, over twelve papers were published on emissions trading regimes in Canada by the National Round Table on the Environment and the Economy (NRTEE), a federal government agency whose members represent stakeholders as varied as business, environmental groups, academics, aboriginal groups and others. One of the recommendations that emerged was for the computer modelling of the possibilities that had been identified for a domestic trading regime in Canada for greenhouse gases. It is unclear whether the modelling was ever performed as the file was taken over by the Finance Department under the umbrella of a special emission trading table that examined Canada's commitment under the Kyoto Protocol. The author examined questions pertaining to whether a domestic trading regime is essential, and what its characteristics should be in case it was deemed essential or advisable to have one. The upstream versus downstream application was looked at, as well as grand-fathering versus auction. Provincial issues were then addressed, followed by meshing with a credit system. International systems were reviewed. Early action was discussed, whereby an emitter seeks credit for action taken toward reductions since the original reference year of 1990. The case of emitters having bought or sold permits since the original reference years will also want those trades recognized under a trading regime. The author indicated that it seems probable that an emission trading system will eventually be implemented and that a debate on the issue should be initiated early.

  19. The Forex Regime and EMU Expansion

    NARCIS (Netherlands)

    P.W. van Foreest; C.G. de Vries (Casper)

    2002-01-01

    textabstractThis paper provides empirical evidence that, irrespective of the foreign exchange rate regime, countries with high monetary volatility have lower relative output growth rates. It is argued that due to the forward looking nature of the foreign exchange market, exchange rate stability hing

  20. Optimal dividend distribution under Markov regime switching

    NARCIS (Netherlands)

    Jiang, Z.; Pistorius, M.

    2012-01-01

    We investigate the problem of optimal dividend distribution for a company in the presence of regime shifts. We consider a company whose cumulative net revenues evolve as a Brownian motion with positive drift that is modulated by a finite state Markov chain, and model the discount rate as a determini

  1. Proliferation Control Regimes: Background and Status

    Science.gov (United States)

    2012-10-25

    1984 OPCW U.N. Conference on Disarmament EAA, 1979 AECA, 1976 Biological Weapons Anti- Terrorism Act Chem- Bio Weapons Control Warfare...Deauville, France. They reaffirmed the goals set out at the 2010 Summit for future Global Partnership activities: nuclear and radiological security, bio ... herbicides and riot control agents. Proliferation Control Regimes: Background and Status Congressional Research Service 44 Author Contact

  2. Scaling Fire Regimes in Space and Time.

    Science.gov (United States)

    Falk, D. A.

    2004-12-01

    Spatial and temporal variability are important properties of the forest fire regimes of coniferous forests of southwestern North America. We use a variety of analytical techniques to examine scaling in a surface fire regime in the Jemez Mountains of northern New Mexico, USA, based on an original data set collected from Monument Canyon Research Natural Area (MCN). Spatio-temporal scale dependence in the fire regime can be analyzed quantitatively using statistical descriptors of the fire regime, such as fire frequency and mean fire interval. We describe a theory of the event-area (EA) relationship, an extension of the species-area relationship for events distributed in space and time; the interval-area (IA) relationship, is a related form for fire intervals. We use the EA and IA to demonstrate scale dependence in the MCN fire regime. The slope and intercept of these functions are influenced by fire size, frequency, and spatial distribution, and thus are potentially useful metrics of spatio-temporal synchrony of events in the paleofire record. Second, we outline a theory of fire interval probability, working from first principles in fire ecology and statistics. Fires are conditional events resulting from the interaction of multiple contingent factors that must be satisfied for an event to occur. Outcomes of this kind represent a multiplicative process for which a lognormal model is the limiting distribution. We examine the application of this framework to two probability models, the Weibull and lognormal distributions, which can be used to characterize the distribution of fire intervals over time. Lastly, we present a general model for the collector's curve, with application to the theory and effects of sample size in fire history. Sources of uncertainty in fire history can be partitioned into an error typology; analytical methods used in fire history (particularly the formation of composite fire records) are designed to minimize certain types of error in inference

  3. The Determinants of Exchange Rate Regimes in Emerging Market Economies

    OpenAIRE

    Mehmet Guclu

    2008-01-01

    The choice of exchange rate regime has become one of the most important issues one more time in many economies after the financial crises in recent years. In the wake of the financial crises, many countries, especially emerging market economies, opted for floating exchange rate regimes by forsaking the pegged regimes. Consequently, an old debate on the choice and determinants of exchange rate regimes has been triggered. Economists have started to debate what appropriate exchange rate regime f...

  4. Phospho-MEK1/2 and uPAR Expression Determine Sensitivity of AML Blasts to a Urokinase-Activated Anthrax Lethal Toxin (PrAgU2/LF

    Directory of Open Access Journals (Sweden)

    Amira Bekdash

    2015-10-01

    Full Text Available In this study, we attempt to target both the urokinase plasminogen activator and the mitogen-activated protein kinase pathway in acute myeloid leukemia (AML cell lines and primary AML blasts using PrAgU2/LF, a urokinase-activated anthrax lethal toxin. PrAgU2/LF was cytotoxic to five out of nine AML cell lines. Cytotoxicity of PrAgU2/LF appeared to be nonapoptotic and was associated with MAPK activation and urokinase activity because all the PrAgU2/LF-sensitive cell lines showed both uPAR expression and high levels of MEK1/2 phosphorylation. Inhibition of uPAR or desensitization of cells to MEK1/2 inhibition blocked toxicity of PrAgU2/LF, indicating requirement for both uPAR expression and MAPK activation for activity. PrAgU2/LF was also cytotoxic to primary blasts from AML patients, with blasts from four out of five patients showing a cytotoxic response to PrAgU2/LF. Cytotoxicity of primary AML blasts was also dependent on uPAR expression and phos-MEK1/2 levels. CD34+ bone marrow blasts and peripheral blood mononuclear cells lacked uPAR expression and were resistant to PrAgU2/LF, demonstrating the lack of toxicity to normal hematological cells and, therefore, the tumor selectivity of this approach. Dose escalation in mice revealed that the maximal tolerated dose of PrAgU2/LF is at least 5.7-fold higher than that of the wild-type anthrax lethal toxin, PrAg/LF, further demonstrating the increased safety of this molecule. We have shown, in this study, that PrAgU2/LF is a novel, dual-specific molecule for the selective targeting of AML.

  5. Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells

    DEFF Research Database (Denmark)

    Schnack Nielsen, Boye; Rank, Fritz; Engelholm, Lars H;

    2002-01-01

    The urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR) are key components in the plasminogen activation system, serving to promote specific events of extracellular matrix degradation in connection with tissue remodeling and cancer invasion. We recently described a new uPAR-ass...... lesions. Whereas the normal breast tissue was uPARAP-negative, all benign lesions and ductal carcinoma in situ lesions showed immunoreactivity in fibroblast-like cells and myoepithelial cells associated with the lesion. In invasive carcinoma, uPARAP immunoreactivity was limited to tumor...

  6. 尿激酶和肝素钠在断指再植术后的应用%Comparison of curative effect of urokinase and heparin sodium after digital replantation

    Institute of Scientific and Technical Information of China (English)

    吴晓华; 樊涛; 严明忠

    2013-01-01

    Objective To contrast the curative effect of urokinase and heparin sodium after digital replantation.Methods All of 259 patients were randomly divided into urokinase group with 130 cases(217 fingers) and Heparin sodium group with 129 cases (199 fingers).Two groups received the same basic therapy,and respectively injected with urokinase and heparin sodium.The incidence rate of vascular crisis,survival percent of fingers and the recovery of finger function of two group were compared.Results The incidence rate of vascular crisis was 26.7 % and 36.7 % (P < 0.05),the survival percent of fingers was 88.9 % and 81.9 % (P < 0.05),the excellent and good rate of finger function was 69.3 % and 53.8% (P < 0.05),in 2 groups respectively.Conclusion Urokinase has more advantages than heparin sodium in treatment after digital replantation,with reducing the occurrence of vascular crisis,improving the survival rate of replantation of finger and promoting the finger function recovery.%目的 对比分析尿激酶和肝素钠应用在断指再植术后的治疗效果.方法 将259例断指伤患者随机分成尿激酶组130例(217指)和肝素钠组129例(199指),在基础治疗相同的情况下,分别使用尿激酶、肝素钠对再植术后断指进行治疗,比较2组的血管危象发生率、患指成活率、功能恢复等情况.结果 在尿激酶组、肝素钠组中,血管危象发生率分别为26.7%和36.7%(P<0.05),患指成活率分别为88.9%和81.9% (P <0.05),活动功能优良率分别为69.3%和53.8% (P <0.05).结论 在断指再植术后治疗中,尿激酶较肝素钠更能减少血管危象的发生率,提高患指的成活率,促进患指功能恢复.

  7. Choice of exchange rate regimes for African countries: Fixed or Flexible Exchange rate regimes?

    OpenAIRE

    Simwaka, Kisu

    2010-01-01

    The choice of an appropriate exchange rate regime has been a subject of ongoing debate in international economics. The majority of African countries are small open economies and thus where the choice of the exchange rate regime is an important policy issue. Aside from factors such as interest rates and inflation, the exchange rate is one of the most important determinants of a country’s relative level of economic health. For this reason, exchange rates are among the most watched analyzed and ...

  8. 尿激酶治疗结核性胸腔积液的研究进展%Urokinase therapy for tuberculous pleural effusion

    Institute of Scientific and Technical Information of China (English)

    黄超文; 冯起校

    2010-01-01

    近年来结核病发病率未见下降趋势.虽然目前研究显示早期积极抗结核治疗、开放引流可有效避免胸膜肥厚、粘连,然而结核病起病隐匿,由于患者发现迟、就诊时间晚或疗程不足,胸腔积液处理不及时,容易产生胸水包裹、分房等,即使在影像学辅助下也难以抽液、充分引流,引起患者治疗难度增加,住院时间增加,最终引起肺功能下降、限制性通气功能障碍等不可逆改变,造成生活质量下降.临床上有用胸腔注入激素、抗结核药的方法 ,但仅仅是减轻炎症渗出而未处理已渗出的积液.近年来临床发现胸腔注入尿激酶可以防治胸膜肥厚、粘连.本文结合近年来研究进展,对结核性胸腔积液病理及尿激酶治疗结核性胸腔积液、预防胸膜肥厚的作用机理做一综述.%The incidence of tuberculosis (TB) has not declined in recent years.Although recent studies have shown that early,aggressive anti-TB treatment combined with tube thoracostomy can effectively prevent pleural thickening and adhesion,pleural effusion is easy to be enveloped and separated because of late medical diagnosis,inadequate treatment,or prolonged pleural effusion.The fluid is difficult to be fully removed even with the assistance of radiology,resulting in the increases in the difficulties of treatment and length of hospital stay,and in eventually the decrease in lung function and in the development of restrictive ventilation dysfunction and other irreversible changes; quality of life in patients declines.Available therapies with pleural injections of hormones or anti-tuberculosis agents only reduce inflammatory infiltration but not completely control the existing effusion.Recent research shows pleural effusion of urokinase can prevent and treat pleural thickening and adhesion.This literature narrates the pathology of tubercular pleural effusion and the mechanism of action of urokinase for effusion to prevent pleural

  9. Regime variance testing - a quantile approach

    CERN Document Server

    gajda, Janusz; Wyłomańska, Agnieszka

    2012-01-01

    This paper is devoted to testing time series that exhibit behavior related to two or more regimes with different statistical properties. Motivation of our study are two real data sets from plasma physics with observable two-regimes structure. In this paper we develop estimation procedure for critical point of division the structure change of a time series. Moreover we propose three tests for recognition such specific behavior. The presented methodology is based on the empirical second moment and its main advantage is lack of the distribution assumption. Moreover, the examined statistical properties we express in the language of empirical quantiles of the squared data therefore the methodology is an extension of the approach known from the literature. The theoretical results we confirm by simulations and analysis of real data of turbulent laboratory plasma.

  10. Regimes de espaço

    Directory of Open Access Journals (Sweden)

    Eric Landowski

    2015-06-01

    Full Text Available Space Regimes - Based on a general model of interaction, the present analysis attempts to account for the diversity of the ways space may be apprehended in lived experience. It leads to the definition of four configurations that correspond to as many regimes of relation with the environing world. The conventional space of the circulation of values takes the archetypical shape of the net (incarnated today by Internet. The operational space is that of our dealing with objects within a material environment seen as a tissue of stable and intelligible relations. The experienced space of bodies’ movement, to which one may give as an emblem the spiral, expresses the dynamics of sensitive relationships between the self and the other. The existential space is that of our presence in a universe without boundaries, which no one can properly represent oneself but that nonetheless haunts art and thought: its figure is the abyss.

  11. Online recognition of the multiphase flow regime

    Institute of Scientific and Technical Information of China (English)

    BAI BoFeng; ZHANG ShaoJun; ZHAO Liang; ZHANG XiMin; GUO LieJin

    2008-01-01

    The key reasons that the present method cannot be used to solve the industrial multi-phase flow pattern recognition are clarified firstly. The prerequisite to realize the online recognition is proposed and recognition rules for partial flow pattern are obtained based on the massive experimental data. The standard templates for every flow regime feature are calculated with self-organization cluster algorithm. The multi-sensor data fusion method is proposed to realize the online recognition of multiphase flow regime with the pressure and differential pressure signals, which overcomes the severe influence of fluid flow velocity and the oil fraction on the recognition. The online recognition method is tested in the practice, which has less than 10 percent measurement error. The method takes advantages of high confidence, good fault tolerance and less requirement of single sensor performance.

  12. Online recognition of the multiphase flow regime

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The key reasons that the present method cannot be used to solve the industrial multi- phase flow pattern recognition are clarified firstly. The prerequisite to realize the online recognition is proposed and recognition rules for partial flow pattern are obtained based on the massive experimental data. The standard templates for every flow regime feature are calculated with self-organization cluster algorithm. The multi-sensor data fusion method is proposed to realize the online recognition of multiphase flow regime with the pressure and differential pressure signals, which overcomes the severe influence of fluid flow velocity and the oil fraction on the recognition. The online recognition method is tested in the practice, which has less than 10 percent measurement error. The method takes advantages of high confidence, good fault tolerance and less requirement of single sensor performance.

  13. Cluster analysis of multiple planetary flow regimes

    Science.gov (United States)

    Mo, Kingtse; Ghil, Michael

    1988-01-01

    A modified cluster analysis method developed for the classification of quasi-stationary events into a few planetary flow regimes and for the examination of transitions between these regimes is described. The method was applied first to a simple deterministic model and then to a 500-mbar data set for Northern Hemisphere (NH), for which cluster analysis was carried out in the subspace of the first seven empirical orthogonal functions (EOFs). Stationary clusters were found in the low-frequency band of more than 10 days, while transient clusters were found in the band-pass frequency window between 2.5 and 6 days. In the low-frequency band, three pairs of clusters determined EOFs 1, 2, and 3, respectively; they exhibited well-known regional features, such as blocking, the Pacific/North American pattern, and wave trains. Both model and low-pass data exhibited strong bimodality.

  14. Flamelet Regime Diagram for Turbulent Combustion Simulations

    Science.gov (United States)

    Chan, Wai Lee; Ihme, Matthias; Kolla, Hemanth; Chen, Jacqueline

    2016-11-01

    The flamelet model has been widely used in numerical combustion investigations, particularly for the closure of large-eddy simulations (LES) of turbulent reacting flows. In most cases, the simulation results demonstrated good agreements with their experimental counterparts. However, a systematic analysis of the flamelet model's applicability, as well as its potential limitations, is seldom conducted, and the model performance is usually based only on a-posteriori comparisons. The objective of this work is to derive a metric that can formally quantify the suitability of the flamelet model in different flame configurations. For this purpose, a flamelet regime diagram has been developed and studied in the context of direct numerical simulations (DNS) of a turbulent lifted jet flame. The implementation of the regime diagram in LES has been investigated through explicit filtering of the DNS results.

  15. Serum Soluble Urokinase-Type Plasminogen Activator Receptor Is Associated with Low Left Ventricular Ejection Fraction and Elevated Plasma Brain-Type Natriuretic Peptide Level

    Science.gov (United States)

    Fujita, Shu-ichi; Tanaka, Suguru; Maeda, Daichi; Morita, Hideaki; Fujisaka, Tomohiro; Takeda, Yoshihiro; Ito, Takahide; Ishizaka, Nobukazu

    2017-01-01

    Background Recent studies have suggested that soluble urokinase plasminogen activator receptor (suPAR), a biomarker of subclinical levels of inflammation, is significantly correlated with cardiovascular events. Purpose We investigated the association between suPAR and left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), and plasma B-type natriuretic peptide (BNP) among cardiac inpatients. Methods and Results In total, 242 patients (mean age 71.3 ± 9.8 years; 70 women) admitted to the cardiology department were enrolled in the study. suPAR was significantly correlated with LVEF (R = -0.24, P 3236 pg/mL) was associated with low LVEF ( 300 pg/mL) with an odds ratio of 3.84 (95% confidence interval [CI], 1.22–12.1) and 5.36 (95% CI, 1.32–21.8), respectively, after adjusting for age, sex, log-transformed estimated glomerular filtration rate (log(eGFR)), C-reactive protein, and diuretic use. The association between suPAR and LVMI was not statistically significant. In multivariate receiver operating characteristic analysis, addition of log(suPAR) to the combination of age, sex, log(eGFR) and CRP incrementally improved the prediction of low LVEF (area under the curve [AUC], 0.827 to 0.852, P = 0.046) and BNP ≥ 300 pg/mL (AUC, 0.869 to 0.906; P = 0.029). Conclusions suPAR was associated with low LVEF and elevated BNP, but not with left ventricular hypertrophy, independent of CRP, renal function, and diuretic use among cardiac inpatients who were not undergoing chronic hemodialysis. PMID:28135310

  16. Modulation of Cellular Migration and Survival by c-Myc through the Downregulation of Urokinase (uPA) and uPA Receptor▿ †

    Science.gov (United States)

    Alfano, Daniela; Votta, Giuseppina; Schulze, Almut; Downward, Julian; Caputi, Mario; Stoppelli, Maria Patrizia; Iaccarino, Ingram

    2010-01-01

    It has been proposed that c-Myc proapoptotic activity accounts for most of its restraint of tumor formation. We established a telomerase-immortalized human epithelial cell line expressing an activatable c-Myc protein. We found that c-Myc activation induces, in addition to increased sensitivity to apoptosis, reductions in cell motility and invasiveness. Transcriptome analysis revealed that urokinase (uPA) and uPA receptor (uPAR) were strongly downregulated by c-Myc. Evidence is provided that the repression of uPA and uPAR may account for most of the antimigratory and proapoptotic activities of c-Myc. c-Myc is known to cooperate with Ras in cellular transformation. We therefore investigated if this cooperation could converge in the control of uPA/uPAR expression. We found that Ras is able to block the effects of c-Myc activation on apoptosis and cellular motility but not on cell invasiveness. Accordingly, the activation of c-Myc in the context of Ras expression had only minor influence on uPAR expression but still had a profound repressive effect on uPA expression. Thus, the differential regulation of uPA and uPAR by c-Myc and Ras correlates with the effects of these two oncoproteins on cell motility, invasiveness, and survival. In conclusion, we have discovered a novel link between c-Myc and uPA/uPAR. We propose that reductions of cell motility and invasiveness could contribute to the inhibition of tumorigenesis by c-Myc and that the regulation of uPA and uPAR expression may be a component of the ability of c-Myc to reduce motility and invasiveness. PMID:20123981

  17. Structure-based design of an urokinase-type plasminogen activator receptor-derived peptide inhibiting cell migration and lung metastasis.

    Science.gov (United States)

    Carriero, Maria Vincenza; Longanesi-Cattani, Immacolata; Bifulco, Katia; Maglio, Ornella; Lista, Liliana; Barbieri, Antonio; Votta, Giuseppina; Masucci, Maria Teresa; Arra, Claudio; Franco, Renato; De Rosa, Mario; Stoppelli, Maria Patrizia; Pavone, Vincenzo

    2009-09-01

    The urokinase-type plasminogen activator receptor (uPAR) plays a central role in sustaining the malignant phenotype and promoting tumor metastasis. The Ser(88)-Arg-Ser-Arg-Tyr(92) is the minimum chemotactic sequence of uPAR required to induce the same intracellular signaling as its ligand uPA. Here, we describe the generation of new peptide inhibitors of cell migration and invasion derived from SRSRY by a drug design approach. Ac-Arg-Glu-Arg-Phe-NH(2) (i.e., RERF), which adopts a turned structure in solution, was selected for its ability to potently prevent SRSRY-directed cell migration. Fluorescein-RERF associates with very high affinity to RBL-2H3 rat basophilic leukemia cells expressing the human formyl peptide receptor (FPR). Accordingly, femtomolar concentrations of RERF prevent agonist-dependent internalization of FPR and inhibit N-formyl-Met-Leu-Phe-dependent migration in a dose-dependent manner. In the absence of FPR, fluorescein-RERF binds to cell surface at picomolar concentrations in an alphav integrin-dependent manner. The involvement of vitronectin receptor is further supported by the findings that 100 pmol/L RERF selectively inhibits vitronectin-dependent RBL-2H3 cell migration and prevents SRSRY-triggered uPAR/alphav association. Furthermore, RERF reduces the speed of wound closure and the extent of Matrigel invasion by human fibrosarcoma HT1080 cells without affecting cell proliferation. Finally, a 3- to 5-fold reduction of lung metastasis number and size in nude mice following i.v. injection of green fluorescent protein-expressing HT1080 cells in the presence of 3.32 mg/kg RERF is observed. Our findings indicate that RERF effectively prevents malignant cell invasion in vivo with no signs of toxicity and may represent a promising prototype drug for anticancer therapy.

  18. Modulation of cellular migration and survival by c-Myc through the downregulation of urokinase (uPA) and uPA receptor.

    Science.gov (United States)

    Alfano, Daniela; Votta, Giuseppina; Schulze, Almut; Downward, Julian; Caputi, Mario; Stoppelli, Maria Patrizia; Iaccarino, Ingram

    2010-04-01

    It has been proposed that c-Myc proapoptotic activity accounts for most of its restraint of tumor formation. We established a telomerase-immortalized human epithelial cell line expressing an activatable c-Myc protein. We found that c-Myc activation induces, in addition to increased sensitivity to apoptosis, reductions in cell motility and invasiveness. Transcriptome analysis revealed that urokinase (uPA) and uPA receptor (uPAR) were strongly downregulated by c-Myc. Evidence is provided that the repression of uPA and uPAR may account for most of the antimigratory and proapoptotic activities of c-Myc. c-Myc is known to cooperate with Ras in cellular transformation. We therefore investigated if this cooperation could converge in the control of uPA/uPAR expression. We found that Ras is able to block the effects of c-Myc activation on apoptosis and cellular motility but not on cell invasiveness. Accordingly, the activation of c-Myc in the context of Ras expression had only minor influence on uPAR expression but still had a profound repressive effect on uPA expression. Thus, the differential regulation of uPA and uPAR by c-Myc and Ras correlates with the effects of these two oncoproteins on cell motility, invasiveness, and survival. In conclusion, we have discovered a novel link between c-Myc and uPA/uPAR. We propose that reductions of cell motility and invasiveness could contribute to the inhibition of tumorigenesis by c-Myc and that the regulation of uPA and uPAR expression may be a component of the ability of c-Myc to reduce motility and invasiveness.

  19. The receptor for urokinase-plasminogen activator (uPAR) controls plasticity of cancer cell movement in mesenchymal and amoeboid migration style

    Science.gov (United States)

    Taddei, Maria Letizia; Giannoni, Elisa; Laurenzana, Anna; Biagioni, Alessio; Chillà, Anastasia; Chiarugi, Paola; Fibbi, Gabriella; Rosso1, Mario Del

    2014-01-01

    The receptor for the urokinase plasminogen activator (uPAR) is up-regulated in malignant tumors. Historically the function of uPAR in cancer cell invasion is strictly related to its property to promote uPA-dependent proteolysis of extracellular matrix and to open a path to malignant cells. These features are typical of mesenchymal motility. Here we show that the full-length form of uPAR is required when prostate and melanoma cancer cells convert their migration style from the “path generating” mesenchymal to the “path finding” amoeboid one, thus conferring a plasticity to tumor cell invasiveness across three-dimensional matrices. Indeed, in response to a protease inhibitors-rich milieu, prostate and melanoma cells activated an amoeboid invasion program connoted by retraction of cell protrusions, RhoA-mediated rounding of the cell body, formation of a cortical ring of actin and a reduction of Rac-1 activation. While the mesenchymal movement was reduced upon silencing of uPAR expression, the amoeboid one was almost completely abolished, in parallel with a deregulation of small Rho-GTPases activity. In melanoma and prostate cancer cells we have shown uPAR colocalization with β1/β3 integrins and actin cytoskeleton, as well integrins-actin co-localization under both mesenchymal and amoeboid conditions. Such co-localizations were lost upon treatment of cells with a peptide that inhibits uPAR-integrin interactions. Similarly to uPAR silencing, the peptide reduced mesenchymal invasion and almost abolished the amoeboid one. These results indicate that full-length uPAR bridges the mesenchymal and amoeboid style of movement by an inward-oriented activity based on its property to promote integrin-actin interactions and the following cytoskeleton assembly. PMID:24681666

  20. Decreased expression of intercellular adhesion molecule-1 (ICAM-1) and urokinase-type plasminogen activator receptor (uPAR) is associated with tumor cell spreading in vivo.

    Science.gov (United States)

    Donadio, Ana C; Remedi, María M; Frede, Silvia; Bonacci, Gustavo R; Chiabrando, Gustavo A; Pistoresi-Palencia, María C

    2002-01-01

    The development of an effective antitumor immune response to control tumor growth is influenced by the tumor cell itself and/or by the tumor microenvironment. Tumor invasion and tumor cell spreading require a finely tuned regulation of the formation and loosening of adhesive contacts of tumor cells with the extracellular matrix (ECM). In our laboratory, a rat tumor cell line derived from a spontaneous rat sarcoma revealed, by flow cytometry, a high frequency of intercellular adhesion molecule-1 (ICAM-1, 70.1 +/- 8.7%) and urokinase-type plaminogen activator receptor (uPAR, 51.2 +/- 5.2%) positive cells, while a weak expression of MHC class II (IA, 2.2 +/- 0.2% and IE, 17.4 +/- 3.7%) and B7 (12.1 +/- 2.2%) antigens was detected. In our tumor experimental model, after implantation of tumor cells, visible tumor masses were present at days 5-7 with a relatively fast tumor growth until day 15 (progressive phase) followed by a suppression of the tumor growth (regressive phase). Here we present data that correlates a significant decrease in the frequency of ICAM-1 and uPAR expressing tumor cells with the appearance of tumor cells in sites distant from that of the primary tumor. In addition we describe the development of a cellular immune response which controls the tumor progression and is associated with an increase in the expression of major histocompatibility complex (MHC) class II IA antigen during tumor development. The histological examination at tumor progressive and regressive time points revealed the relevant presence of polymorphonuclear neutrophils (PMNs) evidencing colliquative necrosis in tumor growth areas. Taken together, these results support the idea that the balance between adhesive interactions, proteolytic activity and tumorigenicity may lead to a tumor invasive phenotype.

  1. Epithelial and stromal cell urokinase plasminogen activator receptor expression differentially correlates with survival in rectal cancer stages B and C patients.

    Directory of Open Access Journals (Sweden)

    Seong Beom Ahn

    Full Text Available Urokinase plasminogen activator receptor (uPAR has been proposed as a potential prognostic factor for colorectal cancer (CRC patient survival. However, CRC uPAR expression remains controversial, especially regarding cell types where uPAR is overexpressed (e.g., epithelium (uPARE or stroma-associated cells (uPARS and associated prognostic relevance. In this study, two epitope-specific anti-uPAR monoclonal antibodies (MAbs could discriminate expression of uPARE from uPARS and were used to examine this association with survival of stages B and C rectal cancer (RC patients. Using immunohistochemistry, MAbs #3937 and R4 were used to discriminate uPARE from uPARS respectively in the central and invasive frontal regions of 170 stage B and 179 stage C RC specimens. Kaplan-Meier and Cox regression analyses were used to determine association with survival. uPAR expression occurred in both epithelial and stromal compartments with differential expression observed in many cases, indicating uPARE and uPARS have different cellular roles. In the central and invasive frontal regions, uPARE was adversely associated with overall stage B survival (HR = 1.9; p = 0.014 and HR = 1.5; p = 0.031, respectively reproducing results from previous studies. uPARS at the invasive front was associated with longer stage C survival (HR = 0.6; p = 0.007, reflecting studies demonstrating that macrophage peritumoural accumulation is associated with longer survival. This study demonstrates that different uPAR epitopes should be considered as being expressed on different cell types during tumour progression and at different stages in RC. Understanding how uPARE and uPARS expression affects survival is anticipated to be a useful clinical prognostic marker of stages B and C RC.

  2. [Can mannose-binding lectin and plasma level of soluble urokinase receptor be used in diagnosis and treatment monitorization of brucellosis patients?].

    Science.gov (United States)

    Karsen, Hasan; Cesur, Salih; Karaağaç, Leman; Binici, Irfan; Fidan, Yasemin; Oğüş, Elmas; Demiröz, Ali Pekcan

    2012-07-01

    The aim of this study was to evaluate the diagnostic value of serum mannose-binding lectin (MBL) and plasma soluble urokinase plasminogen activator receptor (SuPAR) levels in monitoring the treatment in patients with brucellosis, by comparing their levels before and after treatment with the values obtained from healthy control group. Thirty brucellosis patients (mean age: 25.8 ± 12.2 years; 15 were male) and 28 healthy controls (mean age: 29.3 ± 12.3 years; 15 were male) were included in the study. Patients were diagnosed with brucellosis according to the characteristic clinical findings and by brucella standard tube agglutination test (SAT) titer ≥ 1/160 and/or blood culture positivity. Serum MBL (Antibodyshop, Denmark) and plasma SuPAR (Virogates, Denmark) levels were investigated with commercial ELISA kits. In our study, no statistical significance was observed between the pre-treatment (13.8 ± 13.4 ng/ml) and post-treatment (12.4 ± 13.1 ng/ml) MBL levels of the patient group and MBL levels of the control group (16.5 ± 14.8 ng/ml) (p> 0.05). Moreover, the mean SuPAR levels measured in pre-treatment and post-treatment plasma samples of the brucellosis patients was 5.1 ± 1.9 ng/ml and 2.9 ± 1.3 ng/ml, respectively, while the mean SuPAR level was 1.8 ± 0.5 ng/ml in the control group. The difference between mean SuPAR levels of patients in pre- and post-treatment samples was found statistically significant (p 0.001). In conclusion, plasma SuPAR level would be a useful marker for the diagnosis and treatment follow up of the patients with brucellosis.

  3. The receptor for urokinase-plasminogen activator (uPAR) controls plasticity of cancer cell movement in mesenchymal and amoeboid migration style.

    Science.gov (United States)

    Margheri, Francesca; Luciani, Cristina; Taddei, Maria Letizia; Giannoni, Elisa; Laurenzana, Anna; Biagioni, Alessio; Chillà, Anastasia; Chiarugi, Paola; Fibbi, Gabriella; Del Rosso, Mario

    2014-03-30

    The receptor for the urokinase plasminogen activator (uPAR) is up-regulated in malignant tumors. Historically the function of uPAR in cancer cell invasion is strictly related to its property to promote uPA-dependent proteolysis of extracellular matrix and to open a path to malignant cells. These features are typical of mesenchymal motility. Here we show that the full-length form of uPAR is required when prostate and melanoma cancer cells convert their migration style from the "path generating" mesenchymal to the "path finding" amoeboid one, thus conferring a plasticity to tumor cell invasiveness across three-dimensional matrices. Indeed, in response to a protease inhibitors-rich milieu, prostate and melanoma cells activated an amoeboid invasion program connoted by retraction of cell protrusions, RhoA-mediated rounding of the cell body, formation of a cortical ring of actin and a reduction of Rac-1 activation. While the mesenchymal movement was reduced upon silencing of uPAR expression, the amoeboid one was almost completely abolished, in parallel with a deregulation of small Rho-GTPases activity. In melanoma and prostate cancer cells we have shown uPAR colocalization with β1/β3 integrins and actin cytoskeleton, as well integrins-actin co-localization under both mesenchymal and amoeboid conditions. Such co-localizations were lost upon treatment of cells with a peptide that inhibits uPAR-integrin interactions. Similarly to uPAR silencing, the peptide reduced mesenchymal invasion and almost abolished the amoeboid one. These results indicate that full-length uPAR bridges the mesenchymal and amoeboid style of movement by an inward-oriented activity based on its property to promote integrin-actin interactions and the following cytoskeleton assembly.

  4. Targeting urokinase and the transferrin receptor with novel, anti-mitotic N-alkylisatin cytotoxin conjugates causes selective cancer cell death and reduces tumor growth.

    Science.gov (United States)

    Vine, K L; Indira Chandran, V; Locke, J M; Matesic, L; Lee, J; Skropeta, D; Bremner, J B; Ranson, M

    2012-01-01

    Tumor-specific delivery of ligand-directed prodrugs can increase the therapeutic window of chemotherapeutics by maintaining efficacy whilst decreasing toxic side effects. We have previously described a series of synthetic N-alkylated isatin cytotoxins that destabilize microtubules and induce apoptosis with 10-fold greater potency than conventional anti-mitotics in vitro. Here, we report the characterization, in vitro cytotoxicity and in vivo efficacy of a lead compound, 5,7-dibromo-N-(p-hydroxymethylbenzyl)isatin (N-AI) conjugated via an esterase-labile linker (N-AIE) to two proven targeting ligands, transferrin (Tf) and plasminogen activator inhibitor type 2 (PAI-2/serpinB2). N-AI was released from N-AIE and the targeting ligands Tf/PAI-2 in an esterase-dependent manner at 37 C and both Tf- and PAI-2-N-AIE conjugates were stable at physiological pH. Human cancer cell lines which vary in their expression levels of Tf receptor (TfR/CD71) and PAI-2 target, receptor bound urokinase (uPA) selectively internalized the conjugates. Tf-N-AIE was up to 24 times more active than the free drug and showed clear selectivity patterns based on TfR levels. PAI-2-N-AIE showed equivalent activity compared to the parent drug and strong selectivity patterns for uPA levels. In preliminary in vivo experiments, the PAI-2- and Tf-N-AIE conjugates were efficacious at 1/20(th) and 1/10(th) of the dose of the free N-AI, respectively, in a metastatic, orthotopic human breast tumor xenograft mouse model. Thus, this strategy specifically delivers and concentrates a novel class of isatin-based, tubulin destabilizing agents to tumors in vivo and warrants further detailed preclinical investigation.

  5. Urokinase-type plasminogen activator (uPA) stimulates triglyceride synthesis in Huh7 hepatoma cells via p38-dependent upregulation of DGAT2.

    Science.gov (United States)

    Paland, Nicole; Gamliel-Lazarovich, Aviva; Coleman, Raymond; Fuhrman, Bianca

    2014-11-01

    The liver is the central organ of fatty acid and triglyceride metabolism. Oxidation and synthesis of fatty acids and triglycerides is under the control of peroxisome-proliferator-activated receptors (PPAR) α. Impairment of these receptors' function contributes to the accumulation of triglycerides in the liver resulting in non-alcoholic fatty liver disease. Urokinase-type plasminogen activator (uPA) was shown to regulate gene expression in the liver involving PPARγ transcriptional activity. In this study we questioned whether uPA modulates triglyceride metabolism in the liver, and investigated the mechanisms involved in the observed processes. Huh7 hepatoma cells were incubated with increasing concentrations of uPA for 24 h uPA dose-dependently increased the cellular triglyceride mass, and this effect resulted from increased de novo triglyceride synthesis mediated by the enzyme diglyceride acyltransferase 2 (DGAT2). Also, the amount of free fatty acids was highly up regulated by uPA through activation of the transcription factor SREBP-1. Chemical activation of PPARα further increased uPA-stimulated triglyceride synthesis, whereas inhibition of p38, an upstream activator of PPARα, completely abolished the stimulatory effect of uPA on both triglyceride synthesis and DGAT2 upregulation. The effect of uPA on triglyceride synthesis in Huh7 cells was mediated via binding to its receptor, the uPAR. In vivo studies in uPAR(-/-) mice demonstrated that no lipid droplets were observed in their livers compared to C57BL/6 mice and the triglyceride levels were significantly lower. This study presents a new biological function of the uPA/uPAR system in the metabolism of triglycerides and might present a new target for an early therapeutic intervention for NAFLD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. A high-protein diet during hospitalization is associated with an accelerated decrease in soluble urokinase plasminogen activator receptor levels in acutely ill elderly medical patients with SIRS.

    Science.gov (United States)

    Tavenier, Juliette; Haupt, Thomas H; Andersen, Aino L; Buhl, Sussi F; Langkilde, Anne; Andersen, Jens R; Jensen, Jens-Erik B; Pedersen, Mette M; Petersen, Janne; Andersen, Ove

    2017-05-01

    Acute illness and hospitalization in elderly individuals are often accompanied by the systemic inflammatory response syndrome (SIRS) and malnutrition, both associated with wasting and mortality. Nutritional support and resistance training were shown to increase muscle anabolism and reduce inflammation in healthy elderly. We hypothesized that nutritional support and resistance training would accelerate the resolution of inflammation in hospitalized elderly patients with SIRS. Acutely admitted patients aged >65 years with SIRS were randomized to an intervention consisting of a high-protein diet (1.7 g/kg per day) during hospitalization, and daily protein supplement (18.8 g) and 3 weekly resistance training sessions for 12 weeks after discharge (Intervention, n=14), or to standard-care (Control, n=15). Plasma levels of the inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR), interleukin-6, C-reactive protein (CRP), and albumin were measured at admission, discharge, and 4 and 13 weeks after discharge. The Intervention group had an earlier decrease in suPAR levels than the Control group: -15.4% vs. +14.5%, P=.007 during hospitalization, and -2.4% vs. -28.6%, P=.007 between discharge and 4 weeks. There were no significant effects of the intervention on the other biomarkers. All biomarkers improved significantly between admission and 13 weeks, although with different kinetics (suPAR: -22%, interleukin-6: -86%, CRP: -89%, albumin: +11%). Nutritional support during hospitalization was associated with an accelerated decrease in suPAR levels, whereas the combined nutrition and resistance training intervention after discharge did not appear to affect the inflammatory state. Our results indicate that improved nutritional care during hospitalization may accelerate recovery in acutely ill elderly medical patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Stochastic Functional Differential Equation under Regime Switching

    Directory of Open Access Journals (Sweden)

    Ling Bai

    2012-01-01

    Full Text Available We discuss stochastic functional differential equation under regime switching dx(t=f(xt,r(t,tdt+q(r(tx(tdW1(t+σ(r(t|x(t|βx(tdW2(t. We obtain unique global solution of this system without the linear growth condition; furthermore, we prove its asymptotic ultimate boundedness. Using the ergodic property of the Markov chain, we give the sufficient condition of almost surely exponentially stable of this system.

  8. Effect of water regime on poplar cultivation

    Directory of Open Access Journals (Sweden)

    Letić Ljubomir

    2006-01-01

    Full Text Available The effect of water regime on the growth and development of plantations of hydrologically conditioned species, poplars was researched in the alluvial plain of the river Tamiš. The investigations were carried out during the period 2000-2003 on the area of FA "Opovo", KO Sakule, and the study results elucidate the very complex relationships between the hydrological conditions of the site and the growth and increment of the study poplar plantations, cl. I-214. .

  9. Fiscal Policy Regimes and Household Consumption

    OpenAIRE

    Jönsson, Kristian

    2004-01-01

    In this paper, we study the effects of fiscal policy during different fiscal policy regimes. More specifically, we investigate how different factors, such as size, duration and composition of fiscal changes, can alter the effects of fiscal policy on private consumption. Using an unbalanced panel of 19 OECD countries during the period 1960-2000, we find that transfer changes are believed to be permanent during fiscal contractions. Hence, it is more likely that an expansionary fiscal contractio...

  10. Deuteron structure in the deep inelastic regime

    CERN Document Server

    Canal, C A Garcìa; Vento, V

    2016-01-01

    We study nuclear effects on the deuteron in the deep inelastic regime using the newest available data analyzing their $Q^2$ dependence. We conclude that precise EMC ratios for large $Q^2$ (> 30, GeV$^2$) cannot be obtained without considering these nuclear effects. For this purpose we use a scheme which parametrizes these effects in a simple manner and compare our results with other recent proposals.

  11. Economic Performance and North Korean Regime Legitimacy

    Science.gov (United States)

    2014-06-01

    As Cha and Anderson note, free markets have become the reliable means of survival in North Korea and these “markets create entrepreneurship , and... entrepreneurship creates an individualist way of thinking alien to the government.”9 If this case is true, the regime’s demise could very well be at...arguments on how the regime works, what has driven its survival, and the social and economic situations that have developed as a result. D. THESIS

  12. Dynamic Regime of Ignition of Solid Propellant

    Directory of Open Access Journals (Sweden)

    Zolotorev Nikolay

    2016-01-01

    Full Text Available This article presents a dynamic regime of exposure of the radiant flux on the sample of gun-cotton. Obtained time the ignition of gun-cotton in the heating conditions of increasing heat flux in the range from 0.2 W/cm2 to 22 W/cm2. A comparison of the delay times of the ignition when heated variable and constant heat flux.

  13. Ion Acceleration in the Laser Transparency Regime

    OpenAIRE

    Steinke, Sven

    2011-01-01

    Im Rahmen dieser Arbeit wurden neue, verbesserte Ansätze zur Ionenbeschleunigung mit kurzen, intensiven Laser Pulsen untersucht und charakterisiert. Die verwendeten Laser Pulse mit relativistischer Intensität und sehr hohem Intensitätskontrast ermöglichten die Verwendung von Folien-Targets mit Dicken unterhalb der Eindringtiefe des Laserspulses (~nm) und somit erstmals Experimente im sog transparenten Regime. Im Gegensatz zu undurchsichtigen, dicken Folientargets, erlauben transparente Target...

  14. Lubrication regimes in lumbar total disc arthroplasty.

    Science.gov (United States)

    Shaheen, A; Shepherd, D E T

    2007-08-01

    A number of total disc arthroplasty devices have been developed. Some concern has been expressed that wear may be a potential failure mode for these devices, as has been seen with hip arthroplasty. The aim of this paper was to investigate the lubrication regimes that occur in lumbar total disc arthroplasty devices. The disc arthroplasty was modelled as a ball-and-socket joint. Elastohydrodynamic lubrication theory was used to calculate the minimum film thickness of the fluid between the bearing surfaces. The lubrication regime was then determined for different material combinations, size of implant, and trunk velocity. Disc arthroplasties with a metal-polymer or metal-metal material combination operate with a boundary lubrication regime. A ceramic-ceramic material combination has the potential to operate with fluid-film lubrication. Disc arthroplasties with a metal-polymer or metal-metal material combination are likely to generate wear debris. In future, it is worth considering a ceramic-ceramic material combination as this is likely to reduce wear.

  15. Detecting spatial regimes in ecosystems | Science Inventory ...

    Science.gov (United States)

    Research on early warning indicators has generally focused on assessing temporal transitions with limited application of these methods to detecting spatial regimes. Traditional spatial boundary detection procedures that result in ecoregion maps are typically based on ecological potential (i.e. potential vegetation), and often fail to account for ongoing changes due to stressors such as land use change and climate change and their effects on plant and animal communities. We use Fisher information, an information theory based method, on both terrestrial and aquatic animal data (US Breeding Bird Survey and marine zooplankton) to identify ecological boundaries, and compare our results to traditional early warning indicators, conventional ecoregion maps, and multivariate analysis such as nMDS (non-metric Multidimensional Scaling) and cluster analysis. We successfully detect spatial regimes and transitions in both terrestrial and aquatic systems using Fisher information. Furthermore, Fisher information provided explicit spatial information about community change that is absent from other multivariate approaches. Our results suggest that defining spatial regimes based on animal communities may better reflect ecological reality than do traditional ecoregion maps, especially in our current era of rapid and unpredictable ecological change. Use an information theory based method to identify ecological boundaries and compare our results to traditional early warning

  16. Utilizing Surface Sensors to Identify Wake Regimes

    Science.gov (United States)

    Wang, Mengying; Hemati, Maziar S.

    2016-11-01

    Marine swimmers often exploit external flow structures to reduce locomotive effort. To achieve this advantage, these swimmers utilize mechanosensory organs on the surface of their bodies to detect hydrodynamic signals from the surrounding fluid, which can then be used to inform the control task. Recently, there has been a growing interest in developing similar flow sensing systems to achieve enhanced propulsive efficiency and maneuverability in human-engineered underwater vehicles. In particular, much attention has been given to the problem of wake sensing; however, these investigations have concentrated on a restricted class of wakes-i.e., Kármán-type vortex streets-whereas more complicated wake structures can arise in practice. In this talk, we will explore the possibility of identifying wake regimes through the use of surface sensors. Potential flow theory is adopted to simulate the interactions of various wakes with a fish-like body. Wakes in different dynamical regimes impart distinct hydrodynamic signatures on the body, which permits these regimes to be distinguished from one another in an automated fashion. Our results can provide guidance for improving flow sensing capabilities in human-engineered systems and hint at how marine swimmers may sense their hydrodynamic surroundings.

  17. QCD in the {delta}-regime

    Energy Technology Data Exchange (ETDEWEB)

    Bietenholz, W. [Universidad Nacional Autonoma de Mexico, Mexico City (Mexico). Inst. de Ciencias Nucleares; Cundy, N. [Seoul National Univ. (Korea, Republic of). Lattice Gauge Theory Research Center; Goeckeler, M. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Horsley, R.; Zanotti, J.M. [Edinburgh Univ. (United Kingdom). School of Physics; Nakamura, Y. [Tsukuba Univ., Ibaraki (Japan). Center for Computational Sciences; Pleiter, D. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Rakow, P.E.L. [Liverpool Univ. (United Kingdom). Theoretical Physics Div.; Schierholz, G. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2011-03-15

    The {delta}-regime of QCD is characterised by light quarks in a small spatial box, but a large extent in (Euclidean) time. In this setting a specific variant of chiral perturbation theory - the {delta}-expansion - applies, based on a quantum mechanical treatment of the quasi onedimensional system. In particular, for vanishing quark masses one obtains a residual pion mass M{sup R}{sub {pi}}, which has been computed to the third order in the {delta}-expansion. A comparison with numerical measurements of this residual mass allows for a new determination of some Low Energy Constants, which appear in the chiral Lagrangian. We first review the attempts to simulate 2-flavour QCD directly in the {delta}-regime. This is very tedious, but results compatible with the predictions for M{sup R}{sub {pi}} have been obtained. Then we show that an extrapolation of pion masses measured in a larger volume towards the {delta}-regime leads to good agreement with the theoretical predictions. From those results, we also extract a value for the (controversial) sub-leading Low Energy Constant anti l{sub 3}. (orig.)

  18. Fish Springs National Wildlife Refuge water regime map

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Water regime map for Fish Springs National Wildlife Refuge. This map of water regimes on the refuge was created along with the National Vegetation Classification...

  19. The discrete regime of flame propagation

    Science.gov (United States)

    Tang, Francois-David; Goroshin, Samuel; Higgins, Andrew

    The propagation of laminar dust flames in iron dust clouds was studied in a low-gravity envi-ronment on-board a parabolic flight aircraft. The elimination of buoyancy-induced convection and particle settling permitted measurements of fundamental combustion parameters such as the burning velocity and the flame quenching distance over a wide range of particle sizes and in different gaseous mixtures. The discrete regime of flame propagation was observed by substitut-ing nitrogen present in air with xenon, an inert gas with a significantly lower heat conductivity. Flame propagation in the discrete regime is controlled by the heat transfer between neighbor-ing particles, rather than by the particle burning rate used by traditional continuum models of heterogeneous flames. The propagation mechanism of discrete flames depends on the spa-tial distribution of particles, and thus such flames are strongly influenced by local fluctuations in the fuel concentration. Constant pressure laminar dust flames were observed inside 70 cm long, 5 cm diameter Pyrex tubes. Equally-spaced plate assemblies forming rectangular chan-nels were placed inside each tube to determine the quenching distance defined as the minimum channel width through which a flame can successfully propagate. High-speed video cameras were used to measure the flame speed and a fiber optic spectrometer was used to measure the flame temperature. Experimental results were compared with predictions obtained from a numerical model of a three-dimensional flame developed to capture both the discrete nature and the random distribution of particles in the flame. Though good qualitative agreement was obtained between model predictions and experimental observations, residual g-jitters and the short reduced-gravity periods prevented further investigations of propagation limits in the dis-crete regime. The full exploration of the discrete flame phenomenon would require high-quality, long duration reduced gravity environment

  20. Expression of urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor in synovial fluid of patients with temporomandibular disorders%颞下颌关节紊乱病关节液中尿纤溶酶原激活物及其受体的表达

    Institute of Scientific and Technical Information of China (English)

    胡蕾; 梁新华; 朱桂全; 胡静; 史宗道

    2008-01-01

    Objective To investigate the level of urokinase-type plasminogen activator(uPA)and urokinase-type plasminogen activator receptor(uPAR)in synovial fluid of patients with temporomandibular disorders and to analyze their relation with temporomandibular disorders(TMD).Methods Synovial fluid was obtained from 64 sides of 56 TMD patients and from 16 sides of 10 asymptomatic healthy volunteers(control).The concentrations of uPA and uPAR in the synovial fluid were measured by ELISA.Forty-eight sides of TMD were divided into 3 groups:arthrosis,structure disorder and osteoarthrosis,each including 16 sides.Resuits The levels of uPA and uPAR were significantly higher in the synovial fluid of TMD patients than that in the control group(P<0.05),and the level of uPA and uPAR in osteoarthrosis group was significantly higher than that in arthrosis and structure disorder group(P<0.05).However,there was no difference in expression of uPA and uPAR between arthrosis and structure disorder groups(P>0.05).Conclusions uPA and uPAR in the synovial fluid may play a role in the pathogenesis of TMD.and the lever of uPA and uPAR in synovial fluid of TMD could be used as a biochemical markers to reflect pathological degree of TMD.%目的 检测颞下颌关节(TMJ)关节液中尿纤溶酶原激活物(urokinase-type plasminogen activator,uPA)及受体(urokinase-type plasminogen activator receptor,uPAR)的分泌量,探讨TMJ液中uPA及uPAR与颞下颌关节紊乱病(TMD)的关系.方法 采用酶联免疫吸附实验法检测56例TMD患者的64侧关节和10名健康志愿者的16侧关节的关节液标本中的uPA及uPAR的量.将符合纳入标准的48侧TMD患者的关节液标本根据临床诊断分为关节炎性组(A组)、结构紊乱组(B组)、骨关节病组(C组),每组16侧;10名健康志愿者的16侧关节液设为对照组(D组).结果 TMD中A组、B组、C组、D组uPA的检出量分别为(51.200±8.786)ng/L、(53.667±11.894)ng/L、(81.278±25.828)ng/L、(17.960±9.859)ng

  1. REVIEW OF REGIME THEORY OF ALLUVIAL CHANNELS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    One of the most important problems in river engineering is to determine a stable cross section geomenry and slope for an alluvial channel. This has been the subject of considerable research for about a century and continues to be of great practical interest. Lgnoring plan geometry, an alluvi-al channel can adjust its slope, depth and width, to develop a dynamic stable condition in which it can transport a certain a-mount of water and sediment. The brief history of regime the-ory and its new development are reviewed in this paper.

  2. Electron acceleration in the bubble regime

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, Oliver

    2014-02-03

    The bubble regime of laser-wakefield acceleration has been studied over the recent years as an important alternative to classical accelerators. Several models and theories have been published, in particular a theory which provides scaling laws for acceleration parameters such as energy gain and acceleration length. This thesis deals with numerical simulations within the bubble regime, their comparison to these scaling laws and data obtained from experiments, as well as some specific phenomenona. With a comparison of the scaling laws with numerical results a parameter scan was able to show a large parameter space in which simulation and theory agree. An investigation of the limits of this parameter space revealed boundaries to other regimes, especially at very high (a{sub 0} > 100) and very low laser amplitudes (a{sub 0} < 4). Comparing simulation data with data from experiments concerning laser pulse development and electron energies, it was found that experimental results can be adequately reproduced using the Virtual-Laser-Plasma-Laboratory code. In collaboration with the Institut fuer Optik und Quantenelektronik at the Friedrich-Schiller University Jena synchrotron radiation emitted from the inside of the bubble was investigated. A simulation of the movement of the electrons inside the bubble together with time dependent histograms of the emitted radiation helped to prove that the majority of radiation created during a bubble acceleration originates from the inside of the bubble. This radiation can be used to diagnose the amplitude of oscillation of the trapped electrons. During a further study it was proven that the polarisation of synchrotron radiation from a bubble contains information about the exact oscillation direction. This oscillation was successfully controlled by using either a laser pulse with a tilted pulse front or an asymmetric laser pulse. First results of ongoing studies concerning injecting electrons into an existing bubble and a scheme called

  3. Efficiency of Rectification: Reversible vs. Irreversible Regimes

    Science.gov (United States)

    Sokolov, I. M.

    2002-11-01

    Both man-made locomotive devices and molecular motors use gears to transform a reciprocating motion into a directed one. One of the most common gears is a rectifier, a mechanically irreversible appliance. The maximal energetic efficiency of an isothermic gear is bounded by unity, as a consequence of the Second Law. However, approaching this ideal efficiency does not imply approaching reversibility. We discuss what properties of a rectifier mostly influence the transduction efficiency and show that an appliance which locks under backward force is just the one which can approach the ideal efficiency either in the reversible or in the irreversible regime.

  4. Muscle's Motion in an Overdamped Regime

    Institute of Scientific and Technical Information of China (English)

    AI Bao-Quan; WANG Xian-Ju; LIU Liang-Gang; M. Nakano; H. Matsuura

    2002-01-01

    Based on the stochastic inclined rods model proposed by H. Matsuura et al., we study the motion of actin myosin system in an overdamped regime. Our model is composed ofan inclined spring (rod), a myosin head and a myosin filament. The results of calculation show that the modelcan convert the random motion to one-directional motion, and the myosin head works as a resonator of random noise, which absorbs the energy through a stochastic resonance. The results show that the inclined rod and the intermolecular potential are very important for the system to move.

  5. Ultracold Molecules: Physics in the Quantum Regime

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, John [Harvard Univ., Cambridge, MA (United States). Dept. of Physics

    2014-11-17

    Our research encompasses approaches to the trapping of diatomic molecules at low temperature plus the cooling and detection of polyatomic molecules in the kelvin temperature regime. We have cooled and trapped CaF and/or CaH molecules, loaded directly from a molecular beam. As part of this work, we are continuing to develop an important trapping technique, optical loading from a buffer-gas beam. This method was invented in our lab. We are also studying cold polyatomic molecules and their interactions with cold atoms.

  6. Langmuir wave filamentation in the kinetic regime

    CERN Document Server

    Silantyev, Denis A; Rose, Harvey A

    2016-01-01

    Nonlinear Langmuir wave in the kinetic regime $k\\lambda_D\\gtrsim0.2$ has a transverse instability, where $k$ is the wavenumber and $\\lambda_D$ is the Debye length. The nonlinear stage of that instability development leads to the filamentation of Langmuir waves. Here we study the linear stage of transverse instability of both Bernstein-Greene-Kruskal (BGK) modes and dynamically prepared BGK-like initial conditions to find the same instability growth rate suggesting the universal mechanism for the kinetic saturation of stimulated Raman scatter in laser-plasma interaction experiments. Multidimensional Vlasov simulations results are compared to the theoretical predictions.

  7. Reconfigurable photoinduced metamaterials in the microwave regime

    CERN Document Server

    Rizza, Carlo; De Paulis, Francesco; Palange, Elia; Orlandi, Antonio; Columbo, Lorenzo; Prati, Franco

    2014-01-01

    We investigate optically reconfigurable dielectric metamaterials at gigahertz frequencies. More precisely, we study the microwave response of a subwavelength grating optically imprinted into a semiconductor slab. In the homogenized regime, we analytically evaluate the ordinary and extraordinary component of the effective permittivity tensor by taking into account the photo-carrier dynamics described by the ambipolar diffusion equation. We analyze the impact of semiconductor parameters on the gigahertz metamaterial response which turns out to be highly reconfigurable by varying the photogenerated grating and which can show a marked anisotropic behavior.

  8. Quality Regimes in Agro-Food Industries

    DEFF Research Database (Denmark)

    Staricco, Juan Ignacio; Ponte, Stefano

    2015-01-01

    In this article, we examine the transformative potential of changing quality regimes in agro-food industries through the analysis of whether Fair Trade wine in Argentina provides a meaningful economic alternative that goes beyond the impact it has on direct beneficiaries. The wine sector has a lo...... producing table wine for the domestic market, Fair Trade is actually further marginalizing them......., challenge and re-interpretation of different quality content. Through the lenses of a sector-adjusted version of regulation theory, we show that the Fair Trade wine sector does not substantially deviate from the conventional wine economy in Argentina. Instead of empowering the most vulnerable groups, those...

  9. Hard and Soft Excitation Regimes of Kerr Frequency Combs

    CERN Document Server

    Matsko, Andrey B; Ilchenko, Vladimir S; Seidel, David; Maleki, Lute

    2011-01-01

    We theoretically study the stability conditions and excitation regimes of hyper-parametric oscillation and Kerr frequency comb generation in continuously pumped nonlinear optical resonators possessing anomalous group velocity dispersion. We show that both hard and soft excitation regimes are possible in the resonators. Selection between the regimes is achieved via change in the parameters of the pumping light.

  10. Level-ARCH Short Rate Models with Regime Switching

    DEFF Research Database (Denmark)

    Christiansen, Charlotte

    This paper introduces regime switching volatility into level- ARCH models for the short rates of the US, the UK, and Germany. Once regime switching and level effects are included there are no gains from including ARCH effects. It is of secondary importance exactly how the regime switching...

  11. The relationship between void waves and flow regime transition

    Energy Technology Data Exchange (ETDEWEB)

    Lahey, R.T. Jr.; Drew, D.A.; Kalkach-Navarro, S.; Park, J.W.

    1992-12-31

    The results of an extensive experimental and analytical study on the relationship between void waves and flow regime transition are presented, in particular, the bubbly/slug flow regime transition. It is shown that void wave instability signals a flow regime transition.

  12. Low-frequency regime transitions and predictability of regimes in a barotropic model

    CERN Document Server

    Nadiga, B T

    2016-01-01

    Predictability of flow is examined in a barotropic vorticity model that admits low frequency regime transitions between zonal and dipolar states. Such transitions in the model were first studied by Bouchet and Simonnet (2009) and are reminiscent of regime change phenomena in the weather and climate systems wherein extreme and abrupt qualitative changes occur, seemingly randomly, after long periods of apparent stability. Mechanisms underlying regime transitions in the model are not well understood yet. From the point of view of atmospheric and oceanic dynamics, a novel aspect of the model is the lack of any source of background gradient of potential-vorticity such as topography or planetary gradient of rotation rate (e.g., as in Charney & DeVore '79). We consider perturbations that are embedded onto the system's chaotic attractor under the full nonlinear dynamics as bred vectors---nonlinear generalizations of the leading (backward) Lyapunov vector. We find that ensemble predictions that use bred vector per...

  13. Variety of synchronous regimes in neuronal ensembles

    Science.gov (United States)

    Komarov, M. A.; Osipov, G. V.; Suykens, J. A. K.

    2008-09-01

    We consider a Hodgkin-Huxley-type model of oscillatory activity in neurons of the snail Helix pomatia. This model has a distinctive feature: It demonstrates multistability in oscillatory and silent modes that is typical for the thalamocortical neurons. A single neuron cell can demonstrate a variety of oscillatory activity: Regular and chaotic spiking and bursting behavior. We study collective phenomena in small and large arrays of nonidentical cells coupled by models of electrical and chemical synapses. Two single elements coupled by electrical coupling show different types of synchronous behavior, in particular in-phase and antiphase synchronous regimes. In an ensemble of three inhibitory synaptically coupled elements, the phenomenon of sequential synchronous dynamics is observed. We study the synchronization phenomena in the chain of nonidentical neurons at different oscillatory behavior coupled with electrical and chemical synapses. Various regimes of phase synchronization are observed: (i) Synchronous regular and chaotic spiking; (ii) synchronous regular and chaotic bursting; and (iii) synchronous regular and chaotic bursting with different numbers of spikes inside the bursts. We detect and study the effect of collective synchronous burst generation due to the cluster formation and the oscillatory death.

  14. Characterizing multistationarity regimes in biochemical reaction networks.

    Directory of Open Access Journals (Sweden)

    Irene Otero-Muras

    Full Text Available Switch like responses appear as common strategies in the regulation of cellular systems. Here we present a method to characterize bistable regimes in biochemical reaction networks that can be of use to both direct and reverse engineering of biological switches. In the design of a synthetic biological switch, it is important to study the capability for bistability of the underlying biochemical network structure. Chemical Reaction Network Theory (CRNT may help at this level to decide whether a given network has the capacity for multiple positive equilibria, based on their structural properties. However, in order to build a working switch, we also need to ensure that the bistability property is robust, by studying the conditions leading to the existence of two different steady states. In the reverse engineering of biological switches, knowledge collected about the bistable regimes of the underlying potential model structures can contribute at the model identification stage to a drastic reduction of the feasible region in the parameter space of search. In this work, we make use and extend previous results of the CRNT, aiming not only to discriminate whether a biochemical reaction network can exhibit multiple steady states, but also to determine the regions within the whole space of parameters capable of producing multistationarity. To that purpose we present and justify a condition on the parameters of biochemical networks for the appearance of multistationarity, and propose an efficient and reliable computational method to check its satisfaction through the parameter space.

  15. Pulse regime in formation of fractal fibers

    Science.gov (United States)

    Smirnov, B. M.

    2016-11-01

    The pulse regime of vaporization of a bulk metal located in a buffer gas is analyzed as a method of generation of metal atoms under the action of a plasma torch or a laser beam. Subsequently these atoms are transformed into solid nanoclusters, fractal aggregates and then into fractal fibers if the growth process proceeds in an external electric field. We are guided by metals in which transitions between s and d-electrons of their atoms are possible, since these metals are used as catalysts and filters in interaction with gas flows. The resistance of metal fractal structures to a gas flow is evaluated that allows one to find optimal parameters of a fractal structure for gas flow propagation through it. The thermal regime of interaction between a plasma pulse or a laser beam and a metal surface is analyzed. It is shown that the basic energy from an external source is consumed on a bulk metal heating, and the efficiency of atom evaporation from the metal surface, that is the ratio of energy fluxes for vaporization and heating, is 10-3-10-4 for transient metals under consideration. A typical energy flux ( 106 W/cm2), a typical surface temperature ( 3000 K), and a typical pulse duration ( 1 μs) provide a sufficient amount of evaporated atoms to generate fractal fibers such that each molecule of a gas flow collides with the skeleton of fractal fibers many times.

  16. Microgravity two-phase flow regime modeling

    Energy Technology Data Exchange (ETDEWEB)

    Lee, D.; Best, F.R.; Faget, N.

    1987-01-01

    A flow pattern or flow regime is the characteristics spatial distribution of the phases of fluid in a duct. Since heat transfer and pressure drop are dependent on the characteristic distribution of the phases, it is necessary to describe flow patterns in an appropriate manner so that a hydrodynamic or heat transfer theory applicable to that pattern can be chosen. The objective of the present analysis is to create a flow regime map based on physical modeling of vapor/liquid interaction phenomena in a microgravity environment. In the present work, four basic flow patterns are defined: dispersed flow, stratified flow, slug flow, and annular flow. Fluid properties, liquid and vapor flow rates, and pipe size were chosen as the principal parameters. It is assumed that a transition from one flow pattern to another will occur when there is a change in the dominant force which controls that flow pattern. The forces considered in this modeling are surface tension force, both force, inertial force, friction, and turbulent fluctuations.

  17. Production of a urokinase plasminogen activator-IgG fusion protein (uPA-IgG) in the baculovirus expression system.

    Science.gov (United States)

    Kost, T A; Ignar, D M; Clay, W C; Andrews, J; Leray, J D; Overton, L; Hoffman, C R; Kilpatrick, K E; Ellis, B; Emerson, D L

    1997-04-29

    Numerous studies have demonstrated the importance of urokinase plasminogen activator (uPA) and its receptor, uPAR, in the processes of tumor progression and metastasis. Thus, the uPA/uPAR interaction may represent an important target for inhibiting metastatic disease. The baculovirus expression system was used to produce high levels of a secreted uPA-Immunoglobulin G fusion protein (uPA-IgG) which could then be used for displacing uPA from the surface of tumor cells. The recombinant uPA-IgG fusion protein was placed under the control of either the viral polyhedrin promoter or a copy of the viral basic protein promoter. Recombinant viruses were then used to infect Sf9 and BTI-Tn-5B1-4 cells. Infection of both cell types resulted in the production of secreted uPA-IgG. The molecular mass of the secreted protein as determined by SDS-PAGE was approximately 40 kDa. The highest level of secreted uPA-IgG, 444 microg/ml, was found in the culture medium of BTI-Tn-5B1-4 cells 72 h post-infection with the basic protein promoter-uPA-IgG virus. In the case of Sf9 cells, the highest level of secreted protein was 195 microg/ml. The amount of cell-associated uPA-IgG in infected BTI-Tn-5B1-4 cells was significantly less than that of infected Sf9 cells, reflecting the superior secretory capability of the BTI-Tn-5B1-4 cells. The uPA-IgG was readily purified using a combination of zinc chelate and sephacryl S-100 column chromatography. Routinely, greater than 100 mg of greater than 95% pure protein could be obtained per liter of culture medium collected at 72 h post-infection of BTI-Tn-5B1-4 cells with the basic protein promoter virus. BIAcore analysis and competition binding assays using LOX human malignant melanoma cells expressing uPAR indicated that the purified recombinant protein possessed similar ligand binding characteristics to that of human uPA.

  18. Nicotine stimulates urokinase-type plasminogen activator receptor expression and cell invasiveness through mitogen-activated protein kinase and reactive oxygen species signaling in ECV304 endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Khoi, Pham Ngoc; Park, Jung Sun; Kim, Nam Ho; Jung, Young Do, E-mail: ydjung@chonnam.ac.kr

    2012-03-01

    Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during inflammation, tissue remodeling and in many human cancers. This study investigated the effect of nicotine, a major alkaloid in tobacco, on uPAR expression and cell invasiveness in ECV304 endothelial cells. Nicotine stimulated uPAR expression in a dose-dependent manner and activated extracellular signal-regulated kinases-1/2 (Erk-1/2), c-Jun amino-terminal kinase (JNK) and p38 mitogen activated protein kinase (MAPK). Specific inhibitors of MEK-1 (PD98059) and JNK (SP600125) inhibited the nicotine-induced uPAR expression, while the p38 MAPK inhibitor SB203580 did not. Expression vectors encoding dominant negative MEK-1 (pMCL-K97M) and JNK (TAM67) also prevented nicotine-induced uPAR promoter activity. The intracellular hydrogen peroxide (H{sub 2}O{sub 2}) content was increased by nicotine treatment. The antioxidant N-acetylcysteine prevented nicotine-activated production of reactive oxygen species (ROS) and uPAR expression. Furthermore, exogenous H{sub 2}O{sub 2} increased uPAR mRNA expression. Deleted and site-directed mutagenesis demonstrated the involvement of the binding sites of transcription factor nuclear factor-kappaB (NF-κB) and activator protein (AP)-1 in the nicotine-induced uPAR expression. Studies with expression vectors encoding mutated NF-κB signaling molecules and AP-1 decoy confirmed that NF-κB and AP-1 were essential for the nicotine-stimulated uPAR expression. MAPK (Erk-1/2 and JNK) and ROS functioned as upstream signaling molecules in the activation of AP-1 and NF-κB, respectively. In addition, ECV304 endothelial cells treated with nicotine displayed markedly enhanced invasiveness, which was partially abrogated by uPAR neutralizing antibodies. The data indicate that nicotine induces uPAR expression via the MAPK/AP-1 and ROS/NF-κB signaling pathways and, in turn, stimulates invasiveness in human ECV304 endothelial cells. -- Highlights: ► Endothelial cells

  19. A combination of desmopressin and docetaxel inhibit cell proliferation and invasion mediated by urokinase-type plasminogen activator (uPA) in human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Hiroshi; Klotz, Laurence H. [Division of Urology, Sunnybrook Health Sciences Center, Toronto, ON (Canada); Sugar, Linda M. [Department of Pathology, Sunnybrook Health Sciences Center, Toronto, ON (Canada); Kiss, Alexander [Department of Research Design and Biostatistics, Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Center, Toronto, ON (Canada); Venkateswaran, Vasundara, E-mail: vasundara.venkateswaran@sunnybrook.ca [Division of Urology, Sunnybrook Health Sciences Center, Toronto, ON (Canada)

    2015-08-28

    Background: This study was designed to assess the effectiveness of a combination treatment using both desmopressin and docetaxel in prostate cancer treatment. Desmopressin is a well-known synthetic analogue of the antidiuretic hormone vasopressin. It has recently been demonstrated to inhibit tumor progression and metastasis in in vivo models. Docetaxel is widely used for the treatment of castration resistant prostate cancer (CRPC) patients. However, durable responses have been uncommon to date. In this study, we investigated the anti-tumor effect of desmopressin in combination with docetaxel in vitro and in vivo. Methods: Two prostate cancer cells (PC3, LNCaP) were treated with different concentrations of desmopressin alone, docetaxel alone, and a combination of desmopressin and docetaxel. Cell proliferation was determined by MTS assay. The anti-invasive and anti-migration potential of desmopressin and in combination with docetaxel were examined by wound healing assay, migration chamber assay, and matrigel invasion assay. Results: The combination of desmopressin and docetaxel resulted in a significant inhibition of PC3 and LNCaP cell proliferation (p < 0.01). Additionally, cell migration and invasion were also inhibited by the combination when compared to that of either treatment alone in PC3 cells (p < 0.01). The anti-tumor effect of this combination treatment was associated with down-regulation of both urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP-2 and MMP-9) in PC3 cells. Conclusions: We are the first to elucidate the anti-tumor and anti-metastatic potential of desmopressin in combination with docetaxel in a prostate cancer model via the uPA-MMP pathway. Our finding could potentially contribute to the therapeutic profile of desmopressin and enhance the efficacy of docetaxel based treatment for CRPC. - Highlights: • Desmopressin inhibits cell proliferation in prostate cancer cells. • The expression of cyclin A and CDK2

  20. Urokinase plasminogen activator inhibits HIV virion release from macrophage-differentiated chronically infected cells via activation of RhoA and PKCε.

    Directory of Open Access Journals (Sweden)

    Francesca Graziano

    Full Text Available BACKGROUND: HIV replication in mononuclear phagocytes is a multi-step process regulated by viral and cellular proteins with the peculiar feature of virion budding and accumulation in intra-cytoplasmic vesicles. Interaction of urokinase-type plasminogen activator (uPA with its cell surface receptor (uPAR has been shown to favor virion accumulation in such sub-cellular compartment in primary monocyte-derived macrophages and chronically infected promonocytic U1 cells differentiated into macrophage-like cells by stimulation with phorbol myristate acetate (PMA. By adopting this latter model system, we have here investigated which intracellular signaling pathways were triggered by uPA/uPAR interaction leading the redirection of virion accumulation in intra-cytoplasmic vesicles. RESULTS: uPA induced activation of RhoA, PKCδ and PKCε in PMA-differentiated U1 cells. In the same conditions, RhoA, PKCδ and PKCε modulated uPA-induced cell adhesion and polarization, whereas only RhoA and PKCε were also responsible for the redirection of virions in intracellular vesicles. Distribution of G and F actin revealed that uPA reorganized the cytoskeleton in both adherent and polarized cells. The role of G and F actin isoforms was unveiled by the use of cytochalasin D, a cell-permeable fungal toxin that prevents F actin polymerization. Receptor-independent cytoskeleton remodeling by Cytochalasin D resulted in cell adhesion, polarization and intracellular accumulation of HIV virions similar to the effects gained with uPA. CONCLUSIONS: These findings illustrate the potential contribution of the uPA/uPAR system in the generation and/or maintenance of intra-cytoplasmic vesicles that actively accumulate virions, thus sustaining the presence of HIV reservoirs of macrophage origin. In addition, our observations also provide evidences that pathways controlling cytoskeleton remodeling and activation of PKCε bear relevance for the design of new antiviral strategies aimed

  1. In IgA Nephropathy, Glomerulosclerosis Is Associated with Increased Urinary CD80 Excretion and Urokinase-Type Plasminogen Activator Receptor-Positive Podocyturia

    Directory of Open Access Journals (Sweden)

    Hernán Trimarchi

    2017-05-01

    Full Text Available Background: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN, the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80 in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis. Methods: The groups were as follows: controls (G1, n = 20 and IgAN group (G2, n = 39, subdivided into M1E0S0T0 (G2A, n = 21 and M1E0S1T0 (G2B, n = 18. Among the included variables, we determined uPAR-positive podocytes/gram of urinary creatinine (gUrCr and uCD80 ng/gUrCr. Biopsies with interstitial fibrosis and tubular atrophy <10% were included. Results: Groups were not different in age and gender; urinary protein-creatinine (uP/C ratio, Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI equation, uPAR-positive podocytes/gUrCr, and uCD80 were significantly increased in G2 versus G1. G2A and G2B were not different in age, gender, hypertension, and follow-up. G2B displayed significantly higher uP/C, uPAR-positive podocytes, uCD80, and lower CKD-EPI versus G2A. Strong significant correlations were encountered between uCD80 and podocyturia in G2A and G2B. However, when G1 was compared to G2A and G2B separately, the differences with respect to uP/C, uPAR-positive podocytes, and podocyturia were significantly stronger versus G2B than versus G2A. Conclusions: IgAN presents elevated uCD80 excretion and uPAR-positive podocyturia, while CD80 correlates with podocyturia. Glomerulosclerosis (S1 at the time of biopsy is associated with higher uP/C, lower renal function, increased uPAR-positive podocyturia, and CD80 excretion, and is independent of M1. In IgAN, uPAR may

  2. Urokinase receptor mediates osteoclastogenesis via M-CSF release from osteoblasts and the c-Fms/PI3K/Akt/NF-κB pathway in osteoclasts.

    Science.gov (United States)

    Kalbasi Anaraki, Parnian; Patecki, Margret; Tkachuk, Sergey; Kiyan, Yulia; Haller, Hermann; Dumler, Inna

    2015-02-01

    Bone remodeling is a dynamic process based on a fine-tuned balance between formation and degradation of bone. Osteoblasts (OBLs) are responsible for bone formation and bone resorption is mediated by osteoclasts (OCLs). The mechanisms regulating the OBL-OCL balance are critical in health and disease; however, they are still far from being understood. We reported recently that the multifunctional urokinase receptor (uPAR) mediates osteogenic differentiation of mesenchymal stem cells (MSCs) to OBLs and vascular calcification in atherosclerosis. Here, we address the question of whether uPAR may also be engaged in regulation of osteoclastogenesis. We show that uPAR mediates this process in a dual fashion. Thus, uPAR affected OBL-OCL interplay. We observed that osteoclastogenesis was significantly impaired in co-culture of monocyte-derived OCLs and in OBLs derived from MSCs lacking uPAR. We show that expression and release, from OBLs, of macrophage colony-stimulating factor (M-CSF), which is indispensable for OCL differentiation, was inhibited by uPAR loss. We further found that uPAR, on the other hand, controlled formation, differentiation, and functional properties of macrophage-derived OCLs. Expression of osteoclastogenic markers, such as tartrate-resistant acid phosphatase (TRAP) and cathepsin K, was impaired in OCLs derived from uPAR-deficient macrophages. The requirement of uPAR for osteoclastogenesis was further confirmed by immunocytochemistry and in bone resorption assay. We provide evidence that the underlying signaling mechanisms involve uPAR association with the M-CSF binding receptor c-Fms followed by c-Fms phosphorylation and activation of the PI3K/Akt/NF-κB pathway in OCLs. We further show that uPAR uses this pathway to regulate a balance between OCL differentiation, apoptosis, and cell proliferation. Our study identified uPAR as an important and multifaceted regulator of OBL-OCL molecular interplay that may serve as an attractive target in bone disease

  3. Distinct transport regimes for two elastically coupled molecular motors.

    Science.gov (United States)

    Berger, Florian; Keller, Corina; Klumpp, Stefan; Lipowsky, Reinhard

    2012-05-18

    Cooperative cargo transport by two molecular motors involves an elastic motor-motor coupling, which can reduce the motors' velocity and/or enhance their unbinding from the filament. We show theoretically that these interference effects lead, in general, to four distinct transport regimes. In addition to a weak coupling regime, kinesin and dynein motors are found to exhibit a strong coupling and an enhanced unbinding regime, whereas myosin motors are predicted to attain a reduced velocity regime. All of these regimes, which we derive by explicit calculations and general time scale arguments, can be explored experimentally by varying the elastic coupling strength.

  4. Essence and Prospect of International Export Control Regimes

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ International export control regimes are referring to the regimes and systems concerning limitation of export and transference of military-use and dual-use items and related parts as well as technologies. In the past couple of years, the control regimes have shown a strengthening posture. In addition, a new global export control regime is brewing. Hence export control has caught the attention of the international community, and particularly of the circles of armament control and commerce. The author would like to make some analyses of the posture and then try to predict the trend of international export control regimes.

  5. Cointegration and causal linkages in fertilizer markets across different regimes

    Science.gov (United States)

    Lahmiri, Salim

    2017-04-01

    Cointegration and causal linkages among five different fertilizer markets are investigated during low and high market regimes. The database includes prices of rock phosphate (RP), triple super phosphate (TSP), diammonium phosphate (DAP), urea, and potassium chloride (PC). It is found that fertilizer markets are closely linked to each other during low and high regimes; and, particularly during high regime (after 2007 international financial crisis). In addition, there is no evidence of bidirectional linear relationship between markets during low and high regime time periods. Furthermore, all significant linkages are only unidirectional. Moreover, some causality effects have emerged during high regime. Finally, the effect of an impulse during high regime time period persists longer and is stronger than the effect of an impulse during low regime time period (before 2007 international financial crisis).

  6. Modern fire regime resembles historical fire regime in a ponderosa pine forest on Native American land

    Science.gov (United States)

    Amanda B. Stan; Peter Z. Fule; Kathryn B. Ireland; Jamie S. Sanderlin

    2014-01-01

    Forests on tribal lands in the western United States have seen the return of low-intensity surface fires for several decades longer than forests on non-tribal lands. We examined the surface fire regime in a ponderosa pinedominated (Pinus ponderosa) forest on the Hualapai tribal lands in the south-western United States. Using fire-scarred trees, we inferred temporal (...

  7. Institutional design and regime effectiveness in transboundary river management – the Elbe water quality regime

    Directory of Open Access Journals (Sweden)

    I. Dombrowsky

    2007-06-01

    Full Text Available The literature on transboundary river management suggests that institutions play an important role in bringing cooperation about. However, the knowledge on how they should be designed in order to do so remains limited. One way to learn more about adequate institutional design is to assess the effectiveness of existing regimes, and to trace the causal relationships leading to the respective outcomes. In order to gain further insights into the relationship of institutional design and regime effectiveness, this paper presents a study on the water quality regime of the International Commission for the Protection of the Elbe (ICPE. The analysis is based on a review of pertinent documents and ten qualitative interviews with Czech and German Commission members and NGO representatives. Particular emphasis has been put on determining the ICPE's specific contribution and the no-regime counterfactual as well as on the perceived expedience of the institutional arrangements. The study shows that overall due to external as well as internal institutional factors the ICPE proved relatively successful, and as such it also provides insights into how institutions matter: The commission served as platform for joint problem solving by identifying priorities for action. These international obligations increased the power of national administrations and their access to funds. At the same time, the Commission's reporting to the public served as an enforcement mechanism. However, the ICPE's contribution towards achieving the various goals varied significantly between the different areas of activity. It was high where the main responsibility for action was with the public authorities, such as in the area of wastewater treatment and the establishment of an international alarm plan and model. It was practically non existent in the reduction of non-point pollution from agriculture, where the success depended on the behavior of individual private actors (farmers. From a

  8. Mobile Networks: Visualizing the Global Refugee Regime

    Directory of Open Access Journals (Sweden)

    Bennett Gabriel Sherry

    2015-08-01

    Full Text Available This article identifies conceptual issues surrounding the visualization of refugee movement in relation to state borders. It argues that social-network-analysis software provides a tool for the creation of visualizations of human movement that are removed from geolocation. Such a method disassociates forced migration from preconceived notions about the importance of geographical proximity and the fixity of state borders. This article provides some brief examples of ways that these methods might be utilized to graph and visualize aspects of the global refugee regime. The global-scale, transnational conceptualization and new visualizations show networks of movement centered on new inter-state communities and highlights the role of non-state actors.

  9. Nonlinear regimes of forced magnetic reconnection

    Energy Technology Data Exchange (ETDEWEB)

    Vekstein, G., E-mail: g.vekstein@manchester.ac.uk [JBCA, School of Physics and Astronomy, University of Manchester, Manchester M13 9PL (United Kingdom); STEL, Nagoya University, Nagoya, Aichi 464-8601 (Japan); Kusano, K. [STEL, Nagoya University, Nagoya, Aichi 464-8601 (Japan)

    2015-09-15

    This letter presents a self-consistent description of nonlinear forced magnetic reconnection in Taylor's model of this process. If external boundary perturbation is strong enough, nonlinearity in the current sheet evolution becomes important before resistive effects come into play. This terminates the current sheet shrinking that takes place at the linear stage and brings about its nonlinear equilibrium with a finite thickness. Then, in theory, this equilibrium is destroyed by a finite plasma resistivity during the skin-time, and further reconnection proceeds in the Rutherford regime. However, realization of such a scenario is unlikely because of the plasmoid instability, which is fast enough to develop before the transition to the Rutherford phase occurs. The suggested analytical theory is entirely different from all previous studies and provides proper interpretation of the presently available numerical simulations of nonlinear forced magnetic reconnection.

  10. Wilson fermions in the epsilon regime

    CERN Document Server

    Bär, Oliver; Schaefer, Stefan

    2009-01-01

    We extend the epsilon-expansion of continuum chiral perturbation theory to nonzero lattice spacing in the framework of Wilson Chiral Perturbation Theory. We distinguish various regimes by defining the relative power counting of the quark mass m and the lattice spacing a. We observe that for m ~ a Lambda^2_QCD, the explicit breaking of chiral symmetry in Wilson fermions is still driven by the quark mass and lattice corrections are highly suppressed. The lattice spacing effects become more pronounced for smaller quark masses and may lead to non-trivial corrections of the continuum results at next-to-leading order. We compute these corrections for standard current and density correlation functions. A fit to lattice data shows that these corrections are small, as expected.

  11. The Great Lakes' regional climate regimes

    Science.gov (United States)

    Sugiyama, Noriyuki

    For the last couple of decades, the Great Lakes have undergone rapid surface warming. In particular, the magnitude of the summer surface-warming trends of the Great Lakes have been much greater than those of surrounding land (Austin and Colman, 2007). Among the Great Lakes, the deepest Lake Superior exhibited the strongest warming trend in its annual, as well as summer surface water temperature. We find that many aspects of this behavior can be explained in terms of the tendency of deep lakes to exhibit multiple regimes characterized, under the same seasonally varying forcing, by the warmer and colder seasonal cycles exhibiting different amounts of wintertime lake-ice cover and corresponding changes in the summertime lake-surface temperatures. In this thesis, we address the problem of the Great Lakes' warming using one-dimensional lake modeling to interpret diverse observations of the recent lake behavior. (Abstract shortened by ProQuest.).

  12. Quantum Error Correction in the Zeno Regime

    CERN Document Server

    Erez, N; Reznik, B; Vaidman, L; Erez, Noam; Aharonov, Yakir; Reznik, Benni; Vaidman, Lev

    2003-01-01

    In order to reduce errors, error correction codes (ECCs) need to be implemented fast. They can correct the errors corresponding to the first few orders in the Taylor expansion of the Hamiltonian of the interaction with the environment. If implemented fast enough, the zeroth order error predominates and the dominant effect is of error prevention by measurement (Zeno Effect) rather than correction. In this ``Zeno Regime'', codes with less redundancy are sufficient for protection. We describe such a simple scheme, which uses two ``noiseless'' qubits to protect a large number, $n$, of information qubits from noise from the environment. The ``noisless qubits'' can be realized by treating them as logical qubits to be encoded by one of the previously introduced encoding schemes.

  13. Regime shifts in models of dryland vegetation

    CERN Document Server

    Zelnik, Yuval R; Yizhaq, Hezi; Bel, Golan; Meron, Ehud

    2013-01-01

    Drylands are pattern-forming systems showing self-organized vegetation patchiness, multiplicity of stable states and fronts separating domains of alternative stable states. Pattern dynamics, induced by droughts or disturbances, can result in desertification shifts from patterned vegetation to bare soil. Pattern-formation theory suggests various scenarios for such dynamics; an abrupt global shift involving a fast collapse to bare soil, a gradual global shift involving the expansion and coalescence of bare-soil domains, and an incipient shift to a hybrid state consisting of stationary bare-soil domains in an otherwise periodic pattern. Using models of dryland vegetation we address the question which of these scenarios can be realized. We found that the models can be split into two groups: models that exhibit multiplicity of periodic-pattern and bare-soil states, and models that exhibit, in addition, multiplicity of hybrid states. Furthermore, in all models we could not identify parameter regimes in which bare-s...

  14. Dynamic Recrystallization: The Dynamic Deformation Regime

    Science.gov (United States)

    Murr, L. E.; Pizaña, C.

    2007-11-01

    Severe plastic deformation (PD), especially involving high strain rates (>103 s 1), occurs through solid-state flow, which is accommodated by dynamic recrystallization (DRX), either in a continuous or discontinuous mode. This flow can be localized in shear instability zones (or adiabatic shear bands (ASBs)) with dimensions smaller than 5 μ, or can include large volumes with flow zone dimensions exceeding centimeters. This article illustrates these microstructural features using optical and electron metallography to examine a host of dynamic deformation examples: shaped charge jet formation, high-velocity and hypervelocity impact crater formation, rod penetration into thick targets (which includes rod and target DRX flow and mixing), large projectile-induced target plug formation and failure, explosive welding, and friction-stir welding and processing. The DRX is shown to be a universal mechanism that accommodates solid-state flow in extreme (or severe) PD regimes.

  15. The Quantum-Gravity Regime under Microgravity

    Science.gov (United States)

    Laemmerzahl, Claus; Könemann, Thorben

    Gravity is the weakest of the four known interactions. Accordingly, one needs either huge masses to explore this interaction or a long time to accumulate its small influence. The latter is possible only under microgravity conditions. In this contribution we would like to focus on three issues related to basic problems in the quantum-gravity regime: (i) Search for fundamental decoherence: Decoherence describes the transition from the quantum world to the classical regime. There are many technical sources of decoherence but the question is whether there is a fundamental mechanism for such a decoherence which would be a solution for the measurement problem in quantum mechanics. Here we describe the estimates on such a fundamental decoherence from experiments with Bose-Einstein condensates in microgravity. (ii) Search for possible self-gravity effects: Self gravity has been proposed e.g. by Penrose to resolve the measurement problem. Self gravitating systems are also give Bose stars which are a model for the pyhsics around black holes or for dark matter. Here we would like to describe effects of self gravity in Bose-Einstein condensates. We calculate stationary spherically symmetric states and discuss the possibility to measure such effects related to self gravity. (iii) Test of the semiclassical Einstein equations. Since General Relativity and quantum theory appear to be incompatible, it has been discussed whether the semiclassical Einstein equations might be valid. Here we would like to discuss a proposal made by Peres and Lindner to use Bose-Einstein condensates for a true quantum test of these semiclassical Einstein equations from which one can decide whether such an ansatz is valid or not.

  16. Cavity Optomechanics in the Quantum Regime

    Science.gov (United States)

    Botter, Thierry Claude Marc

    An exciting scientific goal, common to many fields of research, is the development of ever-larger physical systems operating in the quantum regime. Relevant to this dissertation is the objective of preparing and observing a mechanical object in its motional quantum ground state. In order to sense the object's zero-point motion, the probe itself must have quantum-limited sensitivity. Cavity optomechanics, the interactions between light and a mechanical object inside an optical cavity, provides an elegant means to achieve the quantum regime. In this dissertation, I provide context to the successful cavity-based optical detection of the quantum-ground-state motion of atoms-based mechanical elements; mechanical elements, consisting of the collective center-of-mass (CM) motion of ultracold atomic ensembles and prepared inside a high-finesse Fabry-Perot cavity, were dispersively probed with an average intracavity photon number as small as 0.1. I first show that cavity optomechanics emerges from the theory of cavity quantum electrodynamics when one takes into account the CM motion of one or many atoms within the cavity, and provide a simple theoretical framework to model optomechanical interactions. I then outline details regarding the apparatus and the experimental methods employed, highlighting certain fundamental aspects of optical detection along the way. Finally, I describe background information, both theoretical and experimental, to two published results on quantum cavity optomechanics that form the backbone of this dissertation. The first publication shows the observation of zero-point collective motion of several thousand atoms and quantum-limited measurement backaction on that observed motion. The second publication demonstrates that an array of near-ground-state collective atomic oscillators can be simultaneously prepared and probed, and that the motional state of one oscillator can be selectively addressed while preserving the near-zero-point motion of

  17. The role of the media in establishing international security regimes

    Directory of Open Access Journals (Sweden)

    Chanan Naveh

    2005-04-01

    Full Text Available This article focuses primarily on the media's impact on international security regimes. It explores the ways in which the media affect the lifecycles of international regimes, from the time they are first conceived of, through their establishment, consolidation and stabilization, up until their ultimate demise. Although this paper highlights the media's role in the evolution of security regimes, it is clear that, regardless of the regime in question, media play a role throughout the lifecycle of all international regimes, whatever their character. In order to analyze the relationships of the media with security regimes in general, and specifically their contribution to each stage in their development, the article utilizes methodologies from the field of communication studies. It examines the media's agenda, "news values" and various functions, and their ability to mobilize public support for the particular issue of the regime. To date, most studies have explored the interaction between media communication patterns and global developments at the state level, or in relation to the formulation of foreign policy, while largely ignoring the international dimension of the relationship. This article attempts to remedy this situation, and the relevant processes are analysed in a case study of the anti-Iraq international security regime. It should be noted that although the paper focuses on the specific anti-Iraqi regime, it is part of a more general Anti-Rogue actors regime which includes the war against global terrorism. The study of the development of the anti-Iraq press-security regime teaches us that during international crises the media mobilize and unanimously support the regime fighting the "bad guys." But, when the regime develops and enters disputed turfs and begins to lose its legitimacy, media support diminishes, and the media may even develop into an opposing force and may join the actors fighting against this regime. Moreover, the study of

  18. 胸腔微管引流并注入尿激酶治疗结核性胸膜炎%Curative Effect of Chest Micro-tube Drainage and Injection of Urokinase in Treatment of Tuberculous Pleuritic

    Institute of Scientific and Technical Information of China (English)

    王伟莉

    2016-01-01

    Objective To study the curative effect of chest micro-tube drainage and injection of urokinase in treatment of tuberculous pleuritic. Methods 81 cases of patients with tuberculous pleuritic treated in our institute from January 2010 to January 2014 were selected as the research objects, both groups were given regular antituberculotic treatment, the treatment group (45 cases) were given conventional intrathoracic micro-tube indwelling for pleural effusion drainage, the thoracic cavity was clipped for 12h after injection of 20 mL normal saline and 100,000-unit urokinase and then opened, the control group (36 cases) received conventional thoracocentesis twice a week, and the total treatment effective rate and adverse re-actions were compared between the two groups. Results The effective rate in the treatment group was better than that in the control group, (94.6% vs 75%),P<0.05. Conclusion The curative effect of chest micro-tube drainage and injection of uroki-nase in treatment of tuberculous pleuritic is good, and it is safe and convenient.%目的:探讨胸腔微管引流并注入尿激酶治疗结核性胸膜炎的疗效。方法方便选取该所2010年1月—2014年1月的81例结核性胸膜炎患者为研究对象,在正规抗结核治疗下,治疗组45例常规胸腔内留置微管引流胸腔积液,20 mL生理盐水+尿激酶10万U胸腔注入夹闭12 h后打开;对照组36例行常规胸腔穿刺术,2次/周。对比两组患者治疗总有效率和不良反应。结果治疗组有效率94.6%,对照组有效率75%。治疗组优于对照组(P<0.05)。结论胸腔微管引流并注入尿激酶治疗结核性胸膜炎安全,简便,疗效好。

  19. Effect of intrapleural injection with urokinase in treatment of tuberculous pleuritis%胸腔注入尿激酶治疗结核性胸膜炎的疗效观察

    Institute of Scientific and Technical Information of China (English)

    王卫阳

    2012-01-01

    Objective To investigate the effects of intrapleural injection with urokinase in prevention and treatment of tuberculous pleuri-tis. Methods Eighty patients with tuberculous pleuritis were divided into two groups by random allocation. Therapeutic group of 40 cases received intrapleural injection with urokinase 10 4 added into 0. 9 % sodium chloride injection 20 ml after each thoracic drainage,and control group of 40 cases received intrapleural isoniazid 0. 1 g injection added into 0. 9% sodium chloride injection 20 ml after each thoracic drainage. After the end of treatment we compared catheter detaining time, pleural thickness, chest water absorption and pleural adhesion of the two groups. Results The curative effect was significantly lower in therapeutic group than control group. Conclusions Intrapleural injection with urokinase has certain prevention and treatment in pleural thickening and adhesion due to tuberculous pleuritis. There is no obvious adverse reaction. It has the advantage of simple operation, which is worthy of clinical application.%目的 探讨胸腔内注射尿激酶治疗结核性胸膜炎的临床疗效.方法将90例结核性胸膜炎患者随机分为两组,治疗组45例,用0.9%氯化钠注射液10 ml加尿激酶10万U于每次抽液后行胸腔内注射;对照组45例,用0.9%氯化钠注射液10 ml加异烟肼0.1 g于每次抽液后行胸腔内注射,治疗结束后进行比较,观察两组的导管留置时间、胸膜厚度、胸水吸收以及胸膜黏连情况.结果 治疗组的疗效明显优于对照组,差异有统计学意义.结论 胸腔内注射尿激酶能够促进胸腔积液吸收,使胸膜肥厚减轻、黏连减少,可以缩短静脉导管在胸腔内留置时间;该方法不良反应较少,操作简单,值得临床推广应用.

  20. 尿激酶在老年急性心肌梗死中溶栓效果观察%Efifcacy of Urokinase on Thrombolysis in Elderly Patients With Acute Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    邵军军; 辛建文

    2016-01-01

    Objective To observe the thrombolysis effect of urokinase in elderly patients with acute myocardial infarction (AMI). Methods 45 cases of elderly patients with AMI in our hospital were divided into observation group (n=23) and control group (n=22) according to medication, control group received conventional treatment, treatment group was given urokinase based on control group. Results The IRA opening time of observation group was shorter than that of control group, the difference was statistically significant (P0.05). The clinical recanalization rate of observation group was higher, and the incidence of arrhythmia and bleeding complications were signiifcantly lower than that of control group (P<0.05). Conclusion Urokinase for the treatment of AMI has high clinical recanalization rate, with low incidence of arrhythmia and fewer bleeding complications, worthy of clinical application.%目的:观察尿激酶在老年急性心肌梗死患者中的溶栓效果。方法选取我院45例急性心肌梗死老年患者作为研究对象,根据不同用药,分为观察组(n=23)和对照组(n=22),对照组给予常规治疗,观察组在对照组治疗基础上给予尿激酶。结果观察组IRA开通时间短于对照组(P<0.05)。观察组CK、CK-MB峰值时间与对照组比较,差异无统计学意义(P>0.05)。观察组临床再通率高于对照组,心率失常发生率及出血并发症发生率均显著低于对照组(P<0.05)。结论尿激酶对治疗老年急性心肌梗死有临床再通率高,心率失常发生率及出血并发症少优。

  1. Adaptation or innovation? The effectiveness of global environmental regimes

    OpenAIRE

    2009-01-01

    The growing importance of the discourse on climate change raises some interesting questions regarding the creation and evaluation of international regimes. When is a regime effective? Through analyzing two competing approaches to evaluating regimes, the instrumentalists and critical theorists, this project shows the deficiencies in the current discourse. Instrumentalists focus on observable means-ends standards of efficiency, while critical theorists ask fundamental questions regarding inters...

  2. Clinical application on urokinase, papaverine angiography in diabetic foot%尿激酶、罂粟碱在糖尿病足血管造影中的临床应用

    Institute of Scientific and Technical Information of China (English)

    任毅; 陈君辉; 贺平

    2012-01-01

    To discuss urokinase, papaverine angiography in diabetic foot in clinical application. Methods Forty-seven cases of vascular doppler examination of lower extremity arterial stenosis prompted the merger and the performance of lower limb ischemia in diabetic patients, after the DSA angiography ,nineteen cases who had tibial, peroneal artery, the distal or foot small artery stenosis or occlusion , used transcatheter bolus infusion method using 25 - 50Uten-thousand units of urokinase, papaverine 30 ~60mg. Results Fifteen cases of transcatheter infusion of urokinase, papaverine had marked improvement in the performance of lower limb ischemia, and through the comprehensive medical treatment, target vessel around the collateral vessels increased significantly in the total group of 100 percent of cases, stenosis lumen expansion over the previous was 68% , re-opening of vascular occlusion accounted for 36. 8%. 0 — Ⅱ level surface of foot ulcer disease healed , Ⅱ ~ Ⅳ grade of foot ulcer surface drying, shrinking around the inflammation subsided. Conclusion Intra-arterial infusion of urokinase, papaverine can to some extent to improve lower limb blood circulation, so as to achieve remission in patients with lower extremity pain, numbness and other symptoms , has short-term efficacy, no heroatoma, vascular rupture, distal embolism and other vascular complications occurred.%目的 探讨尿激酶、罂粟碱在糖尿病足血管造影中的临床应用.方法 对47例血管多普勒检查提示下肢动脉狭窄且合并下肢缺血表现糖尿病患者,行DSA血管造影后,对其中19例胫、腓动脉中、远段或足部微小动脉狭窄或闭塞患者,经导管采用团注法灌注尿激酶25~ 50U、罂粟碱30~60mg行溶栓,扩血管治疗.结果 19例经导管灌注尿激酶、罂粟碱患者下肢缺血表现明显改善,并通过内科综合治疗,靶血管周围侧支血管明显增多占全组病例的100%,狭窄段血管腔较前扩张占68%,

  3. Photoaffinity labeling of the human receptor for urokinase-type plasminogen activator using a decapeptide antagonist. Evidence for a composite ligand-binding site and a short interdomain separation

    DEFF Research Database (Denmark)

    Ploug, M; Ostergaard, S; Hansen, L B

    1998-01-01

    labeling. Proteolytic domain mapping using chymotrypsin revealed a specific labeling of both uPAR domain I and domains II + III dependent on the position of the photoprobe in the antagonist. On the basis of these studies, we propose the existence of a composite ligand binding site in uPAR combined......Binding of urokinase-type plasminogen activator (uPA) to its cellular receptor (uPAR) renders the cell surface a favored site for plasminogen activation. Recently, a 15-mer peptide antagonist of the uPA-uPAR interaction, with an IC50 value of 10 nM, was identified using phage display technology...... [Goodson, R. J., Doyle, M. V., Kaufman, S. E., and Rosenberg, S. (1994) Proc. Natl. Acad. Sci. 91, 7129-7133]. In the present study, the molecular aspects of the interaction between this peptide and uPAR have been investigated. We have characterized the real-time receptor binding kinetics...

  4. The pro-inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is associated with incident type 2 diabetes among overweight but not obese individuals with impaired glucose regulation

    DEFF Research Database (Denmark)

    Heraclides, A; Jensen, T M; Rasmussen, S S

    2013-01-01

    Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION) and for whom data on suPAR, BMI and smoking were available. Logistic regression analysis was used to estimate the odds for incident type 2 diabetes per twofold increase in suPAR levels. Interactions between both smoking and body......Recent evidence links the soluble urokinase plasminogen activator receptor (suPAR), a stable biomarker of systemic immune activation, to several chronic diseases, including type 2 diabetes. suPAR is also associated with adiposity and smoking. We hypothesised that this biomarker would be linked...... to incident type 2 diabetes in individuals with impaired glucose regulation and that this association would be modified by smoking and body weight status. The study included 1,933 participants with impaired glucose regulation, who were drawn from the Danish arm of the Anglo-Danish-Dutch Study of Intensive...

  5. Curative Effects of Urokinase Thrombolysis for STEMI on the Onset within 2h%尿激酶溶栓治疗发病2h内急性ST段抬高型心肌梗死的疗效

    Institute of Scientific and Technical Information of China (English)

    盛祖桃; 吕云; 高彦

    2015-01-01

    目的:研究急性ST段抬高型心肌梗死( STEMI)患者在发病的2 h内采用尿激酶溶栓的疗效。方法选取72例2013年2月~2014年2月接收的STEMI患者,依据发病时间的不同分为对照组和研究组,溶栓后2 h内,研究组较对照组的临床再通率明显要高,复合终点事件的总发生率明显低于对照组( P<0.05),具有统计意义。结论发病在2 h内的STEMI患者采取尿激酶溶栓治疗,可明显提高患者的血管再通率,病死率较低,值得推广。%Objective To study the curative effects of urokinase thrombolysis for patients with STEMI on the onset within 2 h.Methods 72 patients with STEMI treated from February 2013 to February 2014 in our hospital were selected and divided into control group and research group according to the duration of disease .The recanalization rate of research group was significantly higher than that of control group;the total incidence of composite endpoint was significantly lower than that of control group (P<0.05).Conclusions The treatment of urokinase thrombolysis for patients with STEMI on the onset within 2 h can significantly improve the recanalization rate and reduce the fatality rate .It is worthy of clinical promotion.

  6. Flavonol-enriched fraction from Vaccinium macrocarpon fruit inhibits matrix metalloproteinase-2, matrix metalloproteinase-9 and urokinase-type plasminogen activator expression in human prostate cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    James MacPhee

    2014-11-01

    Full Text Available Background: Prostate cancer, amongst other cancer types has a genetic and environmental component, which can contribute to prostate cancer development and progression. Vaccinum macrocarpon (American cranberry is a botanical that contains several phytochemicals which have been suggested to play a role in preventing cardiovascular disease, cancer, and urinary tract infections as well as in the maintenance of oral health. Context and purpose of this study: This investigation evaluated the effects of a flavonolenriched fraction (FL from the American cranberry (Vaccinium macrocarpon containing quercetin and myricetin glycosides on matrix metalloproteinase (MMP and urokinase-type plasminogen activator (uPA activities and their associated regulatory proteins in DU145 human prostate cancer cells in vitro. Results: A flavonol-enriched fraction (FL was prepared from Vaccinium macrocarpon berries and the effect of this fraction on prostate cancer cell behaviour was assessed using biochemical and molecular approaches including cytotoxicity assays and Western blot analysis to determine protein expression. Cranberry FL decreased cellular viability of DU145 cells at a concentration of 25 ug/ml by 20% after 6 hours of treatment. Further investigations determined that associated with this cytotoxicity, cranberry FL decreases matrix metalloproteinase (MMP ( specifically MMP-2 and MMP-9 activity and urokinase plasminogen activator (uPA activity through effects on specific temporal MMP regulators and uPA regulators and by affecting either the phosphorylation status and/or expression of specific MAP kinase, PI-3 kinase, NF-kB and AP-1 pathway associated proteins. Conclusion: This study demonstrates, for the first time, the ability of Vaccinium macrocarpon flavonols to modulate cellular pathways associated with migration, invasion, and proliferation, suggesting that cranberry (Vaccinium macrocarpon is a viable candidate for further research as a natural product that

  7. Evaluation of alpha 1-antitrypsin and the levels of mRNA expression of matrix metalloproteinase 7, urokinase type plasminogen activator receptor and COX-2 for the diagnosis of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Luis Bujanda

    Full Text Available BACKGROUND: Colorectal cancer (CRC is the second most common cause of death from cancer in both men and women in the majority of developed countries. Molecular tests of blood could potentially provide this ideal screening tool. AIM: Our objective was to assess the usefulness of serum markers and mRNA expression levels in the diagnosis of CRC. METHODS: In a prospective study, we measured mRNA expression levels of 13 markers (carbonic anhydrase, guanylyl cyclase C, plasminogen activator inhibitor, matrix metalloproteinase 7 (MMP7, urokinase-type plasminogen activator receptor (uPAR, urokinase-type plasminogen activator, survivin, tetranectin, vascular endothelial growth factor (VEGF, cytokeratin 20, thymidylate synthase, cyclooxygenase 2 (COX-2, and CD44 and three proteins in serum (alpha 1 antitrypsin, carcinoembryonic antigen (CEA and activated C3 in 42 patients with CRC and 33 with normal colonoscopy results. RESULTS: Alpha 1-antitrypsin was the serum marker that was most useful for CRC diagnosis (1.79 ± 0.25 in the CRC group vs 1.27 ± 0.25 in the control group, P<0.0005. The area under the ROC curve for alpha 1-antitrypsin was 0.88 (0.79-0.96. The mRNA expression levels of five markers were statistically different between CRC cases and controls: those for which the ROC area was over 75% were MMP7 (0.81 and tetranectin (0.80, COX-2 (0.78, uPAR (0.78 and carbonic anhydrase (0.77. The markers which identified early stage CRC (Stages I and II were alpha 1-antitrypsin, uPAR, COX-2 and MMP7. CONCLUSIONS: Serum alpha 1-antitrypsin and the levels of mRNA expression of MMP7, COX-2 and uPAR have good diagnostic accuracy for CRC, even in the early stages.

  8. TGF-β2 promotes RPE cell invasion into a collagen gel by mediating urokinase-type plasminogen activator (uPA) expression.

    Science.gov (United States)

    Sugioka, Koji; Kodama, Aya; Okada, Kiyotaka; Iwata, Mihoko; Yoshida, Koji; Kusaka, Shunji; Matsumoto, Chota; Kaji, Hiroshi; Shimomura, Yoshikazu

    2013-10-01

    Transforming growth factor-beta (TGF-β) is one of the main epithelial-mesenchymal transition (EMT)-inducing factors. In general, TGF-β-induced EMT promotes cell migration and invasion. TGF-β also acts as a potent regulator of pericellular proteolysis by regulating the expression and secretion of plasminogen activators. Urokinase-type plasminogen activator (uPA) is a serine protease that binds to its cell surface receptor (uPAR) with high affinity. uPA binding to uPAR stimulates uPAR's interaction with transmembrane proteins, such as integrins, to regulate cytoskeletal reorganization and cell migration, differentiation and proliferation. However, the influence of TGF-β and the uPA/uPAR system on EMT in retinal pigment epithelial (RPE) cells is still unclear. The purpose of this study was to determine the effect of TGF-β2, which is the predominant isoform in the retina, and the uPA/uPAR system on RPE cells. In this study, we first examined the effect of TGF-β2 and/or the inhibitor of uPA (u-PA-STOP(®)) on the proliferation of a human retinal pigment epithelial cell line (ARPE-19 cells). Treatment with TGF-β2 or u-PA-STOP(®) suppressed cell proliferation. Combination treatment of TGF-β2 and u-PA-STOP(®) enhanced cell growth suppression. Furthermore, western blot analysis, fibrin zymography and real-time reverse transcription PCR showed that that TGF-β2 induced EMT in ARPE-19 cells and that the expression of uPA and uPAR expression was up-regulated during EMT. The TGF-β inhibitor SB431542 suppressed TGF-β2-stimulated uPA expression and secretion but did not suppress uPAR expression. Furthermore, we seeded ARPE-19 cells onto Transwell chambers and allowed them to invade the collagen matrix in the presence of TGF-β2 alone or with TGF-β2 and u-PA-STOP(®). TGF-β2 treatment induced ARPE-19 cell invasion into the collagen gel. Treatment with a combination of TGF-β2 and the uPA inhibitor strongly inhibited ARPE-19 cell invasion compared with treatment with

  9. Flow regimes in a trapped vortex cell

    Science.gov (United States)

    Lasagna, D.; Iuso, G.

    2016-03-01

    This paper presents results of an experimental investigation on the flow in a trapped vortex cell, embedded into a flat plate, and interacting with a zero-pressure-gradient boundary layer. The objective of the work is to describe the flow features and elucidate some of the governing physical mechanisms, in the light of recent investigations on flow separation control using vortex cells. Hot-wire velocity measurements of the shear layer bounding the cell and of the boundary layers upstream and downstream are reported, together with spectral and correlation analyses of wall-pressure fluctuation measurements. Smoke flow visualisations provide qualitative insight into some relevant features of the internal flow, namely a large-scale flow unsteadiness and possible mechanisms driving the rotation of the vortex core. Results are presented for two very different regimes: a low-Reynolds-number case where the incoming boundary layer is laminar and its momentum thickness is small compared to the cell opening, and a moderately high-Reynolds-number case, where the incoming boundary layer is turbulent and the ratio between the momentum thickness and the opening length is significantly larger than in the first case. Implications of the present findings to flow control applications of trapped vortex cells are also discussed.

  10. Crossing into the substellar regime in Praesepe

    CERN Document Server

    Chappelle, R J; Steele, I A; Dobbie, P D; Magazzù, A

    2005-01-01

    We present the results of a deep optical 2.6 square degree survey with near infrared follow-up measurements of the intermediate-aged Praesepe open cluster. The survey is complete to I=21.3, Z=20.5, corresponding to ~0.06 Solar Masses assuming a cluster age of 0.5 Gyrs. Using 3-5 pass-bands to constrain cluster membership, we identify 32 new low mass cluster members, at least 4 of which are likely to be substellar. We use the low mass census to trace the region where the sequence moves away from the NEXTGEN towards the Dusty regime at Teff = 2200K. In doing so, we identify four unresolved binaries, yielding a substellar binary fraction of ~30 percent. The binary fractions appear to decrease below 0.1 Solar Masses, in contrast to the rising fractions found in the Pleiades. We also identify a paucity of late M dwarfs, thought to be due to a steepening in the mass-luminosity relation at these spectral types, and compare the properties of this gap in the sequence to those observed in younger clusters. We note an o...

  11. On the ontological emergence from quantum regime

    Energy Technology Data Exchange (ETDEWEB)

    Luty, Damian [Adam Mickiewicz University, Poznan (Poland)

    2014-07-01

    There are several views on the relation between quantum physics and theory of relativity (especially General Relativity, GR). A popular perspective is this: GR with its macroscopic gravitational effects will turn out to be a limit of a more fundamental theory which should consider discrete physics and not deal with continuity (like theory of relativity). Thus, GR will emerge from a more basic theory, which should be quantum-like. One could call this an epistemic emergence view towards fundamental theories. The question is, given that scientific realism is valid: should emergence be a fundamental notion in our ontological view about the evolving, physical Universe? Is there an ontological emergence fully compatible with the notion of fundamentality? I argue that if we want to defend ontological emergence (from quantum to macroscopic regime) as something fundamental, we will arrive at the position of metaphysics of dispositions (and I argue, why this is undesirable), or conclude, that we cannot square fully fundamental ontology with the notion of emergence, and that we have to accept an ontological pluralism relativised to a certain scale. I defend the latter proposition, showing, that epistemic emergence doesn't entail (logically) ontological emergence.

  12. Legal regime of water management facilities

    Directory of Open Access Journals (Sweden)

    Salma Jožef

    2013-01-01

    Full Text Available The paper analyzes the legal regime of water management facilities in the light of Serbian, foreign and European law. Different divisions of water management facilities are carried out (to public and private ones, natural and artificial ones, etc., with determination of their legal relevance. Account is taken of the issue of protection from harmful effects of waters to such facilities, as well. The paper points also to rules on the water management facilities, from acts of planning, to individual administrative acts and measures for maintenance of required qualitative and quantitative condition of waters, depending on their purpose (general use or special, commercial use o waters. Albeit special rules on water management facilities exist, due to the natural interlocking between all the components of the environment (water, air and soil, a comprehensive approach is required. A reference is made to other basic principles of protection of water management facilities as well, such as the principle of prevention, principle of sustainable development and the principle "polluter pays". The last one represents the achievement of contemporary law, which deviates from the idea accepted in the second half of 20th century that supported the socialization of risk from harmful effects of waters.

  13. Multimode optomechanical system in the quantum regime

    CERN Document Server

    Nielsen, William H P; Møller, Christoffer B; Polzik, Eugene S; Schliesser, Albert

    2016-01-01

    We realise a simple and robust optomechanical system with a multitude of long-lived ($Q>10^7$) mechanical modes in a phononic-bandgap shielded membrane resonator. An optical mode of a compact Fabry-Perot resonator detects these modes' motion with a measurement rate ($96~\\mathrm{kHz}$) that exceeds the mechanical decoherence rates already at moderate cryogenic temperatures ($10\\,\\mathrm{K}$). Reaching this quantum regime entails, i.~a., quantum measurement backaction exceeding thermal forces, and thus detectable optomechanical quantum correlations. In particular, we observe ponderomotive squeezing of the output light mediated by a multitude of mechanical resonator modes, with quantum noise suppression up to -2.4 dB (-3.6 dB if corrected for detection losses) and bandwidths $\\lesssim 90\\,\\mathrm{ kHz}$. The multi-mode nature of the employed membrane and Fabry-Perot resonators lends itself to hybrid entanglement schemes involving multiple electromagnetic, mechanical, and spin degrees of freedom.

  14. Photonic Crystal Waveguides in Terahertz Regime

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Huaiwu, E-mail: hwzhang@uestc.edu.cn [State Key Laboratory of Electronic Films and Integrated Devices, University of Electronic Science and Technology of China, Chengdu, 610054 (China)

    2011-02-01

    Using the finite difference time domain method, the electromagnetic field distribution of THz waves in photonic crystals (PCs) T-splitters and Y-splitters had been simulated. The simulation results show that those different T-splitters and Y-splitters can divide the power in an input wave guide equally between two output waveguides. By the improved T-splitter with a rod in the junction, we achieved the 84% amplitude- frequency characteristics consistency of pass-band from 1.12 THz to 1.22 THz, and surpass the 76% consistency of common T-splitter. The improved Y-splitter with a rod in the junction and without rod in the corners has widest -3db bandwidth 0.224 THz, and the amplitude reaches 1655.727. The improved Y-splitter has better performance than other Y-splitters. Introducing the photonic band gap structure with L-type defect composed of three defects. Three high-Q resonant frequencies appeared simultaneously in some monitor coordinates. The wavelength-add-drop properties of L-type defects may be used in multi-carrier communication and multi-frequency-monitoring for the THz regime. Also, a carefully designed PCs can be used as high Q narrowband filter in THz band. These results provide a useful guide and a theoretical basis for the developments of THz functional components.

  15. Legal Regime of Shale Gas Extraction

    Directory of Open Access Journals (Sweden)

    Ovidiu – Horia Maican

    2013-12-01

    Full Text Available Some countries with large reserves intend to promote shale gas production, in order to reduce their dependency on imported gas. Shale gas will be an important new aspect in the world energy scene, with many effects.European Union wants secure and affordable sources of energy. Natural gas is the cleanest fossil fuel and a vital component of European Union's energy strategy. One of the most important aspects is that gas produces significantly cleaner energy than other fossil fuels.From a legal point of view, extraction of oil and natural gas is one of the most highly-regulated activities.In European Union, the regulation of shale gas activities is different if we compare with United States. United States has a complete framework of federal and state regulation of shale gas extraction. More than that, these regulations have evolved in order to respond to the United States shale gas boom.Legal regime of shale gas extraction in every member state of European Union must put together national and European Union regulations in this field of activity.

  16. Global fishery prospects under contrasting management regimes

    Science.gov (United States)

    Costello, Christopher; Ovando, Daniel; Clavelle, Tyler; Strauss, C. Kent; Hilborn, Ray; Melnychuk, Michael C.; Branch, Trevor A.; Gaines, Steven D.; Szuwalski, Cody S.; Cabral, Reniel B.; Rader, Douglas N.; Leland, Amanda

    2016-01-01

    Data from 4,713 fisheries worldwide, representing 78% of global reported fish catch, are analyzed to estimate the status, trends, and benefits of alternative approaches to recovering depleted fisheries. For each fishery, we estimate current biological status and forecast the impacts of contrasting management regimes on catch, profit, and biomass of fish in the sea. We estimate unique recovery targets and trajectories for each fishery, calculate the year-by-year effects of alternative recovery approaches, and model how alternative institutional reforms affect recovery outcomes. Current status is highly heterogeneous—the median fishery is in poor health (overfished, with further overfishing occurring), although 32% of fisheries are in good biological, although not necessarily economic, condition. Our business-as-usual scenario projects further divergence and continued collapse for many of the world’s fisheries. Applying sound management reforms to global fisheries in our dataset could generate annual increases exceeding 16 million metric tons (MMT) in catch, $53 billion in profit, and 619 MMT in biomass relative to business as usual. We also find that, with appropriate reforms, recovery can happen quickly, with the median fishery taking under 10 y to reach recovery targets. Our results show that commonsense reforms to fishery management would dramatically improve overall fish abundance while increasing food security and profits. PMID:27035953

  17. Exploiting the downhill folding regime via experiment

    Science.gov (United States)

    Muñoz, Victor; Sadqi, Mourad; Naganathan, Athi N.; de Sancho, David

    2008-01-01

    Traditionally, folding experiments have been directed at determining equilibrium and relaxation rate constants of proteins that fold with two-state-like kinetics. More recently, the combination of free energy surface approaches inspired by theory with the discovery of proteins that fold in the downhill regime has greatly widened the battlefield for experimentalists. Downhill folding proteins cross very small or no free energy barrier at all so that all relevant partially folded conformations become experimentally accessible. From these combined efforts we now have tools to estimate the height of thermodynamic and kinetic folding barriers. Procedures to measure with atomic resolution the structural heterogeneity of conformational ensembles at varying unfolding degrees are also available. Moreover, determining the dynamic modes driving folding and how they change as folding proceeds is finally at our fingertips. These developments allow us to address via experiment fundamental questions such as the origin of folding cooperativity, the relationship between structure and stability, or how to engineer folding barriers. Moreover, the level of detail attained in this new breed of experiments should provide powerful benchmarks for computer simulations of folding and force-field refinement. PMID:19436488

  18. Scaling regimes in spherical shell rotating convection

    CERN Document Server

    Gastine, T; Aubert, J

    2016-01-01

    Rayleigh-B\\'enard convection in rotating spherical shells can be considered as a simplified analogue of many astrophysical and geophysical fluid flows. Here, we use three-dimensional direct numerical simulations to study this physical process. We construct a dataset of more than 200 numerical models that cover a broad parameter range with Ekman numbers spanning $3\\times 10^{-7} \\leq E \\leq 10^{-1}$, Rayleigh numbers within the range $10^3 < Ra < 2\\times 10^{10}$ and a Prandtl number unity. We investigate the scaling behaviours of both local (length scales, boundary layers) and global (Nusselt and Reynolds numbers) properties across various physical regimes from onset of rotating convection to weakly-rotating convection. Close to critical, the convective flow is dominated by a triple force balance between viscosity, Coriolis force and buoyancy. For larger supercriticalities, a subset of our numerical data approaches the asymptotic diffusivity-free scaling of rotating convection $Nu\\sim Ra^{3/2}E^{2}$ in ...

  19. Institutional design and regime effectiveness in transboundary river management – the Elbe water quality regime

    Directory of Open Access Journals (Sweden)

    I. Dombrowsky

    2008-02-01

    Full Text Available The literature on transboundary river management suggests that institutions play an important role in bringing about cooperation. However, knowledge about how such institutions should be designed in order to do so remains limited. One way to learn more about adequate institutional design is to assess the effectiveness of existing regimes, and to trace the causal relationships that lead to the respective outcomes. In order to gain further insights into the relationship between institutional design and regime effectiveness, this paper presents a study on the water quality regime of the International Commission for the Protection of the Elbe (ICPE. The analysis is based on a review of pertinent documents and ten qualitative interviews with Czech and German Commission members and NGO representatives. Particular emphasis has been put on determining the ICPE's specific contribution and the no-regime counterfactual as well as on the perceived expediency of the institutional arrangements. The study shows overall that the countries were relatively successful in improving water quality in the Elbe basin. However, this outcome can only partly be attributed to the ICPE itself. Furthermore, the ICPE's contribution towards achieving the various goals varied significantly between the different areas of activity: it was relatively significant where the main responsibility for action lay with the public authorities, such as in the area of wastewater treatment and the establishment of an international alarm plan and model, but was practically non-existent in the reduction of non-point pollution from agriculture, where success depended on the behavior of individual private actors (farmers. The commission contributed towards problem solving by serving as a forum for the joint identification of priorities for action from a basin-wide perspective. The resulting international obligations increased the power of national water administrations and their access to funds

  20. The seismology of geothermal regimes. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Aki, K.

    1997-04-01

    The authors have been developing seismological interpretation theory and methods applicable to complex structures encountered in geothermal areas for a better understanding of the earth`s geothermal regimes. The questions the y have addressed in their research may be summarized as ``What is going on in the earth`s crust under tectonically active regions; what are the structures and processes responsible for such activities as earthquakes and volcanic eruptions; and how can one capture their essence effectively by means of seismological studies?`` First, the authors found clear evidence for localization of scattered seismic energy in the deep magmatic system of the volcano on the island of Reunion in the Indian Ocean. The seismic coda of local earthquakes show concentrated energy in the intrusive zones as late as 30 to 40 seconds after the origin time. This offers a very effective method for defining a zone of strong heterogeneity on a regional scale, complementary to the high resolution study using trapped modes as pursued in the past project. Secondly, the authors identified about 700 long-period events with various frequencies and durations from the data collected during the past 5 years which included three episodes of eruption. They are applying a finite-element method to the simplest event with the longest period and the shortest duration in order to find the location, geometry and physical properties of their source deterministically. The preliminary result described here suggests that their sources may be a horizontally lying magma-filled crack at a shallow depth under the summit area. In addition to the above work on the Reunion data, they have continued the theoretical and observational studies of attenuation and scattering of seismic waves.

  1. CSDP: Seismology of continental thermal regime

    Energy Technology Data Exchange (ETDEWEB)

    Aki, K.

    1989-04-01

    This is a progress report for the past one year of research (year 2 of 5-year project) under the project titled CSDP: Seismology of Continental Thermal Regime'', in which we proposed to develop seismological interpretation theory and methods applicable to complex structures encountered in continental geothermal areas and apply them to several candidate sites for the Continental Scientific Drilling Project. During the past year, two Ph.D. thesis works were completed under the present project. One is a USC thesis on seismic wave propagation in anisotropic media with application to defining fractures in the earth. The other is a MIT thesis on seismic Q and velocity structure for the magma-hydrothermal system of the Valles Caldera, New Mexico. The P.I. co-organized the first International Workshop on Volcanic Seismology at Capri, Italy in October 1988, and presented the keynote paper on the state-of-art of volcanic seismology''. We presented another paper at the workshop on Assorted Seismic Signals from Kilauea Volcano, Hawaii. Another international meeting, namely, the Chapman Conference on seismic anisotropy in the earth's crust at Berkeley, California in May 1988, was co-organized by the co-P.I. (P.C.L), and we presented our work on seismic waves in heterogeneous and anisotropic media. Adding the publications and presentations made in the past year to the list for the preceding year, the following table lists 21 papers published, submitted or presented in the past two years of the present project. 65 refs., 334 figs., 1 tab.

  2. Transition to ballistic regime for heat transport in helium II

    Energy Technology Data Exchange (ETDEWEB)

    Sciacca, Michele, E-mail: michele.sciacca@unipa.it [Dipartimento Scienze Agrarie e Forestali, Università degli studi di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Departament de Física, Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia (Spain); Sellitto, Antonio, E-mail: ant.sellitto@gmail.com [Dipartimento di Matematica, Informatica ed Economia, Università della Basilicata, Campus Macchia Romana, 85100 Potenza (Italy); Jou, David, E-mail: david.jou@uab.cat [Departament de Física, Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia (Spain); Institut d' Estudis Catalans, Carme 47, 08001 Barcelona, Catalonia (Spain)

    2014-07-04

    The size-dependent and flux-dependent effective thermal conductivity of narrow capillaries filled with superfluid helium is analyzed from a thermodynamic continuum perspective. The classical Landau evaluation of the effective thermal conductivity of quiescent superfluid, or the Gorter–Mellinck regime of turbulent superfluids, is extended to describe the transition to ballistic regime in narrow channels wherein the radius R is comparable to (or smaller than) the phonon mean-free path ℓ in superfluid helium. To do so, we start from an extended equation for the heat flux incorporating non-local terms, and take into consideration a heat slip flow along the walls of the tube. This leads from an effective thermal conductivity proportional to R{sup 2} (Landau regime) to another one proportional to Rℓ (ballistic regime). We consider two kinds of flows: along cylindrical pipes and along two infinite parallel plates. - Highlights: • Heat transport in counterflow helium in the ballistic regime. • The one-fluid model based on the Extended Thermodynamics is used. • The transition from the Landau regime to the ballistic regime. • The transition from quantum turbulence to ballistic regime.

  3. Disciplinary Regimes of "Care" and Complementary Alternative Education

    Science.gov (United States)

    Thomson, Pat; Pennacchia, Jodie

    2016-01-01

    In schools, the notion of "care" is often synonymous with welfare and disciplinary regimes. Drawing on Foucault, and a study of alternative education (AE) across the UK, and looking in depth at two cases of complementary AE, we identify three types of disciplinary regimes at work in schools: (1) dominant performative reward and…

  4. European gas market liberalisation: are regulatory regimes moving towards convergence?

    NARCIS (Netherlands)

    Haase, N.

    2008-01-01

    This study has assessed the evolution of regulatory regimes in European gas markets on the basis of panel data from the old member states (EU15) for the period between 2000 and 2005. The methodology used enabled us to assess whether regulatory regimes are converging. In this context, an index has

  5. Spectral classification of coupling regimes in the quantum Rabi model

    Science.gov (United States)

    Rossatto, Daniel Z.; Villas-Bôas, Celso J.; Sanz, Mikel; Solano, Enrique

    2017-07-01

    The quantum Rabi model is in the scientific spotlight due to the recent theoretical and experimental progress. Nevertheless, a full-fledged classification of its coupling regimes remains as a relevant open question. We propose a spectral classification dividing the coupling regimes into three regions based on the validity of perturbative criteria on the quantum Rabi model, which allows us the use of exactly solvable effective Hamiltonians. These coupling regimes are (i) the perturbative ultrastrong coupling regime which comprises the Jaynes-Cummings model, (ii) a region where nonperturbative ultrastrong and nonperturbative deep strong coupling regimes coexist, and (iii) the perturbative deep strong coupling regime. We show that this spectral classification depends not only on the ratio between the coupling strength and the natural frequencies of the unperturbed parts, but also on the energy to which the system can access. These regimes additionally discriminate the completely different behaviors of several static physical properties, namely the total number of excitations, the photon statistics of the field, and the cavity-qubit entanglement. Finally, we explain the dynamical properties which are traditionally associated with the deep strong coupling regime, such as the collapses and revivals of the state population, in the frame of the proposed spectral classification.

  6. Bargaining among Nations: Culture, History, and Perceptions in Regime Formation.

    Science.gov (United States)

    Lipschutz, Ronnie D.

    1991-01-01

    The formation of regimes (collective international schemes) for managing global problems depends on culture, history, and perceptions. The ways in which these elements affect bargaining among nations over issues of the global commons are discussed. Implications are reviewed for a regime to deal with atmospheric conditions and global warming. (SLD)

  7. Welfare regimes and the incentives to work and get educated

    NARCIS (Netherlands)

    Rodriguez-Pose, Andres; Tselios, Vassilis

    This paper examines whether differences in welfare regimes shape the incentives to work and get educated. Using microeconomic data for more than 100 ON European individuals, we show that welfare regimes make a difference for wages and education. First, people-based and household-based effects

  8. Welfare regimes and the incentives to work and get educated

    NARCIS (Netherlands)

    Rodriguez-Pose, Andres; Tselios, Vassilis

    2012-01-01

    This paper examines whether differences in welfare regimes shape the incentives to work and get educated. Using microeconomic data for more than 100 ON European individuals, we show that welfare regimes make a difference for wages and education. First, people-based and household-based effects (inter

  9. Minxin Pei, China's Crony Capitalism: The Dynamics of Regime Decay

    DEFF Research Database (Denmark)

    Brødsgaard, Kjeld Erik

    2017-01-01

    Book review of: Minxin Pei, China's Crony Capitalism: The Dynamics of Regime Decay. Cambridge, Mass.: Harvard University Press, 2016. 365 pp., including references and index. ISBN 9780674737297.......Book review of: Minxin Pei, China's Crony Capitalism: The Dynamics of Regime Decay. Cambridge, Mass.: Harvard University Press, 2016. 365 pp., including references and index. ISBN 9780674737297....

  10. Fasting and 2-Hour Plasma Glucose and Insulin

    Science.gov (United States)

    Libman, Ingrid M.; Barinas-Mitchell, Emma; Bartucci, Andrea; Chaves-Gnecco, Diego; Robertson, Robert; Arslanian, Silva

    2010-01-01

    OBJECTIVE To determine whether elevated fasting or 2-h plasma glucose and/or insulin better reflects the presence of cardiovascular disease (CVD) risk markers in an overweight pediatric population with normal glucose tolerance. RESEARCH DESIGN AND METHODS A total of 151 overweight youths (8–17 years old) were evaluated with oral glucose tolerance tests and measurement of CVD risk factors. The study population was categorized according to quartiles of fasting and 2-h glucose and insulin levels. ANCOVA, adjusted for age, sex, race, Tanner stage, and percent body fat (measured by dual-energy X-ray absorptiometry), was used to compare metabolic variables between the quartiles of glucose and insulin groups. RESULTS Increasing quartiles of fasting and 2-h insulin were associated with increasing CVD risk factors. Glucose quartiles on the other hand, either fasting or at 2 h, were not. CONCLUSIONS These data suggest that hyperinsulinemia may be the earliest and/or primary metabolic alteration in childhood associated with risk markers for CVD. Prospective studies are needed. PMID:21115769

  11. 29 CFR 2530.200b-2 - Hour of service.

    Science.gov (United States)

    2010-07-01

    ... 80 hours of service for his vacation in computation period III (40 hours per week multiplied by 2... would be credited with 80 hours (2 weeks worked multiplied by 40 hours) plus such credit as may be... a payment made or due which is calculated on the basis of units of time, such as hours, days,...

  12. Boundary between Stable and Unstable Regimes of Accretion. Ordered and Chaotic Unstable Regimes

    CERN Document Server

    Blinova, A A; Lovelace, R V E

    2015-01-01

    We search for the boundary between stable and Rayleigh-Taylor unstable regimes of accretion to magnetized stars in a new set of high grid resolution simulations. We found that the boundary between stable and unstable regimes is mainly determined by the ratio of the corotation radius r_cor (where the Keplerian angular velocity in the disc matches the angular velocity of the star) to the magnetospheric radius r_m (where the magnetic stress in the magnetosphere matches the matter stress in the disc). Instability is stronger when r_cor is larger with respect to r_m, that is, when the gravitational force is larger than the centrifugal force at the inner disc. In the cases of a small tilt of the magnetosphere, Theta=5 deg, and a small alpha-parameter of viscosity, alpha=0.02, the boundary is located at r_cor approx. 1.4 r_m. Instability becomes stronger at higher values of viscosity, and occurs at lower values of r_cor/r_m. At higher values of Theta, the variability associated with instability decreases. Simulation...

  13. Construction of recombinant adenoviruses carrying human urokinase-type plasminogen activator and its expression in hepatic stellate cells in vitro%人尿激酶型纤溶酶原激活剂重组腺病毒的构建及其在肝星形细胞中的表达

    Institute of Scientific and Technical Information of China (English)

    谢渭芬; 林勇; 张新; 张忠兵; 陈伟忠; 程志红; 陈岳祥; 张兴荣

    2002-01-01

    @@ 我们利用AdEasy系统在细菌内构建携带非分泌型尿激酶型纤溶酶原激活剂(urokinase-type plasminogen acti-vator,uPA)和绿色荧光蛋白(green fluorescent protein, GFP)cDNA的复制缺陷型腺病毒,并观察其在肝星形细胞(hepatic stellate cell, HSC)中的表达.

  14. No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels

    DEFF Research Database (Denmark)

    Scott, Robert A; Chu, Audrey Y; Grarup, Niels

    2012-01-01

    Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to dete...

  15. Conceptualization of UN Peacekeeping as an International Regime

    Directory of Open Access Journals (Sweden)

    Jana Urbanovská

    2012-12-01

    Full Text Available It is widely recognized that UN peacekeeping operations are an undertheorized topic. In this respect, scholars call to devote more attention to the incorporation of the study of UN peacekeeping operations into the framework of international relations theories. The article responds to these calls and suggests conceptualizing UN peacekeeping as an international regime. Some authors have already referred to UN peacekeeping as an international regime, however, the references have been rather fragmentary and there is no detailed identification of individual dimensions of this regime. The article uses the conception of Stephen Krasner who defines regimes as “principles, norms, rules, and decision-making procedures around which actors’ expectations converge in a given area of international relations” to carefully identify and characterize the dimensions of the UN peacekeeping regime. The conceptualization of UN peacekeeping as an international regime is understood as a first and necessary step to opening new ground to the theoretical study of UN peacekeeping operations within the regime analysis.

  16. Perspectives on the International and Internal Nuclear Security Regime

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Sung Soon [Korea Nuclear Non-proliferation and Control, Daejeon (Korea, Republic of)

    2015-10-15

    The term, 'Nuclear Security' became more familiar to Korean public after the government hosted 2012 Seoul Nuclear Security Summit. Nuclear Security is prevention of, detection of and response to criminal or intentional unauthorized acts involving or directed at nuclear material, other radioactive material, associated facilities, or associated activities. Nuclear Security includes physical protection, security of radioactive sources, nuclear forensics, nuclear smuggling prevention, border monitoring, and cyber security with regard to nuclear and other radiological materials. This abstract will review recent international trends and discuss the nuclear security regime in the Republic of Korea (ROK). The international Nuclear Security Regime has been strengthened. The upcoming Chicago Summit in 2016 and the entry into force of the Amendment of Convention on Physical Protection of Nuclear Materials (CPPNM) will bring major changes in nuclear security. The Republic of Korea hosted the 2012 Seoul Summit and strengthened domestic regime to meet international standards. The ROK has worked hard to contribute to the international security regime and to establish a robust domestic security regime against terrorist threats. Even if the nuclear security regime is robust, Risk-informed Nuclear Security management should be established to meet international standards and to implement effective as well as an efficient nuclear security regime.

  17. [Heath and political regimes: presidential or parliamentary government for Colombia?].

    Science.gov (United States)

    Idrovo, Alvaro J

    2007-01-01

    Changing the presidential regime for a parliamentarian one is currently be-ing discussed in Colombia. This preliminary study explores the potential effects on health of both presidential and parliamentary regimes by using world-wide data. An ecological study was undertaken using countries from which comparable information concerning life-expectancy at birth, political regime, economic development, inequality in income, social capital (as measured by general-ised trust or Corruption Perceptions Index), political rights, civil freedom and cultural diversity could be obtained. Life-expectancy at birth and macro-determinants were compared between both political regimes. The co-relationship between these macro-determinants was estimated and the relationship between political regimen and life-expectancy at birth was estimated using robust regression. Crude analysis revealed that parliamentary countries have greater life-expectancy at birth than countries having a presidential regime. Significant co-relationships between all macro-determinants were observed. No differential effects were observed between both political regimes regarding life-expectancy at birth in multiple robust regressions. There is no evidence that presidential or parliamentary regimes provide greater levels of health for the population. It is suggested that public health policies be focused on other macro-determinants having more known effects on health, such as income inequality.

  18. Marine regime shifts: drivers and impacts on ecosystems services

    Science.gov (United States)

    Rocha, J.; Yletyinen, J.; Biggs, R.; Blenckner, T.; Peterson, G.

    2015-01-01

    Marine ecosystems can experience regime shifts, in which they shift from being organized around one set of mutually reinforcing structures and processes to another. Anthropogenic global change has broadly increased a wide variety of processes that can drive regime shifts. To assess the vulnerability of marine ecosystems to such shifts and their potential consequences, we reviewed the scientific literature for 13 types of marine regime shifts and used networks to conduct an analysis of co-occurrence of drivers and ecosystem service impacts. We found that regime shifts are caused by multiple drivers and have multiple consequences that co-occur in a non-random pattern. Drivers related to food production, climate change and coastal development are the most common co-occurring causes of regime shifts, while cultural services, biodiversity and primary production are the most common cluster of ecosystem services affected. These clusters prioritize sets of drivers for management and highlight the need for coordinated actions across multiple drivers and scales to reduce the risk of marine regime shifts. Managerial strategies are likely to fail if they only address well-understood or data-rich variables, and international cooperation and polycentric institutions will be critical to implement and coordinate action across the scales at which different drivers operate. By better understanding these underlying patterns, we hope to inform the development of managerial strategies to reduce the risk of high-impact marine regime shifts, especially for areas of the world where data are not available or monitoring programmes are not in place.

  19. 尿激酶对家兔心肺复苏后脑神经细胞凋亡的影响%Influence of urokinase on nerve cell apoptosis after cardiopulmonary resuscitation in rabbits

    Institute of Scientific and Technical Information of China (English)

    郭晓东; 张巍; 郭静; 苏清明; 杨贵荣; 张杰; 孙鲲; 王立祥

    2015-01-01

    Objective To investigate the effect of urokinase on nerve cell apoptosis after cardiac arrest ( CA) and cardiopulmo-nary resuscitation(CPR)in rabbits.Methods 20 rabbits were randomly divided into experimental group and control group , 10 rabbits in each group .Potassium chloride injection combined with asphyxia method was conducted to establish the CA models .CPR and basic life-support were performed in experimental group .Based on above treatments , intervention with urokinase (20 000 U/kg) was con-ducted in experimental group .Neural apoptosis was identified by TUNEL and caspase-3 was detected by immunohistochemistry in order to prove the effect of urokinase on nerve cell apoptosis in rabbits 24 hours after CPR.Results Tunel and caspase-3 positive cells counts of cerebral cortex and hippocampus in experimental group were significantly less than those in control group , respectively .The comparisons were as follows(Tunel positive cells in cerebral cortex 29.22 ±7.86:37.20 ±7.04(t=-2.392,P=0.028), in hippo-campus 18.80 ±7.58:27.4 ±8.15(t=-2.442,P=0.025), Caspase-3 positive cells in cerebral cortex 22.1 ±9.93:33.1 ±12.64 (t=-2.165,P=0.044),in hippocampus 31.3 ±15.23 vs 46.8 ±16.73(t=-2.167,P=0.044);so thrombolytic therapy with u-rokinase can relieve nerve cell apoptosis obviously .Comparison of spontaneous circulation restoration time (s) 307.9 ±96.4:242.0 ± 71.0(t=-1.741, P=0.099), spontaneous breathing restoration time (min) 20.6 ±12.5:19.3 ±10.0 (t=-0.256, P=0.801), mean arterial pressure MAP (mmHg) 65.5 ±6.2:69.0 ±6.7 (t=1.217, P=0.239), there were no differences between the experi-mental group and control group .Conclusions Thrombolytic therapy with urokinase in CPR after CA can improve and lessen nervous lesion resulting from apoptosis in rabbits .%目的 探讨心搏骤停心肺复苏后溶栓药物尿激酶对脑神经细胞凋亡的影响. 方法 20只家兔按随机数字表法被分为溶栓组和常规复苏组,每组10只. 采用氯化钾

  20. Considerations on nonproliferation regime meeting in a changing world

    Energy Technology Data Exchange (ETDEWEB)

    Kurihara, Hiroyoshi; Kikuchi, Masahiro [Nuclear Material Control Center, Tokyo (Japan)

    1994-12-31

    This paper summarizes the past history of worldwide nonproliferation regime, then proposes the future improvements on the regime. Present worldwide nonproliferation regime have been formulated during the cold war era. Therefore, the structure and measures of the regime were heavily influenced by the features of cold war era. Though the cold war was over, still new international order does not seem to be on the horizon, we need to review the present regime and to improve the regime compatible to new world situation. Generally speaking, the nonproliferation regime have gained moderate success so far. We could point out the following features as a kind of success: (1) No increase of overt Nuclear Weapon State (NWS), (2) All five NWSs have finally participated to the NPT, (3) South Africa has destroyed its nuclear weapons and became Non-Nuclear Weapon State (NNWS), (4) Successful conclusions of some regional arrangements, such as Tlatelolco, Ralotonga, and (5) Strengthening of export control on sensitive items. On the other hand, we recognize the following points as the failures of the regime. (6) India, Pakistan and Israel reject to join the NPT, (7) Existence of some violation against NPT regime, i.e. Iraqi case and DPRK case, (8) Insufficient effective measures against brain drain problem, (9) Risk exists for the long term extension of NPT, and (10) Insufficient flexibility to meet changing boundary conditions. We would propose the various measures for strengthening to meet changing boundary conditions, as follows: (11) Measures to be taken along with future civil use of Plutonium, (12) Strengthening and rationalizing international safeguards, (13) Countermeasures for emerging new types of nuclear proliferation, (14) Strengthening nuclear material control in NWS, (15) Measures to be taken for nuclear material from dismantled nuclear weapons, and (16) Nuclear disarmament. (author).

  1. Diversity-Multiplexing Tradeoff in the Low-SNR Regime

    CERN Document Server

    Loyka, Sergey

    2011-01-01

    An extension of the popular diversity-multiplexing tradeoff framework to the low-SNR (or wideband) regime is proposed. The concept of diversity gain is shown to be redundant in this regime since the outage probability is SNR-independent and depends on the multiplexing gain and the channel power gain statistics only. The outage probability under the DMT framework is obtained in an explicit, closed form for a broad class of channels. The low and high-SNR regime boundaries are explicitly determined for the scalar Rayleigh-fading channel, indicating a significant limitation of the SNR-asymptotic DMT when the multiplexing gain is small.

  2. Raman amplification in the broken-wave regime

    CERN Document Server

    Farmer, John P

    2015-01-01

    In regimes far beyond the wavebreaking theshold of Raman amplification, we show that significant amplifcation can occur after the onset of wavebreaking, before phase mixing destroys the coupling between pump and probe. The amplification efficiency in this regime is therefore strongly dependent on the energy-transfer rate when wavebreaking occurs, and is, as such, sensitive to both the probe amplitude and profile. In order to access the higher-efficiency broken-wave regime, a short, intense probe is required. Parameter scans show the marked difference in behaviour compared to below wavebreaking, where longer, more energetic pulses lead to improved efficiencies.

  3. A thermodynamic view of heat transfer in different transport regimes

    Science.gov (United States)

    Schubler, Gulru Babac

    2016-11-01

    The nature of the heat transfer process changes substantially according to transport regime. A thermodynamic view to micro/nano scale flows is considered to get a better understanding within this regime dependent change. The transport processes are expressed as a polytropic process and T-s diagram of different transport regimes are presented. In addition, a molecular dynamic simulation of nano channel flows is presented. Since the polytropic processes are strongly related with the heat capacities, the heat capacity calculations are also taken into account in MD simulations. The theoretical predictions are approved with the molecular dynamic simulations for monatomic gases.

  4. Policy Ideas, Knowledge Regimes and Comparative Political Economy

    DEFF Research Database (Denmark)

    Campbell, John L.; Pedersen, Ove K.

    2015-01-01

    Despite much attention to how ideas affect policy making, where these ideas come from is a blind spot in comparative political economy. We show that an important source of policy ideas are knowledge regimes—fields of policy research organizations. We show as well that the organization of knowledge......, France and Germany. Theoretical implications are explored for two literatures in comparative political economy: ideational analysis and the varieties of capitalism....... regimes is heavily influenced by the organization of their surrounding political economies such that knowledge regimes have particular national characters. Furthermore, when people perceive that the utility of their knowledge regime for the rest of the political economy breaks down, they often try...

  5. Boundary between stable and unstable regimes of accretion. Ordered and chaotic unstable regimes

    Science.gov (United States)

    Blinova, A. A.; Romanova, M. M.; Lovelace, R. V. E.

    2016-07-01

    We present a new study of the Rayleigh-Taylor unstable regime of accretion on to rotating magnetized stars in a set of high grid resolution three-dimensional magnetohydrodynamic simulations performed in low-viscosity discs. We find that the boundary between the stable and unstable regimes is determined almost entirely by the fastness parameter ωs = Ω⋆/ΩK(rm), where Ω⋆ is the angular velocity of the star and ΩK(rm) is the angular velocity of the Keplerian disc at the disc-magnetosphere boundary r = rm. We found that accretion is unstable if ωs ≲ 0.6. Accretion through instabilities is present in stars with different magnetospheric sizes. However, only in stars with relatively small magnetospheres, rm/R⋆ ≲ 7, do the unstable tongues produce chaotic hotspots on the stellar surface and irregular light curves. At even smaller values of the fastness parameter, ωs ≲ 0.45, multiple irregular tongues merge, forming one or two ordered unstable tongues that rotate with the angular frequency of the inner disc. This transition occurs in stars with even smaller magnetospheres, rm/R⋆ ≲ 4.2. Most of our simulations were performed at a small tilt of the dipole magnetosphere, Θ = 5°, and a small viscosity parameter α = 0.02. Test simulations at higher α values show that many more cases become unstable, and the light curves become even more irregular. Test simulations at larger tilts of the dipole Θ show that instability is present, however, accretion in two funnel streams dominates if Θ ≳ 15°. The results of these simulations can be applied to accreting magnetized stars with relatively small magnetospheres: Classical T Tauri stars, accreting millisecond X-ray pulsars, and cataclysmic variables.

  6. Analysis of light regime in continuous light distributions in photobioreactors.

    Science.gov (United States)

    Brindley, Celeste; Fernández, F G Acién; Fernández-Sevilla, J M

    2011-02-01

    Maximum photobioreactor (PBR) efficiency is a must in applications such as the obtention of microalgae-derived fuels. Improving PBR performance requires a better understanding of the "light regime", the varying irradiance that microalgal cells moving in a dense culture are exposed to. We propose a definition of light regime that can be used consistently to describe the continuously varying light patterns in PBRs as well as in light/dark cycles. Equivalent continuous and light/dark regimes have been experimentally compared and the results show that continuous variations are not well represented by light/dark cycles, as had been widely accepted. It has been shown that a correct light regime allows obtaining photosynthetic rates higher than the corresponding to continuous light, the so-called "flashing light effect" and that this is possible in commercial PBRs. A correct PBR operation could result in photosynthetic efficiency close to the optimum eight quanta per O(2).

  7. Regime-Switching Risk: To Price or Not to Price?

    Directory of Open Access Journals (Sweden)

    Tak Kuen Siu

    2011-01-01

    “normative” issues to be addressed in pricing contingent claims under a Markovian, regime-switching, Black-Scholes-Merton model. We address this issue using a minimal relative entropy approach. Firstly, we apply a martingale representation for a double martingale to characterize the canonical space of equivalent martingale measures which may be viewed as the largest space of equivalent martingale measures to incorporate both the diffusion risk and the regime-switching risk. Then we show that an optimal equivalent martingale measure over the canonical space selected by minimizing the relative entropy between an equivalent martingale measure and the real-world probability measure does not price the regime-switching risk. The optimal measure also justifies the use of the Esscher transform for option valuation in the regime-switching market.

  8. Nonequilibrium electron transport through quantum dots in the Kondo regime

    DEFF Research Database (Denmark)

    Wölfle, Peter; Paaske, Jens; Rosch, Achim

    2005-01-01

    Electron transport at large bias voltage through quantum dots in the Kondo regime is described within the perturbative renormalization group extended to nonequilibrium. The conductance, local magnetization, dynamical spin susceptibility and local spectral function are calculated. We show how the ...

  9. Evolution of human-driven fire regimes in Africa

    CSIR Research Space (South Africa)

    Archibald, S

    2012-01-01

    Full Text Available Human ability to manipulate fire and the landscape has increased over evolutionary time, but the impact of this on fire regimes and consequences for biodiversity and biogeochemistry are hotly debated. Reconstructing historical changes in human...

  10. A new regime for future telecommunication network operations

    NARCIS (Netherlands)

    Gustafsson, S.; Trommelen, P.H.; Vos, C. de

    2010-01-01

    The increasingly crucial role that telecommunications plays in today's information society calls for a new regime for telecommunication network operations. An unbundling of business roles and associated responsibilities is proposed, providing more economic network operations and higher availability

  11. The organization of global negotiations: constructing the climate change regime

    National Research Council Canada - National Science Library

    Depledge, Joanna

    2005-01-01

    "Using a theatrical metaphor, this book describes the enormous and skilful organization required by the UN to create an effective international regime, producing the UN Framework Convention on Climate...

  12. Determination of three characteristic regimes of weakly charged polyelectrolytes monolayers

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Farhan [Department of Materials Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Shin, Kwanwoo [Department of Chemistry and Interdisciplinary Program of Integrated Biotechnology, Sogang University, Seoul 121-742 (Korea, Republic of)], E-mail: kshin@sogang.ac.kr; Choi, Jae-Hak [Advanced Radiation Technology Institute, KAERI, Jeongeup 580-185 (Korea, Republic of); Satija, Sushil K. [National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Kim, Joon-Seop [Department of Polymer Science and Engineering, Chosun University (Korea, Republic of); Rafailovich, Miriam H.; Sokolov, Jon [Department of Materials Science and Engineering, Stony Brook University, Stony Brook, NY 11794 (United States)

    2008-09-15

    We have demonstrated that monolayer films of randomly charged polystyrene sulfonated acid (PSSA) can be produced by the Langmuir technique, and observed the micro-domain structures, produced by the phase separation of electrostatically charged moieties and the hydrophobic moieties. Using atomic force microscopy and Langmuir isotherm, we found three specific regimes for the polyelectrolytes with various degrees of sulfonation (4-35%); very low charged PSSA (4-5%) in the hydrophobic regime, moderately charged PSSA (6-16%) which possessed a well-balanced nature between electrostatic and the hydrophobic interactions, and strongly amphiphilic nature of PSSA (6-16%) in the ionomer regime. Finally, we could categorize PSSA 35% in the polyelectrolyte regime, due to the dominance of the electrostatic interactions over the hydrophobic interactions.

  13. Regime change and oscillation thresholds in recorder-like instruments.

    Science.gov (United States)

    Auvray, Roman; Fabre, Benoît; Lagrée, Pierre-Yves

    2012-02-01

    Based on results from the literature, a description of sound generation in a recorder is developed. Linear and non-linear analysis are performed to study the dependence of the frequency on the jet velocity. The linear analysis predicts that the frequency is a function of the jet velocity. The non-linear resolution provides information about limit cycle oscillation and hysteretic regime change thresholds. A comparison of the frequency between linear theory and experiments on a modified recorder shows good agreement except at very low jet velocities. Although the predicted threshold for the onset of the first regime shows an important deviation from experiments, the hysteresis of threshold to higher regimes is accurately estimated. Furthermore, a qualitative analysis of the influence of different parameters in the model on the sound generation and regime changes is presented.

  14. Crossflow and water banks in viscous dominant regimes of waterflooding

    DEFF Research Database (Denmark)

    Yuan, Hao; Zhang, Xuan; Shapiro, Alexander

    2014-01-01

    Understanding the crossflow in multilayered reservoirs is of great importance for designing mobility control methods for enhanced oil recovery. The authors reveal saturation profiles in stratified reservoirs to study the interlayer communication in the viscous dominant regime. The displacement...

  15. Regime shifts and resilience in China's coastal ecosystems.

    Science.gov (United States)

    Zhang, Ke

    2016-02-01

    Regime shift often results in large, abrupt, and persistent changes in the provision of ecosystem services and can therefore have significant impacts on human wellbeing. Understanding regime shifts has profound implications for ecosystem recovery and management. China's coastal ecosystems have experienced substantial deterioration within the past decades, at a scale and speed the world has never seen before. Yet, information about this coastal ecosystem change from a dynamics perspective is quite limited. In this review, I synthesize existing information on coastal ecosystem regime shifts in China and discuss their interactions and cascading effects. The accumulation of regime shifts in China's coastal ecosystems suggests that the desired system resilience has been profoundly eroded, increasing the potential of abrupt shifts to undesirable states at a larger scale, especially given multiple escalating pressures. Policy and management strategies need to incorporate resilience approaches in order to cope with future challenges and avoid major losses in China's coastal ecosystem services.

  16. Shock-Induced Flows through Packed Beds: Transient Regimes

    CERN Document Server

    Shtemler, Yuri M; Britan, Alex

    2006-01-01

    The early stage of the transient regimes in the shock-induced flows within solid-packed beds are investigated in the linear longwave and high-frequency approximation. The transient resistance law is refined as the Duhameltime integral that follows from the general concept of dynamic tortuosity and compressibility of the packed beds. A closed-form solution is expected to describe accurately the early stage of the transient regime flow and is in qualitative agreement with available experimental data.

  17. Ignition Regime for Fusion in a Degenerate Plasma

    Energy Technology Data Exchange (ETDEWEB)

    Son, S.; Fisch, N.J.

    2005-12-01

    We identify relevant parameter regimes in which aneutronic fuels can undergo fusion ignition in hot-ion degenerate plasma. Because of relativistic effects and partial degeneracy, the self-sustained burning regime is considerably larger than previously calculated. Inverse bremsstrahlung plays a major role in containing the reactor energy. We solve the radiation transfer equation and obtain the contribution to the heat conductivity from inverse bremsstrahlung.

  18. Observation of Modulation Transfer Spectroscopy in the Deep Modulation Regime

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zi-Chao; WEI Rong; SHI Chun-Yan; WANG Yu-Zhu

    2010-01-01

    @@ We observe the modulation transfer spectroscopy on the D2 line of87 Rb in a rubidium cell with acoustic-optic modulator in the deep modulation regime.In this regime,the sidebands of the pump beam are involved in the four-wave mixing processes,which increase the signM gradients and the peak-to-peak amplitudes of both the absorption and dispersion components.

  19. Peaceful Protest, Political Regimes, and the Social Media Challenge

    Science.gov (United States)

    2016-06-01

    asserts democracies must meet the following conditions to fulfill the democratic promises; empowerment of its citizens, free supply, free demand...techniques, such as its “Great Firewall” and government-employed Internet police, to filter Internet users ’ content. China’s restrictions...peaceful protest as its social media user rates rise. Anocratic regimes, or intermediate regimes, display both democratic and authoritarian

  20. International regime formation: Ozone depletion and global climate change

    Energy Technology Data Exchange (ETDEWEB)

    Busmann, N.E.

    1994-03-01

    Two theoretical perspectives, neorealism and neoliberal institutionalism, dominate in international relations. An assessment is made of whether these perspectives provide compelling explanations of why a regime with specific targets and timetables was formed for ozone depletion, while a regime with such specificity was not formed for global climate change. In so doing, the assumptions underlying neorealism and neoliberal institutionalism are examined. A preliminary assessment is offered of the policymaking and institutional bargaining process. Patterns of interstate behavior are evolving toward broader forms of cooperation, at least with regard to global environmental issues, although this process is both slow and cautious. State coalitions on specific issues are not yet powerful enough to create a strong community of states in which states are willing to devolve power to international institutions. It is shown that regime analysis is a useful analytic framework, but it should not be mistaken for theory. Regime analysis provides an organizational framework offering a set of questions regarding the principles and norms that govern cooperation and conflict in an issue area, and whether forces independent of states exist which affect the scope of state behavior. An examination of both neorealism and neoliberal institutionalism, embodied by four approaches to regime formation, demonstrates that neither has sufficient scope to account for contextual dynamics in either the ozone depletion or global climate change regime formation processes. 261 refs.

  1. Do family policy regimes matter for children's well-being?

    Science.gov (United States)

    Engster, Daniel; Stensöta, Helena Olofsdotter

    2011-01-01

    Researchers have studied the impact of different welfare state regimes, and particularly family policy regimes, on gender equality. Very little research has been conducted, however, on the association between different family policy regimes and children's well-being. This article explores how the different family policy regimes of twenty OECD countries relate to children's well-being in the areas of child poverty, child mortality, and educational attainment and achievement. We focus specifically on three family policies: family cash and tax benefits, paid parenting leaves, and public child care support. Using panel data for the years 1995, 2000, and 2005, we test the association between these policies and child well-being while holding constant for a number of structural and policy variables. Our analysis shows that the dual-earner regimes, combining high levels of support for paid parenting leaves and public child care, are strongly associated with low levels of child poverty and child mortality. We find little long-term effect of family policies on educational achievement, but a significant positive correlation between high family policy support and higher educational attainment. We conclude that family policies have a significant impact on improving children's well-being, and that dual-earner regimes represent the best practice for promoting children's health and development.

  2. Oscillations of a highly discrete breather with a critical regime

    Science.gov (United States)

    Coquet; Remoissenet; Dinda

    2000-10-01

    We analyze carefully the essential features of the dynamics of a stationary discrete breather in the ultimate degree of energy localization in a nonlinear Klein-Gordon lattice with an on-site double-well potential. We demonstrate the existence of three different regimes of oscillatory motion in the breather dynamics, which are closely related to the motion of the central particle in an effective potential having two nondegenerate wells. In given parameter regions, we observe an untrapped regime, in which the central particle executes large-amplitude oscillations from one to the other side of the potential barrier. In other parameter regions, we find the trapped regime, in which the central particle oscillates in one of the two wells of the effective potential. Between these two regimes we find a critical regime in which the central particle undergoes several temporary trappings within an untrapped regime. Importantly, our study reveals that in the presence of purely anharmonic coupling forces, the breather compactifies, i.e., the energy becomes abruptly localized within the breather.

  3. Sensitivity of streamflows to hydroclimatic fluctuations: resilience and regime shifts

    Science.gov (United States)

    Botter, Gianluca; Basso, Stefano; Rodriguez-Iturbe, Ignacio; Rinaldo, Andrea

    2016-04-01

    Landscape and climate alterations foreshadow global-scale shifts of river flow regimes. However, a theory that identifies the range of foreseen impacts on streamflows resulting from inhomogeneous forcings and sensitivity gradients across diverse regimes is lacking. In this contribution, we use a dimensionless index embedding simple climate and landscape attributes (the ratio of the mean interarrival of streamflow-producing rainfall events and the mean catchment response time) to discriminate erratic regimes with enhanced intra-seasonal streamflow variability from persistent regimes endowed with regular flow patterns. The proposed classification is successfully applied to 110 seasonal streamflow distributions observed in 44 catchments of the Alps and the United States, allowing the identification of emerging patterns in space and time. In the same framework, the impact of multi-scale fluctuations of the underlying climatic drivers (temperature, precipitation) on the streamflow distributions can be analyzed. Theoretical and empirical data show that erratic regimes, typical of rivers with low mean discharges, are highly resilient in that they hold a reduced sensitivity to variations in the external forcing. Specific temporal trajectories of streamflow distributions and flow regime shifts driven by land-cover change and rainfall patterns can be also evidenced. The approach developed offers an objective basis for the analysis and prediction of the impact of climate/landscape change on water resources.

  4. O-regime dynamics and modeling in Tore Supra

    Science.gov (United States)

    Turco, F.; Giruzzi, G.; Imbeaux, F.; Udintsev, V. S.; Artaud, J. F.; Barana, O.; Dumont, R.; Mazon, D.; Ségui, J.-L.

    2009-06-01

    The regime of nonlinear temperature oscillations (O-regime), characteristic of noninductive discharges on Tore Supra [Équipe Tore Supra, Proceedings of the 12th International Conference on Plasma Physics and Controlled Nuclear Fusion Research, Nice, France, 1988 (International Atomic Energy Agency, Vienna, 1989), Vol. 1, p. 9], is investigated in its triggering and suppressing mechanism. This regime can be described by two nonlinearly coupled equations for the current density j(r ) and the electron temperature Te(r) where the equation coefficients are functions of j and Te themselves. Both the integrated modeling code CRONOS [V. Basiuk et al., Nucl. Fusion 43, 822 (2003)] and a two-patch predator-prey system with diffusion and noise have been used and results have been compared to the experimental observations of the O-regime. A database of discharges is analyzed which features monotonic, flat, and reversed safety factor (q) profiles in order to characterize the action of external actuators on the regime dynamics with the widest generality. Electron cyclotron current drive and neutral beam injections have been used in order to induce localized perturbations in the total current profile j(r ) as well as to change the plasma confinement conditions in the central region. Magnetic shear perturbations and modifications of the heat transport turn out to be the central parameters governing the dynamics of the O-regime.

  5. Exchange Rate Regimes – A periodical overview and a critical analysis of exchange rate regimes in Kosovo

    OpenAIRE

    Flamur Bunjaku

    2015-01-01

    Exchange rate regimes and the monetary policy are the key instruments governments use to achieve their economic and financial objectives. Moreover, due to global financial crisis the latter instruments get more importance. Empirical evidences show that exchange rate regimes in Kosovo and its monetary policy throughout their development were mainly influenced by different political and historical developments. In regard of Euroisation of monetary system in Kosovo it was found that this action ...

  6. The Fall of the Vanishing Interim Regime Hypothesis: Towards a New Paradigm of the Choice of the Exchange Rate Regimes

    OpenAIRE

    Michal Jurek

    2010-01-01

    This paper verifies strong and weak versions of the vanishing interim regime hypothesis (so-called bipolar view). It is shown herein that the strong as well as weak version of this hypothesis can be discredited. Empirical observations support the bipolar view only for the advanced countries, but not for emerging and developing ones. On the contrary – the number of interim regimes, used by emerging and developing countries more than doubled in the 1999–2008 period. Results of the logistic regr...

  7. Control of Chaotic Regimes in Encryption Algorithm Based on Dynamic Chaos

    OpenAIRE

    Sidorenko, V.; Mulyarchik, K. S.

    2013-01-01

    Chaotic regime of a dynamic system is a necessary condition determining cryptographic security of an encryption algorithm. A chaotic dynamic regime control method is proposed which uses parameters of nonlinear dynamics regime for an analysis of encrypted data.

  8. 全身炎症反应综合征患者血浆尿激酶型纤溶酶原激活物及其特异性受体动态变化的研究%Dynamic changes in plasma levels of urokinase type plasminogen activator and urokinase type plasminogen activator receptor in patients with systemic inflammatory response syndrome

    Institute of Scientific and Technical Information of China (English)

    武晓灵; 喻莉; 龙鼎; 杨军辉; 张远超; 耿峰

    2011-01-01

    目的 观察全身炎症反应综合征(SIRS)患者血浆尿激酶型纤溶酶原激活物(uPA)及其特异性受体(uPAR)的动态变化以及对预后的影响.方法 采用前瞻性病例对照研究设计方法,将85例住院患者按SIRS诊断标准分为SIRS组(50例)和非SlRS组(35例);SIRS组再按病情分为单纯SIRS组(26例)和合并多器官功能障碍综合征(MODS)组(24例),按预后分为生存组(35例)和死亡组(15例);另选择同期30例健康体检者作为对照.非SIRS组于入院当日,SIRS组于发生SIRS后的1、3、5、7 d,健康对照组于体检时采集空腹静脉血2 ml,用双抗体夹心酶联免疫吸附法(ELISA)测定血浆uPA和uPAR含量,并分析SIRS患者血浆uPAR含量与急性生理学与慢性健康状况评分系统I(APACHE I)评分的相关性.结果 单纯SIRS组、合并MODS组患者血浆uPA和uPAR含量均较非SIRS组和健康对照组显著升高[uPA(μg/L):1.208±0.264、1.120±0.276比0.744±0.190、0.782±0.257;uPAR(μg/L):3.704±1.018、4.970±1.284比1.892±0.476、1.823±0.797,均P<0.01],且合并MODS组uPAR含量明显高于单纯SIRS组(P<0.01).与生存组比较,死亡组5 d、7 d血浆uPA含量(μg/L)明显升高(5 d:1.177±0.185比0.856±0.223,7 d:1.377±0.185比0.836±0.223,均P<0.01),1、3、5、7 d血浆uPAR含量(μg/L)显著增高(1 d:5.301±1.410比3.888±1.015,3 d:4.017±0.898比2.994±0.638,5 d:5.032±1.238比2.536±1.017,7 d:5.232±1.238比3.536±1.017,均P<0.01).SIRS患者血浆uPAR含量与APACHE I评分呈显著正相关(r=0.640,P<0.O1).结论 SIRS患者存在凝血功能障碍,血浆uPA、uPAR含量显著增高,uPAR含量的升高提示预后不良.%Objective To study the dynamic changes in plasma levels of urokinase type plasminogen activator (uPA) and urokinase type plasminogen activator receptor (uPAR) and their influence on prognosis in patients with systemic inflammatory response syndrome (SIRS). Methods In this study, a prospective clinical case-control study was

  9. Study on Effect of Shenmai Injection Protecting Myocardium against Ischemia-Reperfusion Injury in Thrombolytic Therapy with Urokinase for Acute Myocardial Infarction Patient Evaluated by 99mTc-MIBI Myocardial Imaging

    Institute of Scientific and Technical Information of China (English)

    郭松鹏; 张言镇

    2001-01-01

    Objective: To evaluate the myocardial protecting effect of Shenmai injection (SMI) against ischemia/reperfusion injury in thrombolytic therapy with urokinase (UK) for acute myocardial infarction patients by 99mTc-MIBI myocardial imaging (SPECT). Methods: Five hundred and thirty-seven patients were divided into two groups randomly. The SMI group (n=292) was treated with thrombolytictreatment plus SMI and the control group (n=245) with thrombolytic treatment solely. Single photon emission computed tomography (SPECT) was carried out on the 7th day after thrombolysis to determine the ischemic myocardial area (IMA) and ejection fraction (EF) in both groups and compared. Results: The infarction related area (IRA) of reperfusion rate in the two groups was not different significantly (72.26% vs 72.65%, P >0.05). The IMA in patients of the SMI group, no matter with or without reperfused IRA (211 cases and 81 cases) respectively, was significantly lower than that in the control group (178 cases and 67 cases) respectively, P<0.01 and P<0.05 respectively. The EF value in the SMI group was significantly higher than that in the control group (P<0.01). Conclusion:Using SMI in early stage of thrombolytic treatment in acute myocardial infarction could significantly reduce IMA and increase EF. SMI showed good protective effect against myocardial ischemia/reperfusion injury in thrombolytic treatment.

  10. Study on Effect of Shenmai Injection Protecting Myocardium against Ischemia-Reperfusion Injury in Thrombolytic Therapy with Urokinase for Acute Myocardial Infarction Patient Evaluated by 99mTc-MIBI Myocardial Imaging

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To evaluate the myocardial protecting effect of Shenmai injection (SMI) against ischemia/reperfusion injury in thrombolytic therapy with urokinase (UK) for acute myocardial infarction patients by 99mTc-MIBI myocardial imaging (SPECT). Methods: Five hundred and thirty-seven patients were divided into two groups randomly. The SMI group (n=292) was treated with thrombolytictreatment plus SMI and the control group (n=245) with thrombolytic treatment solely. Single photon emission computed tomography (SPECT) was carried out on the 7th day after thrombolysis to determine the ischemic myocardial area (IMA) and ejection fraction (EF) in both groups and compared. Results: The infarction related area (IRA) of reperfusion rate in the two groups was not different significantly (72.26% vs 72.65%, P >0.05). The IMA in patients of the SMI group, no matter with or without reperfused IRA (211 cases and 81 cases) respectively, was significantly lower than that in the control group (178 cases and 67 cases) respectively, P<0.01 and P<0.05 respectively. The EF value in the SMI group was significantly higher than that in the control group (P<0.01). Conclusion:Using SMI in early stage of thrombolytic treatment in acute myocardial infarction could significantly reduce IMA and increase EF. SMI showed good protective effect against myocardial ischemia/reperfusion injury in thrombolytic treatment.

  11. Stochastic Parametrisations and Regime Behaviour of Atmospheric Models

    Science.gov (United States)

    Arnold, Hannah; Moroz, Irene; Palmer, Tim

    2013-04-01

    The presence of regimes is a characteristic of non-linear, chaotic systems (Lorenz, 2006). In the atmosphere, regimes emerge as familiar circulation patterns such as the El-Nino Southern Oscillation (ENSO), the North Atlantic Oscillation (NAO) and Scandinavian Blocking events. In recent years there has been much interest in the problem of identifying and studying atmospheric regimes (Solomon et al, 2007). In particular, how do these regimes respond to an external forcing such as anthropogenic greenhouse gas emissions? The importance of regimes in observed trends over the past 50-100 years indicates that in order to predict anthropogenic climate change, our climate models must be able to represent accurately natural circulation regimes, their statistics and variability. It is well established that representing model uncertainty as well as initial condition uncertainty is important for reliable weather forecasts (Palmer, 2001). In particular, stochastic parametrisation schemes have been shown to improve the skill of weather forecast models (e.g. Berner et al., 2009; Frenkel et al., 2012; Palmer et al., 2009). It is possible that including stochastic physics as a representation of model uncertainty could also be beneficial in climate modelling, enabling the simulator to explore larger regions of the climate attractor including other flow regimes. An alternative representation of model uncertainty is a perturbed parameter scheme, whereby physical parameters in subgrid parametrisation schemes are perturbed about their optimal value. Perturbing parameters gives a greater control over the ensemble than multi-model or multiparametrisation ensembles, and has been used as a representation of model uncertainty in climate prediction (Stainforth et al., 2005; Rougier et al., 2009). We investigate the effect of including representations of model uncertainty on the regime behaviour of a simulator. A simple chaotic model of the atmosphere, the Lorenz '96 system, is used to study

  12. How Welfare Regimes Generate and Erode Social Capital

    DEFF Research Database (Denmark)

    Larsen, Christian Albrekt

    2007-01-01

    Comparative studies of social capital, operationalised as social trust between citizens, have revealed two major puzzles. The first puzzle has to do with the decline in social trust in the USA, which fuelled considerable debate about social capital. The question is why social capital erodes in th...... with the presence or absence of a poor and culturally distinct underclass. The social democratic welfare regimes hinder – while the liberal welfare regime generate – such underclass phenomena.......Comparative studies of social capital, operationalised as social trust between citizens, have revealed two major puzzles. The first puzzle has to do with the decline in social trust in the USA, which fuelled considerable debate about social capital. The question is why social capital erodes...... in the USA and other liberal welfare regimes, while social capital is stable in the so-called social democratic and conservative welfare regimes. The second puzzle is why the group of social democratic regimes have extremely high levels of social trust. It is argued that both puzzles have to do...

  13. Early signatures of regime shifts in complex dynamical systems

    Indian Academy of Sciences (India)

    Indrani Bose; Mainak Pal

    2015-02-01

    A large number of studies have recently been carried out on the early signatures of regime shifts in a number of dynamical systems, e.g., ecosystems, the climate, fish and wildlife populations, financial markets, complex diseases and gene circuits. The underlying model in most cases is that of the fold-bifurcation in which a sudden regime shift occurs at a bifurcation point. The shift involves a discontinuous jump from one type of stable steady state to another. The dynamics of natural systems have both deterministic and stochastic components. The early signatures of abrupt regime shifts include the critical slowing down as a transition point is approached, rising variance and the lag-1 autocorrelation function, increased skewness of the steady-state probability distribution and the ratio of two mean first passage times for the exits from the stable steady states as the bifurcation point is approached. Noise-induced regime shifts are also possible for which the vicinity of the bifurcation point is not essential. In this paper, we review examples of regime shifts in natural systems and the associated early signatures. We further discuss how such approaches provide useful insights on a cell biological process involving the fold-bifurcation.

  14. Control of Synchronization Regimes in Networks of Mobile Interacting Agents

    Science.gov (United States)

    Perez-Diaz, Fernando; Zillmer, Ruediger; Groß, Roderich

    2017-05-01

    We investigate synchronization in a population of mobile pulse-coupled agents with a view towards implementations in swarm-robotics systems and mobile sensor networks. Previous theoretical approaches dealt with range and nearest-neighbor interactions. In the latter case, a synchronization-hindering regime for intermediate agent mobility is found. We investigate the robustness of this intermediate regime under practical scenarios. We show that synchronization in the intermediate regime can be predicted by means of a suitable metric of the phase response curve. Furthermore, we study more-realistic K -nearest-neighbor and cone-of-vision interactions, showing that it is possible to control the extent of the synchronization-hindering region by appropriately tuning the size of the neighborhood. To assess the effect of noise, we analyze the propagation of perturbations over the network and draw an analogy between the response in the hindering regime and stable chaos. Our findings reveal the conditions for the control of clock or activity synchronization of agents with intermediate mobility. In addition, the emergence of the intermediate regime is validated experimentally using a swarm of physical robots interacting with cone-of-vision interactions.

  15. The political use of psychiatry: A comparison between totalitarian regimes.

    Science.gov (United States)

    Buoli, Massimiliano; Giannuli, Aldo Sabino

    2017-03-01

    After the end of Second World War, the recent experience of the Nazi horrors stimulated a debate about the political use of psychiatry. Over the years, the focus shifted on major dictatorships of the time and especially on Soviet Union. This article aims to provide a critical review of the ways in which psychiatry was used by totalitarian regimes of the 20th century. We summarized relevant literature about political use of psychiatry in totalitarian regimes of the 20th century, with particular focus on Fascism, Nazism, Argentina dictatorship, Soviet Union and China. One of the features that are common to most of the dictatorships is that the use of psychiatry has become more prominent when the regimes have had the need to make more acceptable the imprisonment of enemies in the eyes of the world. This for example happened in the Nazi regime when sterilization and killing of psychiatric patients was explained as a kind of euthanasia, or in the Soviet Union after the formal closure of the corrective labor camps and the slow resumption of relations with the capitalistic world, or in China to justify persecution of religious minorities and preserve economic relations with Western countries. Psychiatry has been variously used by totalitarian regimes as a means of political persecution and especially when it was necessary to make acceptable to public opinion the imprisonment of political opponents.

  16. Differentially Rotating White Dwarfs I: Regimes of Internal Rotation

    Science.gov (United States)

    Ghosh, Pranab; Wheeler, J. Craig

    2017-01-01

    Most viable models of Type Ia supernovae (SNe Ia) require the thermonuclear explosion of a carbon/oxygen white dwarf that has evolved in a binary system. Rotation could be an important aspect of any model for SNe Ia, whether single or double degenerate, with the white dwarf mass at, below, or above the Chandrasekhar limit. Differential rotation is specifically invoked in attempts to account for the apparent excess mass in the super-Chandrasekhar events. Some earlier work has suggested that only uniform rotation is consistent with the expected mechanisms of angular momentum transport in white dwarfs, while others have found pronounced differential rotation. We show that if the baroclinic instability is active in degenerate matter and the effects of magnetic fields are neglected, both nearly uniform rotation and strongly differential rotation are possible. We classify rotation regimes in terms of the Richardson number, Ri. At small values of Ri ≤slant 0.1, we find both the low-viscosity Zahn regime with a nonmonotonic angular velocity profile and a new differential rotation regime for which the viscosity is high and scales linearly with the shear, σ. Employment of Kelvin–Helmholtz viscosity alone yields differential rotation. Large values of Ri ≫ 1 produce a regime of nearly uniform rotation for which the baroclinic viscosity is of intermediate value and scales as {σ }3. We discuss the gap in understanding of the behavior at intermediate values of Ri and how observations may constrain the rotation regimes attained by nature.

  17. Weather Regimes: The Challenge in Extended-Range Forecasting

    Science.gov (United States)

    Reinhold, Brian

    1987-01-01

    A hypothesis to explain the low-frequency (10- to 90-day) variance of the mid-latitude atmosphere is presented. In this hypothesis it is proposed that the planetary-scale waves forced by topography or other zonal inhomogeneities and the day-to-day weather disturbances (synoptic scales) influence each other to generate weather regimes. These quasi-stable flow configurations are responsible for short-range climate anomalies such as droughts, heat waves, deep freezes, and excessive precipitation, as the weather-producing disturbances are organized into storm tracks. Onset and disruption of the weather regimes may be induced by the anomalous development of perhaps a single cyclonic disturbance, which can throw the quasi equilibrium out of balance. Thus, rapid changes in flow regimes can occur almost at random. The development and transition of weather regimes may then be purely internal (that is, depending only upon the properties of the fluid motions themselves) to the atmospheric dynamics. This internal quality suggests that the chaotic, abrupt short-range climatic behavior of the mid-latitudes is a natural behavior of the system that requires no assistance from the outside. The weather regime concept presents a different view of the extended-range atmospheric behavior than the stimulus-response model, such as the atmospheric response to the El Nino.

  18. Regime switching model for financial data: Empirical risk analysis

    Science.gov (United States)

    Salhi, Khaled; Deaconu, Madalina; Lejay, Antoine; Champagnat, Nicolas; Navet, Nicolas

    2016-11-01

    This paper constructs a regime switching model for the univariate Value-at-Risk estimation. Extreme value theory (EVT) and hidden Markov models (HMM) are combined to estimate a hybrid model that takes volatility clustering into account. In the first stage, HMM is used to classify data in crisis and steady periods, while in the second stage, EVT is applied to the previously classified data to rub out the delay between regime switching and their detection. This new model is applied to prices of numerous stocks exchanged on NYSE Euronext Paris over the period 2001-2011. We focus on daily returns for which calibration has to be done on a small dataset. The relative performance of the regime switching model is benchmarked against other well-known modeling techniques, such as stable, power laws and GARCH models. The empirical results show that the regime switching model increases predictive performance of financial forecasting according to the number of violations and tail-loss tests. This suggests that the regime switching model is a robust forecasting variant of power laws model while remaining practical to implement the VaR measurement.

  19. Nonlinear regime-switching state-space (RSSS) models.

    Science.gov (United States)

    Chow, Sy-Miin; Zhang, Guangjian

    2013-10-01

    Nonlinear dynamic factor analysis models extend standard linear dynamic factor analysis models by allowing time series processes to be nonlinear at the latent level (e.g., involving interaction between two latent processes). In practice, it is often of interest to identify the phases--namely, latent "regimes" or classes--during which a system is characterized by distinctly different dynamics. We propose a new class of models, termed nonlinear regime-switching state-space (RSSS) models, which subsumes regime-switching nonlinear dynamic factor analysis models as a special case. In nonlinear RSSS models, the change processes within regimes, represented using a state-space model, are allowed to be nonlinear. An estimation procedure obtained by combining the extended Kalman filter and the Kim filter is proposed as a way to estimate nonlinear RSSS models. We illustrate the utility of nonlinear RSSS models by fitting a nonlinear dynamic factor analysis model with regime-specific cross-regression parameters to a set of experience sampling affect data. The parallels between nonlinear RSSS models and other well-known discrete change models in the literature are discussed briefly.

  20. Burning plasma regime for Fussion-Fission Research Facility

    Science.gov (United States)

    Zakharov, Leonid E.

    2010-11-01

    The basic aspects of burning plasma regimes of Fusion-Fission Research Facility (FFRF, R/a=4/1 m/m, Ipl=5 MA, Btor=4-6 T, P^DT=50-100 MW, P^fission=80-4000 MW, 1 m thick blanket), which is suggested as the next step device for Chinese fusion program, are presented. The mission of FFRF is to advance magnetic fusion to the level of a stationary neutron source and to create a technical, scientific, and technology basis for the utilization of high-energy fusion neutrons for the needs of nuclear energy and technology. FFRF will rely as much as possible on ITER design. Thus, the magnetic system, especially TFC, will take advantage of ITER experience. TFC will use the same superconductor as ITER. The plasma regimes will represent an extension of the stationary plasma regimes on HT-7 and EAST tokamaks at ASIPP. Both inductive discharges and stationary non-inductive Lower Hybrid Current Drive (LHCD) will be possible. FFRF strongly relies on new, Lithium Wall Fusion (LiWF) plasma regimes, the development of which will be done on NSTX, HT-7, EAST in parallel with the design work. This regime will eliminate a number of uncertainties, still remaining unresolved in the ITER project. Well controlled, hours long inductive current drive operation at P^DT=50-100 MW is predicted.

  1. Protective effect of urokinase on vascular walls of the affected vessels in rats with deep vein thrombosis%尿激酶对急性深静脉血栓大鼠受累血管管壁的保护作用

    Institute of Scientific and Technical Information of China (English)

    王护国; 哈尔满·阿吉汗; 赛力克·马高维亚; 罗军

    2012-01-01

    目的:观察不同剂量尿激酶对急性深静脉血栓形成大鼠不同时期治疗后受累血管管壁的影响.方法:将96只SD大鼠制备急性深静脉血栓模型后,随机按血栓形成后的时间(1,3,7,14d)分期,均分为:Ⅰ,Ⅱ,Ⅲ,Ⅳ期;每期再均分为:模型组,尿激酶小剂量组[2万U/(kg·d)],尿激酶中剂量组[4万U/(kg·d)],尿激酶大剂量组[(8万U/(kg·d)].尿激酶每日以尾静脉注射,连续7d.实验结束后获取受累段血管,分别通过HE染色和苦味酸-天狼猩红染色观察各组血管内皮细胞数量和胶原含量的变化.结果:在Ⅰ,Ⅱ,Ⅲ期,尿激酶3个剂量组内皮细胞数量均明显高于模型组(均P<0.05),但尿激酶3个剂量组间差异无统计学意义(P>0.05);胶原阳性染色面积百分比均明显低于模型组(均P<0.05),且随着尿激酶剂量的增加而减少.在Ⅳ期,尿激酶3个剂量组内皮细胞数量与模型组比较均无统计学的差异(均P>0.05);但尿激酶3个剂量组胶原阳性染色面积百分比仍明显低于模型组(均P<0.05).结论:在血栓形成14d内,尿激酶对受累血管的内皮细胞有保护作用,对胶原增生均有抑制作用.在血栓形成14d后,尿激酶对内皮细胞无保护作用,但对胶原增生仍有抑制作用.%Objective: To observe the effects of different doses of urokinase, given at different times after thrombus formation, on the vascular wall of the affected vessels in rats with deep vein thrombosis (DVT). Methods: Ninety-six SD rats were equally randomized into stage Ⅰ, stage Ⅱ, stage Ⅲ and stage IV groups according to the time elapsed since thrombus formation (l, 3, 7, and 14 d) after the establishment of DVT model. The rats of each stage group were equally randomized again into model group, low-dose urokinase [20 000 U/(kg·d)] group, mid-dose [40 000 U/(kg·d)] urokinase group and high-dose [80 000 U/(kg.d)] urokinase group. Urokinase was administered by tail vein injection for 7 days

  2. Adelie penguin foraging location predicted by tidal regime switching.

    Directory of Open Access Journals (Sweden)

    Matthew J Oliver

    Full Text Available Penguin foraging and breeding success depend on broad-scale environmental and local-scale hydrographic features of their habitat. We investigated the effect of local tidal currents on a population of Adélie penguins on Humble Is., Antarctica. We used satellite-tagged penguins, an autonomous underwater vehicle, and historical tidal records to model of penguin foraging locations over ten seasons. The bearing of tidal currents did not oscillate daily, but rather between diurnal and semidiurnal tidal regimes. Adélie penguins foraging locations changed in response to tidal regime switching, and not to daily tidal patterns. The hydrography and foraging patterns of Adélie penguins during these switching tidal regimes suggest that they are responding to changing prey availability, as they are concentrated and dispersed in nearby Palmer Deep by variable tidal forcing on weekly timescales, providing a link between local currents and the ecology of this predator.

  3. The history of research into improved confinement regimes

    Science.gov (United States)

    Wagner, F.

    2017-01-01

    Increasing the pressure by additional heating of magnetically confined plasmas had the consequence that turbulent processes became more violent and plasma confinement degraded. Since this experience from the early 1980ies, fusion research was dominated by the search for confinement regimes with improved properties. It was a gratifying experience that toroidally confined plasmas are able to self-organise in such a way that turbulence diminishes, resulting in a confinement with good prospects to reach the objectives of fusion R&D. The understanding of improved confinement regimes revolutionized the understanding of turbulent transport in high-temperature plasmas. In this paper the story of research into improved confinement regimes will be narrated starting with 1980.

  4. Inhomogeneous stationary and oscillatory regimes in coupled chaotic oscillators.

    Science.gov (United States)

    Liu, Weiqing; Volkov, Evgeny; Xiao, Jinghua; Zou, Wei; Zhan, Meng; Yang, Junzhong

    2012-09-01

    The dynamics of linearly coupled identical Lorenz and Pikovsky-Rabinovich oscillators are explored numerically and theoretically. We concentrate on the study of inhomogeneous stable steady states ("oscillation death (OD)" phenomenon) and accompanying periodic and chaotic regimes that emerge at an appropriate choice of the coupling matrix. The parameters, for which OD occurs, are determined by stability analysis of the chosen steady state. Three model-specific types of transitions to and from OD are observed: (1) a sharp transition to OD from a nonsymmetric chaotic attractor containing random intervals of synchronous chaos; (2) transition to OD from the symmetry-breaking chaotic regime created by negative coupling; (3) supercritical bifurcation of OD into inhomogeneous limit cycles and further evolution of the system to inhomogeneous chaotic regimes that coexist with complete synchronous chaos. These results may fill a gap in the understanding of the mechanism of OD in coupled chaotic systems.

  5. Nonlinear double Compton scattering in the full quantum regime

    CERN Document Server

    Mackenroth, F

    2012-01-01

    A detailed analysis of the process of two photon emission by an electron scattered from a high-intensity laser pulse is presented. The calculations are performed in the framework of strong-field QED and include exactly the presence of the laser field, described as a plane wave. We investigate the full quantum regime of interaction, where photon recoil plays an essential role in the emission process, and substantially alters the emitted photon spectra as compared to those in previously-studied regimes. We provide a semiclassical explanation for such differences, based on the possibility of assigning a trajectory to the electron in the laser field before and after each quantum photon emission. Our numerical results indicate the feasibility of investigating experimentally the full quantum regime of nonlinear double Compton scattering with already available plasma-based electron accelerator and laser technology.

  6. Adaptive management of ecosystem services across different land use regimes.

    Science.gov (United States)

    Ruhl, J B

    2016-12-01

    Using adaptive management to manage desired flows of ecosystem services may seem on the surface to be a good fit, but many social, economic, environmental, legal, and political factors influence how good a fit. One strongly influential factor is the land use regime within which the profile of ecosystem services is being managed. Shaped largely by legal mandates, market forces, and social and cultural practices, different land use regimes present different opportunities for and constraints on goals for ecosystem services and pose different decision making environments. Even where all other conditions appear amenable to using adaptive management, therefore, it is essential to consider the constraining (or liberating) effects of different land use regimes when deciding whether to adopt adaptive management to achieve those goals and, if so, how to implement it. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. The difficulties of the Chinese and Indian exchange rate regimes

    Directory of Open Access Journals (Sweden)

    Ila Patnaik

    2009-06-01

    Full Text Available China and India have both sought control over the exchange rate in order to maintain export competitiveness, manage current account balance, and pursue independent monetary policy. In this paper, we examine structural change in the Chinese and Indian de facto exchange rate regimes, focusing on the period from 1998 to 2007. With increasing capital account openness, exchange rate inflexibility has been associated with significant monetary policy distortions. In both countries, the short-term rate expressed in real terms dropped, and achieved very low values, in the unprecedented business cycle expansion of the early 2000s. In the Indian case, difficulties of sterilisation led to a modification of the exchange rate regime, moving towards greater flexibility. In China, in contrast, the exchange rate regime did not change.

  8. Hydrodynamic interaction of swimming organisms in an inertial regime

    Science.gov (United States)

    Li, Gaojin; Ostace, Anca; Ardekani, Arezoo M.

    2016-11-01

    We numerically investigate the hydrodynamic interaction of swimming organisms at small to intermediate Reynolds number regimes, i.e., Re˜O (0.1 -100 ) , where inertial effects are important. The hydrodynamic interaction of swimming organisms in this regime is significantly different from the Stokes regime for microorganisms, as well as the high Reynolds number flows for fish and birds, which involves strong flow separation and detached vortex structures. Using an archetypal swimmer model, called a "squirmer," we find that the inertial effects change the contact time and dispersion dynamics of a pair of pusher swimmers, and trigger hydrodynamic attraction for two pullers. These results are potentially important in investigating predator-prey interactions, sexual reproduction, and the encounter rate of marine organisms such as copepods, ctenophora, and larvae.

  9. A Markov Switching Regime Model of Malaysia Property Cycle

    Directory of Open Access Journals (Sweden)

    Abdul M. Beksin

    2011-01-01

    Full Text Available Problem statement: Non-linear models such as the Markov Switching regime (MS method of modelling business cycles, in principle can be used to model property cyle. Approach: The MS model can distinguish property cycle in recession and expansion phases and is sufficiently flexible to allow different relationships to apply over these phases. In this study, the Malaysian property cycle is modelled using a MS model. Results: This technique can be used to simultaneously estimate the data generating process of real GDP growth and classify each observation into one of two regimes (i.e., low-growth and high-growth regimes. Conclusions: This finding has important policy implications, since the yield spread was used to generate the time-varying probabilities of the MS model as well as the recession probabilities of the logit model. In other words, a strong relationship exists between interest rates and the business cycle, where interest rates lead the business cycle.

  10. How will climate change modify river flow regimes in Europe?

    Directory of Open Access Journals (Sweden)

    C. Schneider

    2013-01-01

    Full Text Available Worldwide, flow regimes are being modified by various anthropogenic impacts and climate change induces an additional risk. Rising temperatures, declining snow cover and changing precipitation patterns will interact differently at different locations. Consequently, in distinct climate zones, unequal consequences can be expected in matters of water stress, flood risk, water quality, and food security. In particular, river ecosystems and their vital ecosystem services will be compromised as their species richness and composition have evolved over long time under natural flow conditions. This study aims at evaluating the exclusive impacts of climate change on river flow regimes in Europe. Various flow characteristics are taken into consideration and diverse dynamics are identified for each distinct climate zone in Europe. In order to simulate present-day natural flow regimes and future flow regimes under climate change, the global hydrology model WaterGAP3 is applied. All calculations for current and future conditions (2050s are carried out on a 5' × 5' European grid. To address uncertainty, bias-corrected climate forcing data of three different global climate models are used to drive WaterGAP3. Finally, the hydrological alterations of different flow characteristics are quantified by the Indicators of Hydrological Alteration approach. Results of our analysis indicate that on the European scale, climate change can be expected to modify flow regimes remarkably. This is especially the case in the Mediterranean (due to drier conditions with reduced precipitation across the year and in the boreal climate zone (due to reduced snowmelt, increased precipitation, and strong temperature rises. In the temperate climate zone, impacts increase from oceanic to continental. Regarding single flow characteristics, strongest impacts on timing were found for the boreal climate zone. This applies for both high and low flows. Flow magnitudes, in turn, will be

  11. Modeling whistler wave generation regimes in magnetospheric cyclotron maser

    Directory of Open Access Journals (Sweden)

    D. L. Pasmanik

    2004-11-01

    Full Text Available Numerical analysis of the model for cyclotron instability in the Earth's magnetosphere is performed. This model, based on the self-consistent set of equations of quasi-linear plasma theory, describes different regimes of wave generation and related energetic particle precipitation. As the source of free energy the injection of energetic electrons with transverse anisotropic distribution function to the interaction region is considered. A parametric study of the model is performed. The main attention is paid to the analysis of generation regimes for different characteristics of energetic electron source, such as the shape of pitch angle distributions and its intensity. Two mechanisms of removal of energetic electrons from a generation region are considered, one is due to the particle precipitation through the loss cone and another one is related to the magnetic drift of energetic particles.

    It was confirmed that two main regimes occur in this system in the presence of a constant particle source, in the case of precipitation losses. At small source intensity relaxation oscillations were found, whose parameters are in good agreement with simplified analytical theory developed earlier. At a larger source intensity, transition to a periodic generation occurs. In the case of drift losses the regime of self-sustained periodic generation regime is realized for source intensity higher than some threshold. The dependencies of repetition period and dynamic spectrum shape on the source parameters were studied in detail. In addition to simple periodic regimes, those with more complex spectral forms were found. In particular, alteration of spikes with different spectral shape can take place. It was also shown that quasi-stationary generation at the low-frequency band can coexist with periodic modulation at higher frequencies.

    On the basis of the results obtained, the model for explanation of

  12. Jovem aprisionado em regime semi-aberto: um estudo transdisciplinar

    OpenAIRE

    Lazzaron, Leandra Regina

    2008-01-01

    A presente dissertação, vinculada à linha de pesquisa “Criminologia e Controle Social”, do Programa de Pós-Graduação em Ciências Criminais, da Faculdade de Direito da Pontifícia Universidade Católica do Rio Grande do Sul, identifica o perfil do jovem apenado, aprisionado em regime semi-aberto, no Instituto Penal de Viamão, com base na escala PCL-R. O estudo de campo foi realizado na instituição prisional e avaliou 40 jovens, com idade de 18 a 23 anos, que cumprem pena em regime semi-aberto. O...

  13. Measurement of flow in supercritical flow regime using cutthroat flumes

    Indian Academy of Sciences (India)

    Shrikant A Tekade; Avinash D Vasudeo; Aniruddha D Ghare; Ramesh N Ingle

    2016-02-01

    Cutthroat flume is commonly used for measurement of subcritical flow in open channel because of its simplicity and ease of construction. No experimental data is available in literature for measurement of flow in supercritical regime using cutthroat flume. The present paper finds the feasibility of cutthroat flume as a measurement device for flow in supercritical regime. Experimental data are generated to develop the relation between discharge and observed head at a specified location on upstream of throat section. Regression analysis for discharge and head indicated a good correlation. Based on all the experimental data generated, a relationship between discharge and head is proposed.

  14. The Semiclassical Regime of the Chaotic Quantum-Classical Transition

    CERN Document Server

    Greenbaum, B D; Shizume, K; Sundaram, B; Greenbaum, Benjamin D.; Habib, Salman; Shizume, Kosuke; Sundaram, Bala

    2004-01-01

    An analysis of the semiclassical regime of the quantum-classical transition is given for open, bounded, one dimensional chaotic dynamical systems. Previous numerical work has shown that in this regime, the results from a quantum master equation are very close to those obtained from a classical Fokker-Planck equation. We provide an explanation of these results by demonstrating that environmental noise plays the dual roles of suppressing the development of fine structure in classical phase space and damping nonlocal contributions to the semiclassical Wigner function. A numerical investigation of the chaotic Duffing oscillator supports these conclusions.

  15. Terahertz Quantum Plasmonics of Nanoslot Antennas in Nonlinear Regime.

    Science.gov (United States)

    Kim, Joon-Yeon; Kang, Bong Joo; Park, Joohyun; Bahk, Young-Mi; Kim, Won Tae; Rhie, Jiyeah; Jeon, Hyeongtag; Rotermund, Fabian; Kim, Dai-Sik

    2015-10-14

    Quantum tunneling in plasmonic nanostructures has presented an interesting aspect of incorporating quantum mechanics into classical optics. However, the study has been limited to the subnanometer gap regime. Here, we newly extend quantum plasmonics to gap widths well over 1 nm by taking advantage of the low-frequency terahertz regime. Enhanced electric fields of up to 5 V/nm induce tunneling of electrons in different arrays of ring-shaped nanoslot antennas of gap widths from 1.5 to 10 nm, which lead to a significant nonlinear transmission decrease. These observations are consistent with theoretical calculations considering terahertz-funneling-induced electron tunneling across the gap.

  16. PREDICTION OF FLOW REGIMES IN SPOUT-FLUIDIZED BEDS

    Institute of Scientific and Technical Information of China (English)

    Jiyu Zhang; Fengxiang Tang

    2006-01-01

    Five main flow regimes in spout-fluidized bed were identified in this study, namely, fixed bed, spout with aeration, spout-fluidization, jet in fluidized bed and slugging, together with their corresponding major frequencies translated from pressure signals. The empirical equation A=aBb, in which A=Fr* /(H/Di) and B=(Fr*/(H/D))/(μg/μmf) are respectively the spout-geometry and spout-geometry-fluidization dimensionless numbers, was proposed to distinguish these flow regimes.

  17. Explicit Mapping of Acoustic Regimes For Wind Instruments

    CERN Document Server

    Missoum, Samy; Doc, Jean-Baptiste

    2014-01-01

    This paper proposes a methodology to map the various acoustic regimes of wind instruments. The maps can be generated in a multi-dimensional space consisting of design, control parameters, and initial conditions. The bound- aries of the maps are obtained explicitly in terms of the parameters using a support vector machine (SVM) classifier as well as a dedicated adaptive sam- pling scheme. The approach is demonstrated on a simplified clarinet model for which several maps are generated based on different criteria. Examples of computation of the probability of occurrence of a specific acoustic regime are also provided. In addition, the approach is demonstrated on a design optimization example for optimal intonation.

  18. THE CASE FOR AN INTERMEDIATE EXCHANGE RATE REGIME

    OpenAIRE

    JOHN WILLIAMSON

    2007-01-01

    The argument that any exchange rate regimes other than firmly fixed and freely floating rates were infeasible — the so-called bipolarity thesis — acquired great popularity in the wake of the Asian crisis of a decade ago, but it has almost vanished today. One reason is surely the unkind empirical evidence, which shows that intermediate regimes — measured as those where both reserve and exchange rate changes lie in an intermediate range — are not in fact tending to disappear (Levy Yeyati and St...

  19. Synchronization of Spatiotemporal Chaos The regime of coupled Spatiotemporal Intermittency

    CERN Document Server

    Amengual, A; Montagne, R; Miguel, M S

    1996-01-01

    Synchronization of spatiotemporally chaotic extended systems is considered in the context of coupled one-dimensional Complex Ginzburg-Landau equations (CGLE). A regime of coupled spatiotemporal intermittency (STI) is identified and described in terms of the space-time synchronized chaotic motion of localized structures. A quantitative measure of synchronization as a function of coupling parameter is given through distribution functions and information measures. The coupled STI regime is shown to dissapear into regular dynamics for situations of strong coupling, hence a description in terms of a single CGLE is not appropiate.

  20. Selection Criteria in Regime Switching Conditional Volatility Models

    Directory of Open Access Journals (Sweden)

    Thomas Chuffart

    2015-05-01

    Full Text Available A large number of nonlinear conditional heteroskedastic models have been proposed in the literature. Model selection is crucial to any statistical data analysis. In this article, we investigate whether the most commonly used selection criteria lead to choice of the right specification in a regime switching framework. We focus on two types of models: the Logistic Smooth Transition GARCH and the Markov-Switching GARCH models. Simulation experiments reveal that information criteria and loss functions can lead to misspecification ; BIC sometimes indicates the wrong regime switching framework. Depending on the Data Generating Process used in the experiments, great care is needed when choosing a criterion.

  1. Regime Switches in the Risk-Return Trade-off

    OpenAIRE

    Ghysels, Eric; Guérin, Pierre; Marcellino, Massimiliano

    2013-01-01

    This paper deals with the estimation of the risk-return trade-off. We use a MIDAS model for the conditional variance and allow for possible switches in the risk-return relation through a Markov-switching specification. We find strong evidence for regime changes in the risk-return relation. This finding is robust to a large range of specifications. In the first regime characterized by low ex-post returns and high volatility, the risk-return relation is reversed, whereas the intuitive positive ...

  2. Space as a low-temperature regime of graphs

    CERN Document Server

    Conrady, Florian

    2010-01-01

    I define a statistical model of graphs in which 2-dimensional spaces arise at low temperature. The configurations are given by graphs with a fixed number of edges and the Hamiltonian is a simple, local function of the graphs. Simulations show that there is a transition between a low-temperature regime in which the graphs form triangulations of 2-dimensional surfaces and a high-temperature regime, where the surfaces disappear. I use data for the specific heat and other observables to discuss whether this is a phase transition. The surface states are analyzed with regard to topology and defects.

  3. Political humor as a confrontational tool against the syrian regime

    OpenAIRE

    Camps-Febrer, Blanca

    2012-01-01

    The aim of this working paper is to analyze the inclusion of political humor into the set of actions used by opponents to the Syrian regime during the first year of a state-wide uprising in 2011. The research ar-gues that although political humor has traditionally been seen mainly as a concealed voice against dominant elites, it can nevertheless take a confrontational stance and challenge a regime. In this paper we assess the role of political humor in challenging the legitimacy of the Syrian...

  4. The rise of a learning regime in Europe

    DEFF Research Database (Denmark)

    Ehlers, Søren

    2017-01-01

    Policy terms lead to change. They appear and disappear in policy papers across time and space and instigate continuity or discontinuity. To understand how this happens, policy terms need to be mapped. It could be done through a systematic analysis of models, hypotheses, quantitative data, antonyms...... and studies of time and space – in comparison. Appearance of the term Lifelong Learning and the change from Teaching Regime to Learning Regime is used as an example in this paper to show how this mapping could be done....

  5. Using Clustering to Establish Climate Regimes from PCM Output

    Science.gov (United States)

    Oglesby, Robert; Arnold, James E. (Technical Monitor); Hoffman, Forrest; Hargrove, W. W.; Erickson, D.

    2002-01-01

    A multivariate statistical clustering technique--based on the k-means algorithm of Hartigan has been used to extract patterns of climatological significance from 200 years of general circulation model (GCM) output. Originally developed and implemented on a Beowulf-style parallel computer constructed by Hoffman and Hargrove from surplus commodity desktop PCs, the high performance parallel clustering algorithm was previously applied to the derivation of ecoregions from map stacks of 9 and 25 geophysical conditions or variables for the conterminous U.S. at a resolution of 1 sq km. Now applied both across space and through time, the clustering technique yields temporally-varying climate regimes predicted by transient runs of the Parallel Climate Model (PCM). Using a business-as-usual (BAU) scenario and clustering four fields of significance to the global water cycle (surface temperature, precipitation, soil moisture, and snow depth) from 1871 through 2098, the authors' analysis shows an increase in spatial area occupied by the cluster or climate regime which typifies desert regions (i.e., an increase in desertification) and a decrease in the spatial area occupied by the climate regime typifying winter-time high latitude perma-frost regions. The patterns of cluster changes have been analyzed to understand the predicted variability in the water cycle on global and continental scales. In addition, representative climate regimes were determined by taking three 10-year averages of the fields 100 years apart for northern hemisphere winter (December, January, and February) and summer (June, July, and August). The result is global maps of typical seasonal climate regimes for 100 years in the past, for the present, and for 100 years into the future. Using three-dimensional data or phase space representations of these climate regimes (i.e., the cluster centroids), the authors demonstrate the portion of this phase space occupied by the land surface at all points in space and time

  6. Educational differentials in disability vary across and within welfare regimes

    DEFF Research Database (Denmark)

    Cambois, Emmanuelle; Solé-Auró, Aïda; Brønnum-Hansen, Henrik;

    2016-01-01

    groups (referred to as disability disadvantage) and of the lower prevalence in high social groups (disability advantage); country-specific advantages/disadvantages are discussed regarding the possible influence of welfare regimes. METHODS: Cross-sectional disability prevalence is measured by longstanding...... health-related activity limitation (AL) in the 2009 European Statistics on Income and Living Conditions (EU-SILC) across 26 countries classified into four welfare regime groups. Logistic models adjusted by country, age and sex (in all 30-79 years and in three age-bands) measured the country-specific ORs...

  7. A faster switching regime for zenithal bistable nematic displays

    Energy Technology Data Exchange (ETDEWEB)

    Rudin, J

    1997-12-01

    A simpler and faster switching regime for Zenithal Bistable Nematic displays is reported. A cell, based on homeotropic alignment of nematic liquid crystal over a continuous blazed monograting on one surface, can be switched using bipolar pulses an order of magnitude faster than monopolar pulses of the same voltage. We propose that this regime relies on simple dielectric coupling to drive the cell into a higher energy state with a long pulse time, and the relaxation into a lower energy state after the creation of surface defects from a shorter applied pulse. Although flexoelectric effects are observed, they do not form the basis of state selection as was proposed for the monopolar pulses

  8. Quantum regime of a free-electron laser: relativistic approach

    Science.gov (United States)

    Kling, Peter; Sauerbrey, Roland; Preiss, Paul; Giese, Enno; Endrich, Rainer; Schleich, Wolfgang P.

    2017-01-01

    In the quantum regime of the free-electron laser, the dynamics of the electrons is not governed by continuous trajectories but by discrete jumps in momentum. In this article, we rederive the two crucial conditions to enter this quantum regime: (1) a large quantum mechanical recoil of the electron caused by the scattering with the laser and the wiggler field and (2) a small energy spread of the electron beam. In contrast to our recent approach based on nonrelativistic quantum mechanics in a co-moving frame of reference, we now pursue a model in the laboratory frame employing relativistic quantum electrodynamics.

  9. NAZI REGIME IN THE PERIODICAL A NOTÍ­CIA.

    Directory of Open Access Journals (Sweden)

    Bruna Luíza Barcellos

    2009-08-01

    Full Text Available The periodical A Notícia, of Joinville, city colonized for Germans, supported the nazi regime since the ascension of Adolf Hitler to the power. Between 1932 and 1944, some editions had printed the figure of Hitler and the nazi symbol, beyond dither messages to that regime. Based in the Análise de conteúdo (BARDIN, 1977, this article searchs to understand the representation made for the periodical A Notícia on this historical landmark, in other words, bring to the light the consequences of a part of occured world-wide history in catarinense territory.

  10. Is the Economic Crisis Challenging the Prevailing Gender Regime?

    DEFF Research Database (Denmark)

    Leschke, Janine; Jepsen, Maria

    2014-01-01

    This paper addresses the question of whether the current economic and financial crisis is challenging the prevailing gender-equality model in four European countries: Denmark, Germany, Slovakia, and the United Kingdom. After situating the countries in relation to the underlying gender regime...... and analysing the corresponding position of women and men in paid and unpaid work, the paper contains an in-depth discussion of the short- and medium-term policy responses to the crisis. Our analysis shows that independent of the prevailing gender regime, scant public attention has been directed to gender...

  11. Using Clustering to Establish Climate Regimes from PCM Output

    Science.gov (United States)

    Oglesby, Robert; Arnold, James E. (Technical Monitor); Hoffman, Forrest; Hargrove, W. W.; Erickson, D.

    2002-01-01

    A multivariate statistical clustering technique--based on the k-means algorithm of Hartigan has been used to extract patterns of climatological significance from 200 years of general circulation model (GCM) output. Originally developed and implemented on a Beowulf-style parallel computer constructed by Hoffman and Hargrove from surplus commodity desktop PCs, the high performance parallel clustering algorithm was previously applied to the derivation of ecoregions from map stacks of 9 and 25 geophysical conditions or variables for the conterminous U.S. at a resolution of 1 sq km. Now applied both across space and through time, the clustering technique yields temporally-varying climate regimes predicted by transient runs of the Parallel Climate Model (PCM). Using a business-as-usual (BAU) scenario and clustering four fields of significance to the global water cycle (surface temperature, precipitation, soil moisture, and snow depth) from 1871 through 2098, the authors' analysis shows an increase in spatial area occupied by the cluster or climate regime which typifies desert regions (i.e., an increase in desertification) and a decrease in the spatial area occupied by the climate regime typifying winter-time high latitude perma-frost regions. The patterns of cluster changes have been analyzed to understand the predicted variability in the water cycle on global and continental scales. In addition, representative climate regimes were determined by taking three 10-year averages of the fields 100 years apart for northern hemisphere winter (December, January, and February) and summer (June, July, and August). The result is global maps of typical seasonal climate regimes for 100 years in the past, for the present, and for 100 years into the future. Using three-dimensional data or phase space representations of these climate regimes (i.e., the cluster centroids), the authors demonstrate the portion of this phase space occupied by the land surface at all points in space and time

  12. Using Clustering to Establish Climate Regimes from PCM Output

    Science.gov (United States)

    Hoffman, F.; Oglesby, R.; Hargrove, W. W.; Erickson, D.

    2002-12-01

    A multivariate statistical clustering technique--based on the k-means algorithm of Hartigan--has been used to extract patterns of climatological significance from 200 years of general circulation model (GCM) output. Originally developed and implemented on a Beowulf-style parallel computer constructed by Hoffman and Hargrove from surplus commodity desktop PCs, the high performance parallel clustering algorithm was previously applied to the derivation of ecoregions from map stacks of 9 and 25 geophysical conditions or variables for the conterminous U.S. at a resolution of 1 sq km. Now applied both across space and through time, the clustering technique yields temporally-varying climate regimes predicted by transient runs of the Parallel Climate Model (PCM). Using a business-as-usual (BAU) scenario and clustering four fields of significance to the global water cycle (surface temperature, precipitation, soil moisture, and snow depth) from 1871 through 2098, the authors' analysis shows an increase in spatial area occupied by the cluster or climate regime which typifies desert regions (i.e., an increase in desertification) and a decrease in the spatial area occupied by the climate regime typifying winter-time high latitude perma-frost regions. The patterns of cluster changes have been analyzed to understand the predicted variability in the water cycle on global and continental scales. In addition, representative climate regimes were determined by taking three 10-year averages of the fields 100 years apart for northern hemisphere winter (December, January, and February) and summer (June, July, and August). The result is global maps of typical seasonal climate regimes for 100 years in the past, for the present, and for 100 years into the future. Using three-dimensional data or phase space representations of these climate regimes (i.e., the cluster centroids), the authors demonstrate the portion of this phase space occupied by the land surface at all points in space and

  13. Syria: The Consolidation of the Asad Regime, 1970-1975.

    Science.gov (United States)

    Olson, Robert W.

    1982-01-01

    Up to 1975-76, Syria's Hafiz al-Asad was successful in consolidating his power, securing the maintenance of his regime, and broadening his base of political power. His system started weakening in 1975 due to increased opposition stemming from Syria's intervention in the Lebanese civil war. (AM)

  14. Political Regime and Human Capital: A Cross-Country Analysis

    Science.gov (United States)

    Klomp, Jeroen; de Haan, Jakob

    2013-01-01

    We examine the relationship between different dimensions of the political regime in place and human capital using a two-step structural equation model. In the first step, we employ factor analysis on 16 human capital indicators to construct two new human capital measures (basic and advanced human capital). In the second step, we estimate the…

  15. Accessing Imagined Communities and Reinscribing Regimes of Truth

    Science.gov (United States)

    Carroll, Sherrie; Motha, Suhanthie; Price, Jeremy N.

    2008-01-01

    In this article, we explore the complex and nebulous terrain between two theoretical concepts, imagined communities (Norton, 2000, 2001), that is, individuals' imagined affiliations with certain groups, and regimes of truth (Foucault, 1980), dominant images inscribed and reinscribed into individual consciousness until they become normative. Using…

  16. Primordial black holes in linear and non-linear regimes

    CERN Document Server

    Allahyari, Alireza; Abolhasani, Ali Akbar

    2016-01-01

    Using the concept of apparent horizon for dynamical black holes, we revisit the formation of primordial black holes (PBH) in the early universe for both linear and non-linear regimes. First, we develop the perturbation theory for spherically symmetric spacetimes to study the formation of spherical PBHs in linear regime and we fix two gauges. We also introduce a well defined gauge invariant quantity for the expansion. Using this quantity, we argue that PBHs do not form in the linear regime. Finally, we study the non-linear regime. We adopt the spherical collapse picture by taking a closed FRW model in the radiation dominated era to investigate PBH formation. Taking the initial condition of the spherical collapse from the linear theory of perturbations, we allow for both density and velocity perturbations. Our model gives a constraint on the velocity perturbation. This model also predicts that the apparent horizon of PBHs forms when $\\delta > 3$. Applying the sound horizon constraint, we have shown the threshol...

  17. Regular and Chaotic Regimes in Scalar Field Cosmology

    Directory of Open Access Journals (Sweden)

    Alexey V. Toporensky

    2006-03-01

    Full Text Available A transient chaos in a closed FRW cosmological model with a scalar field is studied. We describe two different chaotic regimes and show that the type of chaos in this model depends on the scalar field potential. We have found also that for sufficiently steep potentials or for potentials with large cosmological constant the chaotic behavior disappears.

  18. Exploring the epsilon regime with twisted mass fermions

    CERN Document Server

    Jansen, K; Shindler, A; Urbach, C; Wenger, U

    2007-01-01

    In this proceeding contribution we report on a first study in order to explore the so called epsilon regime with Wilson twisted mass (Wtm) fermions. To show the potential of this approach we give a preliminary determination of the chiral condensate.

  19. Consumption, investment and life insurance under different tax regimes

    DEFF Research Database (Denmark)

    Bruun, Kenneth

    2013-01-01

    We study the effects of introducing taxation in classical continuous-time optimization problems with utility from consumption, bequest and retirement savings. Inspired by actual tax favoured retirement savings programs, we formulate and solve the optimization problem for various tax regimes, and ...

  20. Politics, welfare regimes, and population health: controversies and evidence.

    Science.gov (United States)

    Muntaner, Carles; Borrell, Carme; Ng, Edwin; Chung, Haejoo; Espelt, Albert; Rodriguez-Sanz, Maica; Benach, Joan; O'Campo, Patricia

    2011-09-01

    In recent years, a research area has emerged within social determinants of health that examines the role of politics, expressed as political traditions/parties and welfare state characteristics, on population health. To better understand and synthesise this growing body of evidence, the present literature review, informed by a political economy of health and welfare regimes framework, located 73 empirical and comparative studies on politics and health, meeting our inclusion criteria in three databases: PubMed (1948-), Sociological Abstracts (1953-), and ISI Web of Science (1900-). We identified two major research programmes, welfare regimes and democracy, and two emerging programmes, political tradition and globalisation. Primary findings include: (1) left and egalitarian political traditions on population health are the most salutary, consistent, and substantial; (2) the health impacts of advanced and liberal democracies are also positive and large; (3) welfare regime studies, primarily conducted among wealthy countries, find that social democratic regimes tend to fare best with absolute health outcomes yet consistently in terms of relative health inequalities; and (4) globalisation defined as dependency indicators such as trade, foreign investment, and national debt is negatively associated with population health. We end by discussing epistemological, theoretical, and methodological issues for consideration for future research.